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Dolutegravir in pregnant patients with HIV showed more viral suppression at delivery vs. other treatments
“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.
In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.
The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.
The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.
The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.
“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.
Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.
A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.
“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.
“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.
The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.
However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
Findings fill a key research gap
The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.
Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.
The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.
The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”
Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.
The researchers and Dr. Badell had no financial conflicts to disclose.
“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.
In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.
The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.
The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.
The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.
“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.
Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.
A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.
“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.
“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.
The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.
However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
Findings fill a key research gap
The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.
Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.
The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.
The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”
Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.
The researchers and Dr. Badell had no financial conflicts to disclose.
“Dolutegravir is increasingly used in pregnancy in the United States,” Kunjal Patel, DSc, one of the investigators, said in an interview. “While its effectiveness and safety in pregnancy have been compared to efavirenz in previous studies, including three randomized trials, efavirenz isn’t really used in the United States and Europe for treatment of HIV; it is mainly used in Africa,” she said. Therefore, it was important to compare dolutegravir use in pregnancy to the other antiretroviral regimens that are listed as being preferred for use in pregnancy in the U.S., including atazanavir/ritonavir, darunavir/ritonavir, and raltegravir, and others often used in the U.S. and Europe, she said.
In the study published in the New England Journal of Medicine, Dr. Patel, of Harvard T.H. Chan School of Public Health, Boston, and colleagues analyzed data from kids enrolled in the Surveillance and Monitoring for ART Toxicities Dynamic (SMARTT) cohort. This group is part of an ongoing research project focused on evaluating ART toxicities during pregnancy in children who were exposed to HIV perinatally but not infected. It included pregnancies from 2007 until January 2020 that involved use of the ARTs listed.
The study population of 1,257 pregnancies with observed birth outcomes included 120 individuals with an initial ART of dolutegravir (DTG), 464 started on atazanavir–ritonavir (ATV/r), 185 on darunavir–ritonavir (DRV/r), 243 on oral rilpivirine (RPV), 86 on raltegravir (RAL), and 159 on elvitegravir–cobicistat (EVG/c). In approximately half of the pregnancies (51%), ART was started before conception, and the initial ART was changed in 27%.
The primary outcomes were viral suppression at delivery, and adverse birth outcomes, including preterm and very preterm birth, low and very low birth weight, and neonatal death within 14 days.
The median age of the patients at conception was 29 years, and 66% were non-Hispanic Black, representative of persons with HIV of childbearing age in the United States, the researchers noted. Overall, 96.7% of the patients who received dolutegravir showed viral suppression at delivery, compared to 90.1% for darunavir–ritonavir, 89.8% for elvitegravir–cobicistat, 89.2% for raltegravir, and 84.0% for atazanavir–ritonavir.
“We expected that dolutegravir to be similar with regards to viral suppression at delivery compared to raltegravir so were surprised that we observed less viral suppression with raltegravir compared to dolutegravir,” Dr. Patel said in an interview. “Our results may be due to the higher pill burden and lower barrier to resistance with RAL compared to dolutegravir, but we did not assess adherence or resistance in our study,” she noted.
Across ART regimens, the observed risks of preterm birth ranged from 13.6% to 17.6%, risks of low birth weight ranged from 11.9% to 16.7%, and risks of being small for gestational age ranged from 9.1% to 12.5%. For the composite of any adverse birth outcome and any severe adverse birth outcome, the observed risks ranged from 22.6% to 27.9% and 0% to 4.2%, respectively.
A total of 20 very preterm births, including 15 infants with very low birth weight, occurred across patients receiving all ART regimens, and no neonatal deaths occurred. The researchers found no apparent patterns of differences in the observed risk of adverse birth outcomes across all groups related to the timing of ART initiation in pregnancy, but the risks were greater among those who began the drugs during pregnancy compared to those who began before conception.
“Our results confirm the recommendation of DTG as “preferred” in U.S. perinatal guidelines, and provide evidence suggesting ATV/r and RAL provides lower HIV viral suppression at delivery compared to DTG, and support DRV/r as a reasonable alternative when DTG use is not feasible,” Dr. Patel said in an interview.
“With regards to next steps, we are interested in comparing the effectiveness and safety of dolutegravir-based regimens that include tenofovir alafenamide (TAF) vs. tenofovir disoproxil fumarate (TDF) in our U.S. setting,” she said.
The study findings were limited by several factors including the lack of data on predictors of preterm birth and low birth weight, such as previous preterm birth and prepregnancy body mass index, the researchers noted.
However, the results indicate that other common ARTs provide less HIV viral suppression at delivery than dolutegravir, with similar adverse birth outcomes; the results also support darunavir–ritonavir as a reasonable alternative when dolutegravir use is not feasible, as it showed the next highest level of viral suppression after dolutegravir, the researchers concluded.
Findings fill a key research gap
The current study is important given the limited data on effectiveness and outcomes in pregnancy with the use of contemporary HIV regimens in the United States, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.
“Pregnancy is still among exclusion criteria for most drug studies,” said Dr. Badell, who was not involved in the current study. “Dolutegravir-based ART is first line in the U.S. today because of its effectiveness, lower side effects, and higher barrier to resistance; therefore understanding the benefits and birth outcomes in pregnancy is critical,” she explained.
Dr. Badell said she was not surprised by the study findings. “However it is very reassuring to see in a large observational study comparing the dolutegravir regimens to other contemporary regimens in pregnancy, such a high level of viral suppression and no increased risk of adverse perinatal outcomes,” she said.
The study findings will impact clinical practice by reaffirming patient counseling regarding the use of dolutegravir in pregnancy, said Dr. Badell. “The use of ART in pregnancy is complex given the number of drug choices, whether the patient was on ART prior to pregnancy or initiated during pregnancy, and the various factors other than ART that affect perinatal outcomes, such as preterm birth and congenital anomalies, she explained.
The finding that the risk of adverse outcomes was higher for those who initiated ART during pregnancy vs. those who were already on ARTs when they became pregnant contradicts some previous research, said Dr. Badell. But this is “reassuring, as we highly recommend ART with viral suppression prior to pregnancy or to start as early as possible in pregnancy.”
Adverse birth outcomes can be affected by many variables such as age, substance abuse, prior adverse birth outcome and other factors, and larger studies that control for these variables will allow better evaluation of the effect of the ART drugs, Dr. Badell added.
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with the Office of the Director, National Institutes of Health; National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; National Institute of Mental Health; National Institute on Drug Abuse; National Cancer Institute; National Institute on Alcohol Abuse and Alcoholism; and National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health and the Tulane University School of Medicine.
The researchers and Dr. Badell had no financial conflicts to disclose.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Prenatal test can cut time, cost of finding chromosomal abnormalities
A prenatal test can accurately detect an incorrect number of chromosomes more quickly and at about one-tenth the cost of current clinical genetic tests, new data suggest.
Aneuploid pregnancies are a major cause of pregnancy loss, developmental delays, and fetal structural abnormalities, so there is high interest in screening options.
Study leader Zev Williams, MD, PhD, professor of women’s health and chief of the division of reproductive endocrinology and infertility at Columbia University, New York, and colleagues, describe a test they have developed and validated in a letter to the editor published in the New England Journal of Medicine.
The new test is called STORK (Short-Read Transpore Rapid Karyotyping) and can be used in doctors’ offices. The test uses a palm-sized, nanopore-based DNA sequencer to examine tissue from miscarriages or from a biopsy of the placenta or in vitro fertilization (IVF) embryo to determine if it has a normal count of chromosomes.
Results can be delivered in 2 hours, the researchers said. Sequencing times and costs range from 10 minutes and $200 for a single sample to 2 hours and less than $50 per sample when 10 samples are tested simultaneously.
The currently available tests and results cost thousands of dollars and results take days to weeks.
”What’s so exciting is that STORK can be used to rapidly assess chromosomal health across all reproductive tissue types,” Dr. Williams said in a press release.
“For those patients who are trying to get pregnant through IVF, the test gives the ability to conceive sooner,“ he said.
IVF embryos are typically biopsied for chromosomal testing on day 5 or 6 and are frozen for weeks until they can be implanted in a woman’s uterus. Freezing may not be necessary with rapid tests, as embryos found normal could be transferred immediately.
Dr. Williams added: “For those who are already pregnant, it gives more time to make important family-planning decisions. For those who have had a miscarriage, it can show why the loss happened so that steps can be taken to prevent future pregnancy losses.”
Existing tests include two main approaches. One is a rapid and target approach, which tests only a limited number of chromosomes and the other is a whole-genome approach, which takes days or weeks to get results and requires sending samples to specialized laboratories.
”The affordability of this [STORK] test also means that individuals who have suffered a miscarriage do not have to wait until a second or third loss before insurance will cover expensive lab tests, leaving many women in the dark and often blaming themselves,” Dr. Williams said.
The researchers used STORK to perform blinded testing using 218 specimens from miscarriage tissue, placenta samples, amniotic fluid, and biopsy specimens from embryos undergoing preimplantation genetic tests for aneuploidy (PGT-A).
They compared the results from STORK with those obtained using standard clinical testing,
For miscarriage tissue samples and placenta and amniotic-fluid samples, STORK results calculated the number of chromosomes “with 100% accuracy (95% confidence intervals, 94.3%-100%, 93.2%-100%, and 92.9%-100%, respectively),” the authors wrote.
For PGT-A samples, STORK results were 98.1% matched (95% CI, 89.7%-100%) with the clinical diagnosis of the embryos, they report.
According to the Columbia University press release, the researchers are waiting for authorization from the New York State Department of Health before the test can be offered to Columbia patients.
Sarah Wernimont, MD, PhD, a maternal-fetal physician with the University of Minnesota, Minneapolis, who was not part of the study, said in an interview she found the results “exciting.”
“For patients I care for who have abnormal screening results, there’s the potential to receive diagnostic testing in a much faster way that can help parents make serious decisions about pregnancy care in a more timely fashion,” she said.
She said the quickest test they use in her practice for detection of aneuploidy, the fluorescence in situ hybridization test, takes 3 days to get results and tests only a few chromosomes.
The STORK test, she noted, has the potential to test all the chromosomes.
She said the sample size is small and she would like to see more external validation in a larger population, but “their sensitivity and specificity compared to the current standard seems to be excellent.”
The study was supported by the National Institutes of Health, the Biomedical Engineering Technology Accelerator at Columbia University and the Wendy and John Havens Innovation fund. Dr. Williams and one study coauthor are inventors on patents filed related to this work. Dr. Wernimont declared no relevant financial relationships.
A prenatal test can accurately detect an incorrect number of chromosomes more quickly and at about one-tenth the cost of current clinical genetic tests, new data suggest.
Aneuploid pregnancies are a major cause of pregnancy loss, developmental delays, and fetal structural abnormalities, so there is high interest in screening options.
Study leader Zev Williams, MD, PhD, professor of women’s health and chief of the division of reproductive endocrinology and infertility at Columbia University, New York, and colleagues, describe a test they have developed and validated in a letter to the editor published in the New England Journal of Medicine.
The new test is called STORK (Short-Read Transpore Rapid Karyotyping) and can be used in doctors’ offices. The test uses a palm-sized, nanopore-based DNA sequencer to examine tissue from miscarriages or from a biopsy of the placenta or in vitro fertilization (IVF) embryo to determine if it has a normal count of chromosomes.
Results can be delivered in 2 hours, the researchers said. Sequencing times and costs range from 10 minutes and $200 for a single sample to 2 hours and less than $50 per sample when 10 samples are tested simultaneously.
The currently available tests and results cost thousands of dollars and results take days to weeks.
”What’s so exciting is that STORK can be used to rapidly assess chromosomal health across all reproductive tissue types,” Dr. Williams said in a press release.
“For those patients who are trying to get pregnant through IVF, the test gives the ability to conceive sooner,“ he said.
IVF embryos are typically biopsied for chromosomal testing on day 5 or 6 and are frozen for weeks until they can be implanted in a woman’s uterus. Freezing may not be necessary with rapid tests, as embryos found normal could be transferred immediately.
Dr. Williams added: “For those who are already pregnant, it gives more time to make important family-planning decisions. For those who have had a miscarriage, it can show why the loss happened so that steps can be taken to prevent future pregnancy losses.”
Existing tests include two main approaches. One is a rapid and target approach, which tests only a limited number of chromosomes and the other is a whole-genome approach, which takes days or weeks to get results and requires sending samples to specialized laboratories.
”The affordability of this [STORK] test also means that individuals who have suffered a miscarriage do not have to wait until a second or third loss before insurance will cover expensive lab tests, leaving many women in the dark and often blaming themselves,” Dr. Williams said.
The researchers used STORK to perform blinded testing using 218 specimens from miscarriage tissue, placenta samples, amniotic fluid, and biopsy specimens from embryos undergoing preimplantation genetic tests for aneuploidy (PGT-A).
They compared the results from STORK with those obtained using standard clinical testing,
For miscarriage tissue samples and placenta and amniotic-fluid samples, STORK results calculated the number of chromosomes “with 100% accuracy (95% confidence intervals, 94.3%-100%, 93.2%-100%, and 92.9%-100%, respectively),” the authors wrote.
For PGT-A samples, STORK results were 98.1% matched (95% CI, 89.7%-100%) with the clinical diagnosis of the embryos, they report.
According to the Columbia University press release, the researchers are waiting for authorization from the New York State Department of Health before the test can be offered to Columbia patients.
Sarah Wernimont, MD, PhD, a maternal-fetal physician with the University of Minnesota, Minneapolis, who was not part of the study, said in an interview she found the results “exciting.”
“For patients I care for who have abnormal screening results, there’s the potential to receive diagnostic testing in a much faster way that can help parents make serious decisions about pregnancy care in a more timely fashion,” she said.
She said the quickest test they use in her practice for detection of aneuploidy, the fluorescence in situ hybridization test, takes 3 days to get results and tests only a few chromosomes.
The STORK test, she noted, has the potential to test all the chromosomes.
She said the sample size is small and she would like to see more external validation in a larger population, but “their sensitivity and specificity compared to the current standard seems to be excellent.”
The study was supported by the National Institutes of Health, the Biomedical Engineering Technology Accelerator at Columbia University and the Wendy and John Havens Innovation fund. Dr. Williams and one study coauthor are inventors on patents filed related to this work. Dr. Wernimont declared no relevant financial relationships.
A prenatal test can accurately detect an incorrect number of chromosomes more quickly and at about one-tenth the cost of current clinical genetic tests, new data suggest.
Aneuploid pregnancies are a major cause of pregnancy loss, developmental delays, and fetal structural abnormalities, so there is high interest in screening options.
Study leader Zev Williams, MD, PhD, professor of women’s health and chief of the division of reproductive endocrinology and infertility at Columbia University, New York, and colleagues, describe a test they have developed and validated in a letter to the editor published in the New England Journal of Medicine.
The new test is called STORK (Short-Read Transpore Rapid Karyotyping) and can be used in doctors’ offices. The test uses a palm-sized, nanopore-based DNA sequencer to examine tissue from miscarriages or from a biopsy of the placenta or in vitro fertilization (IVF) embryo to determine if it has a normal count of chromosomes.
Results can be delivered in 2 hours, the researchers said. Sequencing times and costs range from 10 minutes and $200 for a single sample to 2 hours and less than $50 per sample when 10 samples are tested simultaneously.
The currently available tests and results cost thousands of dollars and results take days to weeks.
”What’s so exciting is that STORK can be used to rapidly assess chromosomal health across all reproductive tissue types,” Dr. Williams said in a press release.
“For those patients who are trying to get pregnant through IVF, the test gives the ability to conceive sooner,“ he said.
IVF embryos are typically biopsied for chromosomal testing on day 5 or 6 and are frozen for weeks until they can be implanted in a woman’s uterus. Freezing may not be necessary with rapid tests, as embryos found normal could be transferred immediately.
Dr. Williams added: “For those who are already pregnant, it gives more time to make important family-planning decisions. For those who have had a miscarriage, it can show why the loss happened so that steps can be taken to prevent future pregnancy losses.”
Existing tests include two main approaches. One is a rapid and target approach, which tests only a limited number of chromosomes and the other is a whole-genome approach, which takes days or weeks to get results and requires sending samples to specialized laboratories.
”The affordability of this [STORK] test also means that individuals who have suffered a miscarriage do not have to wait until a second or third loss before insurance will cover expensive lab tests, leaving many women in the dark and often blaming themselves,” Dr. Williams said.
The researchers used STORK to perform blinded testing using 218 specimens from miscarriage tissue, placenta samples, amniotic fluid, and biopsy specimens from embryos undergoing preimplantation genetic tests for aneuploidy (PGT-A).
They compared the results from STORK with those obtained using standard clinical testing,
For miscarriage tissue samples and placenta and amniotic-fluid samples, STORK results calculated the number of chromosomes “with 100% accuracy (95% confidence intervals, 94.3%-100%, 93.2%-100%, and 92.9%-100%, respectively),” the authors wrote.
For PGT-A samples, STORK results were 98.1% matched (95% CI, 89.7%-100%) with the clinical diagnosis of the embryos, they report.
According to the Columbia University press release, the researchers are waiting for authorization from the New York State Department of Health before the test can be offered to Columbia patients.
Sarah Wernimont, MD, PhD, a maternal-fetal physician with the University of Minnesota, Minneapolis, who was not part of the study, said in an interview she found the results “exciting.”
“For patients I care for who have abnormal screening results, there’s the potential to receive diagnostic testing in a much faster way that can help parents make serious decisions about pregnancy care in a more timely fashion,” she said.
She said the quickest test they use in her practice for detection of aneuploidy, the fluorescence in situ hybridization test, takes 3 days to get results and tests only a few chromosomes.
The STORK test, she noted, has the potential to test all the chromosomes.
She said the sample size is small and she would like to see more external validation in a larger population, but “their sensitivity and specificity compared to the current standard seems to be excellent.”
The study was supported by the National Institutes of Health, the Biomedical Engineering Technology Accelerator at Columbia University and the Wendy and John Havens Innovation fund. Dr. Williams and one study coauthor are inventors on patents filed related to this work. Dr. Wernimont declared no relevant financial relationships.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Fertility doctors, IVF families, post Roe: ‘We’re anxious’
Married for nearly 5 years, Jessica King, 34, and her wife, Sarah, agreed on some things right from the start. “We always knew kids were in the equation,” Jessica says.
Now, Jessica is nearly 20 weeks pregnant, thanks to in vitro fertilization, or IVF. They did “reciprocal” IVF, with Sarah’s egg mixed with donor sperm and the embryo transferred into Jessica. “We’re excited – and terrified,” Jessica says.
But that terror goes beyond the typical concerns of excess weight gain and long labors. They live in Missouri, one of 13 states with so-called trigger laws that went into effect after the Supreme Court overturned Roe v. Wade and the constitutional right to abortion, giving states the power to regulate it. States with trigger laws either banned abortion immediately or within a specified time frame after the ruling. In all, 26 states are expected to have abortion restrictions.
Missouri now allows abortion only for medical emergencies. If her upcoming ultrasound shows serious issues, Jessica says they could easily travel to another state and pay for an abortion. She realizes not everyone can.
However, the concern about trigger laws goes well beyond abortion. Many experts worry about the “spill-over” effects the abortion laws – both the existing ones and future proposals – may have on fertility care and treatments.
‘Personhood’ laws drive the concern
“The current trigger laws on the books are not impacting people’s access to IVF,” says Barbara Collura, president and CEO of RESOLVE, an advocacy group for those with fertility issues. “What we are concerned about is they will come back and make them stronger.”
The chief concern for reproductive rights advocates is so-called “personhood” legislation. According to the Guttmacher Institute, at least six bills about personhood have been introduced in five states, including Iowa, Oklahoma, South Carolina, Vermont, and West Virginia. One of the two Oklahoma bills has gone the farthest, passed by one chamber.
Since the Guttmacher report, Ohio introduced its own personhood legislation July 11, recognizing the personhood of an unborn person from conception.
Personhood legislation defines a fertilized egg or embryo as a legal human entity, says Sean Tipton, chief policy and advocacy officer for the Washington-based American Society of Reproductive Medicine, a nonprofit advocacy group.
“If the legal status of fertilized eggs or early embryos is codified, in vitro fertilization procedures may become legally risky for patients, physicians and staff,” Mr. Tipton wrote in late June in Contemporary OB/GYN Journal. The American Society for Reproductive Medicine has posted a report on state abortion trigger laws and their potential implications for reproductive medicine. Of the 13 with trigger laws in effect, the report found concern about the potential effect on IVF only with Utah’s.
‘Safe’ states?
Even in states without trigger laws or personhood bills, IVF patients say they are anxious about how the Supreme Court ruling may ultimately affect care. Thanks to IVF, Shelly Battista and her husband Robert are expecting twins in December, little sisters to their daughter Emilia, who is 2½.
They live in Illinois, where abortion is legal. “Even though we are safe now, I think the overturning of Roe has made it clear to all of us that none of our freedoms are safe, especially reproductive rights,” Ms. Shelly says.
About one in eight U.S. couples are infertile, according to RESOLVE, In 2019, 2% of all babies born in the United States, or about 78,000 infants, were conceived with the use of assisted reproductive technologies, according to the Centers for Disease Control and Prevention. The most common assisted reproductive technology is IVF, in which the sperm fertilizes the egg outside the body and an embryo is then transferred. The standard of practice is to transfer a single embryo, freezing others for future use.
Trigger state doctors weigh in
Some fertility doctors in those “trigger” states are keeping a close eye on proposed legislation and talking to legislators for interpretation of current and proposed laws.
Eli Reshef, MD, a reproductive endocrinologist and fertility specialist at Bennett Fertility Institute in Oklahoma City, notes that his state has “the strictest abortion law in the land.” The law prohibits all abortions with few exceptions, such as the removal of an ectopic pregnancy (when a fertilized egg implants outside the uterus, such as in the fallopian tubes).
While IVF will not be affected for now, he worries that the Oklahoma law allows a private citizen to sue a health care provider that they feel is performing abortion. The Oklahoma law leaves interpretation of abortion up to the general public, who may be unfamiliar with the language of the law, House Bill 4327.
Dean Moutos, MD, a reproductive endocrinologist and medical director of Arkansas Fertility and Gynecology in Little Rock, says his state’s current trigger law should not affect IVF. “When you read the bill, it says abortion means to terminate the pregnancy of a woman.” Still, he says, “we are concerned about what might happen in the future” and the possibility that some legislators may interpret that differently.
A minority approach
John David Gordon, MD, a reproductive endocrinologist and medical director of Southeastern Fertility Center for Fertility and Reproductive Surgery in Knoxville, Tenn., is also in a trigger state. However, it’s not likely any personhood laws would affect his practice.
That’s because his center, which he acknowledges is clearly in the minority, only performs natural-cycle IVF, which usually results in a single egg, or “mini-stim IVF,” which usually results in three to eight eggs in order to limit the number that may be potentially fertilized. Often, he says, patients choose to freeze unfertilized eggs (alone) to avoid creating an excessive number of embryos. He has a “no discard” program, with any viable embryos frozen or transferred. Abandoned embryos are donated to others.
“This may work for young women,” says Marcelle Cedars, MD, director of reproductive endocrinology at the University of California, San Francisco, and president of the American Society of Reproductive Medicine. However, she says, it will be very inefficient for older patients, since they have a higher percentage of abnormal eggs.
Overall, that approach will also drive up costs, especially for older women, Dr. Cedars says. An average cycle of IVF costs $12,400, and most Americans’ insurance plans don’t cover IVF, according to Mr. Tipton.
Top concerns for IVF
“Personhood” legislation has the potential to upend many common IVF practices, experts say.
Of greatest concern to fertility practices are potential restrictions on the freezing or discarding of embryos, Dr. Cedars says. “This could have a critical impact on practicing the safest, most evidence-based medicine,” she says.
Most children born in the United States as a result of IVF procedures are born from frozen embryos, according to the Society for Assisted Reproductive Technology, an organization for reproductive specialists.
“The practice of IVF really requires that we generate more embryos than will be used in a given [IVF] cycle,” agrees Kara Goldman, MD, associate professor of obstetrics and gynecology and medical director of the fertility preservation program at Northwestern University, Chicago. She performed the embryo transfer for the Battistas.
In nature, she says, it’s known that only a small number of eggs will be competent to generate a baby. “We see the same thing in IVF.” In a single cycle, 20 eggs may be retrieved, but many fewer typically reach successful fertilization and are able to be implanted.
When patients have completed their family, unused embryos are donated to research, donated for adoption, or destroyed. If embryo destruction is outlawed, Dr. Goldman says, it will have serious ramifications for the practice of IVF.
And if personhood legislation prohibits destroying any embryos, others wonder: Would a lab technician who accidentally dropped and destroyed an embryo be subject to charges? If laws prohibit destruction of embryos, others wonder if will families be forced to pay the embryo storage fees, generally $500-$1,000 a year, in perpetuity.
If an embryo is declared a person, it could also affect a practice called preimplantation genetic testing, or PGT. In PGT, cells are retrieved from an embryo and checked for genetic disorders such as sickle cell anemia and cystic fibrosis, with some parents choosing to discard embryos that are found to be affected.
Some potential parents choose this testing because they know they are carriers for genetic diseases that are serious and even incompatible with life, says Art Caplan, PhD, head of the division of medical ethics at New York University. They may choose to discard embryos that show evidence of the diseases.
Also under fire could be “selective reduction,” reducing multiple fetuses to a single or twin, to reduce risks to babies and mother.
Dr. Caplan predicts if states have many restrictions, some providers will adopt the attitude that “if no one reports, it did not happen.” And those prospective parents with the means, he says, will go to court and fight restrictions. “When they do it, they are saying, ‘You say you are pro-life; I’m trying to have a child. What are you doing getting in my way?’”
IVF families: Tough decisions, emotional times
The Battistas, of Illinois, have had an especially rough road. Shelly was diagnosed with a fast-growing breast cancer in 2020, when Emilia was just an infant. Warned that the chemotherapy she needed would suppress her ovaries, Shelly underwent egg retrieval before starting the cancer treatment.
She opted to have a double mastectomy and her ovaries removed after learning she carried the BRCA1 genetic mutation, boosting the risk of both breast and ovarian cancer.
Once she was cancer-free, she was cleared to start IVF. The first two embryo transfers failed. The third transfer, of a single embryo, was successful. But it split, a rare occurrence, producing two embryos. “It was a big shock, but in the best way,” she says about learning they were having twins. “Now we are over the moon.”
Five frozen embryos remain. At the start, the Battistas decided to discard unused embryos. She and Robert are discussing what to do next. If they decide they are done building their family after the twins’ birth, she wonders, “do we need to discard our [other] embryos before that becomes something that isn’t eligible [possible] for us any longer?” She doesn’t want to be rushed into that decision, however, especially with her medical history.
Jessica King and Sarah have 20 more embryos.
The couple had decided to donate unused embryos for research, when the time comes, and for different reasons. Her wife’s decision is based on her belief in science, while Jessica cites her faith. “As a Jew, it is part of our faith, that we should be doing everything we can to advance humanity,” she says.
In the midst of all the uncertainty, Jessica says, only half-jokingly, that she is tempted to claim the frozen embryos as dependents. “If you are truly going to claim these are precious human lives, you should be giving me all the benefits from having children,” she says.
Shelly knows that having one daughter, with two more on the way, affects her thinking about the court’s ruling. “My overall wish would be that Roe v. Wade is reinstated, and my daughters have the same rights and options that I have … or I did have until my current 36 years of life.”
A version of this article first appeared on WebMD.com.
Married for nearly 5 years, Jessica King, 34, and her wife, Sarah, agreed on some things right from the start. “We always knew kids were in the equation,” Jessica says.
Now, Jessica is nearly 20 weeks pregnant, thanks to in vitro fertilization, or IVF. They did “reciprocal” IVF, with Sarah’s egg mixed with donor sperm and the embryo transferred into Jessica. “We’re excited – and terrified,” Jessica says.
But that terror goes beyond the typical concerns of excess weight gain and long labors. They live in Missouri, one of 13 states with so-called trigger laws that went into effect after the Supreme Court overturned Roe v. Wade and the constitutional right to abortion, giving states the power to regulate it. States with trigger laws either banned abortion immediately or within a specified time frame after the ruling. In all, 26 states are expected to have abortion restrictions.
Missouri now allows abortion only for medical emergencies. If her upcoming ultrasound shows serious issues, Jessica says they could easily travel to another state and pay for an abortion. She realizes not everyone can.
However, the concern about trigger laws goes well beyond abortion. Many experts worry about the “spill-over” effects the abortion laws – both the existing ones and future proposals – may have on fertility care and treatments.
‘Personhood’ laws drive the concern
“The current trigger laws on the books are not impacting people’s access to IVF,” says Barbara Collura, president and CEO of RESOLVE, an advocacy group for those with fertility issues. “What we are concerned about is they will come back and make them stronger.”
The chief concern for reproductive rights advocates is so-called “personhood” legislation. According to the Guttmacher Institute, at least six bills about personhood have been introduced in five states, including Iowa, Oklahoma, South Carolina, Vermont, and West Virginia. One of the two Oklahoma bills has gone the farthest, passed by one chamber.
Since the Guttmacher report, Ohio introduced its own personhood legislation July 11, recognizing the personhood of an unborn person from conception.
Personhood legislation defines a fertilized egg or embryo as a legal human entity, says Sean Tipton, chief policy and advocacy officer for the Washington-based American Society of Reproductive Medicine, a nonprofit advocacy group.
“If the legal status of fertilized eggs or early embryos is codified, in vitro fertilization procedures may become legally risky for patients, physicians and staff,” Mr. Tipton wrote in late June in Contemporary OB/GYN Journal. The American Society for Reproductive Medicine has posted a report on state abortion trigger laws and their potential implications for reproductive medicine. Of the 13 with trigger laws in effect, the report found concern about the potential effect on IVF only with Utah’s.
‘Safe’ states?
Even in states without trigger laws or personhood bills, IVF patients say they are anxious about how the Supreme Court ruling may ultimately affect care. Thanks to IVF, Shelly Battista and her husband Robert are expecting twins in December, little sisters to their daughter Emilia, who is 2½.
They live in Illinois, where abortion is legal. “Even though we are safe now, I think the overturning of Roe has made it clear to all of us that none of our freedoms are safe, especially reproductive rights,” Ms. Shelly says.
About one in eight U.S. couples are infertile, according to RESOLVE, In 2019, 2% of all babies born in the United States, or about 78,000 infants, were conceived with the use of assisted reproductive technologies, according to the Centers for Disease Control and Prevention. The most common assisted reproductive technology is IVF, in which the sperm fertilizes the egg outside the body and an embryo is then transferred. The standard of practice is to transfer a single embryo, freezing others for future use.
Trigger state doctors weigh in
Some fertility doctors in those “trigger” states are keeping a close eye on proposed legislation and talking to legislators for interpretation of current and proposed laws.
Eli Reshef, MD, a reproductive endocrinologist and fertility specialist at Bennett Fertility Institute in Oklahoma City, notes that his state has “the strictest abortion law in the land.” The law prohibits all abortions with few exceptions, such as the removal of an ectopic pregnancy (when a fertilized egg implants outside the uterus, such as in the fallopian tubes).
While IVF will not be affected for now, he worries that the Oklahoma law allows a private citizen to sue a health care provider that they feel is performing abortion. The Oklahoma law leaves interpretation of abortion up to the general public, who may be unfamiliar with the language of the law, House Bill 4327.
Dean Moutos, MD, a reproductive endocrinologist and medical director of Arkansas Fertility and Gynecology in Little Rock, says his state’s current trigger law should not affect IVF. “When you read the bill, it says abortion means to terminate the pregnancy of a woman.” Still, he says, “we are concerned about what might happen in the future” and the possibility that some legislators may interpret that differently.
A minority approach
John David Gordon, MD, a reproductive endocrinologist and medical director of Southeastern Fertility Center for Fertility and Reproductive Surgery in Knoxville, Tenn., is also in a trigger state. However, it’s not likely any personhood laws would affect his practice.
That’s because his center, which he acknowledges is clearly in the minority, only performs natural-cycle IVF, which usually results in a single egg, or “mini-stim IVF,” which usually results in three to eight eggs in order to limit the number that may be potentially fertilized. Often, he says, patients choose to freeze unfertilized eggs (alone) to avoid creating an excessive number of embryos. He has a “no discard” program, with any viable embryos frozen or transferred. Abandoned embryos are donated to others.
“This may work for young women,” says Marcelle Cedars, MD, director of reproductive endocrinology at the University of California, San Francisco, and president of the American Society of Reproductive Medicine. However, she says, it will be very inefficient for older patients, since they have a higher percentage of abnormal eggs.
Overall, that approach will also drive up costs, especially for older women, Dr. Cedars says. An average cycle of IVF costs $12,400, and most Americans’ insurance plans don’t cover IVF, according to Mr. Tipton.
Top concerns for IVF
“Personhood” legislation has the potential to upend many common IVF practices, experts say.
Of greatest concern to fertility practices are potential restrictions on the freezing or discarding of embryos, Dr. Cedars says. “This could have a critical impact on practicing the safest, most evidence-based medicine,” she says.
Most children born in the United States as a result of IVF procedures are born from frozen embryos, according to the Society for Assisted Reproductive Technology, an organization for reproductive specialists.
“The practice of IVF really requires that we generate more embryos than will be used in a given [IVF] cycle,” agrees Kara Goldman, MD, associate professor of obstetrics and gynecology and medical director of the fertility preservation program at Northwestern University, Chicago. She performed the embryo transfer for the Battistas.
In nature, she says, it’s known that only a small number of eggs will be competent to generate a baby. “We see the same thing in IVF.” In a single cycle, 20 eggs may be retrieved, but many fewer typically reach successful fertilization and are able to be implanted.
When patients have completed their family, unused embryos are donated to research, donated for adoption, or destroyed. If embryo destruction is outlawed, Dr. Goldman says, it will have serious ramifications for the practice of IVF.
And if personhood legislation prohibits destroying any embryos, others wonder: Would a lab technician who accidentally dropped and destroyed an embryo be subject to charges? If laws prohibit destruction of embryos, others wonder if will families be forced to pay the embryo storage fees, generally $500-$1,000 a year, in perpetuity.
If an embryo is declared a person, it could also affect a practice called preimplantation genetic testing, or PGT. In PGT, cells are retrieved from an embryo and checked for genetic disorders such as sickle cell anemia and cystic fibrosis, with some parents choosing to discard embryos that are found to be affected.
Some potential parents choose this testing because they know they are carriers for genetic diseases that are serious and even incompatible with life, says Art Caplan, PhD, head of the division of medical ethics at New York University. They may choose to discard embryos that show evidence of the diseases.
Also under fire could be “selective reduction,” reducing multiple fetuses to a single or twin, to reduce risks to babies and mother.
Dr. Caplan predicts if states have many restrictions, some providers will adopt the attitude that “if no one reports, it did not happen.” And those prospective parents with the means, he says, will go to court and fight restrictions. “When they do it, they are saying, ‘You say you are pro-life; I’m trying to have a child. What are you doing getting in my way?’”
IVF families: Tough decisions, emotional times
The Battistas, of Illinois, have had an especially rough road. Shelly was diagnosed with a fast-growing breast cancer in 2020, when Emilia was just an infant. Warned that the chemotherapy she needed would suppress her ovaries, Shelly underwent egg retrieval before starting the cancer treatment.
She opted to have a double mastectomy and her ovaries removed after learning she carried the BRCA1 genetic mutation, boosting the risk of both breast and ovarian cancer.
Once she was cancer-free, she was cleared to start IVF. The first two embryo transfers failed. The third transfer, of a single embryo, was successful. But it split, a rare occurrence, producing two embryos. “It was a big shock, but in the best way,” she says about learning they were having twins. “Now we are over the moon.”
Five frozen embryos remain. At the start, the Battistas decided to discard unused embryos. She and Robert are discussing what to do next. If they decide they are done building their family after the twins’ birth, she wonders, “do we need to discard our [other] embryos before that becomes something that isn’t eligible [possible] for us any longer?” She doesn’t want to be rushed into that decision, however, especially with her medical history.
Jessica King and Sarah have 20 more embryos.
The couple had decided to donate unused embryos for research, when the time comes, and for different reasons. Her wife’s decision is based on her belief in science, while Jessica cites her faith. “As a Jew, it is part of our faith, that we should be doing everything we can to advance humanity,” she says.
In the midst of all the uncertainty, Jessica says, only half-jokingly, that she is tempted to claim the frozen embryos as dependents. “If you are truly going to claim these are precious human lives, you should be giving me all the benefits from having children,” she says.
Shelly knows that having one daughter, with two more on the way, affects her thinking about the court’s ruling. “My overall wish would be that Roe v. Wade is reinstated, and my daughters have the same rights and options that I have … or I did have until my current 36 years of life.”
A version of this article first appeared on WebMD.com.
Married for nearly 5 years, Jessica King, 34, and her wife, Sarah, agreed on some things right from the start. “We always knew kids were in the equation,” Jessica says.
Now, Jessica is nearly 20 weeks pregnant, thanks to in vitro fertilization, or IVF. They did “reciprocal” IVF, with Sarah’s egg mixed with donor sperm and the embryo transferred into Jessica. “We’re excited – and terrified,” Jessica says.
But that terror goes beyond the typical concerns of excess weight gain and long labors. They live in Missouri, one of 13 states with so-called trigger laws that went into effect after the Supreme Court overturned Roe v. Wade and the constitutional right to abortion, giving states the power to regulate it. States with trigger laws either banned abortion immediately or within a specified time frame after the ruling. In all, 26 states are expected to have abortion restrictions.
Missouri now allows abortion only for medical emergencies. If her upcoming ultrasound shows serious issues, Jessica says they could easily travel to another state and pay for an abortion. She realizes not everyone can.
However, the concern about trigger laws goes well beyond abortion. Many experts worry about the “spill-over” effects the abortion laws – both the existing ones and future proposals – may have on fertility care and treatments.
‘Personhood’ laws drive the concern
“The current trigger laws on the books are not impacting people’s access to IVF,” says Barbara Collura, president and CEO of RESOLVE, an advocacy group for those with fertility issues. “What we are concerned about is they will come back and make them stronger.”
The chief concern for reproductive rights advocates is so-called “personhood” legislation. According to the Guttmacher Institute, at least six bills about personhood have been introduced in five states, including Iowa, Oklahoma, South Carolina, Vermont, and West Virginia. One of the two Oklahoma bills has gone the farthest, passed by one chamber.
Since the Guttmacher report, Ohio introduced its own personhood legislation July 11, recognizing the personhood of an unborn person from conception.
Personhood legislation defines a fertilized egg or embryo as a legal human entity, says Sean Tipton, chief policy and advocacy officer for the Washington-based American Society of Reproductive Medicine, a nonprofit advocacy group.
“If the legal status of fertilized eggs or early embryos is codified, in vitro fertilization procedures may become legally risky for patients, physicians and staff,” Mr. Tipton wrote in late June in Contemporary OB/GYN Journal. The American Society for Reproductive Medicine has posted a report on state abortion trigger laws and their potential implications for reproductive medicine. Of the 13 with trigger laws in effect, the report found concern about the potential effect on IVF only with Utah’s.
‘Safe’ states?
Even in states without trigger laws or personhood bills, IVF patients say they are anxious about how the Supreme Court ruling may ultimately affect care. Thanks to IVF, Shelly Battista and her husband Robert are expecting twins in December, little sisters to their daughter Emilia, who is 2½.
They live in Illinois, where abortion is legal. “Even though we are safe now, I think the overturning of Roe has made it clear to all of us that none of our freedoms are safe, especially reproductive rights,” Ms. Shelly says.
About one in eight U.S. couples are infertile, according to RESOLVE, In 2019, 2% of all babies born in the United States, or about 78,000 infants, were conceived with the use of assisted reproductive technologies, according to the Centers for Disease Control and Prevention. The most common assisted reproductive technology is IVF, in which the sperm fertilizes the egg outside the body and an embryo is then transferred. The standard of practice is to transfer a single embryo, freezing others for future use.
Trigger state doctors weigh in
Some fertility doctors in those “trigger” states are keeping a close eye on proposed legislation and talking to legislators for interpretation of current and proposed laws.
Eli Reshef, MD, a reproductive endocrinologist and fertility specialist at Bennett Fertility Institute in Oklahoma City, notes that his state has “the strictest abortion law in the land.” The law prohibits all abortions with few exceptions, such as the removal of an ectopic pregnancy (when a fertilized egg implants outside the uterus, such as in the fallopian tubes).
While IVF will not be affected for now, he worries that the Oklahoma law allows a private citizen to sue a health care provider that they feel is performing abortion. The Oklahoma law leaves interpretation of abortion up to the general public, who may be unfamiliar with the language of the law, House Bill 4327.
Dean Moutos, MD, a reproductive endocrinologist and medical director of Arkansas Fertility and Gynecology in Little Rock, says his state’s current trigger law should not affect IVF. “When you read the bill, it says abortion means to terminate the pregnancy of a woman.” Still, he says, “we are concerned about what might happen in the future” and the possibility that some legislators may interpret that differently.
A minority approach
John David Gordon, MD, a reproductive endocrinologist and medical director of Southeastern Fertility Center for Fertility and Reproductive Surgery in Knoxville, Tenn., is also in a trigger state. However, it’s not likely any personhood laws would affect his practice.
That’s because his center, which he acknowledges is clearly in the minority, only performs natural-cycle IVF, which usually results in a single egg, or “mini-stim IVF,” which usually results in three to eight eggs in order to limit the number that may be potentially fertilized. Often, he says, patients choose to freeze unfertilized eggs (alone) to avoid creating an excessive number of embryos. He has a “no discard” program, with any viable embryos frozen or transferred. Abandoned embryos are donated to others.
“This may work for young women,” says Marcelle Cedars, MD, director of reproductive endocrinology at the University of California, San Francisco, and president of the American Society of Reproductive Medicine. However, she says, it will be very inefficient for older patients, since they have a higher percentage of abnormal eggs.
Overall, that approach will also drive up costs, especially for older women, Dr. Cedars says. An average cycle of IVF costs $12,400, and most Americans’ insurance plans don’t cover IVF, according to Mr. Tipton.
Top concerns for IVF
“Personhood” legislation has the potential to upend many common IVF practices, experts say.
Of greatest concern to fertility practices are potential restrictions on the freezing or discarding of embryos, Dr. Cedars says. “This could have a critical impact on practicing the safest, most evidence-based medicine,” she says.
Most children born in the United States as a result of IVF procedures are born from frozen embryos, according to the Society for Assisted Reproductive Technology, an organization for reproductive specialists.
“The practice of IVF really requires that we generate more embryos than will be used in a given [IVF] cycle,” agrees Kara Goldman, MD, associate professor of obstetrics and gynecology and medical director of the fertility preservation program at Northwestern University, Chicago. She performed the embryo transfer for the Battistas.
In nature, she says, it’s known that only a small number of eggs will be competent to generate a baby. “We see the same thing in IVF.” In a single cycle, 20 eggs may be retrieved, but many fewer typically reach successful fertilization and are able to be implanted.
When patients have completed their family, unused embryos are donated to research, donated for adoption, or destroyed. If embryo destruction is outlawed, Dr. Goldman says, it will have serious ramifications for the practice of IVF.
And if personhood legislation prohibits destroying any embryos, others wonder: Would a lab technician who accidentally dropped and destroyed an embryo be subject to charges? If laws prohibit destruction of embryos, others wonder if will families be forced to pay the embryo storage fees, generally $500-$1,000 a year, in perpetuity.
If an embryo is declared a person, it could also affect a practice called preimplantation genetic testing, or PGT. In PGT, cells are retrieved from an embryo and checked for genetic disorders such as sickle cell anemia and cystic fibrosis, with some parents choosing to discard embryos that are found to be affected.
Some potential parents choose this testing because they know they are carriers for genetic diseases that are serious and even incompatible with life, says Art Caplan, PhD, head of the division of medical ethics at New York University. They may choose to discard embryos that show evidence of the diseases.
Also under fire could be “selective reduction,” reducing multiple fetuses to a single or twin, to reduce risks to babies and mother.
Dr. Caplan predicts if states have many restrictions, some providers will adopt the attitude that “if no one reports, it did not happen.” And those prospective parents with the means, he says, will go to court and fight restrictions. “When they do it, they are saying, ‘You say you are pro-life; I’m trying to have a child. What are you doing getting in my way?’”
IVF families: Tough decisions, emotional times
The Battistas, of Illinois, have had an especially rough road. Shelly was diagnosed with a fast-growing breast cancer in 2020, when Emilia was just an infant. Warned that the chemotherapy she needed would suppress her ovaries, Shelly underwent egg retrieval before starting the cancer treatment.
She opted to have a double mastectomy and her ovaries removed after learning she carried the BRCA1 genetic mutation, boosting the risk of both breast and ovarian cancer.
Once she was cancer-free, she was cleared to start IVF. The first two embryo transfers failed. The third transfer, of a single embryo, was successful. But it split, a rare occurrence, producing two embryos. “It was a big shock, but in the best way,” she says about learning they were having twins. “Now we are over the moon.”
Five frozen embryos remain. At the start, the Battistas decided to discard unused embryos. She and Robert are discussing what to do next. If they decide they are done building their family after the twins’ birth, she wonders, “do we need to discard our [other] embryos before that becomes something that isn’t eligible [possible] for us any longer?” She doesn’t want to be rushed into that decision, however, especially with her medical history.
Jessica King and Sarah have 20 more embryos.
The couple had decided to donate unused embryos for research, when the time comes, and for different reasons. Her wife’s decision is based on her belief in science, while Jessica cites her faith. “As a Jew, it is part of our faith, that we should be doing everything we can to advance humanity,” she says.
In the midst of all the uncertainty, Jessica says, only half-jokingly, that she is tempted to claim the frozen embryos as dependents. “If you are truly going to claim these are precious human lives, you should be giving me all the benefits from having children,” she says.
Shelly knows that having one daughter, with two more on the way, affects her thinking about the court’s ruling. “My overall wish would be that Roe v. Wade is reinstated, and my daughters have the same rights and options that I have … or I did have until my current 36 years of life.”
A version of this article first appeared on WebMD.com.
Race difference seen in prenatal pot screens
Black patients and those with public insurance are more likely than their White, wealthier counterparts to be screened for marijuana use during pregnancy, researchers have found.
The data build on a growing body of evidence that disparities in age, insurance type, and race affect which women undergo drug testing during pregnancy and come under scrutiny from state social service agencies.
Many states require health care facilities to notify child protective services or law enforcement of a positive drug screening, but the consequences for women vary greatly from state to state. Twenty-four states and the District of Columbia consider prenatal drug use to be child abuse. But recent evidence suggests that urine drug screenings may not be reliable but can lead to separation of parents and babies.
“In many ways, the health system is better equipped to address these concerns than the criminal justice system,” Rebecca Stone, PhD, associate professor of sociology and criminal justice at Suffolk University, Boston, told this news organization. “They shouldn’t be criminal justice problems in many cases,” added Dr. Stone, who was not involved with the study.
The researchers analyzed data from the 2,045 patients who gave birth between January and July 2020. Of those, roughly one-fourth (24%) underwent a urine drug screening. The most common reason for a screen was that clinicians either suspected or patients self-reported use of marijuana during or shortly before pregnancy, according to the researchers, who presented their findings at the American College of Obstetricians and Gynecologists (ACOG) 2022 Annual Meeting.
Nearly 80% of the 209 patients who underwent drug testing because of suspected marijuana use were Black, and nearly 61% had public insurance. The median age of persons who underwent drug testing was 25 years; the overall median age of pregnant patients was 29 years.
Of the 1,561 patients who didn’t undergo drug screening, 43% were Black, and 37% had public insurance coverage.
Clinicians reported that nearly all patients (117/125; 94%) who tested positive for marijuana were reported to the Missouri child abuse/neglect hotline. Only four women who tested positive for marijuana use also tested positive for at least one other illegal drug.
“Marijuana did not predict other drug exposure; thus, we suggest that a history of marijuana use should not be used as a criteria for sending a urine drug screen on patients [who are admitted to the labor unit],” said Jeannie Kelly, MD, medical director of maternal-fetal transport and labor and delivery at the Washington University School of Medicine, St. Louis, who is the senior author of the study. “In our experience, this is a policy that increases inequitable screening without improving our ability to identify families who need extra support or monitoring.”
All patients in the study verbally agreed to a urine drug screening. Hospitals around the country have faced lawsuits for failing to gain consent from women undergoing such tests. A 2001 ruling from the U.S. Supreme Court made informed consent mandatory in the absence of a warrant.
Legal consequences of a positive test
Children exposed to marijuana in the womb are at heightened risk for impaired cognition and learning disabilities, according to a 2015 report from ACOG’s Committee on Obstetric Practice. However, a lack of care before birth can be harmful to infants and result in low birth weight and severe neurologic and other problems.
In a 2015 study, Dr. Stone found that women were less likely to seek prenatal care if they worried about the legal consequences of a positive test.
Dr. Kelly said the threat of interference from child protective services is often the top worry of pregnant women with substance use disorders. She argued that clinicians should treat marijuana the same way they do tobacco: discourage its use without reporting patients to law enforcement.
“Our suggestion is that this history you elicit of someone using marijuana probably shouldn’t be used [as a trigger for drug screening],” Dr. Kelly said.
She added that doctors can use discretion in choosing to screen for drugs, and she urged clinicians and health care institutions to reevaluate their drug screening practices to reduce harm and increase equitable care.
“We can only work the system in the places that we have control over,” she said. “I can’t control the downward cascade, but I can definitely control who I send a urine drug screen on.”
Dr. Kelly and Dr. Stone reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Black patients and those with public insurance are more likely than their White, wealthier counterparts to be screened for marijuana use during pregnancy, researchers have found.
The data build on a growing body of evidence that disparities in age, insurance type, and race affect which women undergo drug testing during pregnancy and come under scrutiny from state social service agencies.
Many states require health care facilities to notify child protective services or law enforcement of a positive drug screening, but the consequences for women vary greatly from state to state. Twenty-four states and the District of Columbia consider prenatal drug use to be child abuse. But recent evidence suggests that urine drug screenings may not be reliable but can lead to separation of parents and babies.
“In many ways, the health system is better equipped to address these concerns than the criminal justice system,” Rebecca Stone, PhD, associate professor of sociology and criminal justice at Suffolk University, Boston, told this news organization. “They shouldn’t be criminal justice problems in many cases,” added Dr. Stone, who was not involved with the study.
The researchers analyzed data from the 2,045 patients who gave birth between January and July 2020. Of those, roughly one-fourth (24%) underwent a urine drug screening. The most common reason for a screen was that clinicians either suspected or patients self-reported use of marijuana during or shortly before pregnancy, according to the researchers, who presented their findings at the American College of Obstetricians and Gynecologists (ACOG) 2022 Annual Meeting.
Nearly 80% of the 209 patients who underwent drug testing because of suspected marijuana use were Black, and nearly 61% had public insurance. The median age of persons who underwent drug testing was 25 years; the overall median age of pregnant patients was 29 years.
Of the 1,561 patients who didn’t undergo drug screening, 43% were Black, and 37% had public insurance coverage.
Clinicians reported that nearly all patients (117/125; 94%) who tested positive for marijuana were reported to the Missouri child abuse/neglect hotline. Only four women who tested positive for marijuana use also tested positive for at least one other illegal drug.
“Marijuana did not predict other drug exposure; thus, we suggest that a history of marijuana use should not be used as a criteria for sending a urine drug screen on patients [who are admitted to the labor unit],” said Jeannie Kelly, MD, medical director of maternal-fetal transport and labor and delivery at the Washington University School of Medicine, St. Louis, who is the senior author of the study. “In our experience, this is a policy that increases inequitable screening without improving our ability to identify families who need extra support or monitoring.”
All patients in the study verbally agreed to a urine drug screening. Hospitals around the country have faced lawsuits for failing to gain consent from women undergoing such tests. A 2001 ruling from the U.S. Supreme Court made informed consent mandatory in the absence of a warrant.
Legal consequences of a positive test
Children exposed to marijuana in the womb are at heightened risk for impaired cognition and learning disabilities, according to a 2015 report from ACOG’s Committee on Obstetric Practice. However, a lack of care before birth can be harmful to infants and result in low birth weight and severe neurologic and other problems.
In a 2015 study, Dr. Stone found that women were less likely to seek prenatal care if they worried about the legal consequences of a positive test.
Dr. Kelly said the threat of interference from child protective services is often the top worry of pregnant women with substance use disorders. She argued that clinicians should treat marijuana the same way they do tobacco: discourage its use without reporting patients to law enforcement.
“Our suggestion is that this history you elicit of someone using marijuana probably shouldn’t be used [as a trigger for drug screening],” Dr. Kelly said.
She added that doctors can use discretion in choosing to screen for drugs, and she urged clinicians and health care institutions to reevaluate their drug screening practices to reduce harm and increase equitable care.
“We can only work the system in the places that we have control over,” she said. “I can’t control the downward cascade, but I can definitely control who I send a urine drug screen on.”
Dr. Kelly and Dr. Stone reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Black patients and those with public insurance are more likely than their White, wealthier counterparts to be screened for marijuana use during pregnancy, researchers have found.
The data build on a growing body of evidence that disparities in age, insurance type, and race affect which women undergo drug testing during pregnancy and come under scrutiny from state social service agencies.
Many states require health care facilities to notify child protective services or law enforcement of a positive drug screening, but the consequences for women vary greatly from state to state. Twenty-four states and the District of Columbia consider prenatal drug use to be child abuse. But recent evidence suggests that urine drug screenings may not be reliable but can lead to separation of parents and babies.
“In many ways, the health system is better equipped to address these concerns than the criminal justice system,” Rebecca Stone, PhD, associate professor of sociology and criminal justice at Suffolk University, Boston, told this news organization. “They shouldn’t be criminal justice problems in many cases,” added Dr. Stone, who was not involved with the study.
The researchers analyzed data from the 2,045 patients who gave birth between January and July 2020. Of those, roughly one-fourth (24%) underwent a urine drug screening. The most common reason for a screen was that clinicians either suspected or patients self-reported use of marijuana during or shortly before pregnancy, according to the researchers, who presented their findings at the American College of Obstetricians and Gynecologists (ACOG) 2022 Annual Meeting.
Nearly 80% of the 209 patients who underwent drug testing because of suspected marijuana use were Black, and nearly 61% had public insurance. The median age of persons who underwent drug testing was 25 years; the overall median age of pregnant patients was 29 years.
Of the 1,561 patients who didn’t undergo drug screening, 43% were Black, and 37% had public insurance coverage.
Clinicians reported that nearly all patients (117/125; 94%) who tested positive for marijuana were reported to the Missouri child abuse/neglect hotline. Only four women who tested positive for marijuana use also tested positive for at least one other illegal drug.
“Marijuana did not predict other drug exposure; thus, we suggest that a history of marijuana use should not be used as a criteria for sending a urine drug screen on patients [who are admitted to the labor unit],” said Jeannie Kelly, MD, medical director of maternal-fetal transport and labor and delivery at the Washington University School of Medicine, St. Louis, who is the senior author of the study. “In our experience, this is a policy that increases inequitable screening without improving our ability to identify families who need extra support or monitoring.”
All patients in the study verbally agreed to a urine drug screening. Hospitals around the country have faced lawsuits for failing to gain consent from women undergoing such tests. A 2001 ruling from the U.S. Supreme Court made informed consent mandatory in the absence of a warrant.
Legal consequences of a positive test
Children exposed to marijuana in the womb are at heightened risk for impaired cognition and learning disabilities, according to a 2015 report from ACOG’s Committee on Obstetric Practice. However, a lack of care before birth can be harmful to infants and result in low birth weight and severe neurologic and other problems.
In a 2015 study, Dr. Stone found that women were less likely to seek prenatal care if they worried about the legal consequences of a positive test.
Dr. Kelly said the threat of interference from child protective services is often the top worry of pregnant women with substance use disorders. She argued that clinicians should treat marijuana the same way they do tobacco: discourage its use without reporting patients to law enforcement.
“Our suggestion is that this history you elicit of someone using marijuana probably shouldn’t be used [as a trigger for drug screening],” Dr. Kelly said.
She added that doctors can use discretion in choosing to screen for drugs, and she urged clinicians and health care institutions to reevaluate their drug screening practices to reduce harm and increase equitable care.
“We can only work the system in the places that we have control over,” she said. “I can’t control the downward cascade, but I can definitely control who I send a urine drug screen on.”
Dr. Kelly and Dr. Stone reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACOG 2022
Clinical Edge Journal Scan Commentary: Prenatal Testing, May 2022
Detection of fetal heart defects is an important aspect of prenatal diagnostic ultrasound. A recent study by Haberer and colleagues in the Journal of the American Society of Echocardiography investigated the diagnostic accuracy of fetal echocardiography. They looked at all of the fetuses with major cardiac anomalies diagnosed at a single institution over an 11-year period and compared the fetal echocardiogram reports with postnatal imaging, surgical reports, and autopsies. Of the almost 600 cases examined, 90% of the diagnoses were accurate. The highest rate of accuracy was for univentricular hearts defects (97.6%) and the lowest was with heterotaxy (71.1%). This article is important because findings show that diagnostic accuracy of fetal echocardiography was high for major fetal cardiac defects.
The ability to accurately diagnose placenta accreta prenatally is important to obstetricians because of the increased risk it poses for maternal morbidity and mortality. This issue is considered in a recent systematic review and meta-analysis by Hong and colleagues in the journal Insights into Imaging. They compared ultrasound to MRI for diagnostic accuracy of placenta accreta spectrum disorder (PAS). In the studies they examined, the diagnostic accuracy of ultrasound for PAS had a sensitivity of 0.9 and a specificity of 0.83, while the diagnostic accuracy of MRI had a sensitivity of 0.89 and a specificity of 0.87. This shows that the diagnostic accuracy of PAS is similar for both ultrasound and MRI. Given the significant expense of an MRI, this raises the question of its importance in the role of evaluating patients suspected of placenta accreta.
Precise prenatal diagnosis of estimated fetal weight (EFW) is central to the care of pregnant patients. It allows for appropriate timing of delivery to decrease the risk for stillbirth. A recent article by Visentin and colleagues evaluates prenatal methods for estimation of fetal weight and prediction of small-for-gestational-age (SGA) fetuses. The researchers performed a retrospective review of singleton gestations that were at increased risk for fetal growth restriction from two hospitals. They found that EFW z-scores derived from either the Hadlock method or the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) assessment were similar and more accurate than abdominal circumference (AC) z-scores for detecting SGA infants. This study should open the debate again on how to best measure estimated fetal weight: EFW alone or assessment of both EFW and AC.
Detection of fetal heart defects is an important aspect of prenatal diagnostic ultrasound. A recent study by Haberer and colleagues in the Journal of the American Society of Echocardiography investigated the diagnostic accuracy of fetal echocardiography. They looked at all of the fetuses with major cardiac anomalies diagnosed at a single institution over an 11-year period and compared the fetal echocardiogram reports with postnatal imaging, surgical reports, and autopsies. Of the almost 600 cases examined, 90% of the diagnoses were accurate. The highest rate of accuracy was for univentricular hearts defects (97.6%) and the lowest was with heterotaxy (71.1%). This article is important because findings show that diagnostic accuracy of fetal echocardiography was high for major fetal cardiac defects.
The ability to accurately diagnose placenta accreta prenatally is important to obstetricians because of the increased risk it poses for maternal morbidity and mortality. This issue is considered in a recent systematic review and meta-analysis by Hong and colleagues in the journal Insights into Imaging. They compared ultrasound to MRI for diagnostic accuracy of placenta accreta spectrum disorder (PAS). In the studies they examined, the diagnostic accuracy of ultrasound for PAS had a sensitivity of 0.9 and a specificity of 0.83, while the diagnostic accuracy of MRI had a sensitivity of 0.89 and a specificity of 0.87. This shows that the diagnostic accuracy of PAS is similar for both ultrasound and MRI. Given the significant expense of an MRI, this raises the question of its importance in the role of evaluating patients suspected of placenta accreta.
Precise prenatal diagnosis of estimated fetal weight (EFW) is central to the care of pregnant patients. It allows for appropriate timing of delivery to decrease the risk for stillbirth. A recent article by Visentin and colleagues evaluates prenatal methods for estimation of fetal weight and prediction of small-for-gestational-age (SGA) fetuses. The researchers performed a retrospective review of singleton gestations that were at increased risk for fetal growth restriction from two hospitals. They found that EFW z-scores derived from either the Hadlock method or the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) assessment were similar and more accurate than abdominal circumference (AC) z-scores for detecting SGA infants. This study should open the debate again on how to best measure estimated fetal weight: EFW alone or assessment of both EFW and AC.
Detection of fetal heart defects is an important aspect of prenatal diagnostic ultrasound. A recent study by Haberer and colleagues in the Journal of the American Society of Echocardiography investigated the diagnostic accuracy of fetal echocardiography. They looked at all of the fetuses with major cardiac anomalies diagnosed at a single institution over an 11-year period and compared the fetal echocardiogram reports with postnatal imaging, surgical reports, and autopsies. Of the almost 600 cases examined, 90% of the diagnoses were accurate. The highest rate of accuracy was for univentricular hearts defects (97.6%) and the lowest was with heterotaxy (71.1%). This article is important because findings show that diagnostic accuracy of fetal echocardiography was high for major fetal cardiac defects.
The ability to accurately diagnose placenta accreta prenatally is important to obstetricians because of the increased risk it poses for maternal morbidity and mortality. This issue is considered in a recent systematic review and meta-analysis by Hong and colleagues in the journal Insights into Imaging. They compared ultrasound to MRI for diagnostic accuracy of placenta accreta spectrum disorder (PAS). In the studies they examined, the diagnostic accuracy of ultrasound for PAS had a sensitivity of 0.9 and a specificity of 0.83, while the diagnostic accuracy of MRI had a sensitivity of 0.89 and a specificity of 0.87. This shows that the diagnostic accuracy of PAS is similar for both ultrasound and MRI. Given the significant expense of an MRI, this raises the question of its importance in the role of evaluating patients suspected of placenta accreta.
Precise prenatal diagnosis of estimated fetal weight (EFW) is central to the care of pregnant patients. It allows for appropriate timing of delivery to decrease the risk for stillbirth. A recent article by Visentin and colleagues evaluates prenatal methods for estimation of fetal weight and prediction of small-for-gestational-age (SGA) fetuses. The researchers performed a retrospective review of singleton gestations that were at increased risk for fetal growth restriction from two hospitals. They found that EFW z-scores derived from either the Hadlock method or the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) assessment were similar and more accurate than abdominal circumference (AC) z-scores for detecting SGA infants. This study should open the debate again on how to best measure estimated fetal weight: EFW alone or assessment of both EFW and AC.
Prenatal DNA tests lead to false alarms, FDA warns
Expectant parents and their health care providers should not entirely rely on the results of prenatal blood tests that claim to predict the chances a newborn will have a rare and potentially serious disease, the Food and Drug Administration said in a new warning.
These tests – called noninvasive prenatal screening tests – use a blood sample from a pregnant mother to look for signs that her fetus has a genetic abnormality. They tell parents the risk that a fetus has a particular genetic abnormality, but they may be wrong, the FDA said.
The FDA said expectant parents should discuss the pros and cons of genetic screening with a genetic counselor before getting the tests and seek a follow-up diagnostic test if the screening result is concerning.
The diagnostic tests that confirm or rule out a genetic abnormality, such as an amniocentesis, are more invasive than the blood draws used for genetic screening and have a small risk of miscarriage. But the diagnostic tests are more accurate, the FDA said.
The agency said some people have made critical decisions about a pregnancy, including termination, after receiving worrisome results from genetic screening tests, none of which have received FDA approval.
“Without confirming the results with a diagnostic test, there is no way to know whether the fetus actually had the genetic abnormality reported by the screening test,” the agency said in an April 19 statement. “The FDA is aware of cases where a screening test reported a genetic abnormality and a confirmatory diagnostic test later found that the fetus was healthy.”
The FDA’s notice comes several months after the New York Times reported that 85% of positive screening test results for some conditions are incorrect, despite marketing from screening companies about how their tests are “reliable” and bring “peace of mind.”
Prenatal genetic screening tests look for abnormalities that would cause a disorder, such as missing chromosomes or pieces of chromosomes, or extra chromosomes. But while these tests are often accurate for more common conditions like Down syndrome, they are much less reliable for rare diseases, the New York Times report said.
The story highlights multiple women who got diagnostic tests that disproved the scary results of their genetic screening, including the experience of Cloey Canida, a 25-year-old California woman whose genetic screening said with 99% certainty that her baby would have a disease called Patau syndrome. The test is almost always wrong for women of Ms. Canida’s age, her doctor assured her. After more than $1,000 worth of tests, Ms. Canida learned that her pregnancy was indeed healthy.
“I wish that we would have been informed of the false positive rate before I agreed to the test,” she told the Times. “I was given zero information about that.”
A version of this article first appeared on WebMD.com.
Expectant parents and their health care providers should not entirely rely on the results of prenatal blood tests that claim to predict the chances a newborn will have a rare and potentially serious disease, the Food and Drug Administration said in a new warning.
These tests – called noninvasive prenatal screening tests – use a blood sample from a pregnant mother to look for signs that her fetus has a genetic abnormality. They tell parents the risk that a fetus has a particular genetic abnormality, but they may be wrong, the FDA said.
The FDA said expectant parents should discuss the pros and cons of genetic screening with a genetic counselor before getting the tests and seek a follow-up diagnostic test if the screening result is concerning.
The diagnostic tests that confirm or rule out a genetic abnormality, such as an amniocentesis, are more invasive than the blood draws used for genetic screening and have a small risk of miscarriage. But the diagnostic tests are more accurate, the FDA said.
The agency said some people have made critical decisions about a pregnancy, including termination, after receiving worrisome results from genetic screening tests, none of which have received FDA approval.
“Without confirming the results with a diagnostic test, there is no way to know whether the fetus actually had the genetic abnormality reported by the screening test,” the agency said in an April 19 statement. “The FDA is aware of cases where a screening test reported a genetic abnormality and a confirmatory diagnostic test later found that the fetus was healthy.”
The FDA’s notice comes several months after the New York Times reported that 85% of positive screening test results for some conditions are incorrect, despite marketing from screening companies about how their tests are “reliable” and bring “peace of mind.”
Prenatal genetic screening tests look for abnormalities that would cause a disorder, such as missing chromosomes or pieces of chromosomes, or extra chromosomes. But while these tests are often accurate for more common conditions like Down syndrome, they are much less reliable for rare diseases, the New York Times report said.
The story highlights multiple women who got diagnostic tests that disproved the scary results of their genetic screening, including the experience of Cloey Canida, a 25-year-old California woman whose genetic screening said with 99% certainty that her baby would have a disease called Patau syndrome. The test is almost always wrong for women of Ms. Canida’s age, her doctor assured her. After more than $1,000 worth of tests, Ms. Canida learned that her pregnancy was indeed healthy.
“I wish that we would have been informed of the false positive rate before I agreed to the test,” she told the Times. “I was given zero information about that.”
A version of this article first appeared on WebMD.com.
Expectant parents and their health care providers should not entirely rely on the results of prenatal blood tests that claim to predict the chances a newborn will have a rare and potentially serious disease, the Food and Drug Administration said in a new warning.
These tests – called noninvasive prenatal screening tests – use a blood sample from a pregnant mother to look for signs that her fetus has a genetic abnormality. They tell parents the risk that a fetus has a particular genetic abnormality, but they may be wrong, the FDA said.
The FDA said expectant parents should discuss the pros and cons of genetic screening with a genetic counselor before getting the tests and seek a follow-up diagnostic test if the screening result is concerning.
The diagnostic tests that confirm or rule out a genetic abnormality, such as an amniocentesis, are more invasive than the blood draws used for genetic screening and have a small risk of miscarriage. But the diagnostic tests are more accurate, the FDA said.
The agency said some people have made critical decisions about a pregnancy, including termination, after receiving worrisome results from genetic screening tests, none of which have received FDA approval.
“Without confirming the results with a diagnostic test, there is no way to know whether the fetus actually had the genetic abnormality reported by the screening test,” the agency said in an April 19 statement. “The FDA is aware of cases where a screening test reported a genetic abnormality and a confirmatory diagnostic test later found that the fetus was healthy.”
The FDA’s notice comes several months after the New York Times reported that 85% of positive screening test results for some conditions are incorrect, despite marketing from screening companies about how their tests are “reliable” and bring “peace of mind.”
Prenatal genetic screening tests look for abnormalities that would cause a disorder, such as missing chromosomes or pieces of chromosomes, or extra chromosomes. But while these tests are often accurate for more common conditions like Down syndrome, they are much less reliable for rare diseases, the New York Times report said.
The story highlights multiple women who got diagnostic tests that disproved the scary results of their genetic screening, including the experience of Cloey Canida, a 25-year-old California woman whose genetic screening said with 99% certainty that her baby would have a disease called Patau syndrome. The test is almost always wrong for women of Ms. Canida’s age, her doctor assured her. After more than $1,000 worth of tests, Ms. Canida learned that her pregnancy was indeed healthy.
“I wish that we would have been informed of the false positive rate before I agreed to the test,” she told the Times. “I was given zero information about that.”
A version of this article first appeared on WebMD.com.
Prenatal estimated fetal weight standards better at diagnosing SGA fetuses than other biometric methods
Key clinical point: Prenatal standard estimated fetal weight (EFW) z-scores can predict small-for-gestational-age (SGA) fetuses with greater accuracy than abdominal circumference (AC) z-scores and postnatal reference standards.
Major finding: The INTERGROWTH-21st project-derived EFW z-scores showed higher accuracy in identifying fetuses with a birthweight of <10th and <3rd percentiles than AC z-scores (both P < .05) and postnatal standards (both P < .05). The Hadlock group-derived EFW z-scores performed better in identifying fetuses <10th percentiles (P < .05) and similarly in identifying fetuses <3rd percentile (P = .344) than AC z-scores, whereas they were more accurate than postnatal standards with both birth-weight percentiles (both P < .05).
Study details: This retrospective study included 406 singleton pregnant women at an increased risk for fetal growth restriction who underwent ultrasound examinations between 24 and 36 weeks of gestation.
Disclosures: The study received no financial support. No conflicts of interest were reported.
Source: Visentin S et al. A prenatal standard for fetal weight improves the prenatal diagnosis of small for gestational age fetuses in pregnancies at increased risk. BMC Pregnancy Childbirth. 2022;22:254 (Mar 26). Doi: 10.1186/s12884-022-04545-x
Key clinical point: Prenatal standard estimated fetal weight (EFW) z-scores can predict small-for-gestational-age (SGA) fetuses with greater accuracy than abdominal circumference (AC) z-scores and postnatal reference standards.
Major finding: The INTERGROWTH-21st project-derived EFW z-scores showed higher accuracy in identifying fetuses with a birthweight of <10th and <3rd percentiles than AC z-scores (both P < .05) and postnatal standards (both P < .05). The Hadlock group-derived EFW z-scores performed better in identifying fetuses <10th percentiles (P < .05) and similarly in identifying fetuses <3rd percentile (P = .344) than AC z-scores, whereas they were more accurate than postnatal standards with both birth-weight percentiles (both P < .05).
Study details: This retrospective study included 406 singleton pregnant women at an increased risk for fetal growth restriction who underwent ultrasound examinations between 24 and 36 weeks of gestation.
Disclosures: The study received no financial support. No conflicts of interest were reported.
Source: Visentin S et al. A prenatal standard for fetal weight improves the prenatal diagnosis of small for gestational age fetuses in pregnancies at increased risk. BMC Pregnancy Childbirth. 2022;22:254 (Mar 26). Doi: 10.1186/s12884-022-04545-x
Key clinical point: Prenatal standard estimated fetal weight (EFW) z-scores can predict small-for-gestational-age (SGA) fetuses with greater accuracy than abdominal circumference (AC) z-scores and postnatal reference standards.
Major finding: The INTERGROWTH-21st project-derived EFW z-scores showed higher accuracy in identifying fetuses with a birthweight of <10th and <3rd percentiles than AC z-scores (both P < .05) and postnatal standards (both P < .05). The Hadlock group-derived EFW z-scores performed better in identifying fetuses <10th percentiles (P < .05) and similarly in identifying fetuses <3rd percentile (P = .344) than AC z-scores, whereas they were more accurate than postnatal standards with both birth-weight percentiles (both P < .05).
Study details: This retrospective study included 406 singleton pregnant women at an increased risk for fetal growth restriction who underwent ultrasound examinations between 24 and 36 weeks of gestation.
Disclosures: The study received no financial support. No conflicts of interest were reported.
Source: Visentin S et al. A prenatal standard for fetal weight improves the prenatal diagnosis of small for gestational age fetuses in pregnancies at increased risk. BMC Pregnancy Childbirth. 2022;22:254 (Mar 26). Doi: 10.1186/s12884-022-04545-x
Ultrasonography and MRI can prenatally diagnose placenta accreta spectrum with comparable accuracy
Key clinical point: Accuracy of ultrasonography for the prenatal diagnosis of placenta accreta spectrum (PAS) disorder is comparable with that of magnetic resonance imaging (MRI).
Major finding: Ultrasonography and MRI showed similar sensitivity (0.90; 95% CI 0.86-0.93 vs. 0.89; 95% CI 0.85-0.92), specificity (0.83; 95% CI 0.79-0.86 vs. 0.87; 95% CI 0.83-0.89), and diagnostic odds ratio (39.5; 95% CI 19.6-79.7 vs. 37.4; 95% CI 17.0-82.3) for PAS diagnosis, with no significant difference between their pooled diagnostic sensitivity (P = .808) and specificity (P = .413).
Study details: This is a meta-analysis of 18 studies including 861 pregnancies at a potential risk for PAS, of which 339 were diagnosed with PAS.
Disclosures: The study was sponsored by the Natural Science Foundation of Science and Technology Commission of Shanghai Municipality. The authors declared no conflicts of interest.
Source: Hong S et al. Performance comparison of ultrasonography and magnetic resonance imaging in their diagnostic accuracy of placenta accreta spectrum disorders: A systematic review and meta-analysis. Insights Imaging. 2022;13:50 (Mar 22). Doi: 10.1186/s13244-022-01192-w
Key clinical point: Accuracy of ultrasonography for the prenatal diagnosis of placenta accreta spectrum (PAS) disorder is comparable with that of magnetic resonance imaging (MRI).
Major finding: Ultrasonography and MRI showed similar sensitivity (0.90; 95% CI 0.86-0.93 vs. 0.89; 95% CI 0.85-0.92), specificity (0.83; 95% CI 0.79-0.86 vs. 0.87; 95% CI 0.83-0.89), and diagnostic odds ratio (39.5; 95% CI 19.6-79.7 vs. 37.4; 95% CI 17.0-82.3) for PAS diagnosis, with no significant difference between their pooled diagnostic sensitivity (P = .808) and specificity (P = .413).
Study details: This is a meta-analysis of 18 studies including 861 pregnancies at a potential risk for PAS, of which 339 were diagnosed with PAS.
Disclosures: The study was sponsored by the Natural Science Foundation of Science and Technology Commission of Shanghai Municipality. The authors declared no conflicts of interest.
Source: Hong S et al. Performance comparison of ultrasonography and magnetic resonance imaging in their diagnostic accuracy of placenta accreta spectrum disorders: A systematic review and meta-analysis. Insights Imaging. 2022;13:50 (Mar 22). Doi: 10.1186/s13244-022-01192-w
Key clinical point: Accuracy of ultrasonography for the prenatal diagnosis of placenta accreta spectrum (PAS) disorder is comparable with that of magnetic resonance imaging (MRI).
Major finding: Ultrasonography and MRI showed similar sensitivity (0.90; 95% CI 0.86-0.93 vs. 0.89; 95% CI 0.85-0.92), specificity (0.83; 95% CI 0.79-0.86 vs. 0.87; 95% CI 0.83-0.89), and diagnostic odds ratio (39.5; 95% CI 19.6-79.7 vs. 37.4; 95% CI 17.0-82.3) for PAS diagnosis, with no significant difference between their pooled diagnostic sensitivity (P = .808) and specificity (P = .413).
Study details: This is a meta-analysis of 18 studies including 861 pregnancies at a potential risk for PAS, of which 339 were diagnosed with PAS.
Disclosures: The study was sponsored by the Natural Science Foundation of Science and Technology Commission of Shanghai Municipality. The authors declared no conflicts of interest.
Source: Hong S et al. Performance comparison of ultrasonography and magnetic resonance imaging in their diagnostic accuracy of placenta accreta spectrum disorders: A systematic review and meta-analysis. Insights Imaging. 2022;13:50 (Mar 22). Doi: 10.1186/s13244-022-01192-w
Routine prenatal fetal RHD screening after 11 weeks of pregnancy yields encouraging results
Key clinical point: Noninvasive prenatal fetal rhesus D (RHD) screening after 11 weeks of gestation offers high accuracy and reliability in routine clinical practice.
Major finding: Fetal RHD testing had a 100% sensitivity (95% CI 95.3%-100.0%) and a 100% specificity (95% CI 91.6%-100.0%), with the negative and positive predictive values being 100.0%. No false-negative or false-positive screening results were reported.
Study details: This was a single-center study wherein fetal RHD testing (real-time polymerase chain reaction targeting RHD exons 5 and 7) was performed using blood samples from 205 RHD-negative pregnant women at ≥11 weeks of gestation and test performance was evaluated using cord blood samples obtained from 62% (n = 127) of women.
Disclosures: The study was sponsored by the Scientific Fund of Hematology. The authors reported no conflicts of interest.
Source: Blomme S et al. Routine noninvasive prenatal screening for fetal Rh D in maternal plasma—A 2-year experience from a single center in Belgium. Transfusion. 2022 (Mar 30). Doi: 10.1111/trf.16868
Key clinical point: Noninvasive prenatal fetal rhesus D (RHD) screening after 11 weeks of gestation offers high accuracy and reliability in routine clinical practice.
Major finding: Fetal RHD testing had a 100% sensitivity (95% CI 95.3%-100.0%) and a 100% specificity (95% CI 91.6%-100.0%), with the negative and positive predictive values being 100.0%. No false-negative or false-positive screening results were reported.
Study details: This was a single-center study wherein fetal RHD testing (real-time polymerase chain reaction targeting RHD exons 5 and 7) was performed using blood samples from 205 RHD-negative pregnant women at ≥11 weeks of gestation and test performance was evaluated using cord blood samples obtained from 62% (n = 127) of women.
Disclosures: The study was sponsored by the Scientific Fund of Hematology. The authors reported no conflicts of interest.
Source: Blomme S et al. Routine noninvasive prenatal screening for fetal Rh D in maternal plasma—A 2-year experience from a single center in Belgium. Transfusion. 2022 (Mar 30). Doi: 10.1111/trf.16868
Key clinical point: Noninvasive prenatal fetal rhesus D (RHD) screening after 11 weeks of gestation offers high accuracy and reliability in routine clinical practice.
Major finding: Fetal RHD testing had a 100% sensitivity (95% CI 95.3%-100.0%) and a 100% specificity (95% CI 91.6%-100.0%), with the negative and positive predictive values being 100.0%. No false-negative or false-positive screening results were reported.
Study details: This was a single-center study wherein fetal RHD testing (real-time polymerase chain reaction targeting RHD exons 5 and 7) was performed using blood samples from 205 RHD-negative pregnant women at ≥11 weeks of gestation and test performance was evaluated using cord blood samples obtained from 62% (n = 127) of women.
Disclosures: The study was sponsored by the Scientific Fund of Hematology. The authors reported no conflicts of interest.
Source: Blomme S et al. Routine noninvasive prenatal screening for fetal Rh D in maternal plasma—A 2-year experience from a single center in Belgium. Transfusion. 2022 (Mar 30). Doi: 10.1111/trf.16868
Pre-labor placental growth factor level can predict cesarean delivery due to fetal indications
Key clinical point: Maternal placental growth factor (PlGF) levels measured before labor may aid the prediction of cesarean delivery owing to fetal dysfunction and fetal heart rate (FHR) function at delivery.
Major finding: Women having vaginal delivery had significantly higher pre-labor PlGF levels than those having a cesarean delivery owing to fetal dysfunction (157 ± 106 vs. 74 ± 62 pg/mL; P = .03). PlGF levels showed a significant negative correlation (r = −0.42; P = .01) with FHR findings at delivery according to the five-tier classification system.
Study details: The study analyzed PlGF levels in 33 primiparous singleton pregnant women at 35-42 weeks of gestation who were hospitalized before the onset of labor, of which 26 women had vaginal delivery and 7 had a cesarean delivery due to fetal indications.
Disclosures: The study received no financial support. The authors declared no conflicts of interest.
Source: Tanaka H et al. Placental growth factor level is correlated with intrapartum fetal heart rate findings. BMC Pregnancy Childbirth. 2022;22:215 (Mar 17). Doi: 10.1186/s12884-022-04562-w
Key clinical point: Maternal placental growth factor (PlGF) levels measured before labor may aid the prediction of cesarean delivery owing to fetal dysfunction and fetal heart rate (FHR) function at delivery.
Major finding: Women having vaginal delivery had significantly higher pre-labor PlGF levels than those having a cesarean delivery owing to fetal dysfunction (157 ± 106 vs. 74 ± 62 pg/mL; P = .03). PlGF levels showed a significant negative correlation (r = −0.42; P = .01) with FHR findings at delivery according to the five-tier classification system.
Study details: The study analyzed PlGF levels in 33 primiparous singleton pregnant women at 35-42 weeks of gestation who were hospitalized before the onset of labor, of which 26 women had vaginal delivery and 7 had a cesarean delivery due to fetal indications.
Disclosures: The study received no financial support. The authors declared no conflicts of interest.
Source: Tanaka H et al. Placental growth factor level is correlated with intrapartum fetal heart rate findings. BMC Pregnancy Childbirth. 2022;22:215 (Mar 17). Doi: 10.1186/s12884-022-04562-w
Key clinical point: Maternal placental growth factor (PlGF) levels measured before labor may aid the prediction of cesarean delivery owing to fetal dysfunction and fetal heart rate (FHR) function at delivery.
Major finding: Women having vaginal delivery had significantly higher pre-labor PlGF levels than those having a cesarean delivery owing to fetal dysfunction (157 ± 106 vs. 74 ± 62 pg/mL; P = .03). PlGF levels showed a significant negative correlation (r = −0.42; P = .01) with FHR findings at delivery according to the five-tier classification system.
Study details: The study analyzed PlGF levels in 33 primiparous singleton pregnant women at 35-42 weeks of gestation who were hospitalized before the onset of labor, of which 26 women had vaginal delivery and 7 had a cesarean delivery due to fetal indications.
Disclosures: The study received no financial support. The authors declared no conflicts of interest.
Source: Tanaka H et al. Placental growth factor level is correlated with intrapartum fetal heart rate findings. BMC Pregnancy Childbirth. 2022;22:215 (Mar 17). Doi: 10.1186/s12884-022-04562-w