Key clinical point: Three countries that implemented an immediate postpartum family planning (IPPFP) intervention that focused on long-acting reversible contraception (LARC) showed a significant increase in the number of girls and women who opted for an IUD or implant within 48 hours of delivery. 

Major finding: The mean percentage of IPP LARC adoption among all deliveries in the countries that implemented the intervention programs was 10.01%, compared to 0.77% in countries providing standard postpartum care without the intervention.

Study details: The data come from a review of immediate postpartum long-acting reversible contraception (IPP LARC) from 2016 to 2019 in three countries that focused on LARC intervention (Democratic Republic of Congo, Somalia, and Pakistan) including training delivery-room providers on counseling and provision of IPPFP; and three countries the did not implement this intervention (Rwanda, Syria, and Yemen).

Disclosures: The study was supported by an anonymous foundation. The researchers had no financial conflicts to disclose.

Source: Gallagher MC et al. Front Glob Womens Health. 2021 Apr 6. doi: 10.3389/fgwh.2021.613338.

Key clinical point: Three countries that implemented an immediate postpartum family planning (IPPFP) intervention that focused on long-acting reversible contraception (LARC) showed a significant increase in the number of girls and women who opted for an IUD or implant within 48 hours of delivery. 

Major finding: The mean percentage of IPP LARC adoption among all deliveries in the countries that implemented the intervention programs was 10.01%, compared to 0.77% in countries providing standard postpartum care without the intervention.

Study details: The data come from a review of immediate postpartum long-acting reversible contraception (IPP LARC) from 2016 to 2019 in three countries that focused on LARC intervention (Democratic Republic of Congo, Somalia, and Pakistan) including training delivery-room providers on counseling and provision of IPPFP; and three countries the did not implement this intervention (Rwanda, Syria, and Yemen).

Disclosures: The study was supported by an anonymous foundation. The researchers had no financial conflicts to disclose.

Source: Gallagher MC et al. Front Glob Womens Health. 2021 Apr 6. doi: 10.3389/fgwh.2021.613338.

Key clinical point: Three countries that implemented an immediate postpartum family planning (IPPFP) intervention that focused on long-acting reversible contraception (LARC) showed a significant increase in the number of girls and women who opted for an IUD or implant within 48 hours of delivery. 

Major finding: The mean percentage of IPP LARC adoption among all deliveries in the countries that implemented the intervention programs was 10.01%, compared to 0.77% in countries providing standard postpartum care without the intervention.

Study details: The data come from a review of immediate postpartum long-acting reversible contraception (IPP LARC) from 2016 to 2019 in three countries that focused on LARC intervention (Democratic Republic of Congo, Somalia, and Pakistan) including training delivery-room providers on counseling and provision of IPPFP; and three countries the did not implement this intervention (Rwanda, Syria, and Yemen).

Disclosures: The study was supported by an anonymous foundation. The researchers had no financial conflicts to disclose.

Source: Gallagher MC et al. Front Glob Womens Health. 2021 Apr 6. doi: 10.3389/fgwh.2021.613338.

Key clinical point: Contraceptive use among adolescents in the United States increased overall from 2006 to 2019, although consistent condom use declined.

Major finding: From 2006-2010 to 2015-2019, adolescents aged 15 to 19 years reported an 86% increased use of any contraception, a 26% increased use of multiple contraception methods, and a 3% increased use of IUDs or implants. 

Study details: The data come from a review of adolescents aged 15 to 19 years from the National Surveys of Family Growth, including 4,662 individuals from 2006-2010, 4,134 from 2011-2015, and 3,182 from 2015-2019.

Disclosures: The study was supported by an anonymous foundation. The researchers had no financial conflicts to disclose.

Source: Lindberg LD et al. Contraception: X. 2021 Apr 8. doi: 10.1016/j.conx.2021.100064.

Key clinical point: Contraceptive use among adolescents in the United States increased overall from 2006 to 2019, although consistent condom use declined.

Major finding: From 2006-2010 to 2015-2019, adolescents aged 15 to 19 years reported an 86% increased use of any contraception, a 26% increased use of multiple contraception methods, and a 3% increased use of IUDs or implants. 

Study details: The data come from a review of adolescents aged 15 to 19 years from the National Surveys of Family Growth, including 4,662 individuals from 2006-2010, 4,134 from 2011-2015, and 3,182 from 2015-2019.

Disclosures: The study was supported by an anonymous foundation. The researchers had no financial conflicts to disclose.

Source: Lindberg LD et al. Contraception: X. 2021 Apr 8. doi: 10.1016/j.conx.2021.100064.

Key clinical point: Contraceptive use among adolescents in the United States increased overall from 2006 to 2019, although consistent condom use declined.

Major finding: From 2006-2010 to 2015-2019, adolescents aged 15 to 19 years reported an 86% increased use of any contraception, a 26% increased use of multiple contraception methods, and a 3% increased use of IUDs or implants. 

Study details: The data come from a review of adolescents aged 15 to 19 years from the National Surveys of Family Growth, including 4,662 individuals from 2006-2010, 4,134 from 2011-2015, and 3,182 from 2015-2019.

Disclosures: The study was supported by an anonymous foundation. The researchers had no financial conflicts to disclose.

Source: Lindberg LD et al. Contraception: X. 2021 Apr 8. doi: 10.1016/j.conx.2021.100064.

Key clinical point: The generally positive attitudes towards contraception but low levels of use highlight the need for greater communication about behavior change among health professionals and medical students to increase their roles as change agents in their communities.

Major finding: Although 58% of the respondents were sexually active, only 18% were using a contraceptive at the time of the survey; however, 83% of contraceptive users were satisfied with past use. In addition, approximately half of respondents discussed contraception with their partners and four-fifths said they would encourage others in contraceptive use, although only 18% were involved in providing family planning methods.

Study details: The data come from a cross-sectional survey of 400 health workers and clinical care medical students in Ghana between January 1, 2018, and June 30, 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Agbeno EK et al. Int J Reprod Med. 2021 Mar 22. doi: 10.1155/2021/6631790. 

Key clinical point: The generally positive attitudes towards contraception but low levels of use highlight the need for greater communication about behavior change among health professionals and medical students to increase their roles as change agents in their communities.

Major finding: Although 58% of the respondents were sexually active, only 18% were using a contraceptive at the time of the survey; however, 83% of contraceptive users were satisfied with past use. In addition, approximately half of respondents discussed contraception with their partners and four-fifths said they would encourage others in contraceptive use, although only 18% were involved in providing family planning methods.

Study details: The data come from a cross-sectional survey of 400 health workers and clinical care medical students in Ghana between January 1, 2018, and June 30, 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Agbeno EK et al. Int J Reprod Med. 2021 Mar 22. doi: 10.1155/2021/6631790. 

Key clinical point: The generally positive attitudes towards contraception but low levels of use highlight the need for greater communication about behavior change among health professionals and medical students to increase their roles as change agents in their communities.

Major finding: Although 58% of the respondents were sexually active, only 18% were using a contraceptive at the time of the survey; however, 83% of contraceptive users were satisfied with past use. In addition, approximately half of respondents discussed contraception with their partners and four-fifths said they would encourage others in contraceptive use, although only 18% were involved in providing family planning methods.

Study details: The data come from a cross-sectional survey of 400 health workers and clinical care medical students in Ghana between January 1, 2018, and June 30, 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Agbeno EK et al. Int J Reprod Med. 2021 Mar 22. doi: 10.1155/2021/6631790. 

Key clinical point: Levonorgestrel was noninferior to copper IUD for emergency contraception, with similar pregnancy rates and adverse events reported for both methods.

Major finding: Pregnancy rates were 1 in 317 (0.3%) in the levonorgestrel group and 0 in 321 (0%) in the copper IUD group in the modified intent-to-treat analysis.

Study details: The data come from a randomized trial of 317 women who received levonorgestrel IUD and 321 who received copper IUDs and provided 1-month outcome data.

Disclosures: The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); the University of Utah, with funding in part from the National Institutes of Health (NIH) National Center for Research Resources and National Center for Advancing Translational Sciences; and grants to the lead author and several coauthors from the NIH Office of Research on Women’s Health and the Eunice Kennedy Shriver NICHD.

Source:  Turok DK et al.  N Engl J Med. 2021 Jan 28. doi: 10.1056/NEJMoa2022141.

Key clinical point: Levonorgestrel was noninferior to copper IUD for emergency contraception, with similar pregnancy rates and adverse events reported for both methods.

Major finding: Pregnancy rates were 1 in 317 (0.3%) in the levonorgestrel group and 0 in 321 (0%) in the copper IUD group in the modified intent-to-treat analysis.

Study details: The data come from a randomized trial of 317 women who received levonorgestrel IUD and 321 who received copper IUDs and provided 1-month outcome data.

Disclosures: The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); the University of Utah, with funding in part from the National Institutes of Health (NIH) National Center for Research Resources and National Center for Advancing Translational Sciences; and grants to the lead author and several coauthors from the NIH Office of Research on Women’s Health and the Eunice Kennedy Shriver NICHD.

Source:  Turok DK et al.  N Engl J Med. 2021 Jan 28. doi: 10.1056/NEJMoa2022141.

Key clinical point: Levonorgestrel was noninferior to copper IUD for emergency contraception, with similar pregnancy rates and adverse events reported for both methods.

Major finding: Pregnancy rates were 1 in 317 (0.3%) in the levonorgestrel group and 0 in 321 (0%) in the copper IUD group in the modified intent-to-treat analysis.

Study details: The data come from a randomized trial of 317 women who received levonorgestrel IUD and 321 who received copper IUDs and provided 1-month outcome data.

Disclosures: The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); the University of Utah, with funding in part from the National Institutes of Health (NIH) National Center for Research Resources and National Center for Advancing Translational Sciences; and grants to the lead author and several coauthors from the NIH Office of Research on Women’s Health and the Eunice Kennedy Shriver NICHD.

Source:  Turok DK et al.  N Engl J Med. 2021 Jan 28. doi: 10.1056/NEJMoa2022141.

Key clinical point: Use of progestin-only contraception was associated with greater breast hypertrophy and pain in adolescents with macromastia.

Major finding: Compared to controls, macromastia patients who used progestin-only contraceptives were 500% more likely to report breast pain (odds ratio 4.94); macromastia patients who used progestin-only contraception also had significantly more breast tissue resected during mammaplasty and greater musculoskeletal pain. 

Study details: The data come from a retrospective study of 378 macromastia patients aged 12 to 21 years and 378 controls; 5.3% of macromastia patients and 28.0% of controls used progestin-only contraception.

Disclosures: The study was supported in part by the Plastic Surgery Foundation. The researchers had no financial conflicts to disclose.

Source: Nuzzi LC et al. Plast Reconstr Surg Glob Open. 2021 Feb 12. doi: 10.1097/GOX.0000000000003421.

Key clinical point: Use of progestin-only contraception was associated with greater breast hypertrophy and pain in adolescents with macromastia.

Major finding: Compared to controls, macromastia patients who used progestin-only contraceptives were 500% more likely to report breast pain (odds ratio 4.94); macromastia patients who used progestin-only contraception also had significantly more breast tissue resected during mammaplasty and greater musculoskeletal pain. 

Study details: The data come from a retrospective study of 378 macromastia patients aged 12 to 21 years and 378 controls; 5.3% of macromastia patients and 28.0% of controls used progestin-only contraception.

Disclosures: The study was supported in part by the Plastic Surgery Foundation. The researchers had no financial conflicts to disclose.

Source: Nuzzi LC et al. Plast Reconstr Surg Glob Open. 2021 Feb 12. doi: 10.1097/GOX.0000000000003421.

Key clinical point: Use of progestin-only contraception was associated with greater breast hypertrophy and pain in adolescents with macromastia.

Major finding: Compared to controls, macromastia patients who used progestin-only contraceptives were 500% more likely to report breast pain (odds ratio 4.94); macromastia patients who used progestin-only contraception also had significantly more breast tissue resected during mammaplasty and greater musculoskeletal pain. 

Study details: The data come from a retrospective study of 378 macromastia patients aged 12 to 21 years and 378 controls; 5.3% of macromastia patients and 28.0% of controls used progestin-only contraception.

Disclosures: The study was supported in part by the Plastic Surgery Foundation. The researchers had no financial conflicts to disclose.

Source: Nuzzi LC et al. Plast Reconstr Surg Glob Open. 2021 Feb 12. doi: 10.1097/GOX.0000000000003421.

Key clinical point: Among healthy young women taking oral contraceptives, pulse wave velocity was lower in active women compared with inactive women, suggesting that physical activity may mitigate the risk of arterial stiffness associated with OC use.   

Major finding: Pulse wave velocity as an indicator of arterial stiffness was similar in oral contraceptive users and non-users, however, PWV was significantly lower in active women vs. inactive women (5.4 ms ^-1 vs. 6.3 ms ^-1).

Study details: The data come from a cross-sectional study of 49 healthy young women with an average age of 21.9 years, divided into four groups (inactive vs. active, OC use vs. non-OC use).

Disclosures: The study was supported in part by the European Union and the New Aquitaine region through the Habisan program (CPER-FEDER). The researchers had no financial conflicts to disclose.

Source: Enea C et al. Int J Environ Res Public Health. 2021 Mar 25. doi: 10.3390/ijerph18073393.

Key clinical point: Among healthy young women taking oral contraceptives, pulse wave velocity was lower in active women compared with inactive women, suggesting that physical activity may mitigate the risk of arterial stiffness associated with OC use.   

Major finding: Pulse wave velocity as an indicator of arterial stiffness was similar in oral contraceptive users and non-users, however, PWV was significantly lower in active women vs. inactive women (5.4 ms ^-1 vs. 6.3 ms ^-1).

Study details: The data come from a cross-sectional study of 49 healthy young women with an average age of 21.9 years, divided into four groups (inactive vs. active, OC use vs. non-OC use).

Disclosures: The study was supported in part by the European Union and the New Aquitaine region through the Habisan program (CPER-FEDER). The researchers had no financial conflicts to disclose.

Source: Enea C et al. Int J Environ Res Public Health. 2021 Mar 25. doi: 10.3390/ijerph18073393.

Key clinical point: Among healthy young women taking oral contraceptives, pulse wave velocity was lower in active women compared with inactive women, suggesting that physical activity may mitigate the risk of arterial stiffness associated with OC use.   

Major finding: Pulse wave velocity as an indicator of arterial stiffness was similar in oral contraceptive users and non-users, however, PWV was significantly lower in active women vs. inactive women (5.4 ms ^-1 vs. 6.3 ms ^-1).

Study details: The data come from a cross-sectional study of 49 healthy young women with an average age of 21.9 years, divided into four groups (inactive vs. active, OC use vs. non-OC use).

Disclosures: The study was supported in part by the European Union and the New Aquitaine region through the Habisan program (CPER-FEDER). The researchers had no financial conflicts to disclose.

Source: Enea C et al. Int J Environ Res Public Health. 2021 Mar 25. doi: 10.3390/ijerph18073393.

The holy grail of assisted reproductive technology (ART) is the delivery of a healthy child. From the world’s first successful ART cycle of in vitro fertilization in 1978 (3 years later in the United States), the goal of every cycle is to provide the woman with an embryo that has the highest potential for implantation and, ultimately, a single live birth.

Embryo aneuploidy is a major factor in the success of human reproduction. As women age, aneuploidy is reported in less than 30% of women aged younger than 35 years but rises to 90% for those in their mid-40s. Intuitively and through randomized, controlled trials, chromosome testing of embryos is a reasonable approach toward improved cycle outcomes and allows for the transfer of a single euploid embryo.

Recently, the phrase “add-ons” has entered the vernacular of editorials on IVF. These additional procedures are offered to patients with the expectation of improving results, yet many have not been supported by rigorous scientifically controlled research trials, e.g., endometrial scratch, embryo glue, and time-lapse imaging of embryos. Where does preimplantation genetic testing (PGT) belong in the IVF armamentarium and why, after 30 years, are there two diametrically opposed views on its benefit? (We will not address testing for single gene defects or chromosome structural rearrangements.)
 

How did we get here?

The first iteration of PGT used fluorescence in situ hybridization to not only identify X-linked recessive diseases (Hum Genet. 1992;89:18-22) but also the most common chromosome disorders (13, 18, 21, X, Y) by removing one to two blastomere cells from a day 3 embryo (six- to eight-cell stage). Despite wide enthusiasm, the technique was eventually determined to reduce implantation by nearly 40% and was abandoned; presumably impairing the embryo by removing up to one-third of its make-up.

Because of extended embryo culture to the blastocyst stage along with the improved cryopreservation process of vitrification, the next generation of embryo analysis surfaced, what we now refer to as PGT 2.0. Currently, approximately five to six cells from the outer embryo trophectoderm are removed and sent to a specialized laboratory for 24-chromosome screening while the biopsied embryos are cryopreserved. Outcome data (aneuploidy rates, mosaicism) have been influenced by the evolution of genetic platforms – from array comparative genome hybridization to single-nucleotide polymorphism array, to quantitative polymerase chain reaction, to next-generation sequencing (NGS). The newest platform, NGS with high resolution, provides the most extensive degree of analysis by detecting unbalanced translocations and a low cut-off percentage for mosaicism (20%). The clinical error rate is approximately 1%-2%, improved from the 2%-4% of earlier techniques.

The phenomenon of mosaicism describes two distinct cell lines in one embryo (typically one normal and one abnormal) and is defined based on the percentage of mosaicism – currently, the lower limit is 20%. Embryos with less than 20%-30% mosaicism are considered euploid and those greater than 70%-80% are aneuploid. Of note, clinics that do not request the reporting of mosaicism can result in the potential discarding of embryos labeled as aneuploid that would otherwise have potentially resulted in a live birth. The higher the cut-off value for designating mosaicism, the lower the false-positive rate (declaring an embryo aneuploid when euploid). While there is no safe degree of mosaicism, most transfers have resulted in chromosomally normal infants despite a lower implantation rate and higher miscarriage rate.
 

Current status

The greatest advantage of PGT for aneuploidy (PGT-A) is its increase in promoting a single embryo transfer. Medical evidence supports pregnancy outcomes equivalent from a single euploid embryo transfer versus a double “untested” embryo transfer.

Only a handful of randomized, controlled trials have evaluated the efficacy of PGT-A. Outcomes have favored improved live birth rates; however, criticism exists for enrolling only good prognosis patients given their high likelihood of developing blastocyst embryos to biopsy. The only trial that used an “intention to treat” protocol (rather than randomization at the time of biopsy) did not demonstrate any difference in live birth or miscarriage comparing embryo selection by PGT-A versus embryo morphology alone. However, post hoc analysis did show a benefit with PGT-A in the 35- to 40-year-old age group, not in the less than 35-year-old group. All other trials demonstrated a reduction in miscarriage with PGT-A but only as a secondary outcome.

The medical literature does not support PGT-A to manage patients with recurrent pregnancy loss and there is no evidence for improvement in women aged less than 35 years or egg donors (F&S Reports. 2021;2:36-42). PGT-A has been effective in patients wishing family balancing.
 

Controversy

Enthusiasm for PGT-A is countered by lingering concerns. Trophectoderm cells are not in 100% concordance with the inner cell mass, which presumably explains the reports of chromosomally normal live births from the transfer of aneuploid embryos. Biopsy techniques among embryologists are not standardized. As a result, damage to the embryo has been raised as a possible explanation for equivalent pregnancy rates in studies showing no superiority of PGT-A in pregnancy outcome, although this point has recently been refuted.

PGT-A also embraces the “blast-or-bust” credo whereby no embryo transfer occurs unless a blastocyst embryo develops. This continues to beg the unanswerable question – would a woman who did not develop a blastocyst embryo for potential biopsy still conceive if she underwent a day 3 cleavage stage embryo transfer?
 

Future

Exciting iterations are encroaching for PGT 3.0. One method is blastocyst fluid aspiration to obtain DNA suitable for analysis by molecular genetic methods. Another is noninvasive PGT whereby spent media from the embryo is analyzed using cell-free DNA. Concordance with inner cell mass is reasonably good (approximately 85%) but needs to improve. A major advantage is the biopsy skill set among embryologists is eliminated. A criticism of noninvasive PGT is the risk of false-positive results from contamination of aneuploid cell secretion by physiologic apoptotic cells. Confined placental mosaicism can also increase aneuploidy in cell-free DNA thereby contributing to false positives.

Conclusion

PGT-A is robust technology that appears to benefit women aged above 35 years but not the general infertile population. Error rates must be consistent among laboratories and be lowered. Regarding mosaic embryos, the American Society for Reproductive Medicine guidelines recommend offering another egg retrieval if only mosaic embryos are available and to only consider mosaic embryo transfer following extensive genetic counseling. Long-term effects of PGT-A on children are lacking. The Cochrane Database concluded there was insufficient evidence to make PGT-A routine.

So, the debate is clear and ongoing – universal versus discretionary use of PGT-A? As in all things of life, one size does not fit all, and PGT-A is no exception.

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Contact him at obnews@mdedge.com.

The holy grail of assisted reproductive technology (ART) is the delivery of a healthy child. From the world’s first successful ART cycle of in vitro fertilization in 1978 (3 years later in the United States), the goal of every cycle is to provide the woman with an embryo that has the highest potential for implantation and, ultimately, a single live birth.

Embryo aneuploidy is a major factor in the success of human reproduction. As women age, aneuploidy is reported in less than 30% of women aged younger than 35 years but rises to 90% for those in their mid-40s. Intuitively and through randomized, controlled trials, chromosome testing of embryos is a reasonable approach toward improved cycle outcomes and allows for the transfer of a single euploid embryo.

Recently, the phrase “add-ons” has entered the vernacular of editorials on IVF. These additional procedures are offered to patients with the expectation of improving results, yet many have not been supported by rigorous scientifically controlled research trials, e.g., endometrial scratch, embryo glue, and time-lapse imaging of embryos. Where does preimplantation genetic testing (PGT) belong in the IVF armamentarium and why, after 30 years, are there two diametrically opposed views on its benefit? (We will not address testing for single gene defects or chromosome structural rearrangements.)
 

How did we get here?

The first iteration of PGT used fluorescence in situ hybridization to not only identify X-linked recessive diseases (Hum Genet. 1992;89:18-22) but also the most common chromosome disorders (13, 18, 21, X, Y) by removing one to two blastomere cells from a day 3 embryo (six- to eight-cell stage). Despite wide enthusiasm, the technique was eventually determined to reduce implantation by nearly 40% and was abandoned; presumably impairing the embryo by removing up to one-third of its make-up.

Because of extended embryo culture to the blastocyst stage along with the improved cryopreservation process of vitrification, the next generation of embryo analysis surfaced, what we now refer to as PGT 2.0. Currently, approximately five to six cells from the outer embryo trophectoderm are removed and sent to a specialized laboratory for 24-chromosome screening while the biopsied embryos are cryopreserved. Outcome data (aneuploidy rates, mosaicism) have been influenced by the evolution of genetic platforms – from array comparative genome hybridization to single-nucleotide polymorphism array, to quantitative polymerase chain reaction, to next-generation sequencing (NGS). The newest platform, NGS with high resolution, provides the most extensive degree of analysis by detecting unbalanced translocations and a low cut-off percentage for mosaicism (20%). The clinical error rate is approximately 1%-2%, improved from the 2%-4% of earlier techniques.

The phenomenon of mosaicism describes two distinct cell lines in one embryo (typically one normal and one abnormal) and is defined based on the percentage of mosaicism – currently, the lower limit is 20%. Embryos with less than 20%-30% mosaicism are considered euploid and those greater than 70%-80% are aneuploid. Of note, clinics that do not request the reporting of mosaicism can result in the potential discarding of embryos labeled as aneuploid that would otherwise have potentially resulted in a live birth. The higher the cut-off value for designating mosaicism, the lower the false-positive rate (declaring an embryo aneuploid when euploid). While there is no safe degree of mosaicism, most transfers have resulted in chromosomally normal infants despite a lower implantation rate and higher miscarriage rate.
 

Current status

The greatest advantage of PGT for aneuploidy (PGT-A) is its increase in promoting a single embryo transfer. Medical evidence supports pregnancy outcomes equivalent from a single euploid embryo transfer versus a double “untested” embryo transfer.

Only a handful of randomized, controlled trials have evaluated the efficacy of PGT-A. Outcomes have favored improved live birth rates; however, criticism exists for enrolling only good prognosis patients given their high likelihood of developing blastocyst embryos to biopsy. The only trial that used an “intention to treat” protocol (rather than randomization at the time of biopsy) did not demonstrate any difference in live birth or miscarriage comparing embryo selection by PGT-A versus embryo morphology alone. However, post hoc analysis did show a benefit with PGT-A in the 35- to 40-year-old age group, not in the less than 35-year-old group. All other trials demonstrated a reduction in miscarriage with PGT-A but only as a secondary outcome.

The medical literature does not support PGT-A to manage patients with recurrent pregnancy loss and there is no evidence for improvement in women aged less than 35 years or egg donors (F&S Reports. 2021;2:36-42). PGT-A has been effective in patients wishing family balancing.
 

Controversy

Enthusiasm for PGT-A is countered by lingering concerns. Trophectoderm cells are not in 100% concordance with the inner cell mass, which presumably explains the reports of chromosomally normal live births from the transfer of aneuploid embryos. Biopsy techniques among embryologists are not standardized. As a result, damage to the embryo has been raised as a possible explanation for equivalent pregnancy rates in studies showing no superiority of PGT-A in pregnancy outcome, although this point has recently been refuted.

PGT-A also embraces the “blast-or-bust” credo whereby no embryo transfer occurs unless a blastocyst embryo develops. This continues to beg the unanswerable question – would a woman who did not develop a blastocyst embryo for potential biopsy still conceive if she underwent a day 3 cleavage stage embryo transfer?
 

Future

Exciting iterations are encroaching for PGT 3.0. One method is blastocyst fluid aspiration to obtain DNA suitable for analysis by molecular genetic methods. Another is noninvasive PGT whereby spent media from the embryo is analyzed using cell-free DNA. Concordance with inner cell mass is reasonably good (approximately 85%) but needs to improve. A major advantage is the biopsy skill set among embryologists is eliminated. A criticism of noninvasive PGT is the risk of false-positive results from contamination of aneuploid cell secretion by physiologic apoptotic cells. Confined placental mosaicism can also increase aneuploidy in cell-free DNA thereby contributing to false positives.

Conclusion

PGT-A is robust technology that appears to benefit women aged above 35 years but not the general infertile population. Error rates must be consistent among laboratories and be lowered. Regarding mosaic embryos, the American Society for Reproductive Medicine guidelines recommend offering another egg retrieval if only mosaic embryos are available and to only consider mosaic embryo transfer following extensive genetic counseling. Long-term effects of PGT-A on children are lacking. The Cochrane Database concluded there was insufficient evidence to make PGT-A routine.

So, the debate is clear and ongoing – universal versus discretionary use of PGT-A? As in all things of life, one size does not fit all, and PGT-A is no exception.

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Contact him at obnews@mdedge.com.

The holy grail of assisted reproductive technology (ART) is the delivery of a healthy child. From the world’s first successful ART cycle of in vitro fertilization in 1978 (3 years later in the United States), the goal of every cycle is to provide the woman with an embryo that has the highest potential for implantation and, ultimately, a single live birth.

Embryo aneuploidy is a major factor in the success of human reproduction. As women age, aneuploidy is reported in less than 30% of women aged younger than 35 years but rises to 90% for those in their mid-40s. Intuitively and through randomized, controlled trials, chromosome testing of embryos is a reasonable approach toward improved cycle outcomes and allows for the transfer of a single euploid embryo.

Recently, the phrase “add-ons” has entered the vernacular of editorials on IVF. These additional procedures are offered to patients with the expectation of improving results, yet many have not been supported by rigorous scientifically controlled research trials, e.g., endometrial scratch, embryo glue, and time-lapse imaging of embryos. Where does preimplantation genetic testing (PGT) belong in the IVF armamentarium and why, after 30 years, are there two diametrically opposed views on its benefit? (We will not address testing for single gene defects or chromosome structural rearrangements.)
 

How did we get here?

The first iteration of PGT used fluorescence in situ hybridization to not only identify X-linked recessive diseases (Hum Genet. 1992;89:18-22) but also the most common chromosome disorders (13, 18, 21, X, Y) by removing one to two blastomere cells from a day 3 embryo (six- to eight-cell stage). Despite wide enthusiasm, the technique was eventually determined to reduce implantation by nearly 40% and was abandoned; presumably impairing the embryo by removing up to one-third of its make-up.

Because of extended embryo culture to the blastocyst stage along with the improved cryopreservation process of vitrification, the next generation of embryo analysis surfaced, what we now refer to as PGT 2.0. Currently, approximately five to six cells from the outer embryo trophectoderm are removed and sent to a specialized laboratory for 24-chromosome screening while the biopsied embryos are cryopreserved. Outcome data (aneuploidy rates, mosaicism) have been influenced by the evolution of genetic platforms – from array comparative genome hybridization to single-nucleotide polymorphism array, to quantitative polymerase chain reaction, to next-generation sequencing (NGS). The newest platform, NGS with high resolution, provides the most extensive degree of analysis by detecting unbalanced translocations and a low cut-off percentage for mosaicism (20%). The clinical error rate is approximately 1%-2%, improved from the 2%-4% of earlier techniques.

The phenomenon of mosaicism describes two distinct cell lines in one embryo (typically one normal and one abnormal) and is defined based on the percentage of mosaicism – currently, the lower limit is 20%. Embryos with less than 20%-30% mosaicism are considered euploid and those greater than 70%-80% are aneuploid. Of note, clinics that do not request the reporting of mosaicism can result in the potential discarding of embryos labeled as aneuploid that would otherwise have potentially resulted in a live birth. The higher the cut-off value for designating mosaicism, the lower the false-positive rate (declaring an embryo aneuploid when euploid). While there is no safe degree of mosaicism, most transfers have resulted in chromosomally normal infants despite a lower implantation rate and higher miscarriage rate.
 

Current status

The greatest advantage of PGT for aneuploidy (PGT-A) is its increase in promoting a single embryo transfer. Medical evidence supports pregnancy outcomes equivalent from a single euploid embryo transfer versus a double “untested” embryo transfer.

Only a handful of randomized, controlled trials have evaluated the efficacy of PGT-A. Outcomes have favored improved live birth rates; however, criticism exists for enrolling only good prognosis patients given their high likelihood of developing blastocyst embryos to biopsy. The only trial that used an “intention to treat” protocol (rather than randomization at the time of biopsy) did not demonstrate any difference in live birth or miscarriage comparing embryo selection by PGT-A versus embryo morphology alone. However, post hoc analysis did show a benefit with PGT-A in the 35- to 40-year-old age group, not in the less than 35-year-old group. All other trials demonstrated a reduction in miscarriage with PGT-A but only as a secondary outcome.

The medical literature does not support PGT-A to manage patients with recurrent pregnancy loss and there is no evidence for improvement in women aged less than 35 years or egg donors (F&S Reports. 2021;2:36-42). PGT-A has been effective in patients wishing family balancing.
 

Controversy

Enthusiasm for PGT-A is countered by lingering concerns. Trophectoderm cells are not in 100% concordance with the inner cell mass, which presumably explains the reports of chromosomally normal live births from the transfer of aneuploid embryos. Biopsy techniques among embryologists are not standardized. As a result, damage to the embryo has been raised as a possible explanation for equivalent pregnancy rates in studies showing no superiority of PGT-A in pregnancy outcome, although this point has recently been refuted.

PGT-A also embraces the “blast-or-bust” credo whereby no embryo transfer occurs unless a blastocyst embryo develops. This continues to beg the unanswerable question – would a woman who did not develop a blastocyst embryo for potential biopsy still conceive if she underwent a day 3 cleavage stage embryo transfer?
 

Future

Exciting iterations are encroaching for PGT 3.0. One method is blastocyst fluid aspiration to obtain DNA suitable for analysis by molecular genetic methods. Another is noninvasive PGT whereby spent media from the embryo is analyzed using cell-free DNA. Concordance with inner cell mass is reasonably good (approximately 85%) but needs to improve. A major advantage is the biopsy skill set among embryologists is eliminated. A criticism of noninvasive PGT is the risk of false-positive results from contamination of aneuploid cell secretion by physiologic apoptotic cells. Confined placental mosaicism can also increase aneuploidy in cell-free DNA thereby contributing to false positives.

Conclusion

PGT-A is robust technology that appears to benefit women aged above 35 years but not the general infertile population. Error rates must be consistent among laboratories and be lowered. Regarding mosaic embryos, the American Society for Reproductive Medicine guidelines recommend offering another egg retrieval if only mosaic embryos are available and to only consider mosaic embryo transfer following extensive genetic counseling. Long-term effects of PGT-A on children are lacking. The Cochrane Database concluded there was insufficient evidence to make PGT-A routine.

So, the debate is clear and ongoing – universal versus discretionary use of PGT-A? As in all things of life, one size does not fit all, and PGT-A is no exception.

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Contact him at obnews@mdedge.com.

Key clinical point: In a biomechanical ex vivo analysis, metal uterine sounds caused uterine perforation, but the manufacturer’s plastic intrauterine device placement rod did not.

Major finding: The lowest mean maximum force generated for IUD placement was 12.3 Newtons with the levonorgestrel intrauterine system placement instrument, followed by 14.1 Newtons with the copper T380A intrauterine device placement instrument 14.1 Newtons; the highest mean maximum force of 17.9 N occurred with the metal sound (P < 0.01).

Study details: The data come from 16 premenopausal women with benign conditions who provided hysterectomy sections at a single center.

Disclosures: The study was funded indirectly through grants to the University of Utah from Bayer, Bioceptive, Sebela, Medicines 360, Merck, and Cooper Surgical. Lead author Dr. Duncan had no financial conflicts to disclose.

Source: Duncan J et al. BMC Womens Health. 2021 Apr 7. doi: 10.1186/s12905-021-01285-6.

Key clinical point: In a biomechanical ex vivo analysis, metal uterine sounds caused uterine perforation, but the manufacturer’s plastic intrauterine device placement rod did not.

Major finding: The lowest mean maximum force generated for IUD placement was 12.3 Newtons with the levonorgestrel intrauterine system placement instrument, followed by 14.1 Newtons with the copper T380A intrauterine device placement instrument 14.1 Newtons; the highest mean maximum force of 17.9 N occurred with the metal sound (P < 0.01).

Study details: The data come from 16 premenopausal women with benign conditions who provided hysterectomy sections at a single center.

Disclosures: The study was funded indirectly through grants to the University of Utah from Bayer, Bioceptive, Sebela, Medicines 360, Merck, and Cooper Surgical. Lead author Dr. Duncan had no financial conflicts to disclose.

Source: Duncan J et al. BMC Womens Health. 2021 Apr 7. doi: 10.1186/s12905-021-01285-6.

Key clinical point: In a biomechanical ex vivo analysis, metal uterine sounds caused uterine perforation, but the manufacturer’s plastic intrauterine device placement rod did not.

Major finding: The lowest mean maximum force generated for IUD placement was 12.3 Newtons with the levonorgestrel intrauterine system placement instrument, followed by 14.1 Newtons with the copper T380A intrauterine device placement instrument 14.1 Newtons; the highest mean maximum force of 17.9 N occurred with the metal sound (P < 0.01).

Study details: The data come from 16 premenopausal women with benign conditions who provided hysterectomy sections at a single center.

Disclosures: The study was funded indirectly through grants to the University of Utah from Bayer, Bioceptive, Sebela, Medicines 360, Merck, and Cooper Surgical. Lead author Dr. Duncan had no financial conflicts to disclose.

Source: Duncan J et al. BMC Womens Health. 2021 Apr 7. doi: 10.1186/s12905-021-01285-6.

Key clinical point: Use of oral contraceptives by women of reproductive age was not associated with increased risk of heart failure later in life, but the potential impact of different formulations and dosages deserves further research.

Major finding:  Over an average of 12 years’ follow-up, the researchers identified 138 incident cases of heart failure. The incidence of heart failure was not significantly associated with heart failure in multivariate analysis (hazard ratio 0.96); however, any OC use was positively associated with left ventricular end-diastolic mass (P = 0.006) and stroke volume (P = 0.01 and P = 0.005 for left and right ventricles, respectively).

Study details: The data come from a retrospective study of 3,594 women with an average age of 62 years who were enrolled in the Multi‐Ethnic Study of Atherosclerosis and could provide data on oral contraceptive use.

Disclosures: The study was supported by the Guangdong Peak Project, the Science and Technology Planning Project of Guangdong Province, Natural Science Foundation of Guangdong Province, and the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Source: Luo D et al. ESC Heart Fail. 2021 Apr 9. doi: 10.1002/ehf2.13328.

Key clinical point: Use of oral contraceptives by women of reproductive age was not associated with increased risk of heart failure later in life, but the potential impact of different formulations and dosages deserves further research.

Major finding:  Over an average of 12 years’ follow-up, the researchers identified 138 incident cases of heart failure. The incidence of heart failure was not significantly associated with heart failure in multivariate analysis (hazard ratio 0.96); however, any OC use was positively associated with left ventricular end-diastolic mass (P = 0.006) and stroke volume (P = 0.01 and P = 0.005 for left and right ventricles, respectively).

Study details: The data come from a retrospective study of 3,594 women with an average age of 62 years who were enrolled in the Multi‐Ethnic Study of Atherosclerosis and could provide data on oral contraceptive use.

Disclosures: The study was supported by the Guangdong Peak Project, the Science and Technology Planning Project of Guangdong Province, Natural Science Foundation of Guangdong Province, and the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Source: Luo D et al. ESC Heart Fail. 2021 Apr 9. doi: 10.1002/ehf2.13328.

Key clinical point: Use of oral contraceptives by women of reproductive age was not associated with increased risk of heart failure later in life, but the potential impact of different formulations and dosages deserves further research.

Major finding:  Over an average of 12 years’ follow-up, the researchers identified 138 incident cases of heart failure. The incidence of heart failure was not significantly associated with heart failure in multivariate analysis (hazard ratio 0.96); however, any OC use was positively associated with left ventricular end-diastolic mass (P = 0.006) and stroke volume (P = 0.01 and P = 0.005 for left and right ventricles, respectively).

Study details: The data come from a retrospective study of 3,594 women with an average age of 62 years who were enrolled in the Multi‐Ethnic Study of Atherosclerosis and could provide data on oral contraceptive use.

Disclosures: The study was supported by the Guangdong Peak Project, the Science and Technology Planning Project of Guangdong Province, Natural Science Foundation of Guangdong Province, and the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Source: Luo D et al. ESC Heart Fail. 2021 Apr 9. doi: 10.1002/ehf2.13328.

As the U.S. races to vaccinate millions of people against the coronavirus, pregnant women face the extra challenge of not knowing whether the vaccines are safe for them or their unborn babies.

None of the recent COVID-19 vaccine trials, including those for Pfizer, Moderna, and Johnson & Johnson, enrolled pregnant or breastfeeding women because they consider them a high-risk group.

That was despite the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists asking that pregnant and breastfeeding women be included in trials. The Food and Drug Administration even included pregnant women in the COVID-19 vaccine emergency use authorization (EUA) because of their higher risk of having a more severe disease.

Despite that lack of clinical trial data, more and more smaller studies are suggesting that the vaccines are safe for both mother and child.

Pfizer is now studying its two-dose vaccine in 4,000 pregnant and breastfeeding women to see how safe, tolerated, and robust their immune response is. Researchers will also look at how safe the vaccine is for infants and whether mothers pass along antibodies to children. But the preliminary results won’t be available until the end of the year, a Pfizer spokesperson says.

Without that information, pregnant women are less likely to get vaccinated, according to a large international survey. Less than 45% of pregnant women in the United States said they intended to get vaccinated even when they were told the vaccine was safe and 90% effective. That figure rises to 52% of pregnant women in 16 countries, including the United States, compared with 74% of nonpregnant women willing to be vaccinated. The findings were published online March 1, 2021, in the European Journal of Epidemiology.

The vaccine-hesitant pregnant women in the international study were most concerned that the COVID-19 vaccine could harm their developing fetuses, a worry related to the lack of clinical evidence in pregnant women, said lead researcher Julia Wu, ScD, an epidemiologist at the Harvard School of Public Health’s Human Immunomics Initiative in Boston.

The information vacuum also increases the chances that “people will fall victim to misinformation campaigns like the one on social media that claims that the COVID-19 vaccine causes infertility,” Dr. Wu said. This unfounded claim has deterred some women of childbearing age from getting the vaccine.
 

Deciding to get vaccinated

Frontline health care professionals were in the first group eligible to receive the vaccine in December 2020. “All of us who were pregnant ... had to decide whether to wait for the data, because we don’t know what the risks are, or go ahead and get it [the vaccine]. We had been dealing with the pandemic for months and were afraid of being exposed to the virus and infecting family members,” said Jacqueline Parchem, MD, a maternal-fetal medicine specialist at the University of Texas Health Science Center, Houston.

Given the lack of safety data, the CDC guidance to pregnant women has been to consult with their doctors and that it’s a personal choice. The Center for Disease Control and Prevention’s latest vaccine guidance said that “there is no evidence that antibodies formed from COVID-19 vaccination cause any problem with pregnancy, including the development of the placenta.”

The CDC is monitoring vaccinated people through its v-safe program and reported on April 12 that more than 86,000 v-safe participants said they were pregnant when they were vaccinated.

Health care workers who were nursing their infants when they were eligible for the vaccine faced a similar dilemma as pregnant women – they lacked the data on them to make a truly informed decision.

“I was nervous about the vaccine side effects for myself and whether my son Bennett, who was about a year old, would experience any of these himself,” said Christa Carrig, a labor and delivery nurse at Massachusetts General Hospital in Boston, who was breastfeeding at the time.

She and Dr. Parchem know that pregnant women with COVID-19 are more likely to have severe illness and complications such as high blood pressure and preterm delivery. “Pregnancy takes a toll on the body. When a woman gets COVID-19 and that insult is added, women who were otherwise young and healthy get much sicker than you would expect,” said Ms. Carrig.

“As a high-risk pregnancy specialist, I know that, with COVID, that babies don’t do well when moms are sick,” said Dr. Parchem.

Pregnant women accounted for more than 84,629 cases of COVID-19 and 95 deaths in the United States between Jan. 22 last year and April 12 this year, according to the CDC COVID data tracker.

Dr. Parchem and Ms. Carrig decided to get vaccinated because of their high risk of exposure to COVID-19 at work. After the second dose, Ms. Carrig reported chills but Bennett had no side effects from breastfeeding. Dr. Parchem, who delivered a healthy baby boy in February, reported no side effects other than a sore arm.

“There’s also a psychological benefit to returning to some sense of normalcy,” said Dr. Parchem. “My mother was finally able to visit us to see the new baby after we were all vaccinated. This was the first visit in more than a year.”
 

New study results

Ms. Carrig was one of 131 vaccinated hospital workers in the Boston area who took part in the first study to profile the immune response in pregnant and breastfeeding women and compare it with both nonpregnant and pregnant women who had COVID-19.

The study was not designed to evaluate the safety of the vaccines or whether they prevent COVID-19 illness and hospitalizations. That is the role of the large vaccine trials, the authors said.

The participants were aged 18-45 years and received both doses of either Pfizer or Moderna vaccines during one of their trimesters. They provided blood and/or breast milk samples after each vaccine dose, 2-6 weeks after the last dose, and at delivery for the 10 who gave birth during the study.

The vaccines produced a similar strong antibody response among the pregnant/breastfeeding women and nonpregnant women. Their antibody levels were much higher than those found in the pregnant women who had COVID-19, the researchers reported on March 25, 2021, in the American Journal of Obstetrics and Gynecology.

“This is important because a lot of people tend to think once they’ve had COVID-19, they are protected from the virus. This finding suggests that the vaccines produce a stronger antibody response than the infection itself, and this might be important for long-lasting protection against COVID-19,” said Dr. Parchem.

The study also addressed whether newborns benefit from the antibodies produced by their mothers. “In the 10 women who delivered, we detected antibodies in their umbilical cords and breast milk,” says Andrea Edlow, MD, lead researcher and a maternal-fetal medicine specialist at Massachusetts General Hospital.

Newborns are particularly vulnerable to respiratory infections because they have small airways and their immune systems are underdeveloped. These infections can be lethal early in life.

“The public health strategy is to vaccinate mothers against respiratory viruses, bacteria, and parasites that neonates up to 6 months are exposed to. Influenza and pertussis (whooping cough) are two examples of vaccines that we give mothers that we know transfer [antibodies] across the umbilical cord,” said Dr. Edlow.

But this “passive transfer immunity” is different from active immunity, when the body produces its own antibody immune response, she explains.

A different study, also published in March, confirmed that antibodies were transferred from 27 vaccinated pregnant mothers to their infants when they delivered. A new finding was that the women who were vaccinated with both doses and earlier in their third semester passed on more antibodies than the women who were vaccinated later or with only one dose.


 

Impact of the studies

The Society for Maternal-Fetal Medicine updated its guidance on counseling pregnant and lactating patients about the COVID-19 vaccines to include Dr. Edlow’s study.

“We were struck by how much pregnant and breastfeeding women want to participate in research and to help others in the same situation make decisions. I hope this will be an example to drug companies doing research on new vaccines in the future – that they should not be left behind and can make decisions themselves whether to participate after weighing the risks and benefits,” said Dr. Edlow.

She continues to enroll more vaccinated women in her study in the Boston area, including non–health care workers who have asked to take part.

“It was worth getting vaccinated and participating in the study. I know that I have antibodies and it worked and that I passed them on to Bennett. Also, I know that all the information is available for other women who are questioning whether to get vaccinated or not,” said Ms. Carrig.

Dr. Parchem is also taking part in the CDC’s v-safe pregnancy registry, which is collecting health and safety data on vaccinated pregnant women.

Before she was vaccinated, Dr. Parchem said, “my advice was very measured because we lacked data either saying that it definitely works or showing that it was unsafe. Now that we have this data supporting the benefits, I feel more confident in recommending the vaccines.”

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

As the U.S. races to vaccinate millions of people against the coronavirus, pregnant women face the extra challenge of not knowing whether the vaccines are safe for them or their unborn babies.

None of the recent COVID-19 vaccine trials, including those for Pfizer, Moderna, and Johnson & Johnson, enrolled pregnant or breastfeeding women because they consider them a high-risk group.

That was despite the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists asking that pregnant and breastfeeding women be included in trials. The Food and Drug Administration even included pregnant women in the COVID-19 vaccine emergency use authorization (EUA) because of their higher risk of having a more severe disease.

Despite that lack of clinical trial data, more and more smaller studies are suggesting that the vaccines are safe for both mother and child.

Pfizer is now studying its two-dose vaccine in 4,000 pregnant and breastfeeding women to see how safe, tolerated, and robust their immune response is. Researchers will also look at how safe the vaccine is for infants and whether mothers pass along antibodies to children. But the preliminary results won’t be available until the end of the year, a Pfizer spokesperson says.

Without that information, pregnant women are less likely to get vaccinated, according to a large international survey. Less than 45% of pregnant women in the United States said they intended to get vaccinated even when they were told the vaccine was safe and 90% effective. That figure rises to 52% of pregnant women in 16 countries, including the United States, compared with 74% of nonpregnant women willing to be vaccinated. The findings were published online March 1, 2021, in the European Journal of Epidemiology.

The vaccine-hesitant pregnant women in the international study were most concerned that the COVID-19 vaccine could harm their developing fetuses, a worry related to the lack of clinical evidence in pregnant women, said lead researcher Julia Wu, ScD, an epidemiologist at the Harvard School of Public Health’s Human Immunomics Initiative in Boston.

The information vacuum also increases the chances that “people will fall victim to misinformation campaigns like the one on social media that claims that the COVID-19 vaccine causes infertility,” Dr. Wu said. This unfounded claim has deterred some women of childbearing age from getting the vaccine.
 

Deciding to get vaccinated

Frontline health care professionals were in the first group eligible to receive the vaccine in December 2020. “All of us who were pregnant ... had to decide whether to wait for the data, because we don’t know what the risks are, or go ahead and get it [the vaccine]. We had been dealing with the pandemic for months and were afraid of being exposed to the virus and infecting family members,” said Jacqueline Parchem, MD, a maternal-fetal medicine specialist at the University of Texas Health Science Center, Houston.

Given the lack of safety data, the CDC guidance to pregnant women has been to consult with their doctors and that it’s a personal choice. The Center for Disease Control and Prevention’s latest vaccine guidance said that “there is no evidence that antibodies formed from COVID-19 vaccination cause any problem with pregnancy, including the development of the placenta.”

The CDC is monitoring vaccinated people through its v-safe program and reported on April 12 that more than 86,000 v-safe participants said they were pregnant when they were vaccinated.

Health care workers who were nursing their infants when they were eligible for the vaccine faced a similar dilemma as pregnant women – they lacked the data on them to make a truly informed decision.

“I was nervous about the vaccine side effects for myself and whether my son Bennett, who was about a year old, would experience any of these himself,” said Christa Carrig, a labor and delivery nurse at Massachusetts General Hospital in Boston, who was breastfeeding at the time.

She and Dr. Parchem know that pregnant women with COVID-19 are more likely to have severe illness and complications such as high blood pressure and preterm delivery. “Pregnancy takes a toll on the body. When a woman gets COVID-19 and that insult is added, women who were otherwise young and healthy get much sicker than you would expect,” said Ms. Carrig.

“As a high-risk pregnancy specialist, I know that, with COVID, that babies don’t do well when moms are sick,” said Dr. Parchem.

Pregnant women accounted for more than 84,629 cases of COVID-19 and 95 deaths in the United States between Jan. 22 last year and April 12 this year, according to the CDC COVID data tracker.

Dr. Parchem and Ms. Carrig decided to get vaccinated because of their high risk of exposure to COVID-19 at work. After the second dose, Ms. Carrig reported chills but Bennett had no side effects from breastfeeding. Dr. Parchem, who delivered a healthy baby boy in February, reported no side effects other than a sore arm.

“There’s also a psychological benefit to returning to some sense of normalcy,” said Dr. Parchem. “My mother was finally able to visit us to see the new baby after we were all vaccinated. This was the first visit in more than a year.”
 

New study results

Ms. Carrig was one of 131 vaccinated hospital workers in the Boston area who took part in the first study to profile the immune response in pregnant and breastfeeding women and compare it with both nonpregnant and pregnant women who had COVID-19.

The study was not designed to evaluate the safety of the vaccines or whether they prevent COVID-19 illness and hospitalizations. That is the role of the large vaccine trials, the authors said.

The participants were aged 18-45 years and received both doses of either Pfizer or Moderna vaccines during one of their trimesters. They provided blood and/or breast milk samples after each vaccine dose, 2-6 weeks after the last dose, and at delivery for the 10 who gave birth during the study.

The vaccines produced a similar strong antibody response among the pregnant/breastfeeding women and nonpregnant women. Their antibody levels were much higher than those found in the pregnant women who had COVID-19, the researchers reported on March 25, 2021, in the American Journal of Obstetrics and Gynecology.

“This is important because a lot of people tend to think once they’ve had COVID-19, they are protected from the virus. This finding suggests that the vaccines produce a stronger antibody response than the infection itself, and this might be important for long-lasting protection against COVID-19,” said Dr. Parchem.

The study also addressed whether newborns benefit from the antibodies produced by their mothers. “In the 10 women who delivered, we detected antibodies in their umbilical cords and breast milk,” says Andrea Edlow, MD, lead researcher and a maternal-fetal medicine specialist at Massachusetts General Hospital.

Newborns are particularly vulnerable to respiratory infections because they have small airways and their immune systems are underdeveloped. These infections can be lethal early in life.

“The public health strategy is to vaccinate mothers against respiratory viruses, bacteria, and parasites that neonates up to 6 months are exposed to. Influenza and pertussis (whooping cough) are two examples of vaccines that we give mothers that we know transfer [antibodies] across the umbilical cord,” said Dr. Edlow.

But this “passive transfer immunity” is different from active immunity, when the body produces its own antibody immune response, she explains.

A different study, also published in March, confirmed that antibodies were transferred from 27 vaccinated pregnant mothers to their infants when they delivered. A new finding was that the women who were vaccinated with both doses and earlier in their third semester passed on more antibodies than the women who were vaccinated later or with only one dose.


 

Impact of the studies

The Society for Maternal-Fetal Medicine updated its guidance on counseling pregnant and lactating patients about the COVID-19 vaccines to include Dr. Edlow’s study.

“We were struck by how much pregnant and breastfeeding women want to participate in research and to help others in the same situation make decisions. I hope this will be an example to drug companies doing research on new vaccines in the future – that they should not be left behind and can make decisions themselves whether to participate after weighing the risks and benefits,” said Dr. Edlow.

She continues to enroll more vaccinated women in her study in the Boston area, including non–health care workers who have asked to take part.

“It was worth getting vaccinated and participating in the study. I know that I have antibodies and it worked and that I passed them on to Bennett. Also, I know that all the information is available for other women who are questioning whether to get vaccinated or not,” said Ms. Carrig.

Dr. Parchem is also taking part in the CDC’s v-safe pregnancy registry, which is collecting health and safety data on vaccinated pregnant women.

Before she was vaccinated, Dr. Parchem said, “my advice was very measured because we lacked data either saying that it definitely works or showing that it was unsafe. Now that we have this data supporting the benefits, I feel more confident in recommending the vaccines.”

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

As the U.S. races to vaccinate millions of people against the coronavirus, pregnant women face the extra challenge of not knowing whether the vaccines are safe for them or their unborn babies.

None of the recent COVID-19 vaccine trials, including those for Pfizer, Moderna, and Johnson & Johnson, enrolled pregnant or breastfeeding women because they consider them a high-risk group.

That was despite the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists asking that pregnant and breastfeeding women be included in trials. The Food and Drug Administration even included pregnant women in the COVID-19 vaccine emergency use authorization (EUA) because of their higher risk of having a more severe disease.

Despite that lack of clinical trial data, more and more smaller studies are suggesting that the vaccines are safe for both mother and child.

Pfizer is now studying its two-dose vaccine in 4,000 pregnant and breastfeeding women to see how safe, tolerated, and robust their immune response is. Researchers will also look at how safe the vaccine is for infants and whether mothers pass along antibodies to children. But the preliminary results won’t be available until the end of the year, a Pfizer spokesperson says.

Without that information, pregnant women are less likely to get vaccinated, according to a large international survey. Less than 45% of pregnant women in the United States said they intended to get vaccinated even when they were told the vaccine was safe and 90% effective. That figure rises to 52% of pregnant women in 16 countries, including the United States, compared with 74% of nonpregnant women willing to be vaccinated. The findings were published online March 1, 2021, in the European Journal of Epidemiology.

The vaccine-hesitant pregnant women in the international study were most concerned that the COVID-19 vaccine could harm their developing fetuses, a worry related to the lack of clinical evidence in pregnant women, said lead researcher Julia Wu, ScD, an epidemiologist at the Harvard School of Public Health’s Human Immunomics Initiative in Boston.

The information vacuum also increases the chances that “people will fall victim to misinformation campaigns like the one on social media that claims that the COVID-19 vaccine causes infertility,” Dr. Wu said. This unfounded claim has deterred some women of childbearing age from getting the vaccine.
 

Deciding to get vaccinated

Frontline health care professionals were in the first group eligible to receive the vaccine in December 2020. “All of us who were pregnant ... had to decide whether to wait for the data, because we don’t know what the risks are, or go ahead and get it [the vaccine]. We had been dealing with the pandemic for months and were afraid of being exposed to the virus and infecting family members,” said Jacqueline Parchem, MD, a maternal-fetal medicine specialist at the University of Texas Health Science Center, Houston.

Given the lack of safety data, the CDC guidance to pregnant women has been to consult with their doctors and that it’s a personal choice. The Center for Disease Control and Prevention’s latest vaccine guidance said that “there is no evidence that antibodies formed from COVID-19 vaccination cause any problem with pregnancy, including the development of the placenta.”

The CDC is monitoring vaccinated people through its v-safe program and reported on April 12 that more than 86,000 v-safe participants said they were pregnant when they were vaccinated.

Health care workers who were nursing their infants when they were eligible for the vaccine faced a similar dilemma as pregnant women – they lacked the data on them to make a truly informed decision.

“I was nervous about the vaccine side effects for myself and whether my son Bennett, who was about a year old, would experience any of these himself,” said Christa Carrig, a labor and delivery nurse at Massachusetts General Hospital in Boston, who was breastfeeding at the time.

She and Dr. Parchem know that pregnant women with COVID-19 are more likely to have severe illness and complications such as high blood pressure and preterm delivery. “Pregnancy takes a toll on the body. When a woman gets COVID-19 and that insult is added, women who were otherwise young and healthy get much sicker than you would expect,” said Ms. Carrig.

“As a high-risk pregnancy specialist, I know that, with COVID, that babies don’t do well when moms are sick,” said Dr. Parchem.

Pregnant women accounted for more than 84,629 cases of COVID-19 and 95 deaths in the United States between Jan. 22 last year and April 12 this year, according to the CDC COVID data tracker.

Dr. Parchem and Ms. Carrig decided to get vaccinated because of their high risk of exposure to COVID-19 at work. After the second dose, Ms. Carrig reported chills but Bennett had no side effects from breastfeeding. Dr. Parchem, who delivered a healthy baby boy in February, reported no side effects other than a sore arm.

“There’s also a psychological benefit to returning to some sense of normalcy,” said Dr. Parchem. “My mother was finally able to visit us to see the new baby after we were all vaccinated. This was the first visit in more than a year.”
 

New study results

Ms. Carrig was one of 131 vaccinated hospital workers in the Boston area who took part in the first study to profile the immune response in pregnant and breastfeeding women and compare it with both nonpregnant and pregnant women who had COVID-19.

The study was not designed to evaluate the safety of the vaccines or whether they prevent COVID-19 illness and hospitalizations. That is the role of the large vaccine trials, the authors said.

The participants were aged 18-45 years and received both doses of either Pfizer or Moderna vaccines during one of their trimesters. They provided blood and/or breast milk samples after each vaccine dose, 2-6 weeks after the last dose, and at delivery for the 10 who gave birth during the study.

The vaccines produced a similar strong antibody response among the pregnant/breastfeeding women and nonpregnant women. Their antibody levels were much higher than those found in the pregnant women who had COVID-19, the researchers reported on March 25, 2021, in the American Journal of Obstetrics and Gynecology.

“This is important because a lot of people tend to think once they’ve had COVID-19, they are protected from the virus. This finding suggests that the vaccines produce a stronger antibody response than the infection itself, and this might be important for long-lasting protection against COVID-19,” said Dr. Parchem.

The study also addressed whether newborns benefit from the antibodies produced by their mothers. “In the 10 women who delivered, we detected antibodies in their umbilical cords and breast milk,” says Andrea Edlow, MD, lead researcher and a maternal-fetal medicine specialist at Massachusetts General Hospital.

Newborns are particularly vulnerable to respiratory infections because they have small airways and their immune systems are underdeveloped. These infections can be lethal early in life.

“The public health strategy is to vaccinate mothers against respiratory viruses, bacteria, and parasites that neonates up to 6 months are exposed to. Influenza and pertussis (whooping cough) are two examples of vaccines that we give mothers that we know transfer [antibodies] across the umbilical cord,” said Dr. Edlow.

But this “passive transfer immunity” is different from active immunity, when the body produces its own antibody immune response, she explains.

A different study, also published in March, confirmed that antibodies were transferred from 27 vaccinated pregnant mothers to their infants when they delivered. A new finding was that the women who were vaccinated with both doses and earlier in their third semester passed on more antibodies than the women who were vaccinated later or with only one dose.


 

Impact of the studies

The Society for Maternal-Fetal Medicine updated its guidance on counseling pregnant and lactating patients about the COVID-19 vaccines to include Dr. Edlow’s study.

“We were struck by how much pregnant and breastfeeding women want to participate in research and to help others in the same situation make decisions. I hope this will be an example to drug companies doing research on new vaccines in the future – that they should not be left behind and can make decisions themselves whether to participate after weighing the risks and benefits,” said Dr. Edlow.

She continues to enroll more vaccinated women in her study in the Boston area, including non–health care workers who have asked to take part.

“It was worth getting vaccinated and participating in the study. I know that I have antibodies and it worked and that I passed them on to Bennett. Also, I know that all the information is available for other women who are questioning whether to get vaccinated or not,” said Ms. Carrig.

Dr. Parchem is also taking part in the CDC’s v-safe pregnancy registry, which is collecting health and safety data on vaccinated pregnant women.

Before she was vaccinated, Dr. Parchem said, “my advice was very measured because we lacked data either saying that it definitely works or showing that it was unsafe. Now that we have this data supporting the benefits, I feel more confident in recommending the vaccines.”

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