MDedge ObGyn

Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.

But they have long wondered why.

“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”

Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.

Dr. Curtis and colleagues found that, like fingers molding clay, the genes you’re born with can coax the immune system into shape. DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.

“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.

The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.

While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.

“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
 

‘We’re Basically Unearthing the Dark Matter of the Human Genome’

Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.

In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.

“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.

Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).

They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.

“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”

These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.

In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.

But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.

This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.

And that “critical juncture” may very well be the optimal time for intervention.
 

The Precancer Push

Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”

Many labs are trying to understand the biology of precancer and exploring possible vaccines.

The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.

Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.

At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.

Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.

In the years and decades to come, all of this could lead to a new era in cancer treatment.

“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”

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

Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.

But they have long wondered why.

“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”

Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.

Dr. Curtis and colleagues found that, like fingers molding clay, the genes you’re born with can coax the immune system into shape. DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.

“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.

The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.

While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.

“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
 

‘We’re Basically Unearthing the Dark Matter of the Human Genome’

Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.

In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.

“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.

Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).

They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.

“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”

These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.

In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.

But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.

This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.

And that “critical juncture” may very well be the optimal time for intervention.
 

The Precancer Push

Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”

Many labs are trying to understand the biology of precancer and exploring possible vaccines.

The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.

Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.

At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.

Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.

In the years and decades to come, all of this could lead to a new era in cancer treatment.

“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”

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

Some breast cancer types are more likely than others to recur. Researchers have known this for more than a decade.

But they have long wondered why.

“How did those tumor types arise?” said Christina Curtis, PhD, a professor of medicine, genetics and biomedical data science at Stanford University in California. “They’re all breast cancers. They’re all estrogen receptor positive. But these groups are different. When did they become different, and how is that determined?”

Dr. Curtis and colleagues are finally starting to answer these questions. They recently broke new ground in a study linking differences in cancer-related genes to disease subtype and aggressiveness.

Dr. Curtis and colleagues found that, like fingers molding clay, the genes you’re born with can coax the immune system into shape. DNA inherited from our parents is known as the germline genome. It affects whether the immune system attacks or retreats when confronted with variations that may lead to breast cancer.

“It turns out, the germline genome sculpts tumor evolution,” said Dr. Curtis.

The study is part of a growing effort to understand “precancer” — the critical period after cells have started to grow abnormally but before they’ve developed into cancer — a research trend that could trigger a decisive shift in how cancer treatments are realized. Therapeutics could be designed on the basis of the biology of these precancerous cells.

While biotech start-ups push new tests to catch cancer early, researchers like Dr. Curtis hope to stop cancer before it even starts.

“This is a really exciting area of research,” said Susan Domchek, MD, executive director of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, who was not involved in the study. “What we hope for is that, over time, we’re going to have more and more biologically driven interception.”
 

‘We’re Basically Unearthing the Dark Matter of the Human Genome’

Of course, we already have mechanical ways of heading off cancer, like having a precancerous polyp removed. But for the Stanford researchers, biologic interception is the goal. They hope to figure out how to use the immune system to stop the cancer.

In their study, they looked at DNA variabilities known as somatic aberrations or single-nucleotide protein sequences (SNPs). The HER2 gene, for example, can contain SNPs — possibly affecting how the HER2 protein regulates breast cell growth and division.

“There’s been a huge effort through genomewide association studies to link SNPs to cancer outcomes and risk,” Dr. Curtis said.

Focusing on people with a genetic predisposition for breast cancer, Dr. Curtis used machine learning to show that these variabilities can occur in specific epitopes (protein features that can trigger an immune response).

They also found that heightened variability can show up in a region of the genome called the human leukocyte antigen (HLA). Each HLA molecule can contain many epitopes.

“We developed a whole new algorithm to compute this ‘germline epitope burden,’ ” Dr. Curtis said. “We’re basically unearthing the dark matter of the human genome to ask about the interplay between SNPs and HLA class one presentation.”

These aberration-rich regions can grab the immune system’s attention. Sometimes the immune system identifies and eradicates those epitopes.

In that case: “I have immunosurveillance. I’ve cured my cancer,” said Nora Disis, PhD, director of the Cancer Vaccine Institute and a professor of medicine at the University of Washington, Seattle. Dr. Disis was not involved in the study.

But other times, the immune system finds a way around the high “epitope burden,” and the tumors become more aggressive and immunosuppressive. That’s when cancer forms.

This suggests a “critical juncture between preinvasive and invasive disease,” Dr. Curtis said.

And that “critical juncture” may very well be the optimal time for intervention.
 

The Precancer Push

Stanford’s findings add information to prior biomarkers and may provide a way to identify “bad-acting tumors” from a simple blood draw measuring germline epitope burden, Dr. Curtis said. Looking further ahead, “this also reveals a new source of epitopes that might be immunogenic and might be informative for the development of vaccines.”

Many labs are trying to understand the biology of precancer and exploring possible vaccines.

The National Cancer Institute’s Human Tumor Atlas Network is building three-dimensional models of the evolution from precancerous to advanced disease. And researchers at the Cancer Vaccine Institute at the University of Washington are developing a vaccine for a precancerous lesion linked to many ovarian cancers.

Dr. Domchek’s research explores whether breast cancers caused by mutations in the BRCA 1 and 2 genes can be intercepted at very early stages. In a clinical trial of healthy people with those mutations, Dr. Domchek and colleagues are attempting to “rev up the immune system to tackle telomerase,” an enzyme that’s over-expressed in 95% of cancers. The hope is for this experimental vaccine to lower their risk of developing cancer.

At the Fred Hutch Cancer Center, Seattle, Ming Yu, PhD, is studying how senescent cells affect immune cells in precancer. As cells age and stop dividing, she said, they can accumulate and create a “tumor-promoting microenvironment” in older people.

Dr. Yu has found that the antiaging drug rapamycin can eliminate those “zombie cells” in mice. She’s studying whether the “cleanup” can help prevent cancer and expects results in a few months.

In the years and decades to come, all of this could lead to a new era in cancer treatment.

“Most drug development starts with people with advanced cancer and then goes into the earlier and earlier spaces,” said Dr. Domchek. “But it may be that we’re thinking about it all wrong and that you really have to understand the unique biology of early lesions to go after them.”

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

Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.

“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”

The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.

These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.

For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.

And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).

“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”

Here’s what residents are fighting for — right now.
 

Adequate Parental Leave

Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.

“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”

Contract negotiations here continue to be slow — and arduous.

“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”

If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.

“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
 

Fair Pay

In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.

“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”

This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.

Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.

“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.

“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
 

Adequate Healthcare

The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.

“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”

Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.

The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.

“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”

Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.

“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”

Paving the way for future residents is a key motivator, too.

“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”

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

Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.

“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”

The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.

These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.

For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.

And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).

“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”

Here’s what residents are fighting for — right now.
 

Adequate Parental Leave

Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.

“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”

Contract negotiations here continue to be slow — and arduous.

“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”

If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.

“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
 

Fair Pay

In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.

“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”

This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.

Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.

“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.

“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
 

Adequate Healthcare

The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.

“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”

Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.

The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.

“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”

Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.

“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”

Paving the way for future residents is a key motivator, too.

“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”

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

Before the 350 residents finalized their union contract at the University of Vermont (UVM) Medical Center, Burlington, in 2022, Jesse Mostoller, DO, now a third-year pathology resident, recalls hearing about another resident at the hospital who resorted to moonlighting as an Uber driver to make ends meet.

“In Vermont, rent and childcare are expensive,” said Dr. Mostoller, adding that, thanks to union bargaining, first-year residents at UVM are now paid $71,000 per year instead of $61,000. In addition, residents now receive $1800 per year for food (up from $200-$300 annually) and a $1800 annual fund to help pay for board exams that can be carried over for 2 years. “When we were negotiating, the biggest item on our list of demands was to help alleviate the financial pressure residents have been facing for years.”

The UVM residents’ collective bargaining also includes a cap on working hours so that residents don’t work 80 hours a week, paid parental leave, affordable housing, and funds for education and wellness.

These are some of the most common challenges that are faced by residents all over the country, said A. Taylor Walker, MD, MPH, family medicine chief physician at Tufts University School of Medicine/Cambridge Health Alliance in Boston, Massachusetts, and national president of the Committee of Interns and Residents (CIR), which is part of the Service Employees International Union.

For these reasons, residents at Montefiore Medical Center, Stanford Health Care, George Washington University, and the University of Pennsylvania have recently voted to unionize, according to Dr. Walker.

And while there are several small local unions that have picked up residents at local hospitals, CIR is the largest union of physicians in the United States, with a total of 33,000 residents and fellows across the country (15% of the staff at more than 60 hospitals nationwide).

“We’ve doubled in size in the last 4 years,” said Dr. Walker. “The reason is that we’re in a national reckoning on the corporatization of American medicine and the way in which graduate medical education is rooted in a cycle of exploitation that doesn’t center on the health, well-being, or safety of our doctors and ultimately negatively affects our patients.”

Here’s what residents are fighting for — right now.
 

Adequate Parental Leave

Christopher Domanski, MD, a first-year resident in psychiatry at California Pacific Medical Center (CPMC) in San Francisco, is also a new dad to a 5-month-old son and is currently in the sixth week of parental leave. One goal of CPMC’s union, started a year and a half ago, is to expand parental leave to 8 weeks.

“I started as a resident here in mid-June, but the fight with CPMC leaders has been going on for a year and a half,” Dr. Domanski said. “It can feel very frustrating because many times there’s no budge in the conversations we want to have.”

Contract negotiations here continue to be slow — and arduous.

“It goes back and forth,” said Dr. Domanski, who makes about $75,000 a year. “Sometimes they listen to our proposals, but they deny the vast majority or make a paltry increase in salary or time off. It goes like this: We’ll have a negotiation; we’ll talk about it, and then they say, ‘we’re not comfortable doing this’ and it stalls again.”

If a resident hasn’t started a family yet, access to fertility benefits and reproductive healthcare is paramount because most residents are in their 20s and 30s, Dr. Walker said.

“Our reproductive futures are really hindered by what care we have access to and what care is covered,” she added. “We don’t make enough money to pay for reproductive care out of pocket.”
 

Fair Pay

In Boston, the residents at Mass General Brigham certified their union in June 2023, but they still don’t have a contract.

“When I applied for a residency in September 2023, I spoke to the folks here, and I was basically under the impression that we would have a contract by the time I matched,” said Madison Masters, MD, a resident in internal medicine. “We are not there.”

This timeline isn’t unusual — the 1400 Penn Medicine residents who unionized in 2023 only recently secured a tentative union contract at the end of September, and at Stanford, the process to ratify their first contract took 13 months.

Still, the salary issue remains frustrating as resident compensation doesn’t line up with the cost of living or the amount of work residents do, said Dr. Masters, who says starting salaries at Mass General Brigham are $78,500 plus a $10,000 stipend for housing.

“There’s been a long tradition of underpaying residents — we’re treated like trainees, but we’re also a primary labor force,” Dr. Masters said, adding that nurse practitioners and physician assistants are paid almost twice as much as residents — some make $120,000 per year or more, while the salary range for residents nationwide is $49,000-$65,000 per year.

“Every time we discuss the contract and talk about a financial package, they offer a 1.5% raise for the next 3 years while we had asked for closer to 8%,” Dr. Masters said. “Then, when they come back for the next bargaining session, they go up a quarter of a percent each time. Recently, they said we will need to go to a mediator to try and resolve this.”
 

Adequate Healthcare

The biggest — and perhaps the most shocking — ask is for robust health insurance coverage.

“At my hospital, they’re telling us to get Amazon One Medical for health insurance,” Dr. Masters said. “They’re saying it’s hard for anyone to get primary care coverage here.”

Inadequate health insurance is a big issue, as burnout among residents and fellows remains a problem. At UVM, a $10,000 annual wellness stipend has helped address some of these issues. Even so, union members at UVM are planning to return to the table within 18 months to continue their collective bargaining.

The ability to access mental health services anywhere you want is also critical for residents, Dr. Walker said.

“If you can only go to a therapist at your own institution, there is a hesitation to utilize that specialist if that’s even offered,” Dr. Walker said. “Do you want to go to therapy with a colleague? Probably not.”

Ultimately, the residents we spoke to are committed to fighting for their workplace rights — no matter how time-consuming or difficult this has been.

“No administration wants us to have to have a union, but it’s necessary,” Dr. Mostoller said. “As an individual, you don’t have leverage to get a seat at the table, but now we have a seat at the table. We have a wonderful contract, but we’re going to keep fighting to make it even better.”

Paving the way for future residents is a key motivator, too.

“There’s this idea of leaving the campsite cleaner than you found it,” Dr. Mostoller told this news organization. “It’s the same thing here — we’re trying to fix this so that the next generation of residents won’t have to.”

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

In a stunning verdict against Blue Cross and Blue Shield of Louisiana, a New Orleans jury has awarded $421 million in damages to a surgery center over the insurer’s alleged failure to fully pay out-of-network charges.

Insurance specialists told this news organization that the September 20 verdict is unusual. If upheld on appeal, one said, it could give out-of-network providers more power to decide how much insurers must pay them.

The case, which the St. Charles Surgical Hospital and Center for Restorative Breast Surgery first filed in 2017 in Louisiana state court, will be appealed and could ultimately land in federal court. The center has seen mixed results from a similar case it filed in federal court, legal documents show. Physicians from the center declined comment.

At issue: Did Blue Cross fail to fully pay the surgery center for about 7000 out-of-network procedures that it authorized? 

The lawsuit claimed that the insurer’s online system confirmed that claims would be paid and noted the percentage of patient bills that would be reimbursed.

However, “Blue Cross and Blue Shield of Louisiana either slow-paid, low-paid, or no-paid all their bills over an eight-year period, hoping to pressure the doctors and hospital to either come into the network or fail and close down,” the surgery center’s attorney, James Williams, said in a statement.

Blue Cross denied that it acted fraudulently, “arguing that because the hospital is not a member of its provider network, it had no contractual obligation to pay anything,” the Times-Picayune newspaper reported. Authorization of a procedure doesn’t guarantee payment, the insurer argued in court.

In a statement to the media, Blue Cross said it disagrees with the verdict and will appeal.
 

Out-of-Network Free For All

Paul B. Ginsburg, PhD, professor of the Practice of Health Policy at the Price School of Public Policy, University of Southern California, Los Angeles, said out-of-network care doesn’t come with a contractual relationship.

Without a contract, he said, “providers can charge whatever they want, and the insurers will pay them whatever they want, and then it’s up to the provider to see how much additional balance bill they can collect from the patients.” (Some states and the federal government have laws partly protecting patients from balance billing when doctors and insurers conflict over payment.)

He added that “if insurance companies were on the hook to pay whatever any provider charges, nobody would ever belong to a network, and rates would be sky high. Many fewer people would buy insurance. Providers would [then] charge as much as they think they can get from the patients.”

What about the insurer’s apparent authorization of the out-of-network procedures? “They’re authorizing them because they believe the procedures are medically warranted,” Dr. Ginsburg said. “That’s totally separate from how much they’ll pay.”

Dr. Ginsburg added that juries in the South are known for imposing high penalties against companies. “They often come up with crazy verdicts.”

Mark V. Pauly, PhD, MA, professor emeritus of health care management at the Wharton School of the University of Pennsylvania, Philadelphia, questioned why the clinic kept accepting Blue Cross patients.

“Once it became apparent that Blue Cross wasn’t going to pay them well or would give them a lot of grief,” Dr. Pauly said, “the simplest thing would have been to tell patients that we’re going to go back to the old-fashioned way of doing things: You pay us up front, or assure us that you’re going to pay.”

Lawton Robert Burns, PhD, MBA, professor of health care management at the Wharton School, said the case and the verdict are unusual. He noted that insurer contracts with employers often state that out-of-network care will be covered at a specific rate, such as 70% of “reasonable charges.”

A 2020 analysis found that initial breast reconstruction surgeries in the United States cost a median of $24,600-$38,000 from 2009 to 2016. According to the Times-Picayune, the New Orleans clinic billed Blue Cross for $506.7 million, averaging more than $72,385 per procedure.

Dr. Ginsburg, Dr. Pauly, and Dr. Burns had no disclosures.

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

In a stunning verdict against Blue Cross and Blue Shield of Louisiana, a New Orleans jury has awarded $421 million in damages to a surgery center over the insurer’s alleged failure to fully pay out-of-network charges.

Insurance specialists told this news organization that the September 20 verdict is unusual. If upheld on appeal, one said, it could give out-of-network providers more power to decide how much insurers must pay them.

The case, which the St. Charles Surgical Hospital and Center for Restorative Breast Surgery first filed in 2017 in Louisiana state court, will be appealed and could ultimately land in federal court. The center has seen mixed results from a similar case it filed in federal court, legal documents show. Physicians from the center declined comment.

At issue: Did Blue Cross fail to fully pay the surgery center for about 7000 out-of-network procedures that it authorized? 

The lawsuit claimed that the insurer’s online system confirmed that claims would be paid and noted the percentage of patient bills that would be reimbursed.

However, “Blue Cross and Blue Shield of Louisiana either slow-paid, low-paid, or no-paid all their bills over an eight-year period, hoping to pressure the doctors and hospital to either come into the network or fail and close down,” the surgery center’s attorney, James Williams, said in a statement.

Blue Cross denied that it acted fraudulently, “arguing that because the hospital is not a member of its provider network, it had no contractual obligation to pay anything,” the Times-Picayune newspaper reported. Authorization of a procedure doesn’t guarantee payment, the insurer argued in court.

In a statement to the media, Blue Cross said it disagrees with the verdict and will appeal.
 

Out-of-Network Free For All

Paul B. Ginsburg, PhD, professor of the Practice of Health Policy at the Price School of Public Policy, University of Southern California, Los Angeles, said out-of-network care doesn’t come with a contractual relationship.

Without a contract, he said, “providers can charge whatever they want, and the insurers will pay them whatever they want, and then it’s up to the provider to see how much additional balance bill they can collect from the patients.” (Some states and the federal government have laws partly protecting patients from balance billing when doctors and insurers conflict over payment.)

He added that “if insurance companies were on the hook to pay whatever any provider charges, nobody would ever belong to a network, and rates would be sky high. Many fewer people would buy insurance. Providers would [then] charge as much as they think they can get from the patients.”

What about the insurer’s apparent authorization of the out-of-network procedures? “They’re authorizing them because they believe the procedures are medically warranted,” Dr. Ginsburg said. “That’s totally separate from how much they’ll pay.”

Dr. Ginsburg added that juries in the South are known for imposing high penalties against companies. “They often come up with crazy verdicts.”

Mark V. Pauly, PhD, MA, professor emeritus of health care management at the Wharton School of the University of Pennsylvania, Philadelphia, questioned why the clinic kept accepting Blue Cross patients.

“Once it became apparent that Blue Cross wasn’t going to pay them well or would give them a lot of grief,” Dr. Pauly said, “the simplest thing would have been to tell patients that we’re going to go back to the old-fashioned way of doing things: You pay us up front, or assure us that you’re going to pay.”

Lawton Robert Burns, PhD, MBA, professor of health care management at the Wharton School, said the case and the verdict are unusual. He noted that insurer contracts with employers often state that out-of-network care will be covered at a specific rate, such as 70% of “reasonable charges.”

A 2020 analysis found that initial breast reconstruction surgeries in the United States cost a median of $24,600-$38,000 from 2009 to 2016. According to the Times-Picayune, the New Orleans clinic billed Blue Cross for $506.7 million, averaging more than $72,385 per procedure.

Dr. Ginsburg, Dr. Pauly, and Dr. Burns had no disclosures.

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

In a stunning verdict against Blue Cross and Blue Shield of Louisiana, a New Orleans jury has awarded $421 million in damages to a surgery center over the insurer’s alleged failure to fully pay out-of-network charges.

Insurance specialists told this news organization that the September 20 verdict is unusual. If upheld on appeal, one said, it could give out-of-network providers more power to decide how much insurers must pay them.

The case, which the St. Charles Surgical Hospital and Center for Restorative Breast Surgery first filed in 2017 in Louisiana state court, will be appealed and could ultimately land in federal court. The center has seen mixed results from a similar case it filed in federal court, legal documents show. Physicians from the center declined comment.

At issue: Did Blue Cross fail to fully pay the surgery center for about 7000 out-of-network procedures that it authorized? 

The lawsuit claimed that the insurer’s online system confirmed that claims would be paid and noted the percentage of patient bills that would be reimbursed.

However, “Blue Cross and Blue Shield of Louisiana either slow-paid, low-paid, or no-paid all their bills over an eight-year period, hoping to pressure the doctors and hospital to either come into the network or fail and close down,” the surgery center’s attorney, James Williams, said in a statement.

Blue Cross denied that it acted fraudulently, “arguing that because the hospital is not a member of its provider network, it had no contractual obligation to pay anything,” the Times-Picayune newspaper reported. Authorization of a procedure doesn’t guarantee payment, the insurer argued in court.

In a statement to the media, Blue Cross said it disagrees with the verdict and will appeal.
 

Out-of-Network Free For All

Paul B. Ginsburg, PhD, professor of the Practice of Health Policy at the Price School of Public Policy, University of Southern California, Los Angeles, said out-of-network care doesn’t come with a contractual relationship.

Without a contract, he said, “providers can charge whatever they want, and the insurers will pay them whatever they want, and then it’s up to the provider to see how much additional balance bill they can collect from the patients.” (Some states and the federal government have laws partly protecting patients from balance billing when doctors and insurers conflict over payment.)

He added that “if insurance companies were on the hook to pay whatever any provider charges, nobody would ever belong to a network, and rates would be sky high. Many fewer people would buy insurance. Providers would [then] charge as much as they think they can get from the patients.”

What about the insurer’s apparent authorization of the out-of-network procedures? “They’re authorizing them because they believe the procedures are medically warranted,” Dr. Ginsburg said. “That’s totally separate from how much they’ll pay.”

Dr. Ginsburg added that juries in the South are known for imposing high penalties against companies. “They often come up with crazy verdicts.”

Mark V. Pauly, PhD, MA, professor emeritus of health care management at the Wharton School of the University of Pennsylvania, Philadelphia, questioned why the clinic kept accepting Blue Cross patients.

“Once it became apparent that Blue Cross wasn’t going to pay them well or would give them a lot of grief,” Dr. Pauly said, “the simplest thing would have been to tell patients that we’re going to go back to the old-fashioned way of doing things: You pay us up front, or assure us that you’re going to pay.”

Lawton Robert Burns, PhD, MBA, professor of health care management at the Wharton School, said the case and the verdict are unusual. He noted that insurer contracts with employers often state that out-of-network care will be covered at a specific rate, such as 70% of “reasonable charges.”

A 2020 analysis found that initial breast reconstruction surgeries in the United States cost a median of $24,600-$38,000 from 2009 to 2016. According to the Times-Picayune, the New Orleans clinic billed Blue Cross for $506.7 million, averaging more than $72,385 per procedure.

Dr. Ginsburg, Dr. Pauly, and Dr. Burns had no disclosures.

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

The rate of congenital heart defects is higher in newborns conceived using assisted reproductive technologies (ART) than in newborns conceived without assistance. This finding comes from a population-based cohort study led by Dr. Nona Sargisian, a gynecologist at the University of Gothenburg, Sweden, and colleagues, which was published in the European Heart Journal.

The researchers analyzed more than 7 million results of all live-born children in Denmark, Finland, Sweden, and Norway between 1984 and 2015. They found that congenital heart defects occurred more frequently in the ART newborn group (1.85%) than in naturally conceived newborns (1.15%).

The study also revealed that the risk for congenital heart defects in multiple births is higher than in single births, with and without the use of ART. However, the result that congenital heart defects occur more often in ART newborns remained significant when comparing single births from both groups (1.62% vs 1.11%).
 

Relatively Low Prevalence

Barbara Sonntag, MD, PhD, a gynecologist at Amedes Fertility Center in Hamburg, Germany, referred to a “clinically relevant risk increase” with a relatively low prevalence of the condition.

“When 1000 children are born, an abnormality occurs in 18 children after ART, compared with 11 children born after natural conception,” she told the Science Media Center.

Dr. Sonntag emphasized that the risk is particularly increased by a multiple pregnancy. A statement about causality is not possible based on the study, but multiple pregnancies are generally associated with increased risks during pregnancy and for the children.

The large and robust dataset confirms long-known findings, said Georg Griesinger, MD, PhD, medical director of the fertility centers of the University Medical Center Schleswig-Holstein in Lübeck and Manhagen, Germany.

The key figures can be found in single births, he explained. “Among single births conceived by ART, the rate of severe congenital heart defects was 1.62% compared with 1.11% in spontaneously conceived single births, an increase in risk by 1.19 times. For severe heart defects, the rate was 0.31% in ART single births, compared with 0.25% in spontaneously conceived single births.”

The increased risks are consistent with existing literature. Therefore, the current study does not reveal any new risk signals, said Dr. Griesinger.
 

Single Embryo Transfer

The “risks are small but present,” according to Michael von Wolff, MD, head of gynecological endocrinology and reproductive medicine at Bern University Hospital in Switzerland. “Therefore, ART therapy should only be carried out after exhausting conservative treatments,” he recommended. For example, ovarian stimulation with low-dose hormone preparations could be an option.

Dr. Griesinger pointed out that, in absolute numbers, all maternal and fetal or neonatal risks are significantly increased in twins and higher-order multiples, compared with the estimated risk association within the actual ART treatment.

“For this reason, reproductive medicine specialists have been advocating for single-embryo transfer for years to promote the occurrence of single pregnancies through ART,” said Dr. Griesinger.

The study “emphasizes the importance of single embryo transfer to avoid the higher risks associated with multiple pregnancies,” according to Rocío Núñez Calonge, PhD, scientific director of the International Reproduction Unit in Alicante, Spain.

Dr. Sonntag also sees a “strong additional call to avoid multiple pregnancies through a predominant strategy of single-embryo transfer in the data. The increased rate of childhood birth defects is already part of the information provided before assisted reproduction.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The rate of congenital heart defects is higher in newborns conceived using assisted reproductive technologies (ART) than in newborns conceived without assistance. This finding comes from a population-based cohort study led by Dr. Nona Sargisian, a gynecologist at the University of Gothenburg, Sweden, and colleagues, which was published in the European Heart Journal.

The researchers analyzed more than 7 million results of all live-born children in Denmark, Finland, Sweden, and Norway between 1984 and 2015. They found that congenital heart defects occurred more frequently in the ART newborn group (1.85%) than in naturally conceived newborns (1.15%).

The study also revealed that the risk for congenital heart defects in multiple births is higher than in single births, with and without the use of ART. However, the result that congenital heart defects occur more often in ART newborns remained significant when comparing single births from both groups (1.62% vs 1.11%).
 

Relatively Low Prevalence

Barbara Sonntag, MD, PhD, a gynecologist at Amedes Fertility Center in Hamburg, Germany, referred to a “clinically relevant risk increase” with a relatively low prevalence of the condition.

“When 1000 children are born, an abnormality occurs in 18 children after ART, compared with 11 children born after natural conception,” she told the Science Media Center.

Dr. Sonntag emphasized that the risk is particularly increased by a multiple pregnancy. A statement about causality is not possible based on the study, but multiple pregnancies are generally associated with increased risks during pregnancy and for the children.

The large and robust dataset confirms long-known findings, said Georg Griesinger, MD, PhD, medical director of the fertility centers of the University Medical Center Schleswig-Holstein in Lübeck and Manhagen, Germany.

The key figures can be found in single births, he explained. “Among single births conceived by ART, the rate of severe congenital heart defects was 1.62% compared with 1.11% in spontaneously conceived single births, an increase in risk by 1.19 times. For severe heart defects, the rate was 0.31% in ART single births, compared with 0.25% in spontaneously conceived single births.”

The increased risks are consistent with existing literature. Therefore, the current study does not reveal any new risk signals, said Dr. Griesinger.
 

Single Embryo Transfer

The “risks are small but present,” according to Michael von Wolff, MD, head of gynecological endocrinology and reproductive medicine at Bern University Hospital in Switzerland. “Therefore, ART therapy should only be carried out after exhausting conservative treatments,” he recommended. For example, ovarian stimulation with low-dose hormone preparations could be an option.

Dr. Griesinger pointed out that, in absolute numbers, all maternal and fetal or neonatal risks are significantly increased in twins and higher-order multiples, compared with the estimated risk association within the actual ART treatment.

“For this reason, reproductive medicine specialists have been advocating for single-embryo transfer for years to promote the occurrence of single pregnancies through ART,” said Dr. Griesinger.

The study “emphasizes the importance of single embryo transfer to avoid the higher risks associated with multiple pregnancies,” according to Rocío Núñez Calonge, PhD, scientific director of the International Reproduction Unit in Alicante, Spain.

Dr. Sonntag also sees a “strong additional call to avoid multiple pregnancies through a predominant strategy of single-embryo transfer in the data. The increased rate of childhood birth defects is already part of the information provided before assisted reproduction.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The rate of congenital heart defects is higher in newborns conceived using assisted reproductive technologies (ART) than in newborns conceived without assistance. This finding comes from a population-based cohort study led by Dr. Nona Sargisian, a gynecologist at the University of Gothenburg, Sweden, and colleagues, which was published in the European Heart Journal.

The researchers analyzed more than 7 million results of all live-born children in Denmark, Finland, Sweden, and Norway between 1984 and 2015. They found that congenital heart defects occurred more frequently in the ART newborn group (1.85%) than in naturally conceived newborns (1.15%).

The study also revealed that the risk for congenital heart defects in multiple births is higher than in single births, with and without the use of ART. However, the result that congenital heart defects occur more often in ART newborns remained significant when comparing single births from both groups (1.62% vs 1.11%).
 

Relatively Low Prevalence

Barbara Sonntag, MD, PhD, a gynecologist at Amedes Fertility Center in Hamburg, Germany, referred to a “clinically relevant risk increase” with a relatively low prevalence of the condition.

“When 1000 children are born, an abnormality occurs in 18 children after ART, compared with 11 children born after natural conception,” she told the Science Media Center.

Dr. Sonntag emphasized that the risk is particularly increased by a multiple pregnancy. A statement about causality is not possible based on the study, but multiple pregnancies are generally associated with increased risks during pregnancy and for the children.

The large and robust dataset confirms long-known findings, said Georg Griesinger, MD, PhD, medical director of the fertility centers of the University Medical Center Schleswig-Holstein in Lübeck and Manhagen, Germany.

The key figures can be found in single births, he explained. “Among single births conceived by ART, the rate of severe congenital heart defects was 1.62% compared with 1.11% in spontaneously conceived single births, an increase in risk by 1.19 times. For severe heart defects, the rate was 0.31% in ART single births, compared with 0.25% in spontaneously conceived single births.”

The increased risks are consistent with existing literature. Therefore, the current study does not reveal any new risk signals, said Dr. Griesinger.
 

Single Embryo Transfer

The “risks are small but present,” according to Michael von Wolff, MD, head of gynecological endocrinology and reproductive medicine at Bern University Hospital in Switzerland. “Therefore, ART therapy should only be carried out after exhausting conservative treatments,” he recommended. For example, ovarian stimulation with low-dose hormone preparations could be an option.

Dr. Griesinger pointed out that, in absolute numbers, all maternal and fetal or neonatal risks are significantly increased in twins and higher-order multiples, compared with the estimated risk association within the actual ART treatment.

“For this reason, reproductive medicine specialists have been advocating for single-embryo transfer for years to promote the occurrence of single pregnancies through ART,” said Dr. Griesinger.

The study “emphasizes the importance of single embryo transfer to avoid the higher risks associated with multiple pregnancies,” according to Rocío Núñez Calonge, PhD, scientific director of the International Reproduction Unit in Alicante, Spain.

Dr. Sonntag also sees a “strong additional call to avoid multiple pregnancies through a predominant strategy of single-embryo transfer in the data. The increased rate of childhood birth defects is already part of the information provided before assisted reproduction.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Women with hypothyroidism treated with levothyroxine show no significant cognitive decline across the menopausal transition compared with those without thyroid disease.

METHODOLOGY:

• Levothyroxine, the primary treatment for hypothyroidism, has been linked to perceived cognitive deficits, yet it is unclear whether this is due to the underlying condition being inadequately treated or other factors.
• Using data collected from the Study of Women’s Health Across the Nation, which encompasses five ethnic/racial groups from seven centers across the United States, researchers compared cognitive function over time between women with hypothyroidism treated with levothyroxine and those without thyroid disease.
• Participants underwent cognitive testing across three domains — processing speed, working memory, and episodic memory — which were assessed over a mean follow-up of 13 years.
• Further analyses assessed the impact of abnormal levels of thyroid-stimulating hormone on cognitive outcomes.

TAKEAWAY:

• Of 2033 women included, 227 (mean age, 49.8 years) had levothyroxine-treated hypothyroidism and 1806 (mean age, 50.0 years) did not have thyroid disease; the proportion of women with premenopausal or early perimenopausal status at baseline was higher in the hypothyroidism group (54.2% vs 49.8%; P = .010).
• At baseline, levothyroxine-treated women had higher scores for processing speed (mean score, 56.5 vs 54.4; P = .006) and working memory (mean score, 6.8 vs 6.4; P = .018) than those without thyroid disease; however, no difference in episodic memory was observed between the groups.
• Over the study period, there was no significant difference in cognitive decline between the groups.
• There was no significant effect of levothyroxine-treated hypothyroidism on working memory or episodic memory, although an annual decline in processing speed was observed (P < .001).
• Sensitivity analyses determined that abnormal levels of thyroid-stimulating hormone did not affect cognitive outcomes in women with hypothyroidism.

IN PRACTICE:

When cognitive decline is observed in these patients, the authors advised that “clinicians should resist anchoring on inadequate treatment of hypothyroidism as the cause of these symptoms and may investigate other disease processes (eg, iron deficiency, B12 deficiency, sleep apnea, celiac disease).”

SOURCE:

The study, led by Matthew D. Ettleson, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, was published online in Thyroid.

LIMITATIONS:

The cognitive assessments in the study were not designed to provide a thorough evaluation of all aspects of cognitive function. The study may not have been adequately powered to detect small effects of levothyroxine-treated hypothyroidism on cognitive outcomes. The higher levels of education attained by the study population may have acted as a protective factor against cognitive decline, potentially biasing the results.

DISCLOSURES:

The Study of Women’s Health Across the Nation was supported by grants from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Women with hypothyroidism treated with levothyroxine show no significant cognitive decline across the menopausal transition compared with those without thyroid disease.

METHODOLOGY:

• Levothyroxine, the primary treatment for hypothyroidism, has been linked to perceived cognitive deficits, yet it is unclear whether this is due to the underlying condition being inadequately treated or other factors.
• Using data collected from the Study of Women’s Health Across the Nation, which encompasses five ethnic/racial groups from seven centers across the United States, researchers compared cognitive function over time between women with hypothyroidism treated with levothyroxine and those without thyroid disease.
• Participants underwent cognitive testing across three domains — processing speed, working memory, and episodic memory — which were assessed over a mean follow-up of 13 years.
• Further analyses assessed the impact of abnormal levels of thyroid-stimulating hormone on cognitive outcomes.

TAKEAWAY:

• Of 2033 women included, 227 (mean age, 49.8 years) had levothyroxine-treated hypothyroidism and 1806 (mean age, 50.0 years) did not have thyroid disease; the proportion of women with premenopausal or early perimenopausal status at baseline was higher in the hypothyroidism group (54.2% vs 49.8%; P = .010).
• At baseline, levothyroxine-treated women had higher scores for processing speed (mean score, 56.5 vs 54.4; P = .006) and working memory (mean score, 6.8 vs 6.4; P = .018) than those without thyroid disease; however, no difference in episodic memory was observed between the groups.
• Over the study period, there was no significant difference in cognitive decline between the groups.
• There was no significant effect of levothyroxine-treated hypothyroidism on working memory or episodic memory, although an annual decline in processing speed was observed (P < .001).
• Sensitivity analyses determined that abnormal levels of thyroid-stimulating hormone did not affect cognitive outcomes in women with hypothyroidism.

IN PRACTICE:

When cognitive decline is observed in these patients, the authors advised that “clinicians should resist anchoring on inadequate treatment of hypothyroidism as the cause of these symptoms and may investigate other disease processes (eg, iron deficiency, B12 deficiency, sleep apnea, celiac disease).”

SOURCE:

The study, led by Matthew D. Ettleson, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, was published online in Thyroid.

LIMITATIONS:

The cognitive assessments in the study were not designed to provide a thorough evaluation of all aspects of cognitive function. The study may not have been adequately powered to detect small effects of levothyroxine-treated hypothyroidism on cognitive outcomes. The higher levels of education attained by the study population may have acted as a protective factor against cognitive decline, potentially biasing the results.

DISCLOSURES:

The Study of Women’s Health Across the Nation was supported by grants from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Women with hypothyroidism treated with levothyroxine show no significant cognitive decline across the menopausal transition compared with those without thyroid disease.

METHODOLOGY:

• Levothyroxine, the primary treatment for hypothyroidism, has been linked to perceived cognitive deficits, yet it is unclear whether this is due to the underlying condition being inadequately treated or other factors.
• Using data collected from the Study of Women’s Health Across the Nation, which encompasses five ethnic/racial groups from seven centers across the United States, researchers compared cognitive function over time between women with hypothyroidism treated with levothyroxine and those without thyroid disease.
• Participants underwent cognitive testing across three domains — processing speed, working memory, and episodic memory — which were assessed over a mean follow-up of 13 years.
• Further analyses assessed the impact of abnormal levels of thyroid-stimulating hormone on cognitive outcomes.

TAKEAWAY:

• Of 2033 women included, 227 (mean age, 49.8 years) had levothyroxine-treated hypothyroidism and 1806 (mean age, 50.0 years) did not have thyroid disease; the proportion of women with premenopausal or early perimenopausal status at baseline was higher in the hypothyroidism group (54.2% vs 49.8%; P = .010).
• At baseline, levothyroxine-treated women had higher scores for processing speed (mean score, 56.5 vs 54.4; P = .006) and working memory (mean score, 6.8 vs 6.4; P = .018) than those without thyroid disease; however, no difference in episodic memory was observed between the groups.
• Over the study period, there was no significant difference in cognitive decline between the groups.
• There was no significant effect of levothyroxine-treated hypothyroidism on working memory or episodic memory, although an annual decline in processing speed was observed (P < .001).
• Sensitivity analyses determined that abnormal levels of thyroid-stimulating hormone did not affect cognitive outcomes in women with hypothyroidism.

IN PRACTICE:

When cognitive decline is observed in these patients, the authors advised that “clinicians should resist anchoring on inadequate treatment of hypothyroidism as the cause of these symptoms and may investigate other disease processes (eg, iron deficiency, B12 deficiency, sleep apnea, celiac disease).”

SOURCE:

The study, led by Matthew D. Ettleson, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, was published online in Thyroid.

LIMITATIONS:

The cognitive assessments in the study were not designed to provide a thorough evaluation of all aspects of cognitive function. The study may not have been adequately powered to detect small effects of levothyroxine-treated hypothyroidism on cognitive outcomes. The higher levels of education attained by the study population may have acted as a protective factor against cognitive decline, potentially biasing the results.

DISCLOSURES:

The Study of Women’s Health Across the Nation was supported by grants from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

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

TOPLINE: 

Women with premature ovarian insufficiency (POI) have a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis and a 2- to 3-fold increased risk for these diseases after diagnosis.
 

METHODOLOGY:

• Researchers conducted a population-based registry study including 3972 women diagnosed with spontaneous POI between 1988 and 2017.
• A total of 15,708 female population controls matched by age and municipality of residence were included for comparison.
• Autoimmune disease diagnoses were evaluated from childhood until the end of 2017 using the Hospital Discharge Registry.
• Women with a history of cancer or bilateral oophorectomy were excluded from the study.

TAKEAWAY:

• Women with POI had a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis compared to controls (odds ratio [OR], 2.6; 95% CI, 2.2-3.1).
• The prevalence of specific autoimmune diseases such as polyglandular autoimmune diseases (OR, 25.8; 95% CI, 9.0-74.1) and Addison disease (OR, 22.9; 95% CI, 7.9-66.1) was significantly higher in women with POI.
• The standardized incidence ratios for being diagnosed with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI, 2.3-3.4) during the first 3 years, decreasing to 1.3 (95% CI, 1.1-1.6) after 12 years.
• No significant difference was found in the prevalence of diabetes type 1 and ankylosing spondylitis between women with POI and the reference cohort.

IN PRACTICE:

“The study results strengthen the hypothesis that autoimmune mechanisms play an important role in the pathogenesis of POI. Future studies should focus on the immunological mechanism of POI from preventative and curative perspectives,” wrote the authors of the study.

SOURCE:

The study was led by Susanna M. Savukoski, Oulu University Hospital in Finland. It was published online in Human Reproduction.

LIMITATIONS: 

The study included only autoimmune disorders diagnosed in specialized health care, which may underestimate the overall prevalence of autoimmune disorders in women with POI. Additionally, the study did not account for confounders such as body mass index and smoking, which are associated with the risk for autoimmune disease and POI.

DISCLOSURES:

Ms. Savukoski received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. Additional disclosures are noted in the original article. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE: 

Women with premature ovarian insufficiency (POI) have a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis and a 2- to 3-fold increased risk for these diseases after diagnosis.
 

METHODOLOGY:

• Researchers conducted a population-based registry study including 3972 women diagnosed with spontaneous POI between 1988 and 2017.
• A total of 15,708 female population controls matched by age and municipality of residence were included for comparison.
• Autoimmune disease diagnoses were evaluated from childhood until the end of 2017 using the Hospital Discharge Registry.
• Women with a history of cancer or bilateral oophorectomy were excluded from the study.

TAKEAWAY:

• Women with POI had a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis compared to controls (odds ratio [OR], 2.6; 95% CI, 2.2-3.1).
• The prevalence of specific autoimmune diseases such as polyglandular autoimmune diseases (OR, 25.8; 95% CI, 9.0-74.1) and Addison disease (OR, 22.9; 95% CI, 7.9-66.1) was significantly higher in women with POI.
• The standardized incidence ratios for being diagnosed with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI, 2.3-3.4) during the first 3 years, decreasing to 1.3 (95% CI, 1.1-1.6) after 12 years.
• No significant difference was found in the prevalence of diabetes type 1 and ankylosing spondylitis between women with POI and the reference cohort.

IN PRACTICE:

“The study results strengthen the hypothesis that autoimmune mechanisms play an important role in the pathogenesis of POI. Future studies should focus on the immunological mechanism of POI from preventative and curative perspectives,” wrote the authors of the study.

SOURCE:

The study was led by Susanna M. Savukoski, Oulu University Hospital in Finland. It was published online in Human Reproduction.

LIMITATIONS: 

The study included only autoimmune disorders diagnosed in specialized health care, which may underestimate the overall prevalence of autoimmune disorders in women with POI. Additionally, the study did not account for confounders such as body mass index and smoking, which are associated with the risk for autoimmune disease and POI.

DISCLOSURES:

Ms. Savukoski received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. Additional disclosures are noted in the original article. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE: 

Women with premature ovarian insufficiency (POI) have a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis and a 2- to 3-fold increased risk for these diseases after diagnosis.
 

METHODOLOGY:

• Researchers conducted a population-based registry study including 3972 women diagnosed with spontaneous POI between 1988 and 2017.
• A total of 15,708 female population controls matched by age and municipality of residence were included for comparison.
• Autoimmune disease diagnoses were evaluated from childhood until the end of 2017 using the Hospital Discharge Registry.
• Women with a history of cancer or bilateral oophorectomy were excluded from the study.

TAKEAWAY:

• Women with POI had a 2.6 times higher prevalence of severe autoimmune diseases before diagnosis compared to controls (odds ratio [OR], 2.6; 95% CI, 2.2-3.1).
• The prevalence of specific autoimmune diseases such as polyglandular autoimmune diseases (OR, 25.8; 95% CI, 9.0-74.1) and Addison disease (OR, 22.9; 95% CI, 7.9-66.1) was significantly higher in women with POI.
• The standardized incidence ratios for being diagnosed with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI, 2.3-3.4) during the first 3 years, decreasing to 1.3 (95% CI, 1.1-1.6) after 12 years.
• No significant difference was found in the prevalence of diabetes type 1 and ankylosing spondylitis between women with POI and the reference cohort.

IN PRACTICE:

“The study results strengthen the hypothesis that autoimmune mechanisms play an important role in the pathogenesis of POI. Future studies should focus on the immunological mechanism of POI from preventative and curative perspectives,” wrote the authors of the study.

SOURCE:

The study was led by Susanna M. Savukoski, Oulu University Hospital in Finland. It was published online in Human Reproduction.

LIMITATIONS: 

The study included only autoimmune disorders diagnosed in specialized health care, which may underestimate the overall prevalence of autoimmune disorders in women with POI. Additionally, the study did not account for confounders such as body mass index and smoking, which are associated with the risk for autoimmune disease and POI.

DISCLOSURES:

Ms. Savukoski received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. Additional disclosures are noted in the original article. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

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

A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.

The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options. 

Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication. 

Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February. 

“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News. 

Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.

“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
 

Moving the Field Forward

The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology. 

They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.

Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.

Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.

Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.

Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems. 

“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said. 

“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”

Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America. 

Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
 

Clinical Implications

Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.

MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future. 

The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.

Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided. 

Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes. 

Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them. 

The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.

The sources in this story reported no relevant financial conflicts of interest.
 

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

A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.

The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options. 

Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication. 

Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February. 

“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News. 

Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.

“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
 

Moving the Field Forward

The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology. 

They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.

Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.

Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.

Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.

Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems. 

“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said. 

“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”

Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America. 

Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
 

Clinical Implications

Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.

MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future. 

The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.

Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided. 

Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes. 

Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them. 

The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.

The sources in this story reported no relevant financial conflicts of interest.
 

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

A study by researchers at two academic medical centers determined which infertile men may benefit from treatment with anastrozole. They found that those with azoospermia (no sperm in their ejaculate) rarely respond to the drug while those with baseline nonazoospermia, lower levels of luteinizing hormone and follicle-stimulating hormone, and higher levels of testosterone are more likely to obtain improvement in semen parameters.

The retrospective cohort study of 90 infertile men, published in the October 2023 issue of Fertility and Sterility, was conducted by researchers at Cleveland Clinic and the University of California Los Angeles. It is the first project of Male Organ Biology Yielding United Science (MOBYUS), a new, multi-institutional research consortium seeking to better understand male infertility and expand treatment options. 

Launched last year, MOBYUS now includes investigators from 14 large US-based academic medical centers. They select research topics and search their patient population for eligible participants and share resulting deidentified data for analysis and publication. 

Members of the consortium conducted another study which found that combination therapy with clomiphene citrate and anastrozole was associated with modest benefits on semen parameters, including volume, concentration, and motility after treatment, compared with anastrozole monotherapy. That retrospective cohort analysis of 21 men was published online in Translational Andrology and Urology in February. 

“We know that if we treat the right men with these medications, about 40% will improve their fertility, but only if we choose the right population. These studies identified those groups,” Scott Lundy, MD, PhD, section head of male infertility at Cleveland Clinic’s Glickman Urological and Kidney Institute in Cleveland, and director of the clinic’s andrology lab, told Medscape Medical News. 

Dr. Lundy, a coauthor of both papers, conceived MOBYUS to overcome constraints in research into male infertility. Many studies in the field are limited by small numbers of patients and retrospective designs, he said. “I sought to develop a collaborative network of reproductive urologists and hospitals like ours, so that we can combine our data and generate large series of data, even for rare patient groups, so that we can improve their patient outcomes,” he said.

“Our treatments are in the stone age in many ways. We are far behind other types of treatment for other conditions, including female infertility,” Dr. Lundy added. “And so, our goal is to identify new and data-driven ways to help these men become fathers, whether those are medications or surgeries or combinations of treatments.”
 

Moving the Field Forward

The name of the consortium is a cheeky play on Moby Dick, the most famous sperm whale. MOBYUS investigators conveyed the challenges that patients, doctors, and researchers experience in an article published last December in the Journal of Urology. 

They noted that 1 in 6 couples will have difficulty conceiving a child, with male-factor infertility contributing to at least half of such cases. The lead author, Catherine Nam, MD, a principal investigator for MOBYUS at the University of Michigan, in Ann Arbor, said the paper is unusual for a medical journal, as it provides personal accounts of the psychological and emotional aspects of infertility as well as factors that have led to a global decline in sperm counts among men and the financial costs of treatment.

Dr. Nam said infertility is a sensitive topic for couples and families to talk about and there is less conversation about male infertility than female infertility. “I think the only way that we can be able to make headway, both in terms of protocol and policy outcomes, is to really start to raise awareness,” said Dr. Nam, who is doing a fellowship in clinical andrology at Northwestern University, in Chicago.

Dr. Nam said the collaborative environment of MOBYUS has enabled her to learn about different practice patterns across different institutions. “For someone like me just starting off my professional career in male infertility, an opportunity like this is incredibly exciting and makes me very hopeful about the kinds of collaboration and scientific discovery that we’re able to do together as a group,” she said.

Robert E. Brannigan, MD, vice chair of clinical urology at Northwestern University Feinberg School of Medicine, Chicago, said the consortium is drawing on the strength of many individual centers and allowing them to study critical issues in the field. The group’s outstanding clinicians and scientists “are looking to move the field forward, and I applaud them and I’m eager to watch things unfold,” said Dr. Brannigan, who is not a member of the group.

Dr. Brannigan noted that for a large percentage of patients, clinicians cannot identify the root cause of their impaired reproductive potential. Some people may have a recognizable decline in semen parameters over time without clear lifestyle issues or clear hormonal imbalances or anatomical problems. 

“And the question is, what’s causing that? Is there some as yet unrecognized environmental exposure? Is there some underlying genetic issue that’s predisposing to decline in semen parameters over time? We see this, and we don’t have answers,” Dr. Brannigan said. 

“This is where I think the potential power of a large group like MOBYUS comes into play,” he added. “When you’ve got large datasets and very granular information about your patients, sometimes that can provide the opportunity for insights that can then answer the question, ‘What is the root cause of my patient’s challenges?’ ”

Dr. Brannigan was part of a previous group, the Andrology Research Consortium, which collected data on patient history and treatment through a standardized questionnaire. The consortium was founded in 2013 by the Society for the Study of Male Reproduction, a specialty section of the American Urological Association, to obtain data on the demographics, clinical characteristics, and fertility histories and therapies of men referred for a male infertility investigation at clinics across North America. 

Clinicians analyzed data from the questionnaires, which a team in Toronto collected and stored, in a series of studies, including a comparison of fertility characteristics between men in the United States and Canada. Dr. Brannigan said MOBYUS is poised to produce a large dataset that can address retrospective questions and potentially prospectively collect data to answer prospective questions.
 

Clinical Implications

Dr. Lundy said between 100 and 200 practicing reproductive urologists across the country regularly communicate with each other. He first raised the idea of creating a consortium with friends and colleagues and then discussed it at scientific meetings. The network steadily gained traction and is continuing to add institutions. “There’s a great deal of excitement in our community about this,” Dr. Lundy said.

MOBYUS, which is IRB approved, has a database with data from more than 4000 patients. The consortium has not received any industry funding but plans to pursue grant applications in the future. 

The MOBYUS website includes a list of its member institutions and leading investigators and its three proof-of-principle manuscripts published to date. The team identifies new research projects at monthly virtual meetings.

Dr. Lundy said MOBYUS’ main goal is to identify a treatment that will change the avenue available for a couple to get pregnant. For example, he said, if a man has zero sperm in his semen, he often requires surgery to find and remove sperm from the testicle. If medications can produce low sperm counts, sperm found in the ejaculate can be frozen and surgery can be avoided. 

Dr. Lundy said MOBYUS’ two publications on medical therapies have changed clinical practice, as he and many others have begun to provide the treatments on more carefully selected patients with good outcomes. 

Dr. Nam said patients want to know what they can expect from therapies and these research findings will have “a lot of clinical implications” in counseling them. 

The MOBYUS team will be describing the consortium and its goals in an abstract presentation at the American Society for Reproductive Medicine Scientific Congress & Expo, to be held October 19-23 in Denver, Colorado, and in an oral presentation at the Sexual Medicine Society of North America’s annual fall scientific meeting, to be held October 17-20 in Scottsdale, Arizona.

The sources in this story reported no relevant financial conflicts of interest.
 

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

TOPLINE:

Women with hyperandrogenic polycystic ovary syndrome (PCOS) have lower pregnancy (29.9%) and live birth rates (20.1%) than those with nonhyperandrogenic PCOS (40.2% and 33.1%, respectively).

METHODOLOGY:

• Researchers conducted a retrospective cohort study of 1376 participants from the PPCOS I and II trials, all meeting National Institutes of Health diagnostic criteria for PCOS.
• Participants were categorized into hyperandrogenic (A and B) and nonhyperandrogenic (D) PCOS phenotypes on the basis of medical interviews, demographics, physical examinations, and laboratory data.
• Outcomes of interest included clinical pregnancy, pregnancy loss, live birth, obstetric complications, and neonatal outcomes.
• Fasting blood samples were analyzed for hormonal assays, and Homeostatic Model Assessment for Insulin Resistance scores were calculated using fasting glucose and insulin values.

TAKEAWAY:

• Participants with hyperandrogenic PCOS had higher body mass index (35.5 ± 8.9 vs 31.9 ± 9.3; P < .001) and fasting insulin levels (21.6 ± 27.7 vs 14.7 ± 15.0 μIU/mL; P < .001) than those with nonhyperandrogenic PCOS.
• Participants with hyperandrogenic PCOS had lower odds of achieving pregnancy (odds ratio [OR], 0.63; 95% CI, 0.44-0.92) and live birth (OR, 0.51; 95% CI, 0.34-0.76) than those with nonhyperandrogenic PCOS.
• No significant differences were found in pregnancy loss rates (23.9% vs 32.3%, P = .06) or neonatal outcomes between the two groups.
• The study lacked the power to detect differences in neonatal outcomes because of the low prevalence of these outcomes.

IN PRACTICE:

“Patients with nonhyperandrogenic PCOS may represent a different disease process with unique morbidities and outcomes and could be counseled differently than hyperandrogenic PCOS,” wrote the authors of the study.

SOURCE:

The study was led by Jessica L. Chan, MD, MSCE, Cedars-Sinai Medical Center in Los Angeles, California. It was published online in Obstetrics & Gynecology.

LIMITATIONS:

The primary limitation of this study was that it is a secondary analysis of previously collected randomized controlled trial data, which may affect the availability of certain information. Additionally, the lower number of participants in the nonhyperandrogenic PCOS group could affect the power of the results. The study was underpowered to detect statistically significant differences in neonatal outcomes because of their low prevalence.

DISCLOSURES:

The study was supported by a grant from the ASRM/NICHD/Duke Clinical Research/Reproductive Scientist Training Program. One coauthor disclosed receiving payments from Celmatix, Ferring Pharmaceuticals, Exeltis, Organon, and Monsanto; another disclosed receiving payments from Ferring Pharmaceuticals. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Women with hyperandrogenic polycystic ovary syndrome (PCOS) have lower pregnancy (29.9%) and live birth rates (20.1%) than those with nonhyperandrogenic PCOS (40.2% and 33.1%, respectively).

METHODOLOGY:

• Researchers conducted a retrospective cohort study of 1376 participants from the PPCOS I and II trials, all meeting National Institutes of Health diagnostic criteria for PCOS.
• Participants were categorized into hyperandrogenic (A and B) and nonhyperandrogenic (D) PCOS phenotypes on the basis of medical interviews, demographics, physical examinations, and laboratory data.
• Outcomes of interest included clinical pregnancy, pregnancy loss, live birth, obstetric complications, and neonatal outcomes.
• Fasting blood samples were analyzed for hormonal assays, and Homeostatic Model Assessment for Insulin Resistance scores were calculated using fasting glucose and insulin values.

TAKEAWAY:

• Participants with hyperandrogenic PCOS had higher body mass index (35.5 ± 8.9 vs 31.9 ± 9.3; P < .001) and fasting insulin levels (21.6 ± 27.7 vs 14.7 ± 15.0 μIU/mL; P < .001) than those with nonhyperandrogenic PCOS.
• Participants with hyperandrogenic PCOS had lower odds of achieving pregnancy (odds ratio [OR], 0.63; 95% CI, 0.44-0.92) and live birth (OR, 0.51; 95% CI, 0.34-0.76) than those with nonhyperandrogenic PCOS.
• No significant differences were found in pregnancy loss rates (23.9% vs 32.3%, P = .06) or neonatal outcomes between the two groups.
• The study lacked the power to detect differences in neonatal outcomes because of the low prevalence of these outcomes.

IN PRACTICE:

“Patients with nonhyperandrogenic PCOS may represent a different disease process with unique morbidities and outcomes and could be counseled differently than hyperandrogenic PCOS,” wrote the authors of the study.

SOURCE:

The study was led by Jessica L. Chan, MD, MSCE, Cedars-Sinai Medical Center in Los Angeles, California. It was published online in Obstetrics & Gynecology.

LIMITATIONS:

The primary limitation of this study was that it is a secondary analysis of previously collected randomized controlled trial data, which may affect the availability of certain information. Additionally, the lower number of participants in the nonhyperandrogenic PCOS group could affect the power of the results. The study was underpowered to detect statistically significant differences in neonatal outcomes because of their low prevalence.

DISCLOSURES:

The study was supported by a grant from the ASRM/NICHD/Duke Clinical Research/Reproductive Scientist Training Program. One coauthor disclosed receiving payments from Celmatix, Ferring Pharmaceuticals, Exeltis, Organon, and Monsanto; another disclosed receiving payments from Ferring Pharmaceuticals. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Women with hyperandrogenic polycystic ovary syndrome (PCOS) have lower pregnancy (29.9%) and live birth rates (20.1%) than those with nonhyperandrogenic PCOS (40.2% and 33.1%, respectively).

METHODOLOGY:

• Researchers conducted a retrospective cohort study of 1376 participants from the PPCOS I and II trials, all meeting National Institutes of Health diagnostic criteria for PCOS.
• Participants were categorized into hyperandrogenic (A and B) and nonhyperandrogenic (D) PCOS phenotypes on the basis of medical interviews, demographics, physical examinations, and laboratory data.
• Outcomes of interest included clinical pregnancy, pregnancy loss, live birth, obstetric complications, and neonatal outcomes.
• Fasting blood samples were analyzed for hormonal assays, and Homeostatic Model Assessment for Insulin Resistance scores were calculated using fasting glucose and insulin values.

TAKEAWAY:

• Participants with hyperandrogenic PCOS had higher body mass index (35.5 ± 8.9 vs 31.9 ± 9.3; P < .001) and fasting insulin levels (21.6 ± 27.7 vs 14.7 ± 15.0 μIU/mL; P < .001) than those with nonhyperandrogenic PCOS.
• Participants with hyperandrogenic PCOS had lower odds of achieving pregnancy (odds ratio [OR], 0.63; 95% CI, 0.44-0.92) and live birth (OR, 0.51; 95% CI, 0.34-0.76) than those with nonhyperandrogenic PCOS.
• No significant differences were found in pregnancy loss rates (23.9% vs 32.3%, P = .06) or neonatal outcomes between the two groups.
• The study lacked the power to detect differences in neonatal outcomes because of the low prevalence of these outcomes.

IN PRACTICE:

“Patients with nonhyperandrogenic PCOS may represent a different disease process with unique morbidities and outcomes and could be counseled differently than hyperandrogenic PCOS,” wrote the authors of the study.

SOURCE:

The study was led by Jessica L. Chan, MD, MSCE, Cedars-Sinai Medical Center in Los Angeles, California. It was published online in Obstetrics & Gynecology.

LIMITATIONS:

The primary limitation of this study was that it is a secondary analysis of previously collected randomized controlled trial data, which may affect the availability of certain information. Additionally, the lower number of participants in the nonhyperandrogenic PCOS group could affect the power of the results. The study was underpowered to detect statistically significant differences in neonatal outcomes because of their low prevalence.

DISCLOSURES:

The study was supported by a grant from the ASRM/NICHD/Duke Clinical Research/Reproductive Scientist Training Program. One coauthor disclosed receiving payments from Celmatix, Ferring Pharmaceuticals, Exeltis, Organon, and Monsanto; another disclosed receiving payments from Ferring Pharmaceuticals. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.