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Recurrent Pregnancy Loss Association Awareness. Advocacy. Answers.
Role of Uterine Macrophages in Early Placentation and RPL
Dr. Monica Mainigi, MD, University of Pennsylvania
Dr. Mainigi is an Associate Professor in the Division of Reproductive Endocrinology and Infertility at the University of Pennsylvania. Her laboratory focuses on examining the interactions between per-implantation exposures and early placentation utilizing animal models, in vitro culture systems, and human tissues. Her work has been recognized and funded by the American Association of Obstetricians and Gynecologists Foundation (AAOGF), the American Society of Reproductive Medicine (ASRM), March of Dimes, the Chan Zuckerberg Foundation, and the NIH.
Dr. Mainigi earned her medical degree from New York University School of Medicine. She completed both her residency in obstetrics and gynecology and fellowship in reproductive endocrinology and infertility at the University of Pennsylvania.
Research Gift
$40,000 in 2025
Project Description
Immune cells in the uterus, such as macrophages, and cells of the early embryo, trophoblasts, must cooperate to form a placenta that can nourish the fetus during pregnancy. Abnormal number or function of uterine immune cells can lead to poor placental development and result in complications that threaten maternal-child health.
Abnormalities in formation of the placenta and in immune cells are seen in patients with recurrent pregnancy loss, but how these defects lead to miscarriage and how they could be used to identify at-risk patients remains unknown.
With cutting-edge methods to model early human pregnancy (implantation-on-a-chip technology), we plan to study how macrophages contribute to the formation of the placenta. We will also examine how these processes change in patients with multiple miscarriages.
This project will provide new and important information about the function of uterine macrophages in normal and abnormal pregnancies. This work will also provide a strong foundation for the exploration of other uterine immune cells in pregnancy using similar strategies, setting the stage for diagnostic and therapeutic innovations that can improve outcomes for both mother and baby.
Autoimmune, Inflammatory and Epigenetic Disruptors
Dr. Abey Eapen, MBBS, DRCOG, PhD, FCRI, University of Iowa
Dr. Eapen is a Clinical Associate Professor in the Reproductive Endocrinology and Infertility division of Obstetrics and Gynecology at the University of Iowa. His special interests and expertise are in treating persons undergoing assisted conception treatment (IUI, IVF, ICSI, etc.) and those diagnosed with recurrent pregnancy loss and recurrent implantation failure.
Dr. Eapen studied medicine at the University of Calicut, India and completed both his ObGyn residency and specialized training in Reproductive Endocrinology and Infertility in the West Midlands region of the United Kingdom. He received his PhD in Reproductive Medicine from the University of Birmingham, UK, based on his work researching the use of recombinant human granulocyte colony-stimulating factor (RH-GCSF) in women with recurrent miscarriages.
He is member of the American Society of Reproductive Medicine, the European Society of Human Reproduction and Embryology, the British Fertility Society, the American Society for Reproductive Immunology, the American Institute of Ultrasound in Medicine, and the Society for Assisted Reproductive Technologies. He serves as a peer reviewer for multiple medical journals. He is a first-year Clinical Research Training Program Scholar through the ASRM - CREST Scholarship funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. He is also the director for REI Advanced Elective Rotation for medical students at the University of Iowa.
Research Gift
$40,000 in 2024
Project Description
Studies suggest that at least some unexplained miscarriages are due to an abnormal response in the mother's immune system. Scientists believe these unusual changes lead to the failure of an established pregnancy.
While some tests are available to check for inflammation and abnormal changes in the immune system, a major hurdle is the lack of laboratory tests that can diagnose a contributing condition with good confidence. Dr. Eapen believes that there are some simple and inexpensive tests that can help provide more information as to why repeated pregnancy loss happens.
His project plans to select a group of people with a history of repeated miscarriages and offer them some simple and low-cost screening tests (in addition to the standard tests they will receive as part of routine care). His team will combine these laboratory values with overall patient health data.
The hope is that this study will offer crucial information on the causes of some unexplained pregnancy loss and help design further studies to research medications that may prevent future losses.
Role of Sperm DNA Fragmentation in RPL
Dr. Winifred Mak, MD, PhD, University of Texas
Dr. Mak is an Associate Professor at UT Health Science San Antonio as well as Associate Professor at Dell Medical School, UT Austin. She is the director of the Early Pregnancy Loss program at UT Health Austin.
Dr. Mak specializes in understanding oocyte and early embryo biology. Her research focuses on infertility, recurrent pregnancy loss and premature ovarian insufficiency. Her publications have appeared in high-impact journals, and she has received numerous awards at the national and international levels. Dr. Mak's work has been supported by several grants through agencies such as the National Institutes of Health, the American Society for Reproductive Medicine and the Medical Research Council.
Dr. Mak earned her medical degree from the United Medical and Dental Schools of Guy’s and St. Thomas’ Hospitals. She completed a residency in obstetrics and gynecology at Addenbrooke’s Hospital in Cambridge, a second residency in obstetrics and gynecology at Cedars-Sinai Medical Center, and a fellowship in reproductive endocrinology and infertility at the University of Pennsylvania.
Research Gift
$40,000 in 2023
Project Description
There is currently a major knowledge gap in our understanding of the role men and sperm play in recurrent pregnancy loss. Most prior research has focused on the female partner; thus, current diagnostic testing for RPL is mostly female-centered. However, there is growing evidence suggesting a male-factor contribution to recurrent pregnancy loss.
This study aims to identify the types of DNA damage in sperm and how these sperm abnormalities can lead to recurrent pregnancy loss. This could lead to a paradigm shift in the diagnostic work-up of couples to include molecular analysis of sperm.
Inherited Genetic Variants and Unexplained RPL
Dr. Tsegaselassie Workalemahu, PhD, MSc, University of Utah
Dr. Workalemahu is an assistant professor of obstetrics and gynecology in the division of maternal-fetal medicine and an adjunct assistant professor of internal medicine in the division of epidemiology. His research program is investigating the genetic and epigenetic mechanisms related to obstetric complications and their short- and long-term adverse outcomes.
Research Gift
$40,000 in 2022
Project Description
Presently, there are knowledge gaps regarding the causes of pregnancy loss and its recurrence. These knowledge gaps have prompted the use of diagnostic tests and treatments that increase cost, anxiety and even cause harm without clear efficacy.
If the genetic factors that are relevant for pregnancy loss and normal pregnancy are determined, expensive but non-specific, diagnostic evaluations and interventions for couples suffering the loss could be avoided.
This study is aimed at determining specific genetic mutations that cause pregnancy loss by conducting whole genome sequencing analysis of DNA from families who have lost pregnancies.
Conclusions and Impact
Dr. Workalemahu and his team identified inherited genomic regions in the placenta that contribute to stillbirth. They also identified genomic regions implicated in in utero development, pregnancy loss, and infertility which warrant further investigation and functional studies.
These findings provide a springboard for further investigation into the functional roles of inherited risk loci and their contribution to stillbirth, pregnancy loss, and infertility. This deeper understanding can guide the development of diagnostic tools and personalized risk assessments for couples with a family history of pregnancy complications.
Understanding the Lived Experience of Pregnancy Loss
Dr. Dana McQueen, RMA Northern California (previously University of Chicago)
Dr. McQueen is a Reproductive Endocrinologist at RMA in San Francisco and a board-certified OB/GYN. She received her bachelor’s degree from the University of California, Berkeley, medical degree from the University of California, Irvine and a master’s in clinical research from the University of California, San Diego. She then completed her residency in Obstetrics and Gynecology at the University of Chicago and fellowship in Reproductive Endocrinology and Infertility at Northwestern University Feinberg School of Medicine. Dr. McQueen received additional subspecialty training in RPL by completing a fellowship in Recurrent Pregnancy Loss at the University of Illinois.
Research Gift
$5,000 in 2021
Project Description
RPLA partnered with Dr. Dana McQueen and her former team at University of Chicago to conduct a series of interviews with people who had experienced multiple pregnancy losses. To prepare for the interviews, participants selected pictures or images that they felt reflected their experience of recurrent pregnancy loss. The images were discussed during the interviews.
The goal was to identify themes consistent across the experience of recurrent miscarriage to help doctors and scientists understand the patient experience and what they can do to better support our community.
Conclusions and Impact
Dr. McQueen and her team verified that RPL is a complex experience that causes significant and lasting effects on the mental and physical health of people trying to conceive. The interviews identified common stressors for women who experience RPL, namely mental health needs, fear, isolation, obsession, guilt, resentment, and jealously.
There is currently a lack of adequate structured support services to address the emotional burden of RPL. These findings demonstrate areas for improvement within current models of care and highlight action items to improve the patient experience in the future.
Endometrial Causes of Unexplained Pregnancy Loss
Dr. Ruth Lathi, Stanford University School of Medicine
Dr. Ruth Lathi, is a reproductive endocrinologist at the Stanford University School of Medicine. She is a Professor in the Department of Obstetrics and Gynecology, Director of the Multi-specialty Recurrent Pregnancy Loss program, and the Program Director of the REI Fellowship. Dr. Lathi has a special interest in treating recurrent pregnancy loss, the role of preimplantation genetic diagnosis in the treatment of reproductive disorders, and the prognostic value and utility of genetic testing of miscarriage tissues, and long-term outcomes of fertility treatments. (Link)
Research Gift
$8,000 in 2020
Project Description
Endometrial factors contributing to recurrent miscarriage remain poorly defined and represent a promising area of research within the field.
Notch signaling is an evolutionarily conserved pathway that important for cell-to-cell communication. Notch signaling plays a role in tissue homeostasis and repair. Studies in mouse models suggest endometrial Notch signaling through the transcription factor RBPJ facilitates embryo implantation and uterine repair following pregnancy. Small studies in women with unexplained recurrent pregnancy loss revealed decreased expression of RBPJ.
This study aims to determine Notch pathway mRNA and protein expression levels in the decidua of women with and without recurrent miscarriage. This will provide insight as to whether Notch signaling is dysregulated within the endometrium at the time of miscarriage and if it is dysregulated in the setting of recurrent miscarriage.
Conclusions and Impact
Overall, RPL patients displayed similar patterns of Notch pathway levels within decidua and chorionic villi except for NOTCH4 and JAG1. While ubiquitously present, Notch displays variable expression throughout the decidua and chorionic villi perhaps reflecting dynamic spatial expression patterns. Future larger studies to understand the expression of novel pathways, such as Notch, are warranted to advance diagnostics and therapeutics for recurrent miscarriage.