Women's Health

Study 1 Overview (Cortés et al)

Objective: To compare the efficacy and safety of trastuzumab deruxtecan with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxane.

Design: Phase 3, multicenter, open-label randomized trial conducted at 169 centers and 15 countries.

Setting and participants: Eligible patients had to have unresectable or metastatic HER2-positive breast cancer that had progressed during or after treatment with trastuzumab and a taxane or had disease that progressed within 6 months after neoadjuvant or adjuvant treatment involving trastuzumab or taxane. Patients with stable or previously treated brain metastases were eligible. Patients were not eligible for the study if they had symptomatic brain metastases, prior exposure to trastuzumab emtansine, or a history of interstitial lung disease.

Intervention: Patients were randomized in a 1-to-1 fashion to receive either trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or trastuzumab emtansine 3.6 mg/kg every 3 weeks. Patients were stratified according to hormone-receptor status, prior treatment with epratuzumab, and the presence or absence of visceral disease.

Main outcome measures: The primary endpoint of the study was progression-free survival as determined by an independent central review. Secondary endpoints included overall survival, overall response, and safety.

Main results: A total of 524 patients were enrolled in the study, with 261 patients randomized to trastuzumab deruxtecan and 263 patients randomized to trastuzumab emtansine. The demographic and baseline characteristics were similar between the 2 cohorts, and 60% of patients in both groups received prior epratuzumab therapy. Stable brain metastases were present in around 20% of patients in each group, and 70% of patients in each group had visceral disease. The median duration of follow-up was 16.2 months with trastuzumab deruxtecan and 15.3 months with trastuzumab emtansine.

The median progression-free survival was not reached in the trastuzumab deruxtecan group and was 6.8 months in the trastuzumab emtansine group (95% CI, 5.6-8.2). At 12 months the percentage of patients alive without disease progression was significantly larger in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. The hazard ratio for disease progression or death from any cause was 0.28 (95% CI, 0.22-0.37; P < .001). Subgroup analyses showed a benefit in progression-free survival with trastuzumab deruxtecan across all subgroups.

At the time of this analysis, the percentage of patients who were alive at 12 months was 94% with trastuzumab deruxtecan and 85.9% with trastuzumab emtansine. The response rates were significantly higher with trastuzumab deruxtecan compared with trastuzumab emtansine (79.7% vs 34.2%). A complete response was seen in 16% of patients in the trastuzumab deruxtecan arm, compared with 8.7% of patients in the trastuzumab emtansine group. The disease control rate (complete response, partial response, or stable disease) was higher in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group (96.6% vs 76.8%).

Serious adverse events were reported in 19% of patients in the trastuzumab deruxtecan group and 18% of patients in the trastuzumab emtansine group. Discontinuation due to adverse events was higher in the trastuzumab deruxtecan group, with 13.6% of patients discontinuing trastuzumab deruxtecan. Grade 3 or higher adverse events were seen in 52% of patients treated with trastuzumab deruxtecan and 48% of patients treated with trastuzumab emtansine. The most commonly reported adverse event with trastuzumab deruxtecan was nausea/vomiting and fatigue. These adverse events were seen more in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. No drug-related grade 5 adverse events were reported.

In the trastuzumab deruxtecan group, 10.5% of patients receiving trastuzumab deruxtecan developed interstitial lung disease or pneumonitis. Seven patients had grade 1 events, 18 patients had grade 2 events, and 2 patients had grade 3 events. No grade 4 or 5 events were noted in either treatment group. The median time to onset of interstitial lung disease or pneumonitis in those receiving trastuzumab deruxtecan was 168 days (range, 33-507). Discontinuation of therapy due to interstitial lung disease or pneumonitis occurred in 8% of patients receiving trastuzumab deruxtecan and 1% of patients receiving trastuzumab emtansine.

Conclusion: Trastuzumab deruxtecan significantly decreases the risk of disease progression or death compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on prior trastuzumab and taxane-based therapy.

Study 2 Overview (Modi et al)

Objective: To assess the efficacy of trastuzumab deruxtecan in patients with unresectable or metastatic breast cancer with low levels of HER2 expression.

Design: This was a randomized, 2-group, open-label, phase 3 trial.

Setting and participants: The trial was designed with a planned enrollment of 480 patients with hormone receptor–positive disease and 60 patients with hormone receptor–negative disease. Patients were randomized in a 2:1 ratio. Randomization was stratified according to HER2 status (immunohistochemical [IHC] 1+ vs IHC 2+/in situ hybridization [ISH] negative), number of prior lines of therapy, and hormone-receptor status. IHC scores for HER2 expression were determined through central testing. Specimens that had HER2 IHC scores of 2+ were reflexed to ISH. Specimens were considered HER2-low-expressing if they had an IHC score of 1+ or if they had an IHC score of 2+ and were ISH negative.

Eligible patients had to have received chemotherapy for metastatic disease or had disease recurrence during or within 6 months after completing adjuvant chemotherapy. Patients with hormone receptor–positive disease must have had at least 1 line of endocrine therapy. Patients were eligible if they had stable brain metastases. Patients with interstitial lung disease were excluded.

Intervention: Patients were randomized to receive trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel).

Main outcome measures: The primary endpoint was progression-free survival in patients with hormone receptor–positive disease. Secondary endpoints were progression-free survival among all patients, overall survival in hormone receptor–positive patients, and overall survival in all patients. Additional secondary endpoints included objective response rates, duration of response, and efficacy in hormone receptor–negative patients.

Main results: A total of 373 patients were assigned to the trastuzumab deruxtecan group and 184 patients were assigned to the physician’s choice chemotherapy group; 88% of patients in each cohort were hormone receptor–positive. In the physician’s choice chemotherapy group, 51% received eribulin, 20% received capecitabine, 10% received nab-paclitaxel, 10% received gemcitabine, and 8% received paclitaxel. The demographic and baseline characteristics were similar between both cohorts. The median duration of follow-up was 18.4 months.

The median progression-free survival in the hormone receptor–positive cohort was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician’s choice chemotherapy group (HR, 0.51; 95% CI, 0.4-0.64). Subgroup analyses revealed a benefit across all subgroups. The median progression-free survival among patients with a HER2 IHC score of 1+ and those with a HER2 IHC score of 2+/negative ISH were identical. In patients who received a prior CDK 4/6 inhibitor, the median progression-free survival was also 10 months in the trastuzumab deruxtecan group. In those who were CDK 4/6- naïve, the progression-free survival was 11.7 months. The progression-free survival in all patients was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice chemotherapy group (HR, 0.46; 95% CI, 0.24-0.89).

The median overall survival in the hormone receptor–positive cohort was 23.9 months in the trastuzumab deruxtecan group compared with 17.5 months in the physician’s choice chemotherapy group (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The median overall survival in the entire population was 23.4 months in the trastuzumab deruxtecan group vs 16.8 months in the physician’s choice chemotherapy group. In the hormone receptor–negative cohort, the median overall survival was 18.2 months in the trastuzumab deruxtecan group and 8.3 months in the physician’s choice chemotherapy group. Complete responses were seen in 3.6% in the trastuzumab deruxtecan group and 0.6% and the physician’s choice chemotherapy group. The median duration of response was 10.7 months in the trastuzumab deruxtecan group and 6.8 months in the physician’s choice chemotherapy group.

Incidence of serious adverse events was 27% in the trastuzumab deruxtecan group and 25% in the physician’s choice chemotherapy group. Grade 3 or higher events occurred in 52% of the trastuzumab deruxtecan group and 67% of the physician’s choice chemotherapy group. Discontinuation due to adverse events occurred in 16% in the trastuzumab deruxtecan group and 18% in the physician’s choice chemotherapy group; 14 patients in the trastuzumab deruxtecan group and 5 patients in the physician’s choice chemotherapy group had an adverse event that was associated with death. Death due to pneumonitis in the trastuzumab deruxtecan group occurred in 2 patients. Drug-related interstitial lung disease or pneumonitis occurred in 45 patients who received trastuzumab deruxtecan. The majority of these events were grade 1 and grade 2. However, 3 patients had grade 5 interstitial lung disease or pneumonitis.

Conclusion: Treatment with trastuzumab deruxtecan led to a significant improvement in progression-free survival compared to physician’s choice chemotherapy in patients with HER2-low metastatic breast cancer.

Commentary

Trastuzumab deruxtecan is an antibody drug conjugate that consists of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase 1 inhibitor. This antibody drug conjugate is unique compared with prior antibody drug conjugates such as trastuzumab emtansine in that it has a high drug-to-antibody ratio (~8). Furthermore, there appears to be a unique bystander effect resulting in off-target cytotoxicity to neighboring tumor cells, enhancing the efficacy of this novel therapy. Prior studies of trastuzumab deruxtecan have shown durable activity in heavily pretreated patients with metastatic HER2-positive breast cancer.¹

HER2-positive breast cancer represents approximately 20% of breast cancer cases in women.² Historically, HER2 positivity has been defined by strong HER2 expression with IHC staining (ie, score 3+) or HER2 amplification through ISH. Conversely, HER2-negative disease has historically been defined as those with IHC scores of 0 or 1+. This group represents approximately 60% of HER2-negative metastatic breast cancer patients.³ These patients have limited targeted treatment options after progressing on primary therapy. Prior data has shown that patients with low HER2 expression represent a heterogeneous population and thus, the historic categorization of HER2 status as positive or negative may in fact not adequately characterize the proportion of patients who may derive clinical benefit from HER2-directed therapies. Nevertheless, there have been no data to date that have shown improved outcomes in low HER2 expressers with anti-HER2 therapies.

The current studies add to the rapidly growing body of literature outlining the efficacy of the novel antibody drug conjugate trastuzumab deruxtecan. The implications of the data presented in these 2 studies are immediately practice changing.

In the DESTINY-Breast03 trial, Cortéz and colleagues show that trastuzumab deruxtecan therapy significantly prolongs progression-free survival compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on first-line trastuzumab and taxane-based therapy. With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in this trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer. The overall survival in this trial was immature at the time of this analysis, and thus continued follow-up to validate the results noted here are warranted.

The DESTINY-Breast04 trial by Modi et al expands the cohort of patients who benefit from trastuzumab deruxtecan profoundly. This study defines a population of patients with HER2-low metastatic breast cancer who will now be eligible for HER2-directed therapies. These data show that therapy with trastuzumab deruxtecan leads to a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy in patients with metastatic breast cancer with low expression of HER2. This benefit was seen in both the estrogen receptor–positive cohort as well as the entire population, including pre-treated triple-negative disease. Furthermore, this study does not define a threshold of HER2 expression by IHC that predicts benefit with trastuzumab deruxtecan. Patients with an IHC score of 1+ as well as those with a score of 2+/ISH negative both benefit to a similar extent from trastuzumab deruxtecan. Interestingly, in the DAISY trial, antitumor activity was noted with trastuzumab deruxtecan even in those without any detectable HER2 expression on IHC.⁴ Given the inconsistency and potential false negatives of IHC along with heterogeneous HER2 expression, further work is needed to better identify patients with low levels of HER2 expression who may benefit from this novel antibody drug conjugate. Thus, a reliable test to quantitatively assess the level of HER2 expression is needed in order to determine more accurately which patients will benefit from trastuzumab deruxtecan.

Last, trastuzumab deruxtecan has been associated with interstitial lung disease and pneumonitis. Interstitial lung disease and pneumonitis occurred in approximately 10% of patients who received trastuzumab deruxtecan in the DESTINY-Breast03 trial and about 12% of patients in the DESTINY-Breast04 trial. Most of these events were grade 1 and grade 2. Nevertheless, clinicians must be aware of this risk and monitor patients frequently for the development of pneumonitis or interstitial lung disease.

Application for Clinical Practice and System Implementation

The results of the current studies show a longer progression-free survival with trastuzumab deruxtecan in both HER2-low expressing metastatic breast cancer and HER2-positive metastatic breast cancer following taxane and trastuzumab-based therapy. These results are clearly practice changing and represent a new standard of care in these patient populations. It is incumbent upon treating oncologists to work with our pathology colleagues to assess HER2 IHC thoroughly in order to identify all potential patients who may benefit from trastuzumab deruxtecan in the metastatic setting. The continued advancement of anti-HER2 therapy will undoubtedly have a significant impact on patient outcomes going forward.

Practice Points

• With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in the DESTINY-Breast03 trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer.
• In the DESTINY-Breast04 trial, a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy was seen in patients with metastatic breast cancer with low expression of HER2, including both the estrogen receptor–positive cohort as well as the entire population, including those with pre-treated triple-negative disease.

­—Daniel Isaac, DO, MS

Study 1 Overview (Cortés et al)

Objective: To compare the efficacy and safety of trastuzumab deruxtecan with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxane.

Design: Phase 3, multicenter, open-label randomized trial conducted at 169 centers and 15 countries.

Setting and participants: Eligible patients had to have unresectable or metastatic HER2-positive breast cancer that had progressed during or after treatment with trastuzumab and a taxane or had disease that progressed within 6 months after neoadjuvant or adjuvant treatment involving trastuzumab or taxane. Patients with stable or previously treated brain metastases were eligible. Patients were not eligible for the study if they had symptomatic brain metastases, prior exposure to trastuzumab emtansine, or a history of interstitial lung disease.

Intervention: Patients were randomized in a 1-to-1 fashion to receive either trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or trastuzumab emtansine 3.6 mg/kg every 3 weeks. Patients were stratified according to hormone-receptor status, prior treatment with epratuzumab, and the presence or absence of visceral disease.

Main outcome measures: The primary endpoint of the study was progression-free survival as determined by an independent central review. Secondary endpoints included overall survival, overall response, and safety.

Main results: A total of 524 patients were enrolled in the study, with 261 patients randomized to trastuzumab deruxtecan and 263 patients randomized to trastuzumab emtansine. The demographic and baseline characteristics were similar between the 2 cohorts, and 60% of patients in both groups received prior epratuzumab therapy. Stable brain metastases were present in around 20% of patients in each group, and 70% of patients in each group had visceral disease. The median duration of follow-up was 16.2 months with trastuzumab deruxtecan and 15.3 months with trastuzumab emtansine.

The median progression-free survival was not reached in the trastuzumab deruxtecan group and was 6.8 months in the trastuzumab emtansine group (95% CI, 5.6-8.2). At 12 months the percentage of patients alive without disease progression was significantly larger in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. The hazard ratio for disease progression or death from any cause was 0.28 (95% CI, 0.22-0.37; P < .001). Subgroup analyses showed a benefit in progression-free survival with trastuzumab deruxtecan across all subgroups.

At the time of this analysis, the percentage of patients who were alive at 12 months was 94% with trastuzumab deruxtecan and 85.9% with trastuzumab emtansine. The response rates were significantly higher with trastuzumab deruxtecan compared with trastuzumab emtansine (79.7% vs 34.2%). A complete response was seen in 16% of patients in the trastuzumab deruxtecan arm, compared with 8.7% of patients in the trastuzumab emtansine group. The disease control rate (complete response, partial response, or stable disease) was higher in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group (96.6% vs 76.8%).

Serious adverse events were reported in 19% of patients in the trastuzumab deruxtecan group and 18% of patients in the trastuzumab emtansine group. Discontinuation due to adverse events was higher in the trastuzumab deruxtecan group, with 13.6% of patients discontinuing trastuzumab deruxtecan. Grade 3 or higher adverse events were seen in 52% of patients treated with trastuzumab deruxtecan and 48% of patients treated with trastuzumab emtansine. The most commonly reported adverse event with trastuzumab deruxtecan was nausea/vomiting and fatigue. These adverse events were seen more in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. No drug-related grade 5 adverse events were reported.

In the trastuzumab deruxtecan group, 10.5% of patients receiving trastuzumab deruxtecan developed interstitial lung disease or pneumonitis. Seven patients had grade 1 events, 18 patients had grade 2 events, and 2 patients had grade 3 events. No grade 4 or 5 events were noted in either treatment group. The median time to onset of interstitial lung disease or pneumonitis in those receiving trastuzumab deruxtecan was 168 days (range, 33-507). Discontinuation of therapy due to interstitial lung disease or pneumonitis occurred in 8% of patients receiving trastuzumab deruxtecan and 1% of patients receiving trastuzumab emtansine.

Conclusion: Trastuzumab deruxtecan significantly decreases the risk of disease progression or death compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on prior trastuzumab and taxane-based therapy.

Study 2 Overview (Modi et al)

Objective: To assess the efficacy of trastuzumab deruxtecan in patients with unresectable or metastatic breast cancer with low levels of HER2 expression.

Design: This was a randomized, 2-group, open-label, phase 3 trial.

Setting and participants: The trial was designed with a planned enrollment of 480 patients with hormone receptor–positive disease and 60 patients with hormone receptor–negative disease. Patients were randomized in a 2:1 ratio. Randomization was stratified according to HER2 status (immunohistochemical [IHC] 1+ vs IHC 2+/in situ hybridization [ISH] negative), number of prior lines of therapy, and hormone-receptor status. IHC scores for HER2 expression were determined through central testing. Specimens that had HER2 IHC scores of 2+ were reflexed to ISH. Specimens were considered HER2-low-expressing if they had an IHC score of 1+ or if they had an IHC score of 2+ and were ISH negative.

Eligible patients had to have received chemotherapy for metastatic disease or had disease recurrence during or within 6 months after completing adjuvant chemotherapy. Patients with hormone receptor–positive disease must have had at least 1 line of endocrine therapy. Patients were eligible if they had stable brain metastases. Patients with interstitial lung disease were excluded.

Intervention: Patients were randomized to receive trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel).

Main outcome measures: The primary endpoint was progression-free survival in patients with hormone receptor–positive disease. Secondary endpoints were progression-free survival among all patients, overall survival in hormone receptor–positive patients, and overall survival in all patients. Additional secondary endpoints included objective response rates, duration of response, and efficacy in hormone receptor–negative patients.

Main results: A total of 373 patients were assigned to the trastuzumab deruxtecan group and 184 patients were assigned to the physician’s choice chemotherapy group; 88% of patients in each cohort were hormone receptor–positive. In the physician’s choice chemotherapy group, 51% received eribulin, 20% received capecitabine, 10% received nab-paclitaxel, 10% received gemcitabine, and 8% received paclitaxel. The demographic and baseline characteristics were similar between both cohorts. The median duration of follow-up was 18.4 months.

The median progression-free survival in the hormone receptor–positive cohort was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician’s choice chemotherapy group (HR, 0.51; 95% CI, 0.4-0.64). Subgroup analyses revealed a benefit across all subgroups. The median progression-free survival among patients with a HER2 IHC score of 1+ and those with a HER2 IHC score of 2+/negative ISH were identical. In patients who received a prior CDK 4/6 inhibitor, the median progression-free survival was also 10 months in the trastuzumab deruxtecan group. In those who were CDK 4/6- naïve, the progression-free survival was 11.7 months. The progression-free survival in all patients was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice chemotherapy group (HR, 0.46; 95% CI, 0.24-0.89).

The median overall survival in the hormone receptor–positive cohort was 23.9 months in the trastuzumab deruxtecan group compared with 17.5 months in the physician’s choice chemotherapy group (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The median overall survival in the entire population was 23.4 months in the trastuzumab deruxtecan group vs 16.8 months in the physician’s choice chemotherapy group. In the hormone receptor–negative cohort, the median overall survival was 18.2 months in the trastuzumab deruxtecan group and 8.3 months in the physician’s choice chemotherapy group. Complete responses were seen in 3.6% in the trastuzumab deruxtecan group and 0.6% and the physician’s choice chemotherapy group. The median duration of response was 10.7 months in the trastuzumab deruxtecan group and 6.8 months in the physician’s choice chemotherapy group.

Incidence of serious adverse events was 27% in the trastuzumab deruxtecan group and 25% in the physician’s choice chemotherapy group. Grade 3 or higher events occurred in 52% of the trastuzumab deruxtecan group and 67% of the physician’s choice chemotherapy group. Discontinuation due to adverse events occurred in 16% in the trastuzumab deruxtecan group and 18% in the physician’s choice chemotherapy group; 14 patients in the trastuzumab deruxtecan group and 5 patients in the physician’s choice chemotherapy group had an adverse event that was associated with death. Death due to pneumonitis in the trastuzumab deruxtecan group occurred in 2 patients. Drug-related interstitial lung disease or pneumonitis occurred in 45 patients who received trastuzumab deruxtecan. The majority of these events were grade 1 and grade 2. However, 3 patients had grade 5 interstitial lung disease or pneumonitis.

Conclusion: Treatment with trastuzumab deruxtecan led to a significant improvement in progression-free survival compared to physician’s choice chemotherapy in patients with HER2-low metastatic breast cancer.

Commentary

Trastuzumab deruxtecan is an antibody drug conjugate that consists of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase 1 inhibitor. This antibody drug conjugate is unique compared with prior antibody drug conjugates such as trastuzumab emtansine in that it has a high drug-to-antibody ratio (~8). Furthermore, there appears to be a unique bystander effect resulting in off-target cytotoxicity to neighboring tumor cells, enhancing the efficacy of this novel therapy. Prior studies of trastuzumab deruxtecan have shown durable activity in heavily pretreated patients with metastatic HER2-positive breast cancer.¹

HER2-positive breast cancer represents approximately 20% of breast cancer cases in women.² Historically, HER2 positivity has been defined by strong HER2 expression with IHC staining (ie, score 3+) or HER2 amplification through ISH. Conversely, HER2-negative disease has historically been defined as those with IHC scores of 0 or 1+. This group represents approximately 60% of HER2-negative metastatic breast cancer patients.³ These patients have limited targeted treatment options after progressing on primary therapy. Prior data has shown that patients with low HER2 expression represent a heterogeneous population and thus, the historic categorization of HER2 status as positive or negative may in fact not adequately characterize the proportion of patients who may derive clinical benefit from HER2-directed therapies. Nevertheless, there have been no data to date that have shown improved outcomes in low HER2 expressers with anti-HER2 therapies.

The current studies add to the rapidly growing body of literature outlining the efficacy of the novel antibody drug conjugate trastuzumab deruxtecan. The implications of the data presented in these 2 studies are immediately practice changing.

In the DESTINY-Breast03 trial, Cortéz and colleagues show that trastuzumab deruxtecan therapy significantly prolongs progression-free survival compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on first-line trastuzumab and taxane-based therapy. With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in this trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer. The overall survival in this trial was immature at the time of this analysis, and thus continued follow-up to validate the results noted here are warranted.

The DESTINY-Breast04 trial by Modi et al expands the cohort of patients who benefit from trastuzumab deruxtecan profoundly. This study defines a population of patients with HER2-low metastatic breast cancer who will now be eligible for HER2-directed therapies. These data show that therapy with trastuzumab deruxtecan leads to a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy in patients with metastatic breast cancer with low expression of HER2. This benefit was seen in both the estrogen receptor–positive cohort as well as the entire population, including pre-treated triple-negative disease. Furthermore, this study does not define a threshold of HER2 expression by IHC that predicts benefit with trastuzumab deruxtecan. Patients with an IHC score of 1+ as well as those with a score of 2+/ISH negative both benefit to a similar extent from trastuzumab deruxtecan. Interestingly, in the DAISY trial, antitumor activity was noted with trastuzumab deruxtecan even in those without any detectable HER2 expression on IHC.⁴ Given the inconsistency and potential false negatives of IHC along with heterogeneous HER2 expression, further work is needed to better identify patients with low levels of HER2 expression who may benefit from this novel antibody drug conjugate. Thus, a reliable test to quantitatively assess the level of HER2 expression is needed in order to determine more accurately which patients will benefit from trastuzumab deruxtecan.

Last, trastuzumab deruxtecan has been associated with interstitial lung disease and pneumonitis. Interstitial lung disease and pneumonitis occurred in approximately 10% of patients who received trastuzumab deruxtecan in the DESTINY-Breast03 trial and about 12% of patients in the DESTINY-Breast04 trial. Most of these events were grade 1 and grade 2. Nevertheless, clinicians must be aware of this risk and monitor patients frequently for the development of pneumonitis or interstitial lung disease.

Application for Clinical Practice and System Implementation

The results of the current studies show a longer progression-free survival with trastuzumab deruxtecan in both HER2-low expressing metastatic breast cancer and HER2-positive metastatic breast cancer following taxane and trastuzumab-based therapy. These results are clearly practice changing and represent a new standard of care in these patient populations. It is incumbent upon treating oncologists to work with our pathology colleagues to assess HER2 IHC thoroughly in order to identify all potential patients who may benefit from trastuzumab deruxtecan in the metastatic setting. The continued advancement of anti-HER2 therapy will undoubtedly have a significant impact on patient outcomes going forward.

Practice Points

• With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in the DESTINY-Breast03 trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer.
• In the DESTINY-Breast04 trial, a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy was seen in patients with metastatic breast cancer with low expression of HER2, including both the estrogen receptor–positive cohort as well as the entire population, including those with pre-treated triple-negative disease.

­—Daniel Isaac, DO, MS

Study 1 Overview (Cortés et al)

Objective: To compare the efficacy and safety of trastuzumab deruxtecan with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxane.

Design: Phase 3, multicenter, open-label randomized trial conducted at 169 centers and 15 countries.

Setting and participants: Eligible patients had to have unresectable or metastatic HER2-positive breast cancer that had progressed during or after treatment with trastuzumab and a taxane or had disease that progressed within 6 months after neoadjuvant or adjuvant treatment involving trastuzumab or taxane. Patients with stable or previously treated brain metastases were eligible. Patients were not eligible for the study if they had symptomatic brain metastases, prior exposure to trastuzumab emtansine, or a history of interstitial lung disease.

Intervention: Patients were randomized in a 1-to-1 fashion to receive either trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or trastuzumab emtansine 3.6 mg/kg every 3 weeks. Patients were stratified according to hormone-receptor status, prior treatment with epratuzumab, and the presence or absence of visceral disease.

Main outcome measures: The primary endpoint of the study was progression-free survival as determined by an independent central review. Secondary endpoints included overall survival, overall response, and safety.

Main results: A total of 524 patients were enrolled in the study, with 261 patients randomized to trastuzumab deruxtecan and 263 patients randomized to trastuzumab emtansine. The demographic and baseline characteristics were similar between the 2 cohorts, and 60% of patients in both groups received prior epratuzumab therapy. Stable brain metastases were present in around 20% of patients in each group, and 70% of patients in each group had visceral disease. The median duration of follow-up was 16.2 months with trastuzumab deruxtecan and 15.3 months with trastuzumab emtansine.

The median progression-free survival was not reached in the trastuzumab deruxtecan group and was 6.8 months in the trastuzumab emtansine group (95% CI, 5.6-8.2). At 12 months the percentage of patients alive without disease progression was significantly larger in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. The hazard ratio for disease progression or death from any cause was 0.28 (95% CI, 0.22-0.37; P < .001). Subgroup analyses showed a benefit in progression-free survival with trastuzumab deruxtecan across all subgroups.

At the time of this analysis, the percentage of patients who were alive at 12 months was 94% with trastuzumab deruxtecan and 85.9% with trastuzumab emtansine. The response rates were significantly higher with trastuzumab deruxtecan compared with trastuzumab emtansine (79.7% vs 34.2%). A complete response was seen in 16% of patients in the trastuzumab deruxtecan arm, compared with 8.7% of patients in the trastuzumab emtansine group. The disease control rate (complete response, partial response, or stable disease) was higher in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group (96.6% vs 76.8%).

Serious adverse events were reported in 19% of patients in the trastuzumab deruxtecan group and 18% of patients in the trastuzumab emtansine group. Discontinuation due to adverse events was higher in the trastuzumab deruxtecan group, with 13.6% of patients discontinuing trastuzumab deruxtecan. Grade 3 or higher adverse events were seen in 52% of patients treated with trastuzumab deruxtecan and 48% of patients treated with trastuzumab emtansine. The most commonly reported adverse event with trastuzumab deruxtecan was nausea/vomiting and fatigue. These adverse events were seen more in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. No drug-related grade 5 adverse events were reported.

In the trastuzumab deruxtecan group, 10.5% of patients receiving trastuzumab deruxtecan developed interstitial lung disease or pneumonitis. Seven patients had grade 1 events, 18 patients had grade 2 events, and 2 patients had grade 3 events. No grade 4 or 5 events were noted in either treatment group. The median time to onset of interstitial lung disease or pneumonitis in those receiving trastuzumab deruxtecan was 168 days (range, 33-507). Discontinuation of therapy due to interstitial lung disease or pneumonitis occurred in 8% of patients receiving trastuzumab deruxtecan and 1% of patients receiving trastuzumab emtansine.

Conclusion: Trastuzumab deruxtecan significantly decreases the risk of disease progression or death compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on prior trastuzumab and taxane-based therapy.

Study 2 Overview (Modi et al)

Objective: To assess the efficacy of trastuzumab deruxtecan in patients with unresectable or metastatic breast cancer with low levels of HER2 expression.

Design: This was a randomized, 2-group, open-label, phase 3 trial.

Setting and participants: The trial was designed with a planned enrollment of 480 patients with hormone receptor–positive disease and 60 patients with hormone receptor–negative disease. Patients were randomized in a 2:1 ratio. Randomization was stratified according to HER2 status (immunohistochemical [IHC] 1+ vs IHC 2+/in situ hybridization [ISH] negative), number of prior lines of therapy, and hormone-receptor status. IHC scores for HER2 expression were determined through central testing. Specimens that had HER2 IHC scores of 2+ were reflexed to ISH. Specimens were considered HER2-low-expressing if they had an IHC score of 1+ or if they had an IHC score of 2+ and were ISH negative.

Eligible patients had to have received chemotherapy for metastatic disease or had disease recurrence during or within 6 months after completing adjuvant chemotherapy. Patients with hormone receptor–positive disease must have had at least 1 line of endocrine therapy. Patients were eligible if they had stable brain metastases. Patients with interstitial lung disease were excluded.

Intervention: Patients were randomized to receive trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel).

Main outcome measures: The primary endpoint was progression-free survival in patients with hormone receptor–positive disease. Secondary endpoints were progression-free survival among all patients, overall survival in hormone receptor–positive patients, and overall survival in all patients. Additional secondary endpoints included objective response rates, duration of response, and efficacy in hormone receptor–negative patients.

Main results: A total of 373 patients were assigned to the trastuzumab deruxtecan group and 184 patients were assigned to the physician’s choice chemotherapy group; 88% of patients in each cohort were hormone receptor–positive. In the physician’s choice chemotherapy group, 51% received eribulin, 20% received capecitabine, 10% received nab-paclitaxel, 10% received gemcitabine, and 8% received paclitaxel. The demographic and baseline characteristics were similar between both cohorts. The median duration of follow-up was 18.4 months.

The median progression-free survival in the hormone receptor–positive cohort was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician’s choice chemotherapy group (HR, 0.51; 95% CI, 0.4-0.64). Subgroup analyses revealed a benefit across all subgroups. The median progression-free survival among patients with a HER2 IHC score of 1+ and those with a HER2 IHC score of 2+/negative ISH were identical. In patients who received a prior CDK 4/6 inhibitor, the median progression-free survival was also 10 months in the trastuzumab deruxtecan group. In those who were CDK 4/6- naïve, the progression-free survival was 11.7 months. The progression-free survival in all patients was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice chemotherapy group (HR, 0.46; 95% CI, 0.24-0.89).

The median overall survival in the hormone receptor–positive cohort was 23.9 months in the trastuzumab deruxtecan group compared with 17.5 months in the physician’s choice chemotherapy group (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The median overall survival in the entire population was 23.4 months in the trastuzumab deruxtecan group vs 16.8 months in the physician’s choice chemotherapy group. In the hormone receptor–negative cohort, the median overall survival was 18.2 months in the trastuzumab deruxtecan group and 8.3 months in the physician’s choice chemotherapy group. Complete responses were seen in 3.6% in the trastuzumab deruxtecan group and 0.6% and the physician’s choice chemotherapy group. The median duration of response was 10.7 months in the trastuzumab deruxtecan group and 6.8 months in the physician’s choice chemotherapy group.

Incidence of serious adverse events was 27% in the trastuzumab deruxtecan group and 25% in the physician’s choice chemotherapy group. Grade 3 or higher events occurred in 52% of the trastuzumab deruxtecan group and 67% of the physician’s choice chemotherapy group. Discontinuation due to adverse events occurred in 16% in the trastuzumab deruxtecan group and 18% in the physician’s choice chemotherapy group; 14 patients in the trastuzumab deruxtecan group and 5 patients in the physician’s choice chemotherapy group had an adverse event that was associated with death. Death due to pneumonitis in the trastuzumab deruxtecan group occurred in 2 patients. Drug-related interstitial lung disease or pneumonitis occurred in 45 patients who received trastuzumab deruxtecan. The majority of these events were grade 1 and grade 2. However, 3 patients had grade 5 interstitial lung disease or pneumonitis.

Conclusion: Treatment with trastuzumab deruxtecan led to a significant improvement in progression-free survival compared to physician’s choice chemotherapy in patients with HER2-low metastatic breast cancer.

Commentary

Trastuzumab deruxtecan is an antibody drug conjugate that consists of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase 1 inhibitor. This antibody drug conjugate is unique compared with prior antibody drug conjugates such as trastuzumab emtansine in that it has a high drug-to-antibody ratio (~8). Furthermore, there appears to be a unique bystander effect resulting in off-target cytotoxicity to neighboring tumor cells, enhancing the efficacy of this novel therapy. Prior studies of trastuzumab deruxtecan have shown durable activity in heavily pretreated patients with metastatic HER2-positive breast cancer.¹

HER2-positive breast cancer represents approximately 20% of breast cancer cases in women.² Historically, HER2 positivity has been defined by strong HER2 expression with IHC staining (ie, score 3+) or HER2 amplification through ISH. Conversely, HER2-negative disease has historically been defined as those with IHC scores of 0 or 1+. This group represents approximately 60% of HER2-negative metastatic breast cancer patients.³ These patients have limited targeted treatment options after progressing on primary therapy. Prior data has shown that patients with low HER2 expression represent a heterogeneous population and thus, the historic categorization of HER2 status as positive or negative may in fact not adequately characterize the proportion of patients who may derive clinical benefit from HER2-directed therapies. Nevertheless, there have been no data to date that have shown improved outcomes in low HER2 expressers with anti-HER2 therapies.

The current studies add to the rapidly growing body of literature outlining the efficacy of the novel antibody drug conjugate trastuzumab deruxtecan. The implications of the data presented in these 2 studies are immediately practice changing.

In the DESTINY-Breast03 trial, Cortéz and colleagues show that trastuzumab deruxtecan therapy significantly prolongs progression-free survival compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on first-line trastuzumab and taxane-based therapy. With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in this trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer. The overall survival in this trial was immature at the time of this analysis, and thus continued follow-up to validate the results noted here are warranted.

The DESTINY-Breast04 trial by Modi et al expands the cohort of patients who benefit from trastuzumab deruxtecan profoundly. This study defines a population of patients with HER2-low metastatic breast cancer who will now be eligible for HER2-directed therapies. These data show that therapy with trastuzumab deruxtecan leads to a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy in patients with metastatic breast cancer with low expression of HER2. This benefit was seen in both the estrogen receptor–positive cohort as well as the entire population, including pre-treated triple-negative disease. Furthermore, this study does not define a threshold of HER2 expression by IHC that predicts benefit with trastuzumab deruxtecan. Patients with an IHC score of 1+ as well as those with a score of 2+/ISH negative both benefit to a similar extent from trastuzumab deruxtecan. Interestingly, in the DAISY trial, antitumor activity was noted with trastuzumab deruxtecan even in those without any detectable HER2 expression on IHC.⁴ Given the inconsistency and potential false negatives of IHC along with heterogeneous HER2 expression, further work is needed to better identify patients with low levels of HER2 expression who may benefit from this novel antibody drug conjugate. Thus, a reliable test to quantitatively assess the level of HER2 expression is needed in order to determine more accurately which patients will benefit from trastuzumab deruxtecan.

Last, trastuzumab deruxtecan has been associated with interstitial lung disease and pneumonitis. Interstitial lung disease and pneumonitis occurred in approximately 10% of patients who received trastuzumab deruxtecan in the DESTINY-Breast03 trial and about 12% of patients in the DESTINY-Breast04 trial. Most of these events were grade 1 and grade 2. Nevertheless, clinicians must be aware of this risk and monitor patients frequently for the development of pneumonitis or interstitial lung disease.

Application for Clinical Practice and System Implementation

The results of the current studies show a longer progression-free survival with trastuzumab deruxtecan in both HER2-low expressing metastatic breast cancer and HER2-positive metastatic breast cancer following taxane and trastuzumab-based therapy. These results are clearly practice changing and represent a new standard of care in these patient populations. It is incumbent upon treating oncologists to work with our pathology colleagues to assess HER2 IHC thoroughly in order to identify all potential patients who may benefit from trastuzumab deruxtecan in the metastatic setting. The continued advancement of anti-HER2 therapy will undoubtedly have a significant impact on patient outcomes going forward.

Practice Points

• With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in the DESTINY-Breast03 trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer.
• In the DESTINY-Breast04 trial, a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy was seen in patients with metastatic breast cancer with low expression of HER2, including both the estrogen receptor–positive cohort as well as the entire population, including those with pre-treated triple-negative disease.

­—Daniel Isaac, DO, MS

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

The names of the doctors in this story have been changed at their request because of fear of legal repercussions and/or professional retaliation.

When an Ohio ob.gyn. had a patient in need of an abortion in July 2022, he knew he had to move quickly.

Daniel, who also sees patients at an abortion clinic, was treating a woman who came in for an abortion around 5 weeks into her pregnancy. And after going through the mandatory waiting periods, the required ultrasounds at each appointment, the consent process, and the options counseling, she was set for a surgical abortion the following Monday.

But on Monday, pre-op tests showed that her blood pressure was very high, posing a serious health risk if Daniel proceeded with the surgery.

Before the Supreme Court overturned Roe v. Wade in June, Daniel would have sent the patient home with instructions on how to lower her blood pressure over time. But the patient now had just four days to show the necessary improvement.

In this case, everything worked out. The patient returned Thursday and was able to have the procedure. But this is just one of the many day-to-day medical decisions abortion providers are now having to make with the changing legal risks being as top-of-mind to doctors as the safety of their patients.

Daniel said he doesn’t want the Ohio abortion law to change the way he communicates with his patients. As far as he knows, it’s still legal to talk to patients about self-managed abortions, as long as everything is unbiased and clearly stated, he says.

“But I don’t think I would get a lot of institutional support to have those conversations with patients because of the perceived legal liability,” says Daniel. “I will still have those conversations, but I’m not going to tell my employer that I’m having them and I’m not going to document them in the chart.”

Daniel is aware that having these kinds of discussions, or entertaining the possibility of omitting certain information from patient records, runs the risk of legal and professional consequences. Enforcement of these rules is foggy, too.

Under the Ohio law, if a fellow staff member suspects you of violating a law, you could be reported to a supervisor or licensing body. Abortion providers are aware they must be cautious about what they say because anti-abortion activitists, posing as patients, have secretly recorded conversations in the past, Daniel says.
 

Enforcement: The past, present, and future legal risks

Before Roe, enforcement of illegal abortion was spotty, says Mary Ziegler, JD, a professor at Florida State University College of Law, who specializes in the legal history of reproductive rights. At the start of the late 19th century, the doctors who provided illegal abortions would, in most cases, be prosecuted if a patient died as a result of the procedure.

A doctor in Ashland, Pa., named Robert Spencer was known for providing abortions in the small mining town where he practiced in the 1920s. He was reportedly arrested three times – once after a patient died as a result of abortion complications – but was ultimately acquitted.

For many doctors performing abortions at the time, “it was very much a kind of roll of the dice,” Ms. Ziegler says. “There was a sense that these laws were not enforced very much.”

Carole Joffe, PhD, a sociologist with expertise in reproductive health, recalls that there were very few doctors arrested, given the sheer number of abortions that were performed. The American College of Obstetricians and Gynecologists estimates that, in the years leading up to the original Roe decision, about 1.2 million women in the U.S. had illegal abortions – a number that exceeds today’s estimates.

Among the most notable cases of a doctor being detained was the arrest of gynecologist Jane Hodgson, MD, in 1970. Dr. Hodgson intentionally violated Minnesota law, which prohibited all abortions except in cases that were life-threatening to the patient.

After performing an abortion on a patient who had contracted rubella, also known as German measles, Dr. Hodgson was arrested, sentenced to 30 days in jail, and put on a year-long probation. She did not end up serving any time in jail, and her conviction was overturned after the Roe decision in 1973.

Now, the abortion restrictions being passed in many states have authorized much more sweeping penalties than those that existed in the pre-Roe era. According to Joffe, there is one key reason why we can anticipate more doctor arrests now.

“There simply was not the modern anti-abortion movement that we have come to know,” she says. “In the old days, there was not that much legal surveillance, and things were very unsafe. Fast forward to the present, we have much safer options now – like medication abortion pills – but we have a very different legal environment.”

Carmel Shachar, JD, MPH, a law and health policy expert at Harvard Law School, also expects that we will see more frequent prosecutions of doctors who provide abortion.

“There’s so much more data available through medical record-keeping and information generated by our phones and internet searches, that I think it would be much harder for a physician to fly under the radar,” Ms. Shachar says.

Also, Ms. Shachar emphasizes the power of prosecutorial discretion in abortion cases, where one prosecutor may choose to apply a law much more aggressively than another prosecutor in the next county over. Such has been seen in DeKalb County, Ga., which includes parts of Atlanta, where District Attorney Sherry Boston says she plans to use her prosecutorial discretion to address crimes like rape and murder, rather than “potentially investigat[ing] women and doctors for medical decisions,” Bloomberg Law reported. State Sen. Jen Jordan, the Democratic nominee for Georgia attorney general, has also said that, if elected, she would not enforce the state’s new 6-week abortion ban.
 

Is there a legal path forward for abortion care in states that forbid it?

Robin, an ob.gyn., became a complex family planning fellow in Utah to seek out further medical training and education in abortion care. Her plan was to solidify this as an area of expertise, so that, upon completing her fellowship, she could move back to her home state of Arizona to provide services there.

In Utah, where she currently practices, abortion is banned after 18 weeks. In Arizona, abortion is still allowed up to 24-26 weeks, until a pregnancy reaches “viability” (when a fetus is developed enough that it is able to survive outside the uterus with medical assistance). But new restrictions in Arizona may go into effect as early as September which would prohibit abortions after 15 weeks.

Despite the uncertain future of abortion access in Arizona, Robin still plans on moving there after her fellowship, but she hopes to travel to surrounding states to help provide abortion care where it’s less restricted. Even if she isn’t able to provide abortions at all, she says that there are still ways to help patients get safe, above-board abortions so as not to repeat the dangerous and often gruesome outcomes of self-induced abortions or those done by illegitimate practitioners before Roe.

“One of the roles that I think I can have as a physician is helping people with wraparound care for self-managed abortion,” says Robin. “If they can get the [abortion] pills online, then I can do the ultrasound beforehand, I can do the ultrasound after, I can talk them through it. I can help them with all the aspects of this care, I just can’t give them the pills myself.”

Whether a doctor can be penalized for “aiding and abetting” abortions that happen in different states remains an open question. In Texas, for example, Senate Bill 8 – which took effect Sept. 1, 2021 – not only established a fetal heartbeat law but added language that would allow private citizens to sue anyone who “knowingly engages in conduct that aids or abets the performance or inducement of an abortion” or anyone who even intends to do so.

That’s what happened to Alan Braid, MD, an ob.gyn. based in San Antonio. He confessed in a Washington Post op-ed that he had performed an abortion after cardiac activity had been detected in the pregnancy. Aware of the legal risks, he has since been sued by three people, and those cases are still underway.

But Ms. Ziegler says the chances of a doctor from a progressive state actually getting extradited and prosecuted by a state with restrictive abortion laws is pretty low – not zero, but low.

Like Robin, Natalie – an ob.gyn. in her early 30s – is a complex family planning fellow in Massachusetts. After her fellowship, she wants to return to Texas, where she completed her residency training.

“I’m at the point in my training where everyone starts looking for jobs and figuring out their next steps,” says Natalie. “The Dobbs decision introduced a ton of chaos due to the vagueness in the laws and how they get enforced, and then there’s chaos within institutions themselves and what kind of risk tolerance they have.”

Looking towards her future career path, Natalie says that she would not consider a job at an institution that didn’t allow her to teach abortion care to students, speak publicly about abortion rights, or let her travel outside of Texas to continue providing abortion care. She’s also preemptively seeking legal counsel and general guidance – advice that Ms. Ziegler strongly urges doctors to heed, sooner rather than later.

In states that have strict abortion bans with exceptions for life-threatening cases, there is still a lack of clarity around what is actually considered life-threatening enough to pass as an exception.

“Is it life-threatening in the next 6 hours? 24 hours? Seven days? One month?” Robin asks. “In medicine, we don’t necessarily talk about if something is life-threatening or not, we just say that there’s a high risk of X thing happening in X period of time. What’s the threshold at which that meets legal criteria? Nobody has an answer for that.”

Robin explains that, in her patients who have cancer, a pregnancy wouldn’t “necessarily kill them within the span of the next 9 months, but it could certainly accelerate their disease that could kill them within the next year or two.”

Right now, she says she doesn’t know what she would do if and when she is put in that position as a doctor.

“I didn’t go to medical school and become a doctor to become a felon,” says Robin. “Our goal is to make as many legal changes as we can to protect our patients and then practice as much harm reduction and as much care as we can within the letter of the law.”

A version of this article first appeared on WebMD.com.

The names of the doctors in this story have been changed at their request because of fear of legal repercussions and/or professional retaliation.

When an Ohio ob.gyn. had a patient in need of an abortion in July 2022, he knew he had to move quickly.

Daniel, who also sees patients at an abortion clinic, was treating a woman who came in for an abortion around 5 weeks into her pregnancy. And after going through the mandatory waiting periods, the required ultrasounds at each appointment, the consent process, and the options counseling, she was set for a surgical abortion the following Monday.

But on Monday, pre-op tests showed that her blood pressure was very high, posing a serious health risk if Daniel proceeded with the surgery.

Before the Supreme Court overturned Roe v. Wade in June, Daniel would have sent the patient home with instructions on how to lower her blood pressure over time. But the patient now had just four days to show the necessary improvement.

In this case, everything worked out. The patient returned Thursday and was able to have the procedure. But this is just one of the many day-to-day medical decisions abortion providers are now having to make with the changing legal risks being as top-of-mind to doctors as the safety of their patients.

Daniel said he doesn’t want the Ohio abortion law to change the way he communicates with his patients. As far as he knows, it’s still legal to talk to patients about self-managed abortions, as long as everything is unbiased and clearly stated, he says.

“But I don’t think I would get a lot of institutional support to have those conversations with patients because of the perceived legal liability,” says Daniel. “I will still have those conversations, but I’m not going to tell my employer that I’m having them and I’m not going to document them in the chart.”

Daniel is aware that having these kinds of discussions, or entertaining the possibility of omitting certain information from patient records, runs the risk of legal and professional consequences. Enforcement of these rules is foggy, too.

Under the Ohio law, if a fellow staff member suspects you of violating a law, you could be reported to a supervisor or licensing body. Abortion providers are aware they must be cautious about what they say because anti-abortion activitists, posing as patients, have secretly recorded conversations in the past, Daniel says.
 

Enforcement: The past, present, and future legal risks

Before Roe, enforcement of illegal abortion was spotty, says Mary Ziegler, JD, a professor at Florida State University College of Law, who specializes in the legal history of reproductive rights. At the start of the late 19th century, the doctors who provided illegal abortions would, in most cases, be prosecuted if a patient died as a result of the procedure.

A doctor in Ashland, Pa., named Robert Spencer was known for providing abortions in the small mining town where he practiced in the 1920s. He was reportedly arrested three times – once after a patient died as a result of abortion complications – but was ultimately acquitted.

For many doctors performing abortions at the time, “it was very much a kind of roll of the dice,” Ms. Ziegler says. “There was a sense that these laws were not enforced very much.”

Carole Joffe, PhD, a sociologist with expertise in reproductive health, recalls that there were very few doctors arrested, given the sheer number of abortions that were performed. The American College of Obstetricians and Gynecologists estimates that, in the years leading up to the original Roe decision, about 1.2 million women in the U.S. had illegal abortions – a number that exceeds today’s estimates.

Among the most notable cases of a doctor being detained was the arrest of gynecologist Jane Hodgson, MD, in 1970. Dr. Hodgson intentionally violated Minnesota law, which prohibited all abortions except in cases that were life-threatening to the patient.

After performing an abortion on a patient who had contracted rubella, also known as German measles, Dr. Hodgson was arrested, sentenced to 30 days in jail, and put on a year-long probation. She did not end up serving any time in jail, and her conviction was overturned after the Roe decision in 1973.

Now, the abortion restrictions being passed in many states have authorized much more sweeping penalties than those that existed in the pre-Roe era. According to Joffe, there is one key reason why we can anticipate more doctor arrests now.

“There simply was not the modern anti-abortion movement that we have come to know,” she says. “In the old days, there was not that much legal surveillance, and things were very unsafe. Fast forward to the present, we have much safer options now – like medication abortion pills – but we have a very different legal environment.”

Carmel Shachar, JD, MPH, a law and health policy expert at Harvard Law School, also expects that we will see more frequent prosecutions of doctors who provide abortion.

“There’s so much more data available through medical record-keeping and information generated by our phones and internet searches, that I think it would be much harder for a physician to fly under the radar,” Ms. Shachar says.

Also, Ms. Shachar emphasizes the power of prosecutorial discretion in abortion cases, where one prosecutor may choose to apply a law much more aggressively than another prosecutor in the next county over. Such has been seen in DeKalb County, Ga., which includes parts of Atlanta, where District Attorney Sherry Boston says she plans to use her prosecutorial discretion to address crimes like rape and murder, rather than “potentially investigat[ing] women and doctors for medical decisions,” Bloomberg Law reported. State Sen. Jen Jordan, the Democratic nominee for Georgia attorney general, has also said that, if elected, she would not enforce the state’s new 6-week abortion ban.
 

Is there a legal path forward for abortion care in states that forbid it?

Robin, an ob.gyn., became a complex family planning fellow in Utah to seek out further medical training and education in abortion care. Her plan was to solidify this as an area of expertise, so that, upon completing her fellowship, she could move back to her home state of Arizona to provide services there.

In Utah, where she currently practices, abortion is banned after 18 weeks. In Arizona, abortion is still allowed up to 24-26 weeks, until a pregnancy reaches “viability” (when a fetus is developed enough that it is able to survive outside the uterus with medical assistance). But new restrictions in Arizona may go into effect as early as September which would prohibit abortions after 15 weeks.

Despite the uncertain future of abortion access in Arizona, Robin still plans on moving there after her fellowship, but she hopes to travel to surrounding states to help provide abortion care where it’s less restricted. Even if she isn’t able to provide abortions at all, she says that there are still ways to help patients get safe, above-board abortions so as not to repeat the dangerous and often gruesome outcomes of self-induced abortions or those done by illegitimate practitioners before Roe.

“One of the roles that I think I can have as a physician is helping people with wraparound care for self-managed abortion,” says Robin. “If they can get the [abortion] pills online, then I can do the ultrasound beforehand, I can do the ultrasound after, I can talk them through it. I can help them with all the aspects of this care, I just can’t give them the pills myself.”

Whether a doctor can be penalized for “aiding and abetting” abortions that happen in different states remains an open question. In Texas, for example, Senate Bill 8 – which took effect Sept. 1, 2021 – not only established a fetal heartbeat law but added language that would allow private citizens to sue anyone who “knowingly engages in conduct that aids or abets the performance or inducement of an abortion” or anyone who even intends to do so.

That’s what happened to Alan Braid, MD, an ob.gyn. based in San Antonio. He confessed in a Washington Post op-ed that he had performed an abortion after cardiac activity had been detected in the pregnancy. Aware of the legal risks, he has since been sued by three people, and those cases are still underway.

But Ms. Ziegler says the chances of a doctor from a progressive state actually getting extradited and prosecuted by a state with restrictive abortion laws is pretty low – not zero, but low.

Like Robin, Natalie – an ob.gyn. in her early 30s – is a complex family planning fellow in Massachusetts. After her fellowship, she wants to return to Texas, where she completed her residency training.

“I’m at the point in my training where everyone starts looking for jobs and figuring out their next steps,” says Natalie. “The Dobbs decision introduced a ton of chaos due to the vagueness in the laws and how they get enforced, and then there’s chaos within institutions themselves and what kind of risk tolerance they have.”

Looking towards her future career path, Natalie says that she would not consider a job at an institution that didn’t allow her to teach abortion care to students, speak publicly about abortion rights, or let her travel outside of Texas to continue providing abortion care. She’s also preemptively seeking legal counsel and general guidance – advice that Ms. Ziegler strongly urges doctors to heed, sooner rather than later.

In states that have strict abortion bans with exceptions for life-threatening cases, there is still a lack of clarity around what is actually considered life-threatening enough to pass as an exception.

“Is it life-threatening in the next 6 hours? 24 hours? Seven days? One month?” Robin asks. “In medicine, we don’t necessarily talk about if something is life-threatening or not, we just say that there’s a high risk of X thing happening in X period of time. What’s the threshold at which that meets legal criteria? Nobody has an answer for that.”

Robin explains that, in her patients who have cancer, a pregnancy wouldn’t “necessarily kill them within the span of the next 9 months, but it could certainly accelerate their disease that could kill them within the next year or two.”

Right now, she says she doesn’t know what she would do if and when she is put in that position as a doctor.

“I didn’t go to medical school and become a doctor to become a felon,” says Robin. “Our goal is to make as many legal changes as we can to protect our patients and then practice as much harm reduction and as much care as we can within the letter of the law.”

A version of this article first appeared on WebMD.com.

The names of the doctors in this story have been changed at their request because of fear of legal repercussions and/or professional retaliation.

When an Ohio ob.gyn. had a patient in need of an abortion in July 2022, he knew he had to move quickly.

Daniel, who also sees patients at an abortion clinic, was treating a woman who came in for an abortion around 5 weeks into her pregnancy. And after going through the mandatory waiting periods, the required ultrasounds at each appointment, the consent process, and the options counseling, she was set for a surgical abortion the following Monday.

But on Monday, pre-op tests showed that her blood pressure was very high, posing a serious health risk if Daniel proceeded with the surgery.

Before the Supreme Court overturned Roe v. Wade in June, Daniel would have sent the patient home with instructions on how to lower her blood pressure over time. But the patient now had just four days to show the necessary improvement.

In this case, everything worked out. The patient returned Thursday and was able to have the procedure. But this is just one of the many day-to-day medical decisions abortion providers are now having to make with the changing legal risks being as top-of-mind to doctors as the safety of their patients.

Daniel said he doesn’t want the Ohio abortion law to change the way he communicates with his patients. As far as he knows, it’s still legal to talk to patients about self-managed abortions, as long as everything is unbiased and clearly stated, he says.

“But I don’t think I would get a lot of institutional support to have those conversations with patients because of the perceived legal liability,” says Daniel. “I will still have those conversations, but I’m not going to tell my employer that I’m having them and I’m not going to document them in the chart.”

Daniel is aware that having these kinds of discussions, or entertaining the possibility of omitting certain information from patient records, runs the risk of legal and professional consequences. Enforcement of these rules is foggy, too.

Under the Ohio law, if a fellow staff member suspects you of violating a law, you could be reported to a supervisor or licensing body. Abortion providers are aware they must be cautious about what they say because anti-abortion activitists, posing as patients, have secretly recorded conversations in the past, Daniel says.
 

Enforcement: The past, present, and future legal risks

Before Roe, enforcement of illegal abortion was spotty, says Mary Ziegler, JD, a professor at Florida State University College of Law, who specializes in the legal history of reproductive rights. At the start of the late 19th century, the doctors who provided illegal abortions would, in most cases, be prosecuted if a patient died as a result of the procedure.

A doctor in Ashland, Pa., named Robert Spencer was known for providing abortions in the small mining town where he practiced in the 1920s. He was reportedly arrested three times – once after a patient died as a result of abortion complications – but was ultimately acquitted.

For many doctors performing abortions at the time, “it was very much a kind of roll of the dice,” Ms. Ziegler says. “There was a sense that these laws were not enforced very much.”

Carole Joffe, PhD, a sociologist with expertise in reproductive health, recalls that there were very few doctors arrested, given the sheer number of abortions that were performed. The American College of Obstetricians and Gynecologists estimates that, in the years leading up to the original Roe decision, about 1.2 million women in the U.S. had illegal abortions – a number that exceeds today’s estimates.

Among the most notable cases of a doctor being detained was the arrest of gynecologist Jane Hodgson, MD, in 1970. Dr. Hodgson intentionally violated Minnesota law, which prohibited all abortions except in cases that were life-threatening to the patient.

After performing an abortion on a patient who had contracted rubella, also known as German measles, Dr. Hodgson was arrested, sentenced to 30 days in jail, and put on a year-long probation. She did not end up serving any time in jail, and her conviction was overturned after the Roe decision in 1973.

Now, the abortion restrictions being passed in many states have authorized much more sweeping penalties than those that existed in the pre-Roe era. According to Joffe, there is one key reason why we can anticipate more doctor arrests now.

“There simply was not the modern anti-abortion movement that we have come to know,” she says. “In the old days, there was not that much legal surveillance, and things were very unsafe. Fast forward to the present, we have much safer options now – like medication abortion pills – but we have a very different legal environment.”

Carmel Shachar, JD, MPH, a law and health policy expert at Harvard Law School, also expects that we will see more frequent prosecutions of doctors who provide abortion.

“There’s so much more data available through medical record-keeping and information generated by our phones and internet searches, that I think it would be much harder for a physician to fly under the radar,” Ms. Shachar says.

Also, Ms. Shachar emphasizes the power of prosecutorial discretion in abortion cases, where one prosecutor may choose to apply a law much more aggressively than another prosecutor in the next county over. Such has been seen in DeKalb County, Ga., which includes parts of Atlanta, where District Attorney Sherry Boston says she plans to use her prosecutorial discretion to address crimes like rape and murder, rather than “potentially investigat[ing] women and doctors for medical decisions,” Bloomberg Law reported. State Sen. Jen Jordan, the Democratic nominee for Georgia attorney general, has also said that, if elected, she would not enforce the state’s new 6-week abortion ban.
 

Is there a legal path forward for abortion care in states that forbid it?

Robin, an ob.gyn., became a complex family planning fellow in Utah to seek out further medical training and education in abortion care. Her plan was to solidify this as an area of expertise, so that, upon completing her fellowship, she could move back to her home state of Arizona to provide services there.

In Utah, where she currently practices, abortion is banned after 18 weeks. In Arizona, abortion is still allowed up to 24-26 weeks, until a pregnancy reaches “viability” (when a fetus is developed enough that it is able to survive outside the uterus with medical assistance). But new restrictions in Arizona may go into effect as early as September which would prohibit abortions after 15 weeks.

Despite the uncertain future of abortion access in Arizona, Robin still plans on moving there after her fellowship, but she hopes to travel to surrounding states to help provide abortion care where it’s less restricted. Even if she isn’t able to provide abortions at all, she says that there are still ways to help patients get safe, above-board abortions so as not to repeat the dangerous and often gruesome outcomes of self-induced abortions or those done by illegitimate practitioners before Roe.

“One of the roles that I think I can have as a physician is helping people with wraparound care for self-managed abortion,” says Robin. “If they can get the [abortion] pills online, then I can do the ultrasound beforehand, I can do the ultrasound after, I can talk them through it. I can help them with all the aspects of this care, I just can’t give them the pills myself.”

Whether a doctor can be penalized for “aiding and abetting” abortions that happen in different states remains an open question. In Texas, for example, Senate Bill 8 – which took effect Sept. 1, 2021 – not only established a fetal heartbeat law but added language that would allow private citizens to sue anyone who “knowingly engages in conduct that aids or abets the performance or inducement of an abortion” or anyone who even intends to do so.

That’s what happened to Alan Braid, MD, an ob.gyn. based in San Antonio. He confessed in a Washington Post op-ed that he had performed an abortion after cardiac activity had been detected in the pregnancy. Aware of the legal risks, he has since been sued by three people, and those cases are still underway.

But Ms. Ziegler says the chances of a doctor from a progressive state actually getting extradited and prosecuted by a state with restrictive abortion laws is pretty low – not zero, but low.

Like Robin, Natalie – an ob.gyn. in her early 30s – is a complex family planning fellow in Massachusetts. After her fellowship, she wants to return to Texas, where she completed her residency training.

“I’m at the point in my training where everyone starts looking for jobs and figuring out their next steps,” says Natalie. “The Dobbs decision introduced a ton of chaos due to the vagueness in the laws and how they get enforced, and then there’s chaos within institutions themselves and what kind of risk tolerance they have.”

Looking towards her future career path, Natalie says that she would not consider a job at an institution that didn’t allow her to teach abortion care to students, speak publicly about abortion rights, or let her travel outside of Texas to continue providing abortion care. She’s also preemptively seeking legal counsel and general guidance – advice that Ms. Ziegler strongly urges doctors to heed, sooner rather than later.

In states that have strict abortion bans with exceptions for life-threatening cases, there is still a lack of clarity around what is actually considered life-threatening enough to pass as an exception.

“Is it life-threatening in the next 6 hours? 24 hours? Seven days? One month?” Robin asks. “In medicine, we don’t necessarily talk about if something is life-threatening or not, we just say that there’s a high risk of X thing happening in X period of time. What’s the threshold at which that meets legal criteria? Nobody has an answer for that.”

Robin explains that, in her patients who have cancer, a pregnancy wouldn’t “necessarily kill them within the span of the next 9 months, but it could certainly accelerate their disease that could kill them within the next year or two.”

Right now, she says she doesn’t know what she would do if and when she is put in that position as a doctor.

“I didn’t go to medical school and become a doctor to become a felon,” says Robin. “Our goal is to make as many legal changes as we can to protect our patients and then practice as much harm reduction and as much care as we can within the letter of the law.”

A version of this article first appeared on WebMD.com.

The Canadian Task Force on Preventive Health Care recommends against the routine screening of all pregnant and postpartum women for depression using a standard questionnaire, according to its new guideline.

The basis for its position is the lack of evidence that such screening “adds value beyond discussions about overall wellbeing, depression, anxiety, and mood that are currently a part of established perinatal clinical care.

“We should not be using a one-size-fits all approach,” lead author Eddy Lang, MD, professor and head of emergency medicine at the Cumming School of Medicine, University of Calgary (Alta.), told this news organization.

Instead, the task force emphasizes regular clinical care, including asking patients about their wellbeing and support systems. The task force categorizes the recommendation as conditional and as having very low-certainty evidence.

The recommendation was published in CMAJ.
 

One randomized study

The task force is an independent panel of clinicians and scientists that makes recommendations on primary and secondary prevention in primary care. A working group of five members of the task force developed this recommendation with scientific support from Public Health Agency of Canada staff.

In its research, the task force found only one study that showed a benefit of routine depression screening in this population. This study was a randomized controlled trial conducted in Hong Kong. Researchers evaluated 462 postpartum women who were randomly assigned to receive screening with the Edinburgh Postnatal Depression Scale (EPDS) or no screening 2 months post partum.

“We found the effect of screening in this study to be very uncertain for the important outcomes of interest,” said Dr. Lang.

“These included parent-child stress, marital stress, and the number of infant hospital admissions. The effects of screening on all of these outcomes were very uncertain, mainly because it was such a small trial,” he said.

The task force also assessed how pregnant and postpartum women feel about being screened. What these women most wanted was a good relationship with a trusted primary care provider who would initiate discussions about their mental health in a caring atmosphere.

“Although they told us they liked the idea of universal screening, they admitted to their family doctors that they actually preferred to be asked about their wellbeing, [to be asked] how things were going at home, and [to have] a discussion about their mental health and wellbeing, rather than a formal screening process. They felt a discussion about depression with a primary health care provider during the pregnancy and postpartum period is critical,” said Dr. Lang.

Thus, the task force recommends “against instrument-based depression screening using a questionnaire with cutoff score to distinguish ‘screen positive’ and ‘screen negative’ administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth).”
 

Screening remains common

“There’s a lot of uncertainty in the scientific community about whether it’s a good idea to administer a screening test to all pregnant and postpartum women to determine in a systematic way if they might be suffering from depression,” said Dr. Lang.

The task force recommended against screening for depression among perinatal or postpartum women in 2013, but screening is still performed in many provinces, said Dr. Lang.

Dr. Lang emphasized that the recommendation does not apply to usual care, in which the provider asks questions about and discusses a patient’s mental health and proceeds on the basis of their clinical judgment; nor does it apply to diagnostic pathways in which the clinician suspects that the individual may have depression and tests her accordingly.

“What we are saying in our recommendation is that all clinicians should ask about a patient’s wellbeing, about their mood, their anxiety, and these questions are an important part of the clinical assessment of pregnant and postpartum women. But we’re also saying the usefulness of doing so with a questionnaire and using a cutoff score on the questionnaire to decide who needs further assessment or possibly treatment is unproven by the research,” Dr. Lang said.
 

A growing problem

For Diane Francoeur, MD, CEO of the Society of Obstetricians and Gynecologists of Canada, this is all well and good, but the reality is that such screening is better than nothing.

Quebec is the only Canadian province that conducts universal screening for all pregnant and postpartum women, Dr. Francoeur said in an interview. She was not part of the task force.

“I agree that it should be more than one approach, but the problem is that there is such a shortage of resources. There are many issues that can arise when you follow a woman during her pregnancy,” she said.

Dr. Francoeur said that COVID-19 has been particularly tough on women, including pregnant and postpartum women, who are the most vulnerable.

“Especially during the COVID era, it was astonishing how women were not doing well. Their stress level was so high. We need to have a specific approach dedicated to prenatal mental health, because it’s a problem that is bigger than it used to be,” she said.

Violence against women has increased considerably since the beginning of the COVID-19 pandemic, said Dr. Francoeur. “Many more women have been killed by their partners. We have never seen anything like this before, and I hope we will never see this again,” she said.

“Help was more available a few years ago, but now, it’s really hard if and when you need to have a quick consultation with a specialist and the woman is really depressed. It can take forever. So, it’s okay to screen, but then, what’s next? Who is going to be there to take these women and help them? And we don’t have the answer,” Dr. Francoeur said.

Pregnant and postpartum women who suffer from depression need more than pills, she added. “We reassure them and treat their depression pharmacologically, but it’s also a time to give appropriate support and help them through the pregnancy and get well prepared to receive their newborn, because, as we now know, that first year of life is really important for the child, and the mom needs to be supported.”

Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. Dr. Lang and Dr. Francoeur reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Canadian Task Force on Preventive Health Care recommends against the routine screening of all pregnant and postpartum women for depression using a standard questionnaire, according to its new guideline.

The basis for its position is the lack of evidence that such screening “adds value beyond discussions about overall wellbeing, depression, anxiety, and mood that are currently a part of established perinatal clinical care.

“We should not be using a one-size-fits all approach,” lead author Eddy Lang, MD, professor and head of emergency medicine at the Cumming School of Medicine, University of Calgary (Alta.), told this news organization.

Instead, the task force emphasizes regular clinical care, including asking patients about their wellbeing and support systems. The task force categorizes the recommendation as conditional and as having very low-certainty evidence.

The recommendation was published in CMAJ.
 

One randomized study

The task force is an independent panel of clinicians and scientists that makes recommendations on primary and secondary prevention in primary care. A working group of five members of the task force developed this recommendation with scientific support from Public Health Agency of Canada staff.

In its research, the task force found only one study that showed a benefit of routine depression screening in this population. This study was a randomized controlled trial conducted in Hong Kong. Researchers evaluated 462 postpartum women who were randomly assigned to receive screening with the Edinburgh Postnatal Depression Scale (EPDS) or no screening 2 months post partum.

“We found the effect of screening in this study to be very uncertain for the important outcomes of interest,” said Dr. Lang.

“These included parent-child stress, marital stress, and the number of infant hospital admissions. The effects of screening on all of these outcomes were very uncertain, mainly because it was such a small trial,” he said.

The task force also assessed how pregnant and postpartum women feel about being screened. What these women most wanted was a good relationship with a trusted primary care provider who would initiate discussions about their mental health in a caring atmosphere.

“Although they told us they liked the idea of universal screening, they admitted to their family doctors that they actually preferred to be asked about their wellbeing, [to be asked] how things were going at home, and [to have] a discussion about their mental health and wellbeing, rather than a formal screening process. They felt a discussion about depression with a primary health care provider during the pregnancy and postpartum period is critical,” said Dr. Lang.

Thus, the task force recommends “against instrument-based depression screening using a questionnaire with cutoff score to distinguish ‘screen positive’ and ‘screen negative’ administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth).”
 

Screening remains common

“There’s a lot of uncertainty in the scientific community about whether it’s a good idea to administer a screening test to all pregnant and postpartum women to determine in a systematic way if they might be suffering from depression,” said Dr. Lang.

The task force recommended against screening for depression among perinatal or postpartum women in 2013, but screening is still performed in many provinces, said Dr. Lang.

Dr. Lang emphasized that the recommendation does not apply to usual care, in which the provider asks questions about and discusses a patient’s mental health and proceeds on the basis of their clinical judgment; nor does it apply to diagnostic pathways in which the clinician suspects that the individual may have depression and tests her accordingly.

“What we are saying in our recommendation is that all clinicians should ask about a patient’s wellbeing, about their mood, their anxiety, and these questions are an important part of the clinical assessment of pregnant and postpartum women. But we’re also saying the usefulness of doing so with a questionnaire and using a cutoff score on the questionnaire to decide who needs further assessment or possibly treatment is unproven by the research,” Dr. Lang said.
 

A growing problem

For Diane Francoeur, MD, CEO of the Society of Obstetricians and Gynecologists of Canada, this is all well and good, but the reality is that such screening is better than nothing.

Quebec is the only Canadian province that conducts universal screening for all pregnant and postpartum women, Dr. Francoeur said in an interview. She was not part of the task force.

“I agree that it should be more than one approach, but the problem is that there is such a shortage of resources. There are many issues that can arise when you follow a woman during her pregnancy,” she said.

Dr. Francoeur said that COVID-19 has been particularly tough on women, including pregnant and postpartum women, who are the most vulnerable.

“Especially during the COVID era, it was astonishing how women were not doing well. Their stress level was so high. We need to have a specific approach dedicated to prenatal mental health, because it’s a problem that is bigger than it used to be,” she said.

Violence against women has increased considerably since the beginning of the COVID-19 pandemic, said Dr. Francoeur. “Many more women have been killed by their partners. We have never seen anything like this before, and I hope we will never see this again,” she said.

“Help was more available a few years ago, but now, it’s really hard if and when you need to have a quick consultation with a specialist and the woman is really depressed. It can take forever. So, it’s okay to screen, but then, what’s next? Who is going to be there to take these women and help them? And we don’t have the answer,” Dr. Francoeur said.

Pregnant and postpartum women who suffer from depression need more than pills, she added. “We reassure them and treat their depression pharmacologically, but it’s also a time to give appropriate support and help them through the pregnancy and get well prepared to receive their newborn, because, as we now know, that first year of life is really important for the child, and the mom needs to be supported.”

Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. Dr. Lang and Dr. Francoeur reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Canadian Task Force on Preventive Health Care recommends against the routine screening of all pregnant and postpartum women for depression using a standard questionnaire, according to its new guideline.

The basis for its position is the lack of evidence that such screening “adds value beyond discussions about overall wellbeing, depression, anxiety, and mood that are currently a part of established perinatal clinical care.

“We should not be using a one-size-fits all approach,” lead author Eddy Lang, MD, professor and head of emergency medicine at the Cumming School of Medicine, University of Calgary (Alta.), told this news organization.

Instead, the task force emphasizes regular clinical care, including asking patients about their wellbeing and support systems. The task force categorizes the recommendation as conditional and as having very low-certainty evidence.

The recommendation was published in CMAJ.
 

One randomized study

The task force is an independent panel of clinicians and scientists that makes recommendations on primary and secondary prevention in primary care. A working group of five members of the task force developed this recommendation with scientific support from Public Health Agency of Canada staff.

In its research, the task force found only one study that showed a benefit of routine depression screening in this population. This study was a randomized controlled trial conducted in Hong Kong. Researchers evaluated 462 postpartum women who were randomly assigned to receive screening with the Edinburgh Postnatal Depression Scale (EPDS) or no screening 2 months post partum.

“We found the effect of screening in this study to be very uncertain for the important outcomes of interest,” said Dr. Lang.

“These included parent-child stress, marital stress, and the number of infant hospital admissions. The effects of screening on all of these outcomes were very uncertain, mainly because it was such a small trial,” he said.

The task force also assessed how pregnant and postpartum women feel about being screened. What these women most wanted was a good relationship with a trusted primary care provider who would initiate discussions about their mental health in a caring atmosphere.

“Although they told us they liked the idea of universal screening, they admitted to their family doctors that they actually preferred to be asked about their wellbeing, [to be asked] how things were going at home, and [to have] a discussion about their mental health and wellbeing, rather than a formal screening process. They felt a discussion about depression with a primary health care provider during the pregnancy and postpartum period is critical,” said Dr. Lang.

Thus, the task force recommends “against instrument-based depression screening using a questionnaire with cutoff score to distinguish ‘screen positive’ and ‘screen negative’ administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth).”
 

Screening remains common

“There’s a lot of uncertainty in the scientific community about whether it’s a good idea to administer a screening test to all pregnant and postpartum women to determine in a systematic way if they might be suffering from depression,” said Dr. Lang.

The task force recommended against screening for depression among perinatal or postpartum women in 2013, but screening is still performed in many provinces, said Dr. Lang.

Dr. Lang emphasized that the recommendation does not apply to usual care, in which the provider asks questions about and discusses a patient’s mental health and proceeds on the basis of their clinical judgment; nor does it apply to diagnostic pathways in which the clinician suspects that the individual may have depression and tests her accordingly.

“What we are saying in our recommendation is that all clinicians should ask about a patient’s wellbeing, about their mood, their anxiety, and these questions are an important part of the clinical assessment of pregnant and postpartum women. But we’re also saying the usefulness of doing so with a questionnaire and using a cutoff score on the questionnaire to decide who needs further assessment or possibly treatment is unproven by the research,” Dr. Lang said.
 

A growing problem

For Diane Francoeur, MD, CEO of the Society of Obstetricians and Gynecologists of Canada, this is all well and good, but the reality is that such screening is better than nothing.

Quebec is the only Canadian province that conducts universal screening for all pregnant and postpartum women, Dr. Francoeur said in an interview. She was not part of the task force.

“I agree that it should be more than one approach, but the problem is that there is such a shortage of resources. There are many issues that can arise when you follow a woman during her pregnancy,” she said.

Dr. Francoeur said that COVID-19 has been particularly tough on women, including pregnant and postpartum women, who are the most vulnerable.

“Especially during the COVID era, it was astonishing how women were not doing well. Their stress level was so high. We need to have a specific approach dedicated to prenatal mental health, because it’s a problem that is bigger than it used to be,” she said.

Violence against women has increased considerably since the beginning of the COVID-19 pandemic, said Dr. Francoeur. “Many more women have been killed by their partners. We have never seen anything like this before, and I hope we will never see this again,” she said.

“Help was more available a few years ago, but now, it’s really hard if and when you need to have a quick consultation with a specialist and the woman is really depressed. It can take forever. So, it’s okay to screen, but then, what’s next? Who is going to be there to take these women and help them? And we don’t have the answer,” Dr. Francoeur said.

Pregnant and postpartum women who suffer from depression need more than pills, she added. “We reassure them and treat their depression pharmacologically, but it’s also a time to give appropriate support and help them through the pregnancy and get well prepared to receive their newborn, because, as we now know, that first year of life is really important for the child, and the mom needs to be supported.”

Funding for the Canadian Task Force on Preventive Health Care is provided by the Public Health Agency of Canada. Dr. Lang and Dr. Francoeur reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

On June 24, the U.S. Supreme Court overturned Roe v. Wade, a decision that was issued in 1973. From now on, each state will be able to choose the laws that it wants to put in place regarding abortion. Several states have already decided to ban abortion altogether. As a physician, but also as a woman, I am stunned to see this opposition to a right that, in my opinion, is also a matter of public health.

International data

In Belgium, voluntary termination of pregnancy (VTP) has been allowed since 1990. Except in the case of a serious medical problem, the abortion must take place before the end of the 12th week after conception. So, 14 weeks from the last menstrual period (LMP).

Beyond that time frame, a VTP can be performed only when the continuation of the pregnancy endangers the health of the woman or when it is certain that the unborn child will be affected by a condition of particular gravity and recognized as incurable at the time of diagnosis. This is referred to as termination for medical reasons (TFMR).
 

First observation

The annual number of VTPs did not climb following legalization. For the past 20 years in Belgium, that number has remained stable, hovering around 19,000. Abortion continues to be an action – neither trivialized nor minimized – that is difficult for any woman to take, no matter what her reason.

Second observation

Over 60% of women who had an abortion were using a form of contraception. So, while the burden of contraception still rests almost exclusively on the woman, it cannot be said that those who had a VTP did not use some method of birth control.

Even more important, legal abortions have very few complications, either physical or psychological. Studies show that pregnancy itself carries a higher risk for psychopathological manifestations than a VTP. These VTPs are safe, and women quickly recover from them. The most sensitive time seems to be the period before the abortion, and it’s at this stage that most of the psychological and psychopathological manifestations accumulate. The majority of women facing a VTP experience feelings of relief, and only a minority develop psychological problems, usually when there is already a history of mental disorder. The literature shows that the levels of anxiety and depression decrease in the month following the abortion. Being denied a VTP, on the other hand, significantly increases the woman’s risk of developing a mental disorder.

Should a VTP be denied, a woman, if she determines that she doesn’t have any other choice, may then end up turning to a back-alley abortion. The methods used for this are medieval, dangerous, and may not prove successful – things like using chemicals, piercing the amniotic sac with a needle or sharp object (the famous coat hanger), eating or drinking abortifacient herbs, taking large quantities of medication, punching the stomach, falling down stairs, and engaging in intense physical exercise.

From there, these risky methods inevitably lead to numerous complications: Incomplete abortions, infections, septicemia, breakthrough bleeding, subsequent sterility, laceration of the uterine wall, or death.

Around one-third of women who undergo risky abortions develop complications, while less than half receive care.

The World Health Organization estimates that back-alley abortions represent 49% of abortions worldwide. It puts the number of illegal abortions performed each year at 20 million.

Each year, around 60,000 women worldwide die as a result of an unsafe VTP. That’s one woman every 9 minutes. And odds are that these figures are underestimated.

Making the decision to resort to a VTP is always difficult. Ideally, you should be able to discuss it with your partner, when there is one, and with your close friends and family, to have someone go with you as support, to weigh the pros and cons, and to make a choice in line with your convictions and your conscience. But first and foremost, the law must guarantee the right to be able to ask oneself this question, because guaranteeing this right is also guaranteeing the health and safety of women, and that is why this remains a public health imperative.

A version of this article first appeared on Medscape.com. This article was translated from MediQuality.

On June 24, the U.S. Supreme Court overturned Roe v. Wade, a decision that was issued in 1973. From now on, each state will be able to choose the laws that it wants to put in place regarding abortion. Several states have already decided to ban abortion altogether. As a physician, but also as a woman, I am stunned to see this opposition to a right that, in my opinion, is also a matter of public health.

International data

In Belgium, voluntary termination of pregnancy (VTP) has been allowed since 1990. Except in the case of a serious medical problem, the abortion must take place before the end of the 12th week after conception. So, 14 weeks from the last menstrual period (LMP).

Beyond that time frame, a VTP can be performed only when the continuation of the pregnancy endangers the health of the woman or when it is certain that the unborn child will be affected by a condition of particular gravity and recognized as incurable at the time of diagnosis. This is referred to as termination for medical reasons (TFMR).
 

First observation

The annual number of VTPs did not climb following legalization. For the past 20 years in Belgium, that number has remained stable, hovering around 19,000. Abortion continues to be an action – neither trivialized nor minimized – that is difficult for any woman to take, no matter what her reason.

Second observation

Over 60% of women who had an abortion were using a form of contraception. So, while the burden of contraception still rests almost exclusively on the woman, it cannot be said that those who had a VTP did not use some method of birth control.

Even more important, legal abortions have very few complications, either physical or psychological. Studies show that pregnancy itself carries a higher risk for psychopathological manifestations than a VTP. These VTPs are safe, and women quickly recover from them. The most sensitive time seems to be the period before the abortion, and it’s at this stage that most of the psychological and psychopathological manifestations accumulate. The majority of women facing a VTP experience feelings of relief, and only a minority develop psychological problems, usually when there is already a history of mental disorder. The literature shows that the levels of anxiety and depression decrease in the month following the abortion. Being denied a VTP, on the other hand, significantly increases the woman’s risk of developing a mental disorder.

Should a VTP be denied, a woman, if she determines that she doesn’t have any other choice, may then end up turning to a back-alley abortion. The methods used for this are medieval, dangerous, and may not prove successful – things like using chemicals, piercing the amniotic sac with a needle or sharp object (the famous coat hanger), eating or drinking abortifacient herbs, taking large quantities of medication, punching the stomach, falling down stairs, and engaging in intense physical exercise.

From there, these risky methods inevitably lead to numerous complications: Incomplete abortions, infections, septicemia, breakthrough bleeding, subsequent sterility, laceration of the uterine wall, or death.

Around one-third of women who undergo risky abortions develop complications, while less than half receive care.

The World Health Organization estimates that back-alley abortions represent 49% of abortions worldwide. It puts the number of illegal abortions performed each year at 20 million.

Each year, around 60,000 women worldwide die as a result of an unsafe VTP. That’s one woman every 9 minutes. And odds are that these figures are underestimated.

Making the decision to resort to a VTP is always difficult. Ideally, you should be able to discuss it with your partner, when there is one, and with your close friends and family, to have someone go with you as support, to weigh the pros and cons, and to make a choice in line with your convictions and your conscience. But first and foremost, the law must guarantee the right to be able to ask oneself this question, because guaranteeing this right is also guaranteeing the health and safety of women, and that is why this remains a public health imperative.

A version of this article first appeared on Medscape.com. This article was translated from MediQuality.

On June 24, the U.S. Supreme Court overturned Roe v. Wade, a decision that was issued in 1973. From now on, each state will be able to choose the laws that it wants to put in place regarding abortion. Several states have already decided to ban abortion altogether. As a physician, but also as a woman, I am stunned to see this opposition to a right that, in my opinion, is also a matter of public health.

International data

In Belgium, voluntary termination of pregnancy (VTP) has been allowed since 1990. Except in the case of a serious medical problem, the abortion must take place before the end of the 12th week after conception. So, 14 weeks from the last menstrual period (LMP).

Beyond that time frame, a VTP can be performed only when the continuation of the pregnancy endangers the health of the woman or when it is certain that the unborn child will be affected by a condition of particular gravity and recognized as incurable at the time of diagnosis. This is referred to as termination for medical reasons (TFMR).
 

First observation

The annual number of VTPs did not climb following legalization. For the past 20 years in Belgium, that number has remained stable, hovering around 19,000. Abortion continues to be an action – neither trivialized nor minimized – that is difficult for any woman to take, no matter what her reason.

Second observation

Over 60% of women who had an abortion were using a form of contraception. So, while the burden of contraception still rests almost exclusively on the woman, it cannot be said that those who had a VTP did not use some method of birth control.

Even more important, legal abortions have very few complications, either physical or psychological. Studies show that pregnancy itself carries a higher risk for psychopathological manifestations than a VTP. These VTPs are safe, and women quickly recover from them. The most sensitive time seems to be the period before the abortion, and it’s at this stage that most of the psychological and psychopathological manifestations accumulate. The majority of women facing a VTP experience feelings of relief, and only a minority develop psychological problems, usually when there is already a history of mental disorder. The literature shows that the levels of anxiety and depression decrease in the month following the abortion. Being denied a VTP, on the other hand, significantly increases the woman’s risk of developing a mental disorder.

Should a VTP be denied, a woman, if she determines that she doesn’t have any other choice, may then end up turning to a back-alley abortion. The methods used for this are medieval, dangerous, and may not prove successful – things like using chemicals, piercing the amniotic sac with a needle or sharp object (the famous coat hanger), eating or drinking abortifacient herbs, taking large quantities of medication, punching the stomach, falling down stairs, and engaging in intense physical exercise.

From there, these risky methods inevitably lead to numerous complications: Incomplete abortions, infections, septicemia, breakthrough bleeding, subsequent sterility, laceration of the uterine wall, or death.

Around one-third of women who undergo risky abortions develop complications, while less than half receive care.

The World Health Organization estimates that back-alley abortions represent 49% of abortions worldwide. It puts the number of illegal abortions performed each year at 20 million.

Each year, around 60,000 women worldwide die as a result of an unsafe VTP. That’s one woman every 9 minutes. And odds are that these figures are underestimated.

Making the decision to resort to a VTP is always difficult. Ideally, you should be able to discuss it with your partner, when there is one, and with your close friends and family, to have someone go with you as support, to weigh the pros and cons, and to make a choice in line with your convictions and your conscience. But first and foremost, the law must guarantee the right to be able to ask oneself this question, because guaranteeing this right is also guaranteeing the health and safety of women, and that is why this remains a public health imperative.

A version of this article first appeared on Medscape.com. This article was translated from MediQuality.

The World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) has changed the recommendation for vaccines against human papillomavirus (HPV).

From the available evidence, SAGE has concluded that a single dose of vaccine offers solid protection against HPV, comparable to that achieved with two-dose schedules.

This could be a “game-changer for the prevention of the disease,” as it would allow “more doses of the life-saving jab reach more girls,” the WHO declared in a press release.

SAGE recommends updating HPV dose schedules as follows:

• One- or two-dose schedule for the primary target of girls aged 9-14 years.
• One- or two-dose schedule for young women aged 15-20.
• Two doses with a 6-month interval for women older than 21.

The HPV vaccine is highly effective for the prevention of HPV serotypes 16 and 18, which cause 70% of cases of cervical cancer, said Alejandro Cravioto, MD, PhD, SAGE chair, in a statement.

“SAGE urges all countries to introduce HPV vaccines and prioritize multi-age cohort catch up of missed and older cohorts of girls. These recommendations will enable more girls and women to be vaccinated and thus preventing them from having cervical cancer and all its consequences over the course of their lifetimes,” he added.

For individuals who are immunocompromised, including those with HIV, three doses of the vaccine should be given if feasible, and if not, then at least two doses. There is limited evidence regarding the efficacy of a single dose in this group, the advisory group noted.
 

Policy makers need to make changes

Now that the WHO has deemed that one dose of HPV vaccine is sufficient, policy makers should make changes, say experts in a recent editorial comment published in The Lancet Oncology.

“Policy makers should consider modifying their HPV immunization schedules for girls aged 9-14 years from a two-dose regimen to a one-dose regimen,” wrote Jeff D’Souza, PhD, Institute for Better Health, Trillium Health Partners, Mississauga, Ont., and David Nderitu, PhD, Egerton University, Nakuru County, Kenya.

Policy makers also need to consider reorienting their efforts on cervical cancer screening and treatment, and they should ensure that all girls globally have access to an effective HPV vaccination schedule, they add.

The editorialists also make a radical proposal.

Existing supply constraints of the HPV vaccine at the country level are expected to continue for the next 3 years, and the vast majority of new cervical cancer cases and related deaths occur in low- and middle-income countries (LMICs).

To overcome these problems, they suggest that “high-income countries that currently offer two-dose regimens to girls aged 9-14 years should consider opting for a one-dose vaccination schedule, and give any excess of vaccines to countries in greater need of them.”
 

Two doses in high-income countries

But it is unclear whether high-income countries are ready to move to a one-dose schedule.

Approached for comment, Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, Philadelphia, told this news organization that while he can’t say for certain, he suspects that the United States will be slower to accept this recommendation for a single dose of HPV vaccine “as a component of a ‘standard-of-care’ approach.”

However, it “might formally acknowledge that if an individual/parent will only accept a single vaccine dose (or ultimately refuses to return for a recommended second dose), this will be considered a favorable outcome, both for the individual and society.

“I do not know if regulatory bodies in the United States will accept the existing studies performed to address the one-dose vaccination strategy to rather dramatically change the approach in our country,” he said. “The issue would be that if a single dose was stated to be a clinically acceptable option in the United States, it would rapidly become the standard approach, and the regulators would want to be as certain as possible that this would not have a negative effect on what is now recognized to be a remarkably safe and effective cancer prevention effort.”

Another expert who was approached for comment, Stephanie V. Blank, MD, professor of gynecologic oncology at the Icahn School of Medicine at Mount Sinai, New York, said: “In higher-resourced countries, two doses are still preferred, as they are more effective than one.

“The modeling on which the SAGE recommendation is based is all from studies in LMICs and other modeling studies,” she added.

At present, the Centers for Disease Control and Prevention recommends a two-dose schedule of HPV vaccines for individuals who receive the first dose before their 15th birthday. The three-dose schedule is recommended for those who receive the first dose on or after their 15th birthday and for people with certain immunocompromising conditions.

Studies have shown that two doses of HPV vaccine given to children aged 9-14 years provide as good or better protection than three doses given to older adolescents or young adults.

But even with a two-dose schedule, the WHO reports that uptake of the vaccine has been slow, and coverage is much lower than their 90% target. In 2020, global coverage with two doses was only 13%.

Factors that have influenced the slow uptake and low coverage of HPV vaccines include supply challenges, programmatic challenges, and costs related to delivering a two-dose regimen to older girls who are not typically included in childhood vaccination programs. The relatively high cost of HPV vaccines has also been problematic, particularly for middle-income countries.
 

Trials of one-dose schedules

The one-dose vaccine schedule has garnered a lot of interest, with several studies showing efficacy.

The KEN SHE trial, based in Kenya, showed that a single dose of the HPV vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens. Vaccine efficacy was 97.5% (P < .001) against HPV 16/18 for both the bivalent and monovalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers noted.

A study in India found that efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% for the single dose, 93.1% for the two-dose schedule, and 93.3% for the three-dose series.

Commenting on this trial in India in a recent interview with this news organization, Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, said the findings from India would need “to be confirmed by other studies.” The results were nonetheless “excellent news for developing countries where there are challenges when it comes to access to vaccination.”

Speaking at the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases, he emphasized that at this stage, the findings “cannot be extrapolated” to France. HPV vaccination coverage is low in France (it is estimated that the rate is 23.7%, placing the country 28th of 31 countries in Europe), and he recommended continuing with the two- or three-dose schedule for the time being.

“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”
 

Ethics of the vaccine

In their editorial, Dr. D’Souza and Dr. Nderitu note that there are ethical considerations with the HPV vaccine that can “help guide deliberations, covering nonmaleficence, beneficence, health equity, stewardship, and solidarity.”

It would be inequitable and unjustifiable, they write, to offer a two-dose regimen to girls aged 9-14 years without also introducing multi-age cohort catch-up campaigns or programs for women who do not have access. “When it comes to an effective HPV vaccination schedule, no woman or girl should be left behind,” they say.

To achieve the goal of eliminating cervical cancer, “countries must ensure that 90% of girls are vaccinated, 70% of women are screened, and 90% of women with precancerous lesions receive treatment and care,” they write. “Given resource constraints, particularly in low-middle income countries, policy makers have a responsibility to ensure that resources are used in an optimal manner that promotes the right to health of all individuals.”

Thus, countries that are lagging far behind in cervical cancer education, screening, and treatment should consider opting for a one-dose regimen for girls aged 9-14 years, as well as using additional resources to close the gap in these other areas.

Dr. Markman has relationships with Genentech, AstraZeneca, Celgene, Clovis, and Amgen; he is also a regular contributor to Medscape Oncology with the Markamn on Oncology video column. Dr. D’Souza and Dr. Nderitu have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) has changed the recommendation for vaccines against human papillomavirus (HPV).

From the available evidence, SAGE has concluded that a single dose of vaccine offers solid protection against HPV, comparable to that achieved with two-dose schedules.

This could be a “game-changer for the prevention of the disease,” as it would allow “more doses of the life-saving jab reach more girls,” the WHO declared in a press release.

SAGE recommends updating HPV dose schedules as follows:

• One- or two-dose schedule for the primary target of girls aged 9-14 years.
• One- or two-dose schedule for young women aged 15-20.
• Two doses with a 6-month interval for women older than 21.

The HPV vaccine is highly effective for the prevention of HPV serotypes 16 and 18, which cause 70% of cases of cervical cancer, said Alejandro Cravioto, MD, PhD, SAGE chair, in a statement.

“SAGE urges all countries to introduce HPV vaccines and prioritize multi-age cohort catch up of missed and older cohorts of girls. These recommendations will enable more girls and women to be vaccinated and thus preventing them from having cervical cancer and all its consequences over the course of their lifetimes,” he added.

For individuals who are immunocompromised, including those with HIV, three doses of the vaccine should be given if feasible, and if not, then at least two doses. There is limited evidence regarding the efficacy of a single dose in this group, the advisory group noted.
 

Policy makers need to make changes

Now that the WHO has deemed that one dose of HPV vaccine is sufficient, policy makers should make changes, say experts in a recent editorial comment published in The Lancet Oncology.

“Policy makers should consider modifying their HPV immunization schedules for girls aged 9-14 years from a two-dose regimen to a one-dose regimen,” wrote Jeff D’Souza, PhD, Institute for Better Health, Trillium Health Partners, Mississauga, Ont., and David Nderitu, PhD, Egerton University, Nakuru County, Kenya.

Policy makers also need to consider reorienting their efforts on cervical cancer screening and treatment, and they should ensure that all girls globally have access to an effective HPV vaccination schedule, they add.

The editorialists also make a radical proposal.

Existing supply constraints of the HPV vaccine at the country level are expected to continue for the next 3 years, and the vast majority of new cervical cancer cases and related deaths occur in low- and middle-income countries (LMICs).

To overcome these problems, they suggest that “high-income countries that currently offer two-dose regimens to girls aged 9-14 years should consider opting for a one-dose vaccination schedule, and give any excess of vaccines to countries in greater need of them.”
 

Two doses in high-income countries

But it is unclear whether high-income countries are ready to move to a one-dose schedule.

Approached for comment, Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, Philadelphia, told this news organization that while he can’t say for certain, he suspects that the United States will be slower to accept this recommendation for a single dose of HPV vaccine “as a component of a ‘standard-of-care’ approach.”

However, it “might formally acknowledge that if an individual/parent will only accept a single vaccine dose (or ultimately refuses to return for a recommended second dose), this will be considered a favorable outcome, both for the individual and society.

“I do not know if regulatory bodies in the United States will accept the existing studies performed to address the one-dose vaccination strategy to rather dramatically change the approach in our country,” he said. “The issue would be that if a single dose was stated to be a clinically acceptable option in the United States, it would rapidly become the standard approach, and the regulators would want to be as certain as possible that this would not have a negative effect on what is now recognized to be a remarkably safe and effective cancer prevention effort.”

Another expert who was approached for comment, Stephanie V. Blank, MD, professor of gynecologic oncology at the Icahn School of Medicine at Mount Sinai, New York, said: “In higher-resourced countries, two doses are still preferred, as they are more effective than one.

“The modeling on which the SAGE recommendation is based is all from studies in LMICs and other modeling studies,” she added.

At present, the Centers for Disease Control and Prevention recommends a two-dose schedule of HPV vaccines for individuals who receive the first dose before their 15th birthday. The three-dose schedule is recommended for those who receive the first dose on or after their 15th birthday and for people with certain immunocompromising conditions.

Studies have shown that two doses of HPV vaccine given to children aged 9-14 years provide as good or better protection than three doses given to older adolescents or young adults.

But even with a two-dose schedule, the WHO reports that uptake of the vaccine has been slow, and coverage is much lower than their 90% target. In 2020, global coverage with two doses was only 13%.

Factors that have influenced the slow uptake and low coverage of HPV vaccines include supply challenges, programmatic challenges, and costs related to delivering a two-dose regimen to older girls who are not typically included in childhood vaccination programs. The relatively high cost of HPV vaccines has also been problematic, particularly for middle-income countries.
 

Trials of one-dose schedules

The one-dose vaccine schedule has garnered a lot of interest, with several studies showing efficacy.

The KEN SHE trial, based in Kenya, showed that a single dose of the HPV vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens. Vaccine efficacy was 97.5% (P < .001) against HPV 16/18 for both the bivalent and monovalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers noted.

A study in India found that efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% for the single dose, 93.1% for the two-dose schedule, and 93.3% for the three-dose series.

Commenting on this trial in India in a recent interview with this news organization, Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, said the findings from India would need “to be confirmed by other studies.” The results were nonetheless “excellent news for developing countries where there are challenges when it comes to access to vaccination.”

Speaking at the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases, he emphasized that at this stage, the findings “cannot be extrapolated” to France. HPV vaccination coverage is low in France (it is estimated that the rate is 23.7%, placing the country 28th of 31 countries in Europe), and he recommended continuing with the two- or three-dose schedule for the time being.

“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”
 

Ethics of the vaccine

In their editorial, Dr. D’Souza and Dr. Nderitu note that there are ethical considerations with the HPV vaccine that can “help guide deliberations, covering nonmaleficence, beneficence, health equity, stewardship, and solidarity.”

It would be inequitable and unjustifiable, they write, to offer a two-dose regimen to girls aged 9-14 years without also introducing multi-age cohort catch-up campaigns or programs for women who do not have access. “When it comes to an effective HPV vaccination schedule, no woman or girl should be left behind,” they say.

To achieve the goal of eliminating cervical cancer, “countries must ensure that 90% of girls are vaccinated, 70% of women are screened, and 90% of women with precancerous lesions receive treatment and care,” they write. “Given resource constraints, particularly in low-middle income countries, policy makers have a responsibility to ensure that resources are used in an optimal manner that promotes the right to health of all individuals.”

Thus, countries that are lagging far behind in cervical cancer education, screening, and treatment should consider opting for a one-dose regimen for girls aged 9-14 years, as well as using additional resources to close the gap in these other areas.

Dr. Markman has relationships with Genentech, AstraZeneca, Celgene, Clovis, and Amgen; he is also a regular contributor to Medscape Oncology with the Markamn on Oncology video column. Dr. D’Souza and Dr. Nderitu have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) has changed the recommendation for vaccines against human papillomavirus (HPV).

From the available evidence, SAGE has concluded that a single dose of vaccine offers solid protection against HPV, comparable to that achieved with two-dose schedules.

This could be a “game-changer for the prevention of the disease,” as it would allow “more doses of the life-saving jab reach more girls,” the WHO declared in a press release.

SAGE recommends updating HPV dose schedules as follows:

• One- or two-dose schedule for the primary target of girls aged 9-14 years.
• One- or two-dose schedule for young women aged 15-20.
• Two doses with a 6-month interval for women older than 21.

The HPV vaccine is highly effective for the prevention of HPV serotypes 16 and 18, which cause 70% of cases of cervical cancer, said Alejandro Cravioto, MD, PhD, SAGE chair, in a statement.

“SAGE urges all countries to introduce HPV vaccines and prioritize multi-age cohort catch up of missed and older cohorts of girls. These recommendations will enable more girls and women to be vaccinated and thus preventing them from having cervical cancer and all its consequences over the course of their lifetimes,” he added.

For individuals who are immunocompromised, including those with HIV, three doses of the vaccine should be given if feasible, and if not, then at least two doses. There is limited evidence regarding the efficacy of a single dose in this group, the advisory group noted.
 

Policy makers need to make changes

Now that the WHO has deemed that one dose of HPV vaccine is sufficient, policy makers should make changes, say experts in a recent editorial comment published in The Lancet Oncology.

“Policy makers should consider modifying their HPV immunization schedules for girls aged 9-14 years from a two-dose regimen to a one-dose regimen,” wrote Jeff D’Souza, PhD, Institute for Better Health, Trillium Health Partners, Mississauga, Ont., and David Nderitu, PhD, Egerton University, Nakuru County, Kenya.

Policy makers also need to consider reorienting their efforts on cervical cancer screening and treatment, and they should ensure that all girls globally have access to an effective HPV vaccination schedule, they add.

The editorialists also make a radical proposal.

Existing supply constraints of the HPV vaccine at the country level are expected to continue for the next 3 years, and the vast majority of new cervical cancer cases and related deaths occur in low- and middle-income countries (LMICs).

To overcome these problems, they suggest that “high-income countries that currently offer two-dose regimens to girls aged 9-14 years should consider opting for a one-dose vaccination schedule, and give any excess of vaccines to countries in greater need of them.”
 

Two doses in high-income countries

But it is unclear whether high-income countries are ready to move to a one-dose schedule.

Approached for comment, Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, Philadelphia, told this news organization that while he can’t say for certain, he suspects that the United States will be slower to accept this recommendation for a single dose of HPV vaccine “as a component of a ‘standard-of-care’ approach.”

However, it “might formally acknowledge that if an individual/parent will only accept a single vaccine dose (or ultimately refuses to return for a recommended second dose), this will be considered a favorable outcome, both for the individual and society.

“I do not know if regulatory bodies in the United States will accept the existing studies performed to address the one-dose vaccination strategy to rather dramatically change the approach in our country,” he said. “The issue would be that if a single dose was stated to be a clinically acceptable option in the United States, it would rapidly become the standard approach, and the regulators would want to be as certain as possible that this would not have a negative effect on what is now recognized to be a remarkably safe and effective cancer prevention effort.”

Another expert who was approached for comment, Stephanie V. Blank, MD, professor of gynecologic oncology at the Icahn School of Medicine at Mount Sinai, New York, said: “In higher-resourced countries, two doses are still preferred, as they are more effective than one.

“The modeling on which the SAGE recommendation is based is all from studies in LMICs and other modeling studies,” she added.

At present, the Centers for Disease Control and Prevention recommends a two-dose schedule of HPV vaccines for individuals who receive the first dose before their 15th birthday. The three-dose schedule is recommended for those who receive the first dose on or after their 15th birthday and for people with certain immunocompromising conditions.

Studies have shown that two doses of HPV vaccine given to children aged 9-14 years provide as good or better protection than three doses given to older adolescents or young adults.

But even with a two-dose schedule, the WHO reports that uptake of the vaccine has been slow, and coverage is much lower than their 90% target. In 2020, global coverage with two doses was only 13%.

Factors that have influenced the slow uptake and low coverage of HPV vaccines include supply challenges, programmatic challenges, and costs related to delivering a two-dose regimen to older girls who are not typically included in childhood vaccination programs. The relatively high cost of HPV vaccines has also been problematic, particularly for middle-income countries.
 

Trials of one-dose schedules

The one-dose vaccine schedule has garnered a lot of interest, with several studies showing efficacy.

The KEN SHE trial, based in Kenya, showed that a single dose of the HPV vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens. Vaccine efficacy was 97.5% (P < .001) against HPV 16/18 for both the bivalent and monovalent vaccines, which is “comparable to that seen in multidose vaccine trials,” the researchers noted.

A study in India found that efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% for the single dose, 93.1% for the two-dose schedule, and 93.3% for the three-dose series.

Commenting on this trial in India in a recent interview with this news organization, Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, said the findings from India would need “to be confirmed by other studies.” The results were nonetheless “excellent news for developing countries where there are challenges when it comes to access to vaccination.”

Speaking at the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases, he emphasized that at this stage, the findings “cannot be extrapolated” to France. HPV vaccination coverage is low in France (it is estimated that the rate is 23.7%, placing the country 28th of 31 countries in Europe), and he recommended continuing with the two- or three-dose schedule for the time being.

“This poor coverage has nothing to do with health care–related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Dr. Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”
 

Ethics of the vaccine

In their editorial, Dr. D’Souza and Dr. Nderitu note that there are ethical considerations with the HPV vaccine that can “help guide deliberations, covering nonmaleficence, beneficence, health equity, stewardship, and solidarity.”

It would be inequitable and unjustifiable, they write, to offer a two-dose regimen to girls aged 9-14 years without also introducing multi-age cohort catch-up campaigns or programs for women who do not have access. “When it comes to an effective HPV vaccination schedule, no woman or girl should be left behind,” they say.

To achieve the goal of eliminating cervical cancer, “countries must ensure that 90% of girls are vaccinated, 70% of women are screened, and 90% of women with precancerous lesions receive treatment and care,” they write. “Given resource constraints, particularly in low-middle income countries, policy makers have a responsibility to ensure that resources are used in an optimal manner that promotes the right to health of all individuals.”

Thus, countries that are lagging far behind in cervical cancer education, screening, and treatment should consider opting for a one-dose regimen for girls aged 9-14 years, as well as using additional resources to close the gap in these other areas.

Dr. Markman has relationships with Genentech, AstraZeneca, Celgene, Clovis, and Amgen; he is also a regular contributor to Medscape Oncology with the Markamn on Oncology video column. Dr. D’Souza and Dr. Nderitu have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Cee Elliot is afraid of pregnancy. The 29-year-old retail manager in Connecticut said she has felt that way since puberty, when she “finally understood” pregnancy and reproduction. Always squeamish around babies and pregnant people, she said, as she learned more about the complications birth can cause, the idea of carrying a child herself became increasingly repulsive.

Later, Ms. Elliot said, she was treated poorly by a partner because of her fears, leading to regular panic attacks. She moved on from that partner, but her fear of pregnancy did not. Along the way, she felt her fears were dismissed by doctors and peers alike.

Tokophobia – a severe fear of childbirth – goes beyond the typical anxieties about birth or pregnancy that women often experience. The condition can intrude on everyday life, crippling social interaction and interrupting regular sleep patterns. Although statistics in the United States don’t exist, as many as 14% of women internationally are thought to have tokophobia.

Although psychiatric treatment focusing on past traumas can help, many women resort to managing the condition themselves. Some seek sterilization, whereas others take multiple forms of contraception simultaneously – combining intrauterine devices and oral birth control, for example, experts said. Some women have sought abortions and some even have attempted suicide rather than face giving birth, according to Leila Frodsham, MbChB, a women’s health expert at King’s College London, who has studied tokophobia.

The International Classification of Diseases added tokophobia to its list of diagnostic codes in 2018. But the Diagnostic and Statistical Manual of Mental Disorders, used by clinicians in the United States, has yet to do the same. Without this designation, some doctors are more inclined to diagnose tokophobia than others, Dr. Frodsham said.

“I think some clinicians struggle to understand how much this condition affects women. There isn’t training in it, and I’d like to see it discussed more,” Dr. Frodsham told this news organization.

Dr. Frodsham said she has seen hundreds of patients seeking help with their fear of pregnancy. Many of these women don’t know that they might have a condition that could benefit from psychiatric treatment.

Tokophobia typically takes two forms: primary, which affects women who have never given birth; and secondary, which stems from a previous traumatic birth experience.

“It’s not the pain of childbirth they are afraid of, but rather their fear comes out of a sense that they lack control over themselves and the situation of being pregnant,” Dr. Frodsham said.

Although the phenomenon has been studied internationally, particularly in Europe, fear of childbirth remains almost entirely unexplored in the United States literature.

One of the only scientific examinations of tokophobia in this country was a 2016 survey of 22 women with the condition by researchers at the University of Michigan, Ann Arbor. Published in the Journal of Obstetric, Gynecology & Neonatal Nursing, the survey found that many of the women expressed concern that their race, gender, or level of income might affect the quality of their care. Some women surveyed said they had experienced traumas directly related to systemic inequalities in the health care system.

Lee Roosevelt, PhD, MPH, CNM, a nurse and midwife and a coauthor of the study, said fear of the health care system, coupled with concern over the loss of bodily autonomy, can foster severe aversion to childbirth. In her experience, she said, clinicians often handle these patients poorly.

“If a woman is making the decision not to have children, we want it to be because she has decided for her, and her body, that it is the right thing,” added Lisa Kane Low, PhD, CNM, professor of obstetrics and gynecology at the University of Michigan, who worked with Dr. Roosevelt on the survey. “She shouldn’t feel the decision is made because she can’t access what she needs or the health care system is unable to provide it.”

Access to midwives, doulas, or therapists trained in trauma counseling can allow women to have a voice in their treatment, Dr. Roosevelt said.

No specific medication exists to treat tokophobia; however, drugs for depression or anxiety sometimes help, Dr. Low said. “Women with tokophobia may not need medication but would benefit from other therapies like desensitization or biobehavioral approaches or combinations of those,” she said.
 

Treating triggers

According to Dr. Frodsham, women with tokophobia often experience guilt and isolation. They may avoid speaking to women who are pregnant or avoid discussing pregnancy and childbirth, afraid that doing so may trigger their fear.

“They can’t see how they can get close to this catastrophic thing they think is going to happen to them,” she said. “Many of them think they will die.”

Many patients avoid thinking about memories of traumatic events so as to not trigger extreme emotional responses.

Dr. Roosevelt said developing ways to assess and treat tokophobia has become more urgent, since the Supreme Court’s recent decision to overturn Roe v. Wade could lead to more instances of women carrying unwanted pregnancies.
 

Seeking community

The internet has become a place where women with tokophobia and less severe fears about pregnancy can share their experiences. On the online bulletin board Reddit, r/Tokphobia and r/childfree contain thousands of queries and personal stories about the condition, as well as requests for advice.

Jillian Kilcoyne, who lives in New York and attends college in Michigan, said: “Pregnancy has always freaked me out. A part of me believes it’s a biological injustice that women have to go through such pain and be ignored by the medical community just to give birth.” Ms. Kilcoyne said she has not sought counseling or help from a clinician.

“I’m not sure I even want it,” she told this news organization. “Some people want to get over their phobia because they want families, and others don’t want children at all. I think that those individuals should have the help they need.”

Claudia, a South Carolina resident who asked to be identified only by her first name owing to concerns about her privacy, said her tokophobia began when she started having sex. It grew worse when she developed health conditions that could be exacerbated by pregnancy. She said she stocks up on contraceptives and periodically takes a pregnancy test to ease her nerves.

“This started for me when I realized that having children wasn’t a requirement for life. I didn’t even know there was a name for what I was feeling,” Claudia said in an interview. “So, letting women know they have options, and then not making them feel guilty, or ashamed, is the most important thing. We shouldn’t try to convince women that motherhood is the only, or the correct, path.”

Ms. Elliot urged clinicians to have compassion: “Treat tokophobic patients – especially a pregnant one seeking an abortion – like someone with a life-threatening parasite. Don’t belittle or dismiss them. We’re already going to lose so many lives because of unwanted pregnancies and birth. Don’t add to the number.”

A version of this article first appeared on Medscape.com.

Cee Elliot is afraid of pregnancy. The 29-year-old retail manager in Connecticut said she has felt that way since puberty, when she “finally understood” pregnancy and reproduction. Always squeamish around babies and pregnant people, she said, as she learned more about the complications birth can cause, the idea of carrying a child herself became increasingly repulsive.

Later, Ms. Elliot said, she was treated poorly by a partner because of her fears, leading to regular panic attacks. She moved on from that partner, but her fear of pregnancy did not. Along the way, she felt her fears were dismissed by doctors and peers alike.

Tokophobia – a severe fear of childbirth – goes beyond the typical anxieties about birth or pregnancy that women often experience. The condition can intrude on everyday life, crippling social interaction and interrupting regular sleep patterns. Although statistics in the United States don’t exist, as many as 14% of women internationally are thought to have tokophobia.

Although psychiatric treatment focusing on past traumas can help, many women resort to managing the condition themselves. Some seek sterilization, whereas others take multiple forms of contraception simultaneously – combining intrauterine devices and oral birth control, for example, experts said. Some women have sought abortions and some even have attempted suicide rather than face giving birth, according to Leila Frodsham, MbChB, a women’s health expert at King’s College London, who has studied tokophobia.

The International Classification of Diseases added tokophobia to its list of diagnostic codes in 2018. But the Diagnostic and Statistical Manual of Mental Disorders, used by clinicians in the United States, has yet to do the same. Without this designation, some doctors are more inclined to diagnose tokophobia than others, Dr. Frodsham said.

“I think some clinicians struggle to understand how much this condition affects women. There isn’t training in it, and I’d like to see it discussed more,” Dr. Frodsham told this news organization.

Dr. Frodsham said she has seen hundreds of patients seeking help with their fear of pregnancy. Many of these women don’t know that they might have a condition that could benefit from psychiatric treatment.

Tokophobia typically takes two forms: primary, which affects women who have never given birth; and secondary, which stems from a previous traumatic birth experience.

“It’s not the pain of childbirth they are afraid of, but rather their fear comes out of a sense that they lack control over themselves and the situation of being pregnant,” Dr. Frodsham said.

Although the phenomenon has been studied internationally, particularly in Europe, fear of childbirth remains almost entirely unexplored in the United States literature.

One of the only scientific examinations of tokophobia in this country was a 2016 survey of 22 women with the condition by researchers at the University of Michigan, Ann Arbor. Published in the Journal of Obstetric, Gynecology & Neonatal Nursing, the survey found that many of the women expressed concern that their race, gender, or level of income might affect the quality of their care. Some women surveyed said they had experienced traumas directly related to systemic inequalities in the health care system.

Lee Roosevelt, PhD, MPH, CNM, a nurse and midwife and a coauthor of the study, said fear of the health care system, coupled with concern over the loss of bodily autonomy, can foster severe aversion to childbirth. In her experience, she said, clinicians often handle these patients poorly.

“If a woman is making the decision not to have children, we want it to be because she has decided for her, and her body, that it is the right thing,” added Lisa Kane Low, PhD, CNM, professor of obstetrics and gynecology at the University of Michigan, who worked with Dr. Roosevelt on the survey. “She shouldn’t feel the decision is made because she can’t access what she needs or the health care system is unable to provide it.”

Access to midwives, doulas, or therapists trained in trauma counseling can allow women to have a voice in their treatment, Dr. Roosevelt said.

No specific medication exists to treat tokophobia; however, drugs for depression or anxiety sometimes help, Dr. Low said. “Women with tokophobia may not need medication but would benefit from other therapies like desensitization or biobehavioral approaches or combinations of those,” she said.
 

Treating triggers

According to Dr. Frodsham, women with tokophobia often experience guilt and isolation. They may avoid speaking to women who are pregnant or avoid discussing pregnancy and childbirth, afraid that doing so may trigger their fear.

“They can’t see how they can get close to this catastrophic thing they think is going to happen to them,” she said. “Many of them think they will die.”

Many patients avoid thinking about memories of traumatic events so as to not trigger extreme emotional responses.

Dr. Roosevelt said developing ways to assess and treat tokophobia has become more urgent, since the Supreme Court’s recent decision to overturn Roe v. Wade could lead to more instances of women carrying unwanted pregnancies.
 

Seeking community

The internet has become a place where women with tokophobia and less severe fears about pregnancy can share their experiences. On the online bulletin board Reddit, r/Tokphobia and r/childfree contain thousands of queries and personal stories about the condition, as well as requests for advice.

Jillian Kilcoyne, who lives in New York and attends college in Michigan, said: “Pregnancy has always freaked me out. A part of me believes it’s a biological injustice that women have to go through such pain and be ignored by the medical community just to give birth.” Ms. Kilcoyne said she has not sought counseling or help from a clinician.

“I’m not sure I even want it,” she told this news organization. “Some people want to get over their phobia because they want families, and others don’t want children at all. I think that those individuals should have the help they need.”

Claudia, a South Carolina resident who asked to be identified only by her first name owing to concerns about her privacy, said her tokophobia began when she started having sex. It grew worse when she developed health conditions that could be exacerbated by pregnancy. She said she stocks up on contraceptives and periodically takes a pregnancy test to ease her nerves.

“This started for me when I realized that having children wasn’t a requirement for life. I didn’t even know there was a name for what I was feeling,” Claudia said in an interview. “So, letting women know they have options, and then not making them feel guilty, or ashamed, is the most important thing. We shouldn’t try to convince women that motherhood is the only, or the correct, path.”

Ms. Elliot urged clinicians to have compassion: “Treat tokophobic patients – especially a pregnant one seeking an abortion – like someone with a life-threatening parasite. Don’t belittle or dismiss them. We’re already going to lose so many lives because of unwanted pregnancies and birth. Don’t add to the number.”

A version of this article first appeared on Medscape.com.

Cee Elliot is afraid of pregnancy. The 29-year-old retail manager in Connecticut said she has felt that way since puberty, when she “finally understood” pregnancy and reproduction. Always squeamish around babies and pregnant people, she said, as she learned more about the complications birth can cause, the idea of carrying a child herself became increasingly repulsive.

Later, Ms. Elliot said, she was treated poorly by a partner because of her fears, leading to regular panic attacks. She moved on from that partner, but her fear of pregnancy did not. Along the way, she felt her fears were dismissed by doctors and peers alike.

Tokophobia – a severe fear of childbirth – goes beyond the typical anxieties about birth or pregnancy that women often experience. The condition can intrude on everyday life, crippling social interaction and interrupting regular sleep patterns. Although statistics in the United States don’t exist, as many as 14% of women internationally are thought to have tokophobia.

Although psychiatric treatment focusing on past traumas can help, many women resort to managing the condition themselves. Some seek sterilization, whereas others take multiple forms of contraception simultaneously – combining intrauterine devices and oral birth control, for example, experts said. Some women have sought abortions and some even have attempted suicide rather than face giving birth, according to Leila Frodsham, MbChB, a women’s health expert at King’s College London, who has studied tokophobia.

The International Classification of Diseases added tokophobia to its list of diagnostic codes in 2018. But the Diagnostic and Statistical Manual of Mental Disorders, used by clinicians in the United States, has yet to do the same. Without this designation, some doctors are more inclined to diagnose tokophobia than others, Dr. Frodsham said.

“I think some clinicians struggle to understand how much this condition affects women. There isn’t training in it, and I’d like to see it discussed more,” Dr. Frodsham told this news organization.

Dr. Frodsham said she has seen hundreds of patients seeking help with their fear of pregnancy. Many of these women don’t know that they might have a condition that could benefit from psychiatric treatment.

Tokophobia typically takes two forms: primary, which affects women who have never given birth; and secondary, which stems from a previous traumatic birth experience.

“It’s not the pain of childbirth they are afraid of, but rather their fear comes out of a sense that they lack control over themselves and the situation of being pregnant,” Dr. Frodsham said.

Although the phenomenon has been studied internationally, particularly in Europe, fear of childbirth remains almost entirely unexplored in the United States literature.

One of the only scientific examinations of tokophobia in this country was a 2016 survey of 22 women with the condition by researchers at the University of Michigan, Ann Arbor. Published in the Journal of Obstetric, Gynecology & Neonatal Nursing, the survey found that many of the women expressed concern that their race, gender, or level of income might affect the quality of their care. Some women surveyed said they had experienced traumas directly related to systemic inequalities in the health care system.

Lee Roosevelt, PhD, MPH, CNM, a nurse and midwife and a coauthor of the study, said fear of the health care system, coupled with concern over the loss of bodily autonomy, can foster severe aversion to childbirth. In her experience, she said, clinicians often handle these patients poorly.

“If a woman is making the decision not to have children, we want it to be because she has decided for her, and her body, that it is the right thing,” added Lisa Kane Low, PhD, CNM, professor of obstetrics and gynecology at the University of Michigan, who worked with Dr. Roosevelt on the survey. “She shouldn’t feel the decision is made because she can’t access what she needs or the health care system is unable to provide it.”

Access to midwives, doulas, or therapists trained in trauma counseling can allow women to have a voice in their treatment, Dr. Roosevelt said.

No specific medication exists to treat tokophobia; however, drugs for depression or anxiety sometimes help, Dr. Low said. “Women with tokophobia may not need medication but would benefit from other therapies like desensitization or biobehavioral approaches or combinations of those,” she said.
 

Treating triggers

According to Dr. Frodsham, women with tokophobia often experience guilt and isolation. They may avoid speaking to women who are pregnant or avoid discussing pregnancy and childbirth, afraid that doing so may trigger their fear.

“They can’t see how they can get close to this catastrophic thing they think is going to happen to them,” she said. “Many of them think they will die.”

Many patients avoid thinking about memories of traumatic events so as to not trigger extreme emotional responses.

Dr. Roosevelt said developing ways to assess and treat tokophobia has become more urgent, since the Supreme Court’s recent decision to overturn Roe v. Wade could lead to more instances of women carrying unwanted pregnancies.
 

Seeking community

The internet has become a place where women with tokophobia and less severe fears about pregnancy can share their experiences. On the online bulletin board Reddit, r/Tokphobia and r/childfree contain thousands of queries and personal stories about the condition, as well as requests for advice.

Jillian Kilcoyne, who lives in New York and attends college in Michigan, said: “Pregnancy has always freaked me out. A part of me believes it’s a biological injustice that women have to go through such pain and be ignored by the medical community just to give birth.” Ms. Kilcoyne said she has not sought counseling or help from a clinician.

“I’m not sure I even want it,” she told this news organization. “Some people want to get over their phobia because they want families, and others don’t want children at all. I think that those individuals should have the help they need.”

Claudia, a South Carolina resident who asked to be identified only by her first name owing to concerns about her privacy, said her tokophobia began when she started having sex. It grew worse when she developed health conditions that could be exacerbated by pregnancy. She said she stocks up on contraceptives and periodically takes a pregnancy test to ease her nerves.

“This started for me when I realized that having children wasn’t a requirement for life. I didn’t even know there was a name for what I was feeling,” Claudia said in an interview. “So, letting women know they have options, and then not making them feel guilty, or ashamed, is the most important thing. We shouldn’t try to convince women that motherhood is the only, or the correct, path.”

Ms. Elliot urged clinicians to have compassion: “Treat tokophobic patients – especially a pregnant one seeking an abortion – like someone with a life-threatening parasite. Don’t belittle or dismiss them. We’re already going to lose so many lives because of unwanted pregnancies and birth. Don’t add to the number.”

A version of this article first appeared on Medscape.com.

As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.

So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.

Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).

“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”

A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.

Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.

“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.

Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.

A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.

Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.

The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed. 

One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.

Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
 

Transmission dynamics

Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.

Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.

Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
 

More testing, higher positivity rates in men

Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.

As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.

In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.

Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
 

Monkeypox and pregnancy

Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.

“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.

With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.

“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.

“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.

During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.

Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.

“Clinicians should bear this in mind when examining any person,” she said.

A version of this article first appeared on Medscape.com.

As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.

So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.

Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).

“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”

A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.

Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.

“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.

Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.

A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.

Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.

The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed. 

One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.

Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
 

Transmission dynamics

Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.

Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.

Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
 

More testing, higher positivity rates in men

Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.

As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.

In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.

Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
 

Monkeypox and pregnancy

Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.

“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.

With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.

“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.

“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.

During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.

Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.

“Clinicians should bear this in mind when examining any person,” she said.

A version of this article first appeared on Medscape.com.

As cases of monkeypox continue to mount in the United States and abroad, infectious disease experts are closely monitoring one group of people in particular: women.

So far, the overwhelming majority of cases of the viral disease have been reported in men who have sex with men. But in recent days, officials have learned of a handful of cases in women – possibly indicating that the outbreak may be widening.

Researchers are keeping close tabs on the proportion of cases in women to “assess whether the outbreak is moving away” from networks of men who have sex with men, where most of the initial cases have been identified, according to a briefing from the UK Health Security Agency (UKHSA).

“There is insufficient evidence to support a change in the transmission dynamics,” the agency said. “However, over the last few weeks the proportion of female cases has been increasing, so this trend needs to be monitored closely.”

A global collaboration of researchers and clinicians recently described 528 cases of monkeypox in 16 countries – but none were in women.

Since data collection for that study ended in June, the research group has confirmed cases in women, said study coauthor John P. Thornhill, MD, PhD, consultant physician in sexual health and HIV and clinical senior lecturer at Barts Health NHS Trust and Queen Mary University of London.

“Cases in women have certainly been reported but are currently far less common,” Dr. Thornhill told this news organization.

Although infections in women have been outliers during the current outbreak, they can be severe when they do occur. Several women in England have been hospitalized with severe symptoms.

A similar pattern has been seen in New York City, where just one woman is among the 639 total cases, according to a July 21 report from the city’s health agency.

Researchers have recently published guidance on monkeypox for ob.gyns., maternal-fetal medicine subspecialists, and people who are pregnant or breastfeeding in anticipation of the possibility of more cases in women.

The Centers for Disease Control and Prevention advises that “pregnant, recently pregnant, and breastfeeding people should be prioritized for medical treatment” of monkeypox if needed. 

One monkeypox vaccine, Jynneos, can be offered to people who are pregnant or breastfeeding and are otherwise eligible for vaccination on the basis of confirmed or likely contact with cases, ideally within 4 days of exposure. Some people at high risk for exposure, such as laboratory workers, may receive the vaccine preemptively.

Another vaccine, ACAM2000, is contraindicated in people who are pregnant or breastfeeding, according to the CDC.
 

Transmission dynamics

Investigators have not yet identified substantial spread of monkeypox beyond men who have sex with men, although transmission among household contacts, including women and children, has been reported.

Most initial infections during the current outbreak occurred during sexual activity. But monkeypox can spread through any close contact with skin lesions or body fluids and possibly through touching contaminated items like clothing or linens, according to the CDC. It also may spread from mother to child in utero.

Infected pets have been known to spread the disease as well. A multistate monkeypox outbreak in the United States in 2003 was linked to pet prairie dogs, including in childcare and school settings. That year, 55% of the 71 cases occurred in female patients.
 

More testing, higher positivity rates in men

Since May, more men than women in the United Kingdom have undergone testing for monkeypox, with 3,467 tests in men versus 447 tests in women. Among those tested, the positivity rate has been far higher in men than in women, 54% versus 2.2%, respectively.

As of July 20, about 0.65% of U.K. cases with known gender were in women. Two weeks prior, about 0.4% were in women.

In all, 13 monkeypox cases in England have been in women, and four had severe manifestations that required hospitalization, according to the UKHSA.

Globally, more than 16,000 monkeypox cases have been reported, according to the World Health Organization. The agency said that it plans to rename the disease to reduce stigma.
 

Monkeypox and pregnancy

Ob.gyns. are often on the “front line in terms of identifying people with infectious diseases,” said Denise J. Jamieson, MD, MPH, Emory University, Atlanta. Dr. Jamieson coauthored “A Primer on Monkeypox Virus for Obstetrician-Gynecologists,” published in Obstetrics & Gynecology.

“Obstetricians need to be aware of what infectious diseases are circulating and be aware of what is going on in the community,” she said.

With monkeypox, “it is anybody’s guess as to how widespread this is going to be,” Dr. Jamieson said.

“The initial monkeypox cases in the current outbreak have been predominately but not exclusively among men who have sex with men; enhanced transmission in this group may be facilitated by sexual activity and spread through complex sexual networks,” Dr. Thornhill said. “As the outbreak continues, we will likely see more monkeypox infections” outside that group.

“Those working in sexual health should have a high index of suspicion in all individuals presenting with genital and oral ulcers and those with proctitis,” he added.

During previous monkeypox outbreaks, the chain of household transmissions has been short, typically two or three people, said Chloe M. Orkin, MD, professor of HIV medicine at Queen Mary University of London. Dr. Orkin directs the Sexual Health and HIV All East Research (SHARE) Collaborative, which has worked to compile the international case series.

Though monkeypox has mainly been transmitted among men who have sex with men, not all identify as gay and some may also have female and nonbinary partners, Dr. Orkin said.

“Clinicians should bear this in mind when examining any person,” she said.

A version of this article first appeared on Medscape.com.

Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.

The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.

digitalskillet/Thinkstock

Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.

Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
 

Bigger babies

The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).

The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.

“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth. 
 

Welcomed data

This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.

“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”

The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.

A version of this article first appeared on Medscape.com.

Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.

The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.

digitalskillet/Thinkstock

Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.

Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
 

Bigger babies

The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).

The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.

“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth. 
 

Welcomed data

This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.

“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”

The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.

A version of this article first appeared on Medscape.com.

Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.

The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.

digitalskillet/Thinkstock

Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.

Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
 

Bigger babies

The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).

The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.

“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth. 
 

Welcomed data

This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.

“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”

The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.

A version of this article first appeared on Medscape.com.

Women who become pregnant during in vitro fertilization (IVF) from previously frozen embryos have a significantly higher chance of developing hypertensive disorders such as preeclampsia than do women who become pregnant through natural conception, researchers have found.

The new findings come from a study presented at the 2022 annual meeting of the European Society of Human Reproduction and Embryology. In the study, which will soon be published in Hypertension, researchers analyzed more than 4.5 million pregnancies from Denmark, Norway, and Sweden.

“Our findings are significant because frozen embryo transfers are increasingly common all over the world, partly due to the elective freezing of all embryos,” said Sindre Hoff Petersen, PhD, a fellow in the department of public health and nursing at the Norwegian University of Science and Technology, Trondheim, who led the study.

More than 320,000 IVF procedures were performed in the United States in 2020, according to preliminary data from the Centers for Disease Control and Prevention.

Of those, more than 123,000 eggs or embryos were frozen for future use.

The use of assisted reproductive technology, which includes IVF, has more than doubled during the past decade, the CDC reports. Roughly 2% of all babies born in the United States each year are conceived through assisted reproductive technology.

Dr. Petersen and his colleagues compared maternal complications in sibling pregnancies. Women who became pregnant following the transfer of a frozen embryo were 74% more likely to develop a hypertensive disorder than women who became pregnant following natural conception (7.4% vs. 4.3%; adjusted odds ratio, 1.74; 95% confidence interval, P < .001). The difference was even higher with respect to sibling births: Women who became pregnant using frozen embryos were 102% more likely than women who became pregnant using natural conception to develop a hypertensive disorder (adjusted odds ratio 2.02; 95% CI, 1.72-2.39, P < .001).

The researchers found no difference in the risk of hypertensive disorders between women who used fresh embryos during IVF and women who used natural conception (5.9% vs. 4.3%, 95% CI, P = .382).

“When we find that the association between frozen embryo transfer and hypertensive disorders in pregnancy persists in sibling comparisons, we believe we have strong indications that treatment factors might in fact contribute to the higher risk,” Dr. Petersen told this news organization.

Women in the study who became pregnant after natural conception had a 4.3% chance of developing hypertensive disorders. That effect persisted after controlling for maternal body mass index, smoking, and time between deliveries, he said.

The findings can add to discussions between patients and doctors on the potential benefits and harms of freezing embryos on an elective basis if there is no clinical indication, Dr. Petersen said. The frozen method is most often used to transfer a single embryo in order to reduce the incidence of multiple pregnancies, such as twins and triplets, which in turn reduces pregnancy complications.

“The vast majority of IVF pregnancies, including frozen embryo transfer, are healthy and uncomplicated, and both short- and long-term outcomes for both the mother and the children are very reassuring,” Dr. Petersen said.

Women who become pregnant through use of frozen embryos should be more closely monitored for potential hypertensive disorders, although more work is needed to determine the reasons for the association, said Elizabeth S. Ginsburg, MD, at Brigham and Women’s Hospital and professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, both in Boston.

“This is something general ob.gyns. need to be aware of, but it’s not clear which subpopulations of patients are going to be affected,” Dr. Ginsburg said. “More investigation is needed to determine if this is caused by the way the uterus is readied for the embryo transfer or if it’s patient population etiology.”

Some studies have suggested that the absence of a hormone-producing cyst, which forms on the ovary during each menstrual cycle, could explain the link between frozen embryo transfer and heightened preeclampsia risk.

Dr. Petersen and Dr. Ginsburg reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women who become pregnant during in vitro fertilization (IVF) from previously frozen embryos have a significantly higher chance of developing hypertensive disorders such as preeclampsia than do women who become pregnant through natural conception, researchers have found.

The new findings come from a study presented at the 2022 annual meeting of the European Society of Human Reproduction and Embryology. In the study, which will soon be published in Hypertension, researchers analyzed more than 4.5 million pregnancies from Denmark, Norway, and Sweden.

“Our findings are significant because frozen embryo transfers are increasingly common all over the world, partly due to the elective freezing of all embryos,” said Sindre Hoff Petersen, PhD, a fellow in the department of public health and nursing at the Norwegian University of Science and Technology, Trondheim, who led the study.

More than 320,000 IVF procedures were performed in the United States in 2020, according to preliminary data from the Centers for Disease Control and Prevention.

Of those, more than 123,000 eggs or embryos were frozen for future use.

The use of assisted reproductive technology, which includes IVF, has more than doubled during the past decade, the CDC reports. Roughly 2% of all babies born in the United States each year are conceived through assisted reproductive technology.

Dr. Petersen and his colleagues compared maternal complications in sibling pregnancies. Women who became pregnant following the transfer of a frozen embryo were 74% more likely to develop a hypertensive disorder than women who became pregnant following natural conception (7.4% vs. 4.3%; adjusted odds ratio, 1.74; 95% confidence interval, P < .001). The difference was even higher with respect to sibling births: Women who became pregnant using frozen embryos were 102% more likely than women who became pregnant using natural conception to develop a hypertensive disorder (adjusted odds ratio 2.02; 95% CI, 1.72-2.39, P < .001).

The researchers found no difference in the risk of hypertensive disorders between women who used fresh embryos during IVF and women who used natural conception (5.9% vs. 4.3%, 95% CI, P = .382).

“When we find that the association between frozen embryo transfer and hypertensive disorders in pregnancy persists in sibling comparisons, we believe we have strong indications that treatment factors might in fact contribute to the higher risk,” Dr. Petersen told this news organization.

Women in the study who became pregnant after natural conception had a 4.3% chance of developing hypertensive disorders. That effect persisted after controlling for maternal body mass index, smoking, and time between deliveries, he said.

The findings can add to discussions between patients and doctors on the potential benefits and harms of freezing embryos on an elective basis if there is no clinical indication, Dr. Petersen said. The frozen method is most often used to transfer a single embryo in order to reduce the incidence of multiple pregnancies, such as twins and triplets, which in turn reduces pregnancy complications.

“The vast majority of IVF pregnancies, including frozen embryo transfer, are healthy and uncomplicated, and both short- and long-term outcomes for both the mother and the children are very reassuring,” Dr. Petersen said.

Women who become pregnant through use of frozen embryos should be more closely monitored for potential hypertensive disorders, although more work is needed to determine the reasons for the association, said Elizabeth S. Ginsburg, MD, at Brigham and Women’s Hospital and professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, both in Boston.

“This is something general ob.gyns. need to be aware of, but it’s not clear which subpopulations of patients are going to be affected,” Dr. Ginsburg said. “More investigation is needed to determine if this is caused by the way the uterus is readied for the embryo transfer or if it’s patient population etiology.”

Some studies have suggested that the absence of a hormone-producing cyst, which forms on the ovary during each menstrual cycle, could explain the link between frozen embryo transfer and heightened preeclampsia risk.

Dr. Petersen and Dr. Ginsburg reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women who become pregnant during in vitro fertilization (IVF) from previously frozen embryos have a significantly higher chance of developing hypertensive disorders such as preeclampsia than do women who become pregnant through natural conception, researchers have found.

The new findings come from a study presented at the 2022 annual meeting of the European Society of Human Reproduction and Embryology. In the study, which will soon be published in Hypertension, researchers analyzed more than 4.5 million pregnancies from Denmark, Norway, and Sweden.

“Our findings are significant because frozen embryo transfers are increasingly common all over the world, partly due to the elective freezing of all embryos,” said Sindre Hoff Petersen, PhD, a fellow in the department of public health and nursing at the Norwegian University of Science and Technology, Trondheim, who led the study.

More than 320,000 IVF procedures were performed in the United States in 2020, according to preliminary data from the Centers for Disease Control and Prevention.

Of those, more than 123,000 eggs or embryos were frozen for future use.

The use of assisted reproductive technology, which includes IVF, has more than doubled during the past decade, the CDC reports. Roughly 2% of all babies born in the United States each year are conceived through assisted reproductive technology.

Dr. Petersen and his colleagues compared maternal complications in sibling pregnancies. Women who became pregnant following the transfer of a frozen embryo were 74% more likely to develop a hypertensive disorder than women who became pregnant following natural conception (7.4% vs. 4.3%; adjusted odds ratio, 1.74; 95% confidence interval, P < .001). The difference was even higher with respect to sibling births: Women who became pregnant using frozen embryos were 102% more likely than women who became pregnant using natural conception to develop a hypertensive disorder (adjusted odds ratio 2.02; 95% CI, 1.72-2.39, P < .001).

The researchers found no difference in the risk of hypertensive disorders between women who used fresh embryos during IVF and women who used natural conception (5.9% vs. 4.3%, 95% CI, P = .382).

“When we find that the association between frozen embryo transfer and hypertensive disorders in pregnancy persists in sibling comparisons, we believe we have strong indications that treatment factors might in fact contribute to the higher risk,” Dr. Petersen told this news organization.

Women in the study who became pregnant after natural conception had a 4.3% chance of developing hypertensive disorders. That effect persisted after controlling for maternal body mass index, smoking, and time between deliveries, he said.

The findings can add to discussions between patients and doctors on the potential benefits and harms of freezing embryos on an elective basis if there is no clinical indication, Dr. Petersen said. The frozen method is most often used to transfer a single embryo in order to reduce the incidence of multiple pregnancies, such as twins and triplets, which in turn reduces pregnancy complications.

“The vast majority of IVF pregnancies, including frozen embryo transfer, are healthy and uncomplicated, and both short- and long-term outcomes for both the mother and the children are very reassuring,” Dr. Petersen said.

Women who become pregnant through use of frozen embryos should be more closely monitored for potential hypertensive disorders, although more work is needed to determine the reasons for the association, said Elizabeth S. Ginsburg, MD, at Brigham and Women’s Hospital and professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, both in Boston.

“This is something general ob.gyns. need to be aware of, but it’s not clear which subpopulations of patients are going to be affected,” Dr. Ginsburg said. “More investigation is needed to determine if this is caused by the way the uterus is readied for the embryo transfer or if it’s patient population etiology.”

Some studies have suggested that the absence of a hormone-producing cyst, which forms on the ovary during each menstrual cycle, could explain the link between frozen embryo transfer and heightened preeclampsia risk.

Dr. Petersen and Dr. Ginsburg reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.