Women with repeated implantation failure (RIF) and recurrent pregnancy loss (RPL) experienced increased microbiome diversity with pathogenic species and a loss of Lactobacillus dominance in the lower female reproductive , according to findings published in the International Journal of Molecular Sciences.
Findings indicated that a Lactobacillus-dominated vaginal microbiota was beneficial for embryo implantation. In addition, pathogenic species were found in the dysbiotic vaginal microbiomes of women with both RIF and RPL including: Gardnerella, Prevotella, Atopobium, Megasphaera and Sneathia.
“A state of microbiota dysbiosis with an overabundance of pathogenic species or the absence of Lactobacillus-dominated vaginal and endometrial microbiomes might trigger inflammation, hinder the process of embryonic implantation and interfere with early pregnancy,” wrote researchers from Erasmus University Medical Center in The Netherlands.
Biotics to fight the growing prevalence of fertility issues
Commenting independently on the study, Ana Nunes, global business development director of Zinereo Pharma, stressed the importance of the findings for the development of biotics to fight the growing prevalence of fertility issues. Zinereo Pharma markets Fertibiome, a fertility probiotic developed in partnership with Spanish R&D firm Probisearch.
“With 48 million couples and 186 million individuals grappling with infertility, affecting about 15% of couples, there is a critical need for innovative solutions,” Nunes told NutraIngredients. “Approximately 15% to 30% of infertility cases being idiopathic, meaning their causes remain unknown.”
She said the growing body of scientific research, including evidence backing the role of the endometrial and vaginal microbiomes in pregnancy outcomes, has prompted Zinereo Pharma to initiate further clinical trials on Fertibiome.
"Recent scientific studies reveal a paradigm shift – the urogenital tracts are not sterile; they contain 9% of the human microbiome," she explained. "A healthy urogenital microbiome significantly improves implantation rates and pregnancy outcomes, yet 40% of women undergoing assisted reproductive treatment face dysbiosis challenges."
Fertibiome, which contains Ligilactobacillus salivarius PS11610 strain, was initially found to alter the bacterial composition of both female and male urogenital tracts and improve the immune status of couples experiencing infertility due to bacterial dysbiosis, leading to a significant increase in the chances of successful pregnancy in 40% of cases.
"Our collaborative pursuit stems from the evolving understanding of the microbiome's role in fertility," Nunes added. "We believe that our joint expertise and the latest research insights position us to deliver impactful solutions. We are optimistic that the ongoing research will yield promising results, marking an advancement in addressing infertility challenges and improving lives."
The vaginal and endometrial microbiome
There have been significant advancements in fertility treatments in recent years, however the underlying causes of many adverse pregnancy outcomes are largely unknown. This is attributed to the restrictions on investigating the intra-uterine environment around and after human embryonic implantation due to the potential risks in early pregnancy.
The uterine microenvironment and the endometrial lining are crucial during the final stages of pre-implantation during assisted reproductive treatment (ART) to enable successful implantation of the embryo. In addition, the microbiota is known to play a key role in infant health and long-term immunity.
Studies suggest that the microbiome may play a significant role in pregnancy outcomes, with researchers theorising that the microbiota’s interaction with host immunity can imbalance cytokine levels and subsequent embryonic development.
However, the Erasmus University researchers noted that more research is needed to determine how microbial dysbiosis may contribute to pregnancy complications, and thus they set out to review the existing research on the role of the vaginal and endometrial microbiome in early pregnancy.
Compositions and outcomes
The review noted a detectable difference in the vaginal microbiome composition between women suffering from RIF and RPL. The women were also found to be unable to attenuate their microbiome diversity throughout their menstrual cycle.
The researchers also reported correlations between Lactobacillus species and anti-inflammatory cytokine levels, which may explain the negative pregnancy outcomes.
“Inflammation and dysregulated activation of the immune system seem to affect the integrity of the endometrial mucosa, leading to RIF, and subsequently interfere with the receptivity of the endometrium and the processes of implantation and placentation, leading to RPL,” they wrote with regards to the potential mechanisms behind the association.
Source: International Journal of Molecular Sciences
doi: https://doi.org/10.3390/ijms25010622
“Clinical Relevance of Vaginal and Endometrial Microbiome Investigation in Women with Repeated Implantation Failure and Recurrent Pregnancy Loss”
Authors: Xushan Gao et al.