Pregnancy- and abortion-related mortality in the US, 2018-2021
JAMA Network Open
About The Study:
The findings of this study suggest that by taking away the option to end a pregnancy, abortion bans force pregnant people to take on the substantially increased health risks associated with continued pregnancy.
Corresponding Author: To contact the corresponding author, Maria W. Steenland, SD, email msteenla@umd.edu.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamanetworkopen.2025.54793)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.
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About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.
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JAMA Network Open
Study reveals genetic factors influencing pregnancy loss
Variants in maternal genes associated with chromosome errors in embryos
Johns Hopkins University
video:
The gain of an extra chromosome during egg formation. The protein SMC1B is part of the ring-like cohesin complex that holds chromosomes together. The study found that variation in the SMC1B gene contributes to the risk of these errors.
view moreCredit: Thom Leach/Amoeba Studios
By studying genetic data from nearly 140,000 IVF embryos, scientists have with unprecedented detail revealed why fewer than half of human conceptions survive to birth. The research uncovered the strongest evidence yet for how common genetic differences leave some individuals more vulnerable to pregnancy loss.
The vast dataset allowed the Johns Hopkins University-led team to demonstrate robust connections between specific variations in a mother’s DNA and their risk of miscarriage.
The findings shed new light on human reproduction and suggest pathways for developing treatments to lower the risk of pregnancy loss.
The federally-funded work is published today in Nature.
“This work provides the clearest evidence to date of the molecular pathways through which variable risk of chromosomal errors arises in humans,” said senior author Rajiv McCoy, a Johns Hopkins computational biologist focused on the genetics of human reproduction. “These insights deepen our understanding of the earliest stages of human development and open the door for future advances in reproductive genetics and fertility care.”
Pregnancy loss in humans is common, with about 15% of recognized pregnancies resulting in miscarriage and many more conceptions being lost at early stages without people realizing it. Scientists have long known that the main reason is extra or missing chromosomes. Down syndrome, caused by an extra copy of chromosome 21, for example, is one of the few chromosome abnormalities of this type that is survivable.
Most chromosome errors originate in the egg and increase in frequency with a mother’s age. More mysterious is how factors beyond age, such as genetic differences, may predispose a person to produce eggs with abnormal numbers of chromosomes in the first place.
Figuring that out requires analyzing genetic data from large numbers of embryos before pregnancy loss, as well as their biological parents.
“This is a trait closely related to survival and reproductive success, so evolution will only allow genetic differences with small effects to be common in the population,” McCoy said. “You need large samples to be able to detect these small effects.”
The team here, co-led by Johns Hopkins first authors Sara Carioscia, a graduate student, and postdoctoral fellow Arjun Biddanda, studied data from a company that tests the viability of in vitro fertilized embryos through paired analysis of DNA from their parents. Researchers studied 139,000 embryos from 23,000 sets of parents and created a computer program to find patterns within the massive data set.
“Here the power comes from these huge sample sizes,” McCoy said. “That allowed us the scale and resolution to discover several of the first well-characterized associations between the mom’s DNA and her risk of producing embryos that will not survive.”
The strongest associations appear in genes that govern how chromosomes pair, recombine, and are held together during egg formation, including a gene (SMC1B) that encodes part of the ring-shaped structure that encircles and binds chromosomes, the team found. These rings are essential for accurate chromosome segregation and tend to break down as women age.
“This finding is especially compelling,” McCoy said, “because the genes that emerged from our study in humans are exactly the ones that experimental biologists have detailed over decades as critical for recombination and chromosome cohesion in model organisms like mice and worms.”
Strikingly, these same genetic variants that influence the risk of pregnancy loss are also associated with recombination, the genetic shuffling process that generates diversity when eggs and sperm are made, they found.
Female meiosis, or the cell division necessary for reproduction, begins during fetal development, when chromosomes pair and recombine. The process then pauses for decades, until ovulation and fertilization. During this long pause, problems in the machinery that keeps chromosomes together can cause them to separate too soon, leading to an abnormal chromosome count when meiosis resumes.
“Our results demonstrate that inherited differences in these meiotic processes contribute to natural variation in risk of aneuploidy and pregnancy loss between individuals,” McCoy said.
Despite identifying genes associated with this cause of pregnancy loss, it will remain difficult to predict an individual’s risk, McCoy said. That is because individual common genetic variants tend to have a small impact on aneuploidy risk, compared to maternal age and environmental factors. Nevertheless, these genes are promising targets for future drug development.
The team is now studying rare variation in maternal and paternal genomes that may have larger effects on aneuploidy risk. They are also using new technologies to better understand how even smaller, poorly understood genetic changes contribute to pregnancy loss.
Authors include Margaret R. Starostik and Xiaona Tang of Johns Hopkins; Eva R. Hoffmann of the University of Copenhagen, Denmark; and Zachary P. Demko of Natera, Inc.
A routine IVF embryo biopsy for clinical genetic testing, which provided the large-scale genetic data analyzed in this study.
Credit
Thom Leach/Amoeba Studios
Journal
Nature
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