Harnessing the Microbiome: Advancing IVF Success through Targeted Intervention

A prospective cohort–intervention study in 257 IVF patients demonstrates that targeted modification of the endometrial microbiome substantially increases clinical pregnancy rates, identifying a modifiable maternal contributor to implantation failure.

Routine IVF workups rarely include endometrial microbiome profiling, but these data challenge that omission: in expert practice, profiling can function as an actionable diagnostic adjunct and may warrant selective integration into clinic workflows.

Improving a non–Lactobacillus-dominant (non-LDM) state to Lactobacillus dominance was associated with an 81.4% relative improvement in pregnancy success. In the prospective cohort/intervention study with endpoints of clinical and ongoing pregnancy, investigators used targeted treatment and repeat testing after profiling the endometrial microbiome by NGS 16S rRNA; treated non-LDM patients who converted to LDM achieved pregnancy rates equivalent to—or exceeding—those in the original LDM group.

Species-level differences matter: a high relative abundance of Lactobacillus iners (≥74.2%) correlated with lower pregnancy success compared with other Lactobacillus-dominant profiles. Prioritizing species-level reporting helps distinguish L. iners–predominant profiles from more favorable Lactobacillus-dominant states.

Semen microbial composition can also influence male fertility and couple-level IVF outcomes. Current evaluation typically pairs sequencing (16S rRNA or metagenomics) with culture-informed interpretation alongside standard semen analysis. Interventions under study include targeted antibiotic strategies and probiotics, but these approaches lack definitive endorsement—microbiome data should be integrated with traditional fertility metrics before changing management.

Key Takeaways:

• Converting non-LDM to LDM was associated with an 81.4% relative improvement in pregnancy success (prospective cohort/intervention, n=257), identifying a potentially modifiable maternal factor in implantation failure.
• High relative abundance of L. iners (≥74.2%) correlated with poorer pregnancy outcomes; species-level reporting is clinically informative.
• Integrate microbiome profiling selectively and interpret results alongside semen analysis and embryo assessment before altering treatment pathways.