Associate professor awarded $3.4M to study male factors in recurrent pregnancy loss


Winifred Mak, MD, PhD, associate professor in the Department of Obstetrics and Gynecology at The University of Texas Health Science Center at San Antonio, has received the Stephen I. Katz Early Stage Investigator Research Project Grant from the National Institutes of Health’s National Institute of Child Health and Human Development. The 5-year, $3.4 million grant will support her research on the role of sperm in recurrent pregnancy loss.

Headshot of Dr. Winifred Man in a white coat.
Winifred Mak, MD, PhD, associate professor in the Department of Obstetrics and Gynecology.

Mak is a reproductive endocrinologist and fertility specialist with UT Health Physicians. Working with patients who have experienced recurrent pregnancy loss (RPL) led her to pursue this important research.

“About 5% of couples have recurrent miscarriage, defined as having two or more miscarriages,” Mak explained. “But we don’t have answers for 50% of those couples. Investigating new causes for RPL is crucial to help couples to identify a cause and, therefore, possible therapeutic options.”

Mak’s research will also address a major gap in the understanding of recurrent miscarriage by focusing on the largely understudied role of sperm as a potential cause.

“When we do a workup of a couple, most of it focuses on the woman. Clinically, we don’t do much with the male partner,” Mak explained.

Other than a blood test to check for abnormal chromosomes, there are no routine diagnostic tests for men in couples experiencing recurrent miscarriage, she said.

However, there are potential known defects of sperm that are associated with recurrent miscarriage, particularly something known as sperm DNA fragmentation, or broken DNA strands within the sperm, Mak said.

Mak’s research seeks to further connect the dots between this association and delve deeper into understanding how sperm DNA fragmentation causes miscarriage.

“My work will drill down where in the genome these DNA breaks are occurring, and, what I think is most novel about the project, we’re going to sequence the whole genomes of miscarriages, as well as mom and dad.”

In addition to investigating the integrity of the sperm’s genome, other aims in Mak’s project will analyze the sperm’s epigenetics, examining sperm DNA methylation and sperm histones. Epigenetics factors control gene expression by mechanisms that do not change the sequence of the DNA, Mak explained.

By including this comprehensive molecular analysis of sperm genome and epigenome, the project will shift the present clinical diagnostic paradigm for RPL couples from a mainly female-centric approach to a more balanced approach, she said.

“Women have a lot of guilt with recurrent miscarriage; they put a lot on themselves,” Mak said, noting the emotional toll of recurrent pregnancy loss. “But if we have objective evidence, if we know what in the sperm is potentially causing RPL, we can find treatments and be more proactive.”

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