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Microbiome effect on Fertility and on Success of Assisted Reproductive Technologies



According to Veronika Günther and the team from Kiel University, Germany, research has indicated that a microbiome not dominated by Lactobacillus is linked to dysbiosis and potentially bacterial vaginosis. Such imbalances detrimentally affect implantation rates in assisted reproductive technologies (ART) and could lead to recurrent miscarriages. The team suggests that microbiome screening, combined with antibiotic and/or probiotic treatments, could enhance pregnancy outcomes. They state – “crucial factors responsible for successful implantation of the embryo are the endometrium, its microbiome, and immunological aspects”.[1]


Microbiome effect on Fertility and success of in vitro fertilization

In a study conducted by Haahr et al., 84 patients undergoing in vitro fertilization (IVF) treatment were examined. The clinical pregnancy rate was found to be 35% (29 out of 84 patients). Notably, only 9% (2 out of 22 patients) with abnormal vaginal microbiota identified through quantitative polymerase chain reaction (qPCR) achieved clinical pregnancy, indicating a significant correlation (p = 0.004).

A prospective study in the Netherlands, which included 192 women, showed that those with a lower percentage of Lactobacillus species in their vaginal samples prior to starting ART procedures had reduced success rates for embryo implantation. The study's predictive model identified a subset of women (17.7%, n = 34) with diminished pregnancy prospects after fresh embryo transfer. The model accurately predicted unsuccessful outcomes in 32 out of 34 cases, achieving a predictive accuracy of 94%, with 26% sensitivity and 97% specificity.[2]


Recent findings challenge the previously held belief that the endometrium is sterile, revealing that the entire sexual tract is colonized by microbes. Research by Moreno et al. demonstrated that an endometrial microbiota not predominantly composed of Lactobacillus species (less than 90% Lactobacillus species and more than 10% other bacteria) correlated with lower rates of implantation, pregnancy, ongoing pregnancy, and live births. Conversely, a Lactobacillus-dominated endometrial microbiome is significantly associated with higher implantation rates and reduced miscarriage rates. The live birth rate was markedly higher in the Lactobacillus-dominated group (58.8%) compared to the group with a non-Lactobacillus-dominant microbiome (6.7%).[3]


A 2016 pilot study revealed that women with a non-Lactobacillus dominant uterine environment (defined as less than 90% Lactobacillus spp. in overall composition) experienced a 40% decrease in pregnancy rates compared to those with a microbiome composed of more than 90% Lactobacillus spp. It is theorized that lactobacilli reduce inflammation in the endometrium, improving implantation rates. [4]


The findings suggest that imbalances in vaginal flora can be transmitted to the uterus via the vagina, potentially triggering local immune responses through chemokine activation. This could disrupt the local immune system's microcirculation and lead to recurrent miscarriages.


Giovanna Cocomazzi and colleagues emphasize the role of conditions such as bacterial vaginosis, endometritis, pelvic inflammatory disease, and inflammation in contributing to infertility. They propose that female genital tract (FGT) microbiota profiles could serve not only as indicators of pregnancy outcomes but also offer new avenues for intervention. Strategies involving manipulation of the genital tract microbiota may enhance pregnancy rates in women undergoing ART. Evaluating FGT microbiota before ART and possibly integrating probiotic/prebiotic and antibiotic therapies could improve IVF outcomes. [5]


References

[1] Veronika Günther et al. Vaginal Microbiome in Reproductive Medicine. Diagnostics (Basel). 2022 Aug; 12(8): 1948. Published online 2022 Aug 12. doi: 10.3390/diagnostics12081948

[2] Koedooder R., Singer M., Schoenmakers S., Savelkoul P.H.M., Morre S.A., de Jonge J.D., Poort L., Cuypers W., Beckers N.G.M., Broekmans F.J.M. The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: A prospective study. Hum. Reprod. 2019;34:1042–1054. doi: 10.1093/humrep/dez065. [PubMed] [CrossRef] [Google Scholar] [Ref list]

[3] Moreno I., Codoner F.M., Vilella F., Valbuena D., Martinez-Blanch J.F., Jimenez-Almazan J., Alonso R., Alama P., Remohi J., Pellicer A. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am. J. Obstet. Gynecol. 2016;215:684–703. doi: 10.1016/j.ajog.2016.09.075. [PubMed] [CrossRef] [Google Scholar] [Ref list]

[4] Claudia Nakama et al. The Continuum of Microbial Ecosystems along the Female Reproductive Tract: Implications for Health and Fertility. Pathogens. 2022 Nov; 11(11): 1244. Published online 2022 Oct 27. doi: 10.3390/pathogens11111244.

[5] Giovanna Cocomazzi et al. Microorganisms. The Impact of the Female Genital Microbiota on the Outcome of Assisted Reproduction Treatments. 2023 Jun; 11(6): 1443. Published online 2023 May 30. doi: 10.3390/microorganisms11061443.





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