The Seminal Microbiome Emerges as a Factor in IVF Success and Pregnancy Loss

IVF.net Newsdesk

11 August 2026

| | | |

Fertility medicine has long recognised that conception and pregnancy depend on both partners, yet much of the biological investigation surrounding IVF and recurrent pregnancy loss still focuses on the woman. A large Danish study now adds a potentially important male contribution to the picture: the microbial community carried in semen.

Published in The Lancet Obstetrics, Gynaecology, & Women’s Health, the study examined gut, vaginal and seminal microbiomes in two prospective cohorts of couples receiving fertility care or evaluation for recurrent pregnancy loss. The findings do not establish that microbial imbalance causes infertility or miscarriage. They do, however, identify a seminal bacterial profile associated with lower conception and live birth rates and substantially higher odds of pregnancy loss.

The human microbiome is not limited to the gastrointestinal tract. Microbial communities also occupy the reproductive system, including semen. These communities are not necessarily harmful, and their presence should not be confused with a conventional infection caused by a single pathogen. The relevant question is whether the balance and function of the community support reproductive health or represent a state of dysbiosis.

Previous reproductive microbiome research has concentrated heavily on the vagina and endometrium. This emphasis is biologically understandable because these environments directly support implantation and pregnancy. It has also left two potentially influential compartments comparatively understudied: the female gut and the male seminal microbiome.

The new study approached reproduction as a biological system shared by a couple. Researchers analysed samples from more than 350 women and approximately 190 male partners recruited through two Copenhagen University Hospital cohorts. One cohort included couples undergoing IVF or intracytoplasmic sperm injection. The other included couples affected by recurrent pregnancy loss. Recruitment occurred between 2018 and 2023, with participants followed for pregnancy and live birth outcomes.

Vaginal and faecal samples were collected from the women, while semen samples were obtained from the male partners. The researchers used shotgun metagenomic sequencing to characterise the microbial communities, providing greater taxonomic resolution than culture-based methods and many targeted sequencing approaches.

A central finding was the identification of what the investigators called seminal V-dysbiosis. This was a seminal microbiome pattern resembling vaginal community state type IV, a diverse bacterial configuration commonly associated with vaginal dysbiosis and bacterial vaginosis. The classification describes a community-level pattern rather than the presence of one specific infectious organism.

Seminal V-dysbiosis was detected in 23 of 96 men in the IVF cohort, representing 24%, and in 39 of 96 men assessed in the recurrent pregnancy loss cohort, representing 41%. Across the two cohorts, this profile was independently associated with higher odds of pregnancy loss. The pooled odds ratio was 2.56, with a 95% confidence interval of 1.42 to 4.63.

The association remained after adjustment for factors including age, body mass index and infertility diagnosis. In the IVF cohort, seminal V-dysbiosis was also associated with reduced odds of conception per embryo transfer, with an odds ratio of 0.41.

The cumulative live birth figures make the potential clinical relevance easier to see. Among couples undergoing IVF or ICSI, 57% of those in whom the male partner had seminal dysbiosis ultimately achieved a live birth, compared with 85% of couples without the profile.

This microbial information would not be captured by a conventional semen analysis. Standard testing evaluates variables such as sperm concentration, motility and morphology. These remain essential measures of male reproductive function, but they do not describe the bacterial community in seminal fluid. A man could therefore have apparently satisfactory conventional parameters while carrying a microbial profile that may still be relevant to treatment outcome.

The female gut microbiome produced a separate signal. Greater gut dysbiosis was associated with reduced odds of conception in both cohorts, although it was not associated with pregnancy loss. The corresponding odds ratios were 0.76 in the IVF cohort and 0.54 in the recurrent pregnancy loss cohort.

Several mechanisms could plausibly connect the intestinal microbiome with fertility. Gut microorganisms influence systemic inflammation, immune regulation, metabolism and hormone processing, all of which may affect ovarian function, endometrial receptivity or early pregnancy. The present study did not determine which, if any, of these pathways explains the observed association.

Perhaps the most unexpected result concerned the vaginal microbiome. Despite being the compartment most frequently investigated in reproductive microbiome studies, vaginal community composition showed no consistent association with conception, pregnancy loss or live birth in these cohorts. This does not demonstrate that the vaginal microbiome is irrelevant. Previous studies have produced associations between vaginal dysbiosis and adverse reproductive outcomes, and differences in sampling, populations, laboratory methods and clinical endpoints can influence results. The finding does show why examining one microbial compartment in isolation may provide an incomplete picture.

The seminal association raises several mechanistic possibilities. Microorganisms and their products in semen are introduced directly into the female reproductive tract during intercourse. They could alter the local microbial ecosystem, influence mucosal immune signalling or modify the inflammatory environment in which implantation occurs. Seminal microbes might also affect sperm function before fertilisation. These possibilities remain hypotheses because the study was designed to identify associations rather than biological causation.

The work also has important limitations. It was observational, so dysbiosis may be a marker of another reproductive or health factor rather than a direct cause of failure. Some subgroup analyses were based on relatively small numbers. The seminal V-dysbiosis classification was exploratory and requires validation in independent populations. The participants were treated in Denmark, and microbiome composition can vary with geography, diet, lifestyle, medication exposure and population background.

Embryo and pregnancy-loss tissue were not comprehensively assessed for chromosomal status. This is particularly important because embryonic aneuploidy is a major cause of miscarriage and could not be fully separated from the microbial associations. The study also lacked a large comparison cohort of proven fertile couples with uncomplicated pregnancies.

Most importantly, no microbiome-directed treatment was tested. The findings do not show that antibiotics, probiotics, dietary changes or other interventions can improve conception or live birth rates. Indiscriminate antibiotic treatment could disrupt beneficial organisms and contribute to antimicrobial resistance. Clinical intervention should therefore await replicated associations, validated diagnostic definitions and controlled trials demonstrating that modifying the microbiome changes reproductive outcomes.

The immediate value of the study is conceptual. It encourages fertility specialists to regard the reproductive microbiome as a network involving both partners and several connected body sites. It also reinforces the need to investigate the male partner beyond the minimum required to obtain sperm for treatment.

If the findings are confirmed, seminal microbiome profiling could eventually complement conventional semen analysis in selected cases of unexplained infertility, repeated treatment failure or recurrent pregnancy loss. A clinically useful test would need reproducible sampling, robust control of contamination, standardised definitions of dysbiosis and evidence that the result leads to an intervention that improves outcomes.

For now, seminal dysbiosis should be viewed as a promising biomarker under investigation. The study does not offer a ready-made treatment, but it identifies a previously neglected biological variable and provides a strong reason to study fertility at the level of the couple rather than one partner alone.

Sources

4 August 2026. The Lancet