IMBALANCE in the gut microbiome of women and seminal microbiome in men may be linked to infertility and other reproductive issues, a new study shows
Researchers in Denmark investigated the link between vaginal, gut, and seminal microbiomes and reproductive outcomes in couples struggling to conceive or facing repeated loss of pregnancy. They found that gut dysbiosis in women and dysbiosis-associated microbial profiles in semen may be linked to reduced reproductive success
Couple Microbiomes Investigated in Cohort Studies
Researchers in Denmark investigated the vaginal, gut, and seminal microbiomes of couples experiencing infertility or recurrent pregnancy loss (RPL) through two independent, multicentre, prospective cohort studies
They analysed two independent groups: couples undergoing IVF or intracytoplasmic sperm injection (ICSI), and couples who have experienced repeated pregnancy loss (RPL), defined as three or more consecutive losses (including very early, biochemical losses) or two unexplained losses in the second trimester
In total, the IVF cohort included 249 women and 95 men or couples, while the RPL cohort included 104 women and 96 men or couples
To characterize each participant’s microbiome, the team used deep shotgun metagenomic sequencing, a technique that reads the genetic material of all bacteria present in a sample, rather than targeting just one type, on vaginal and gut (rectal/faecal) samples from female participants and semen samples from male partners
Participants were then followed prospectively for reproductive outcomes
Gut Dysbiosis Linked to Reduced Pregnancy Establishment
One of the study’s key findings was an association between higher gut dysbiosis in female participants and poorer reproductive outcomes
Increasing gut dysbiosis (imbalance of microbiome), measured using the Enterotype Dysbiosis Score (EDS), was consistently associated with a longer time to livebirth in both cohorts. Each one-unit increase in the dysbiosis score reduced the rate of achieving livebirth by about 16% for the IVF group and up to 28% for the RPL group
Higher dysbiosis was also associated with a reduced likelihood of pregnancy establishment, which was defined differently for each group. For the IVF cohort, as the pregnancy rate per embryo transfer, and in RPL cohort, as whether the couple conceived within one year
Using the continuous gut dysbiosis score, researchers found that each 1-point increase in gut dysbiosis as per this score was associated with roughly a 6-7 percentage point drop in the chance of pregnancy establishment in both cohorts
Importantly, gut dysbiosis was not associated with pregnancy loss once pregnancy had been established, suggesting its potential influence may occur earlier in the reproductive process
Seminal Microbiome Associated with Pregnancy Loss
The study also identified an association between a dysbiosis-associated microbiome profile of the semen and reproductive outcomes
Because there is currently no validated classification system for seminal dysbiosis, researchers used an exploratory classification called seminal vaginal-dysbiosis (V-dysbiosis), based on similarity to microbial profiles associated with vaginal dysbiosis
Seminal V-dysbiosis was associated with a longer time to livebirth. In the IVF cohort, livebirth occurred in 57% of couples with seminal V-dysbiosis compared with 85% without it
The association was particularly notable for pregnancy loss. Seminal V-dysbiosis was associated with an increased risk of pregnancy loss in both cohorts. When the results were combined, V-dysbiosis was associated with an estimated 21.4-percentage-point increase in pregnancy loss risk
A Couple-Level Approach to Reproductive Health?
Notably, vaginal dysbiosis showed no consistent association with reproductive outcomes
Together, these findings suggest that reproductive microbiome research may need to move beyond the female reproductive tract and consider the microbial environment of both partners. Semen represents a repeated microbial exposure to the female reproductive tract, potentially allowing microbial exchange between partners
However, the findings do not establish causation. The study was observational, included no fertile control group, and the seminal dysbiosis classification has not yet been independently validated
For this reason, researchers emphasise the need for further studies and randomised trials to determine whether microbiome-targeted interventions, such as antimicrobial treatment or probiotics, could improve reproductive outcomes
Reproductive failure affects millions of couples worldwide, yet the underlying cause remains unexplained in many cases. This study provides new evidence that both female gut dysbiosis and the seminal microbiome may be relevant to reproductive success, opening the door to a broader, couple-level understanding of infertility and pregnancy loss
Reference
Behrendt-Møller I et al. Gut, vaginal, and seminal microbiomes in couples with infertility or recurrent pregnancy loss: a two-cohort prospective study of reproductive outcomes. The Lancet Obstetrics, Gynaecology, & Women’s Health, 2026
Featured image: Liubomiron AdobeStock
Author:
Cecilia Adamou
