Probiotic supplement has no effect on vaginal microbiome in women undergoing IVF

A 10-day course of probiotics containing two strains of lactobacilli does not appear to improve vaginal microbiome quality in women planning to undergo in vitro fertilization (IVF), according to results of a recent study presented at ESHRE 2022.

“Use of a vaginal probiotic containing Lactobacillus gasseri and Lactobacillus rhamnosus does not improve the vaginal microbiota compared with placebo in infertile women referred to fertility treatment,” said principal investigator Dr Ida Engberg Jepsen from The Fertility Clinic at Zealand University Hospital, Køge, Denmark.

The single-centre, double-blind trial was conducted between April 2019 and February 2021 and involved 74 women age 18–40 years (mean age 31 years, mean BMI 26.4 kg/m²) with unfavourable vaginal microbiome* (low or medium lactobacillus profile; 76 and 24 percent, respectively) who were scheduled to undergo IVF. They were randomized 1:1 to receive vaginal probiotic capsules (containing >10⁸ CFU of Lactobacillus gasseri and >10⁸ CFU Lactobacillus rhamnosus; n=38) or placebo (n=36) for 10 days. Women who had exposure to oral antibiotics or oral or vaginal probiotics between vaginal swab and study inclusion were excluded from the trial.

At the end of treatment (first sample), 34.2 percent of women experienced improvements in vaginal microbiome (shift in microbiota profile from low to medium, low to high, or medium to high).

Improvement in vaginal microbiome did not significantly differ between women who received probiotics and those who received placebo (28.9 percent vs 40.0 percent; relative risk [RR], 0.72, 95 percent confidence interval [CI], 0.38–1.38; p=0.32). [ESHRE 2022, abstract O-024]

During the first menstrual cycle after treatment (second sample; cycle day 21–25), 31.9 percent of women had experienced improvement in vaginal microbiome compared with baseline. Again, there was no significant difference between women who received probiotics and those who received placebo (30.6 percent vs 33.3 percent; RR, 0.92, 95 percent CI, 0.47–1.80; p=0.80).

“Studies have shown that the vaginal microbiota composition is predictive of IVF treatment outcome and suggest that dysbiosis in the reproductive tract negatively affects the chance of pregnancy through as yet unclear mechanisms,” said Jepsen and co-authors.

“[W]ith microbiota being shown to modulate organ function throughout the body, interest is growing in assessing the vaginal microbiome as a potentially treatable marker of endometrial receptivity and predictor of treatment outcome,” they said.

“The [current] study indicates that administering vaginal lactobacilli probiotics may not improve a suboptimal vaginal microbiome,” said Jepsen. However, the probiotic capsules only contained two lactobacilli strains and as such, did not incorporate all lactobacilli strains that have been implicated in fertility outcomes.

“The specific vaginal probiotic tested in this study had no effect on the favourability of the vaginal microbiome before IVF. But probiotics in general should not yet be discounted,” she pointed out. The single-centre design comprising primarily Caucasian women was also a limitation, she added.

Additionally, the approximately one-third of women who experienced spontaneous improvement regardless of probiotic treatment suggests the need for a change in approach.

“[A] spontaneous improvement rate over a period of 1–3 months may provide the basis for an alternative therapeutic approach. The strategy would involve postponing fertility treatment until spontaneous improvement occurs, but further research is needed,” said Jepsen.