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A Potential Role for Sperm in Repeat Miscarriages

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Sadly, in their bid to conceive a child, some individuals may face recurrent pregnancy loss (RPL), also known as recurrent miscarriage. Defined as the consecutive loss of three or more pregnancies before 20 weeks gestation, RPL affects approximately 1% of women.

Currently, only a handful of clinically accepted physiological causes for RPL exist. These include but are not limited to; parental chromosomal abnormalities, untreated hypothyroidism, uncontrolled diabetes mellitus, uterine anatomic abnormalities, immunologic abnormalities and endocrine disorders. Unfortunately, not all RPL’s fit into one of these categories, and so according to the Miscarriage Association, more than half of all cases will go unexplained.

Women and their partners are often desperate for answers as to the cause of their losses. Channa Jayasena, M.D, Ph.D., of Imperial College London, says: “affected women undergo many tests to determine the cause, but many cases have no identified cause”.

Novel research presented at the Endocrine Society’s annual meeting (ENDO 2019) has investigated the role of sperm DNA damage in the male partner in RPL. “We know that sperm play an important role in the formation of the placenta, which is critical for survival of an unborn baby,” adds Jayasena, lead researcher. The research findings are published in the journal Clinical Chemistry

The study was designed to investigate whether the male partners of women experiencing RPL may have an increased risk of sperm DNA damage, known to adversely affect fertility. The researchers analyzed the sperm of 50 healthy men in comparison to the sperm of 63 men whose partners were affected by RPL.

“We used microscopy to check sperm function, checked the change of color of luminol to measure how much oxidation was in the semen, and Halosperm kits to look for damage in sperm DNA,” explains Jayasena.

The findings showed that men whose female partners had experienced RPL had twice as much sperm DNA damage when compared to the control group of unaffected men, in addition to a four-fold increase in the amount of reactive oxygen species (ROS). ROS cause damage to DNA in cells such as sperm.

Jayasena and his team hope their findings may open up avenues for the development of novel pharmaceutical agents for RPL: “the first step to develop a drug to treat male-related RPL is to identify what causes it. Our study suggests that sperm DNA fragmentation and semen ROS may be involved in RPL. The next step needed is to find ways of reducing sperm DNA fragmentation and semen ROS, then seeing if that can reduce RPL risk."

These findings certainly warrant further work in the field, and it seems that couples experiencing RPL are more than willing to offer their help: “we were struck by the enthusiasm of men with RPL to participate in the study and improve the treatment of future couples with RPL. It was actually much more difficult to recruit healthy volunteers,” adds Jayasena. 

Reference: Jayasena et al. 2019. Reduced Testicular Steroidogenesis and Increased Semen Oxidative Stress in Male Partners as Novel Markers of Recurrent Miscarriage. Clinical Chemistry. DOI: 10.1373/clinchem.2018.289348.