Don't Neglect the Man: Sperm Damage Clues to Recurrent Miscarriage

Tara Haelle

April 01, 2019

NEW ORLEANS — New evidence suggests that oxidative stress and DNA damage in sperm may contribute to repeated miscarriages in female partners, according to a small study presented here at ENDO 2019: The Endocrine Society Annual Meeting.

A strong understanding of female factors that can contribute to recurrent pregnancy loss exists, but researchers know far less about male factors that may play a role, lead researcher Anastasia P. Dimakopoulou, MBBS, of Imperial College London, UK, told attendees.

Recurrent pregnancy loss — at least three consecutive miscarriages (before 20 weeks' gestation) — occurs in 1-2% of couples, and about half of cases are unexplained.

"Affected women undergo many tests to determine the cause, but many cases have no identified cause," second author Channa Jayasena, MD, PhD, also of Imperial College London, said in a prepared statement.

"It's important to know that both males and females need to be screened for conditions that can be acknowledged and investigated when they attend miscarriage clinics," Dimakopoulou told Medscape Medical News.

And it's key "for clinicians to ask male partners what their medical history is, examine them, and maybe offer a further investigation so that we can establish where the problem is," and perhaps offer the couple better treatment, she added.

Asked to comment, Bradley Anawalt, MD, chief of medicine, University of Washington Medical Center in Seattle, and a session moderator, said: "These preliminary findings make you aware of the fact that, when a woman has recurrent pregnancy loss, that doesn't happen in isolation."

"That really reverses the way clinicians often think about this," he told Medscape Medical News. "They're focused on the patient having recurrent pregnancy loss, but there's a partner involved, so the real message is that there may be two components contributing."

But Stephanie Page, MD, PhD, professor of endocrinology at the University of Washington in Seattle, urged caution, noting it is still early days for this work.

"I don't think it's ready for prime time," she told Medscape Medical News, referring to potentially administering the study's tests to male partners in clinical practice. Too many questions need answers, such as when to test, how often, and how to interpret the findings, she stressed.

Sperm Damage May Play a Role in Pregnancy Loss

By way of background, Jayasena explained: "We know that sperm play an important role in the formation of the placenta, which is critical for survival of an unborn baby."

Known risk factors for male infertility include genitourinary infection, varicocele, scrotal heat, and obesity. Dimakopoulou and colleagues hypothesized some of these conditions might contribute to reactive oxygen species in semen, which could then cause sperm DNA fragmentation and subsequent pregnancy loss.

They set out to compare sperm quality and testosterone levels among 50 men whose female partners had recurrent pregnancy loss (RPL) with 63 men of control couples.

The RPL partners (females) were a little older (average age 37 vs 30 years) and had a slightly higher body mass index (27.6 vs 24.8 kg/m2) compared with controls. Rates of smoking and alcohol consumption were similar in both groups.

About 3.4% of sperm had normal morphology among the males of couples whose partners suffered recurrent miscarriages, compared with 4.5% of controls' sperm (P < .001), and DNA damage was more than doubled in RPL male partners (mean DNA fragmentation index [DFI], 16.3) compared with controls (DFI, 7.4; P < .0001).

The greatest difference between the groups was in seminal reactive oxygen species levels, which were fourfold higher in RPL male partners compared with controls (9.3 vs 2.3 RLU/sec/106 sperm; P < .05).

The RPL male partners also had slightly lower but nonsignificant mean serum morning testosterone than controls (15.8 vs 17.9 nmol/L; P > .05).

"Our data have important implications for the management of couples with RPL as male partners of [such] women may benefit from routine assessment of reproductive endocrine and sperm function," note Dimakopoulou and colleagues.

Promising Research but Current Study Has Limitations

Anawalt, session moderator, told Medscape Medical News that although this study can't identify the specific problem, "it does point to the fact that the male partner may be either contributing or even the primary culprit."

Indeed, it may one day "be possible to design future drugs to stop sperm DNA damage to treat couples with recurrent pregnancy loss and reduce the risk of miscarriage," said Jayasena, adding, however, that the possibility is still far off.

Researchers also acknowledge there were study limitations, including that the control males had not been confirmed as proven fathers and no experimental model currently exists to explain how sperm DNA damage could cause recurrent pregnancy loss, Dimakopoulou said.

Another notable limitation was the lack of replicability, or multiple semen samples, noted Page.

Frances Hayes, MBBCh, clinical director of the reproductive endocrine unit at Massachusetts General Hospital, Boston, agreed, telling Medscape Medical News, "Parameters in semen analysis can change a lot from one collection to another even in completely normal, healthy men. So when you see data from just one sample, it's hard to make any firm conclusions."

But she agreed with the researchers and other commentators on the key take-home message: "Don't neglect the male. Sometimes we'll screen both potential parents for balanced translocations in the chromosomes, but most of the focus is typically on the woman."

The study had no external funding. The authors, Anawalt, Page, and Hayes have reported no relevant financial relationships.

ENDO 2019. Presented March 24, 2019. Abstract OR18-5.

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