Megan Hanson was eight (8) weeks pregnant in 2019 when she experienced a miscarriage — her sixth (6th) consecutive loss in as many years. It felt particularly cruel after a second IVF transfer. She and her husband, Ben Burnham, were devastated, physically and financially drained — and deeply frustrated by the lack of answers or support for people like them who had experienced recurrent miscarriages.
Driving to a Seattle clinic for surgery to remove fetal tissue, the two felt the heaviness of the moment. They knew they were done trying. Over the previous six (6) years they had become medical sleuths, reading studies, speaking to doctors, and examining all treatments possible. Most doctors pinned Hanson’s losses on fetal abnormalities; however, she felt there was more to it. The fact that her miscarriages were unexplained, she says now, was “unacceptable.”
Lack of research into miscarriage in the U.S. — its prevalence, its causes, and how best to treat people who’ve experienced pregnancy loss — has helped to reinforce what has long been a culture of silence and shame around miscarriage. That knowledge gap means that people who miscarry, and miscarry repeatedly, like Hanson, are not given the emotional support they need at a time when they are most vulnerable. Equally important, they are not given the medical treatment, screening, and support from the health care system that might help them avert future miscarriages. And research into the possible reasons for recurrent pregnancy loss has been limited and siloed, several experts told STAT.
The dearth of knowledge about pregnancy loss and miscarriage is far greater in the United States than in other industrialized countries, according to physicians, policymakers, and researchers who spoke with STAT. Countries with national health systems such as the United Kingdom (UK) have standardized medical records and better aggregate health data, enabling medical researchers to conduct studies and trials more readily, and to examine the physical, emotional, and economic toll of pregnancy loss. Nordic countries, too, have national health systems that provide more open access to data, enabling researchers to study the impact of loss to a greater extent than it is studied in the U.S.
One U.K. estimate of the economic devastation of miscarriage there pegged it at £471 million, or $611 million, per year. Yet, no such estimate of the economic cost of miscarriage in the U.S. — generally defined as a loss in the first 20 weeks of pregnancy — exists. The Centers for Disease Control and Prevention (CDC) does not publish data on miscarriage; however, estimates suggest that 10% to 25% of all pregnancies in the U.S. end in miscarriage. The American College of Obstetricians and Gynecologists (ACOG) says that fewer than 5 in 100 people have two (2) miscarriages in a row.
Hanson now has two (2) children. However, she knows from her own experience the pain of miscarriage, the mental health cost, and the urgent need for better data and more research in the U.S. “I wish that the system had been better set up to support that piece of it for me,” Hanson said. “It’s like you’re grieving this imagined future that you had.”
Funding research to ‘find answers faster’
Reflecting on their many losses some years ago, Hanson and her husband stepped boldly into the information void: In 2019, after consulting extensively with doctors and researchers, they set up the Recurrent Pregnancy Loss Association (RPLA), focused on eliminating recurrent pregnancy loss and preventing unnecessary losses.
The nonprofit offers support and resources to individuals and couples who’ve experienced the trauma of recurrent miscarriages. And it is partnering with the medical and scientific communities to “find answers faster,” said Hanson, who worked for several years at the pharmaceutical company Baxter and witnessed fruitful partnerships between industry researchers and patient groups. While there are a few organizations that focus on stillbirth — defined as pregnancy loss after 20 weeks of gestation — the RPLA is the first to focus exclusively on recurrent miscarriage research.
So far, the RPLA has distributed $133,000 to reproductive endocrinologists, experts in maternal-fetal medicine, and others to explore how various factors — from sperm DNA fragmentation to endometrial “notch signaling” to abnormal responses in the mother’s immune system — may play a role in pregnancy loss.
Some of the few experts in the U.S. leading research on miscarriage and pregnancy loss are funded by the RPLA, including Winifred Mak at the University of Texas at Austin; Abey Eapen, at the University of Iowa Health Care; and Ruth Lathi, at Stanford University’s School of Medicine . All three (3) are reproductive endocrinologists and infertility researchers.
Historically, the National Institutes of Health underfunded miscarriage research in the United States and there was limited private funding, said Mak. In recent years, that is started to shift. The NIH has funded studies into recurrent miscarriage at Yale and Stanford and Mak’s research on sperm DNA fragmentation, which was also supported by the RPLA.
Mak hopes to discover the precise type of damage to sperm DNA — single-stranded or double-stranded — that is implicated in losses. In cases where it is double-stranded, Mak will do additional molecular analysis to determine the region where the damage is located. Mak, who completed medical school in the U.K., says that it is critical to do research in the United States because European research does not always translate to the diverse and heterogeneous population of the U.S. Greater funding for miscarriage research holds the promise of providing “patients with more answers and hopefully more therapeutic options,” she said.
Before Eapen went to the University of Iowa, he trained at Tommy’s National Center for Miscarriage Research in the U.K. There he witnessed how collaboration among researchers and funding for women’s health made large-scale clinical trials possible. “To finish that type of research in a timely fashion [in the U.S.] would be a big hurdle at this point in time,” he said.
Today Eapen is using funding from the RPLA to test selected patients’ various biomarkers for inflammation and their telomere length for epigenetic changes that may be associated with miscarriage. These are not considered standard tests for miscarriage. The goal is to produce high-quality research using consistent techniques and the same laboratory to ensure accuracy in their results.
At Stanford University’s School of Medicine, reproductive endocrinologist Lathi has seen how “life-altering” miscarriage can be for patients. Fetal tissue, she says, can offer answers in pregnancy loss just as an autopsy would provide clarity after death. However, unlike in Europe, where systems are standardized and early pregnancy centers can provide care and capture fetal tissue when a miscarriage is actually happening, the U.S. does not have that level of focused care — leaving many patients without answers.
Together with partners across multiple universities, Lathi is recruiting participants for the HOPE study, which uses genome sequencing of parental and fetal DNA to determine which genes contribute to pregnancy loss. That is in addition to her research supported by a grant from RPLA, which examines endometrial tissue for notch signaling — a process that is an evolutionary pathway for communication between cells. That work could clarify if the signaling is dysregulated during a miscarriage or recurrent miscarriage.
Researchers like Mak, Eapen, and Lathi say there is potential for more research in the U.S. However, collaboration among researchers, which involves coordinating efforts across multiple universities, requires significant resources. The U.S. would have to vastly increase funding for women’s health — which has been historically deprioritized — to produce the type of large-scale clinical trials on miscarriage and recurrent miscarriages involving thousands of participants like their European counterparts, they said.
REFERENCE: STAT; 21 AUG 2024; Sadia Rafiquddin