Semen microbiome may influence IVF success

A microbial imbalance in semen has been linked to lower live birth rates following IVF and ICSI, suggesting that male microbiome factors may play a greater role in reproductive outcomes than previously recognised.

Both the male and female reproductive tracts harbour microbiomes: communities of bacteria, viruses and fungi whose role in fertility issues has increasingly come under scrutiny. Much of that attention, however, has centred on the female body. In response, researchers from the University of Copenhagen and Copenhagen University Hospitals, Denmark, examined the gut, vaginal and seminal microbiomes of couples experiencing infertility or recurrent pregnancy loss (RPL).

'Current management of infertility and RPL focuses largely on female-directed interventions,' write the authors of the study published in The Lancet Obstetrics, Gynaecology and Women's Health. 'Incorporation of couple-level microbial assessment might represent a novel approach for risk stratification and targeted therapeutic strategies.'

The team followed 353 women and 191 male partners with fertility issues over several years, using deep shotgun metagenomic sequencing to profile their microbiomes.

Around one quarter of the male partners undergoing IVF or ICSI had a pattern of microbes in their semen that resembled the one associated with vaginal dysbiosis, when the microbiome inside the vagina becomes imbalanced and potentially harmful. The researchers called this microbial profile 'seminal V-dysbiosis', noting, however, that such classification remains exploratory and has not yet been validated.

Among couples undergoing IVF or ICSI, 57 percent of those whose male partner had seminal V-dysbiosis went on to have a live birth, compared with 85 percent of those without the microbial pattern. These couples also waited longer before having a baby, with lower rates of pregnancy establishment per embryo transfer.

In addition, the researchers found an association between seminal V-dysbiosis and pregnancy loss. Across the IVF/ICSI and recurrent pregnancy loss groups, couples faced an absolute increase in pregnancy loss risk of 21.4 percentage points if the men had this microbial profile.

Microbiome testing is not currently included in routine fertility assessments, meaning that men with imbalanced microbial profiles could potentially show seemingly normal semen parameters.

Semen comes into contact with the female reproductive tract during intercourse, allowing female and male microbiomes to influence each other. An altered microbiome could negatively impact fertility 'through a higher risk of infections or by triggering an immune response in the woman', lead author Dr Ida Behrendt-Møller told El País.

However, the study did not establish how microbial imbalance in semen might affect implantation or pregnancy, and it could not show that the altered profile directly caused infertility or pregnancy loss.

The team also examined the women's gut microbiome. Greater gut microbial imbalance was associated with lower chances of conception during fertility treatment and a longer time to conceive, but it was not associated with pregnancy loss. The vaginal microbiome showed no consistent association with reproductive outcomes.

These findings highlight the importance of considering both partners when investigating reproductive microbiomes. However, Dr Behrendt-Møller warned that further research is needed before microbiome-based treatments can be recommended. The study remains small-scale and observational, lacking a control group and direct testing of whether altering microbial profiles could improve reproductive outcomes.