Bacteria in semen also condition pregnancy success: ‘Fertility clinics still focus mainly on the woman’

Infertility affects about 48 million couples worldwide and, in a substantial share of cases, the specific cause is never identified. In this context, the study of the relationship between reproductive health and the microorganisms that inhabit our bodies (the microbiome) and reproduction has emerged only recently, and with a strong bias. Attention has focused especially on the female body, but a study just published in The Lancet Obstetrics, Gynaecology & Women’s Health has taken a different approach. The work shifts the focus to the semen microbiome as well, examining its role in miscarriages and the success of fertility treatments.

According to the research team, the community of bacteria, viruses and fungi that live in seminal fluid could influence the chances of achieving a pregnancy. Specifically, the authors found that imbalances in these microorganisms are associated with miscarriages and fewer live births following reproductive treatment.

For Ida Behrendt-Møller, a physician and the article’s lead author, the most important element of the research is that it attempts to overcome the bias with which the microbiome and its relationship to infertility have been studied. “There has been a lot of research on the vaginal microbiome, but not on the seminal. In the latter, studies have been few and very small,” the Danish researcher says.

The study, conducted with couples treated at two university hospitals in Denmark, simultaneously analyzes three microbial ecosystems: the vaginal, the female intestinal and the male seminal. The results suggest that certain alterations in the microbiome, both in semen and in the female gut, are associated with cases of miscarriage and a lower probability of achieving a live birth after treatment.

Paradoxically, the vaginal microbiome — the most studied system to date — did not show a consistent association with live births. However, the author argues that this does not mean the vaginal microbiome has no role. “So far we have only found associations. We have not demonstrated causality,” Behrendt-Møller emphasizes.

Previous studies have linked certain bacterial alterations in the vagina to a higher risk of problems during embryo implantation. “The theory is that an altered microbiome could affect both implantation and the maintenance of pregnancy through a higher risk of infections or by triggering an immune response in the woman,” the physician says.

Pernille Neve Myers, a bioinformatician and co-author of the study, explains that the work was born from an attempt to demonstrate that relationship. If couples constantly exchange microorganisms, she argues, they may also share microbiomes capable of influencing reproduction. “We know that couples can transmit HIV and other sexually transmitted infections during sexual activity. So why wouldn’t they also share beneficial or potentially pathogenic bacteria?” the researcher asks.

A study spanning almost nine years

The study followed couples undergoing in vitro fertilization or intracytoplasmic sperm injection, and couples with recurrent pregnancy loss. They did so over nine years.

The authors explain that the lengthy process was due both to the time needed to recruit participating couples — many of whom were in emotionally difficult circumstances — and to the high cost and complexity of genetic sequencing analyses. “These people are going through something extremely hard, yet they still want to participate to improve treatments for future patients,” Behrendt-Møller says.

More than 350 women and nearly 200 men belonging to two independent cohorts with infertility or recurrent pregnancy loss took part. The patients were aged between 18 and 41 and their male partners were 18 or older.

After analysis they found that cases where semen presented a bacterial profile similar to bacterial vaginosis took longer to achieve a live birth and carried a higher risk of pregnancy loss.

Among couples undergoing in vitro fertilization, 57% of those in which the man showed this profile ultimately achieved a live birth, compared with 85% when that pattern was absent. In both cohorts, the risk of pregnancy loss also increased.

The researchers identified a pattern they called seminal dysbiosis. “We know which bacteria we consider harmful when they appear in the vagina. So we looked to see whether those same bacteria were present in semen and whether they might have the potential to negatively influence the female genital microbiome,” Behrendt-Møller explains.

However, the exact mechanism remains unknown. “It could affect implantation or the maintenance of pregnancy through the woman’s exposure to the seminal microbiome during sexual intercourse,” the physician says.

Research on the gut

Next they studied the female gut. “Our gut plays a very important role in health and disease in general. It can modulate immune response, metabolism and hormones, factors that can also be related to fertility,” the lead author explains.

Women with a more ‘disturbed’ gut microbiome showed lower odds of achieving pregnancy. “We know fertility declines rapidly after age 35, but we found that women with a less disturbed gut microbiome had better chances of conceiving,” Myers says.

They suggest this could be related to inflammation, metabolism or immune regulation. But it is still unclear. “It remains to be tested whether modifying the microbiome can increase the chances of pregnancy,” Behrendt-Møller cautions.

The author urges caution. “I would not recommend using antibiotics because we still do not know whether they would actually change the man’s or woman’s microbiome, nor whether they would improve reproductive outcomes,” she warns. “Nor can we say that a specific diet will improve the chances of pregnancy based on this study,” she adds.

Belén Acevedo Martín, a physician in the Assisted Reproduction Unit at Fundación Jiménez Díaz in Madrid, agrees with that caution. “This cannot be seen as a panacea for the cause of infertility,” says the gynecology and obstetrics expert, who did not take part in the study.

In her view, the findings must be reproduced in larger and more diverse populations, since the work was carried out exclusively with Danish patients. “Microbiome composition can vary depending on diet, geographic origin or genetics. All participants come from the same country and we know there are important differences between populations,” she notes.

She also believes it is necessary to compare these profiles with those of fertile people who have had uncomplicated pregnancies. “We can detect an alteration in patients who suffered miscarriages, but we need to know whether that same alteration is also present in women who have had children without problems,” she says.

Despite these limitations, she considers the study a significant advance. “Until now almost all research had focused on the vaginal microbiome,” she says. “This work understands the couple as a unit that shares microorganisms,” the expert adds.

Reproductive medicine has devoted efforts to understanding female physiology — a historical debt after centuries in which women were excluded from biomedical research — but that necessary shift remains biased. The male body had been left aside.

“Although a very high proportion of patients in fertility clinics receive treatment for a male factor, many times we continue treating primarily the woman,” Behrendt-Møller points out.

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