Infertility is drawing renewed scientific attention as concern over rising rates continues to grow. Although many couples and women are able to conceive with the help of assisted reproductive technologies, the underlying cause of infertility remains unknown in a substantial number of cases, leaving patients without truly effective treatment options.

One avenue of research has been to move beyond purely genital factors and investigate other factors, such as the microbiome. In fact, although the vaginal microbiome has been the focus of much of the research, there is growing interest in determining whether the microbial communities in the gut and the male reproductive tract also play a role in human reproduction.

In this regard, as Esther García Rojo, MD, PhD, a member of the Spanish Association of Urology (AEU), pointed out to El Médico Interactivo, part of the Medscape Professional Network: “According to the guidelines of the European Association of Urology, in approximately 50% of couples with infertility, there is an associated male factor, either on its own or in conjunction with a female factor. Therefore, the current recommendation is to evaluate both partners simultaneously.”

Seminal Microbiome

According to the expert, the evaluation of the male partner should go beyond semen analysis alone. An abnormal semen result may reflect an underlying varicocele, hormonal or genetic disorder, obstruction, infection, prior treatments, toxin exposure, or another cause. In some cases, it may even be related to the seminal microbiome itself.

In fact, new research published in The Lancet Obstetrics, Gynaecology, & Women’s Health simultaneously analyzed the vaginal, intestinal, and seminal microbiomes and linked them to various reproductive outcomes.

One of the most significant findings was the identification of a specific abnormality in the seminal microbiome called seminal V-dysbiosis. This pattern showed similarities to the microbial community patterns associated with states of vaginal dysbiosis. Thus, seminal V-dysbiosis was linked to an increased absolute risk for pregnancy loss in both couples undergoing in vitro fertilization and those with a history of recurrent pregnancy loss.

“This study is particularly interesting, because it highlights an element that, until relatively recently, received little attention in male reproductive evaluation: Semen contains its own microbial community, and its composition may have reproductive implications,” noted Rojo.

Regarding the results, the AEU board member summarized that in the cohort undergoing in vitro fertilization, a live birth was achieved in 57% of couples in which the male exhibited this pattern of seminal dysbiosis compared to 85% of couples in which it was not present. Additionally, an association with a higher risk for pregnancy loss was observed.

Opening New Perspectives on Fertility

However, Rojo urged caution in interpreting the findings. “This is an observational study that demonstrates an association, not causation. We cannot yet assert that seminal dysbiosis is responsible for reproductive failure nor, above all, that modifying it will increase pregnancy or live birth rates.”

Thus, the urologist emphasized that one of the key takeaways from this study is that it once again highlights the need to approach fertility from a couple’s perspective, involving the male partner much more actively.

As she pointed out, “a particularly relevant aspect is that in 30%-40% of men with abnormal semen parameters, we are unable to identify a specific causal factor: what we traditionally refer to as idiopathic male infertility. It is precisely in this group that there is a vast field of research in areas such as oxidative stress, sperm DNA fragmentation, genetics and epigenetics, and, more recently, the microbiome.”

Seminal Microbiome

Furthermore, it should be noted that applying these criteria to clinical practice requires a process that is yet to be defined. To incorporate the seminal microbiome into clinical practice, the field must move from identifying interesting associations to demonstrating that its analysis provides reproducible, clinically relevant information capable of changing patient management.

All of this involves standardizing the collection, storage, and processing of samples. We also need to reach a consensus on sequencing and analysis techniques and, above all, establish what constitutes a normal seminal microbiome and what should be considered dysbiosis.

“We need large-scale, reproducible prospective studies in different populations that link these profiles not only to semen analysis parameters but also to clinically important outcomes. Finally, to truly incorporate this into our practice, we would need to demonstrate, through clinical trials, that intervening on a specific pattern of dysbiosis improves reproductive outcomes. As of today, we are not yet at that point,” summarized Rojo.

Another question is: Should such a diagnosis be reached, what treatment could be offered at this time? Currently, there is no standard treatment for seminal dysbiosis as a clinical entity, and that point is important to emphasize so that practice does not outpace the evidence. At this stage, routine testing or treatment of the seminal microbiome would not be recommended outside of selected clinical or research settings. Future progress will likely depend on identifying specific profiles with established clinical relevance and developing interventions targeted to those findings.

New Avenues for Research

In conclusion, the urologist summarized that “one of the most interesting insights is that it forces us to stop viewing male and female fertility as two separate entities. During sexual intercourse, there is an exchange of microorganisms, and semen comes into direct contact with the female genital tract; therefore, there is a biological interaction between these two ecosystems.”

In the field of reproduction, according to Rojo, this idea opens numerous lines of research: studying whether certain microbial profiles are associated with inflammation, oxidative stress, sperm DNA fragmentation, embryo quality, implantation, or pregnancy loss and, subsequently, determining whether modifying them can improve outcomes.

“There is already data linking certain profiles of the seminal microbiome to sperm quality and DNA damage, although there are still significant limitations. Furthermore, the interest extends beyond semen. Research is underway on the interaction between the gut microbiome and male reproductive function as well as the relationship between the genitourinary microbiome and inflammation and other urological pathologies,” stated the AEU board member.

Therefore, this can be considered “a very promising but still emerging field. The next step should not be to immediately turn the seminal microbiome into a routine commercial test but rather to generate solid evidence that allows us to distinguish which associations have true diagnostic or therapeutic value,” the expert concluded.

Rojo disclosed no relevant financial relationships.

This story was translated from El Médico Interactivo on Univadis, part of the Medscape Professional Network.