Thursday, December 8, 2016

Endometrial microbiome plays a key role in implantation and pregnancy rates in IVF patients.

Clinical pearls:

  • Different bacterial species were detected between vagina and endometrial cavity of the same subjects.
  • The microbiota in the endometrial cavity is labelled as Lactobacillus-dominated microbiota (>90% Lactobacillus spp.) or a non-Lactobacillus-dominated microbiota (<90% Lactobacillus spp. with >10% of other bacteria). 
  • The composition of endometrial microbiome is not regulated by the hormonal cycle and non-Lactobacillus-dominated microbiota during the receptivity phase correlates with significant decrease in implantation, on-going pregnancy, pregnancy and live birth rates. 
It has been believed since last 50 years that uterine cavity and endometrium is sterile and devoid of microbial habitat in the absence of infection. The sterile womb paradigm was coined by the French pediatrician Henry Tissier and postulated that human infants develop in a sterile environment. [1]

Recent advances in genomics and bioinformatics have led to identifying microbiota in many body organs that were previously thought to be sterile by use of 16S rRNA gene-based bacterial detection and identification techniques. By using this newer advances in microbiology it has been proved that upper genital tract harbors a distinct set of microbiome and is differs considerably in health and disease states.

A study published in the December issue of American journal of Obstetrics and Gynecology (ACOG)  by Moreno et al,[2] not only demonstrated that endometrium harbors microbes and endometrial microbiome has a lot in common with vaginal microbiome.  The study further demonstrated that like vaginal microbiome, the endometrial flora is also divided into Lactobacillus dominant (LD) and non-Lactobacillus dominant (NLD) communities.

The researchers obtained paired samples from vagina and endometrial cavity in 13 fertile women in both receptive and prereceptive phases of the same menstrual cycles. (n=52). To study the hormonal influence on endometrial microbiome during the preparation of endometrium for implantation samples of endometrial aspirate collected from 22 fertile women.

Finally, to study the impact of altered endometrial microbiome on reproduction, the endometrial aspirate was assessed by implantation, miscarriage, ongoing pregnancy, and live birth rates in 35 infertile women undergoing IVF by endometrial receptivity array (ERA).

The study results showed that:

Different bacterial species were detected between vagina and endometrial cavity of the same subjects.

The microbiota in the endometrial cavity is labelled as Lactobacillus-dominated microbiota (>90% Lactobacillus spp.) or a non-Lactobacillus-dominated microbiota (<90% Lactobacillus spp. with >10% of other bacteria). 

The composition of endometrial microbiome is not regulated by the hormonal cycle and non-Lactobacillus-dominated microbiota during the receptivity phase correlates with significant decrease in implantation, on-going pregnancy, pregnancy and live birth rates.

This pilot study has opened the doors for many basic, translational and clinical studies in future. It has also drawn our attention to the fact that reproductive success does not solely rely on endometrial histology and gene expression.

Linda C. Giudice, MD, PhD, Distinguished Professor and reproductive endocrinologist at the University of California San Francisco said in an accompanying editorial “The ongoing revolution in technology, science, multiple omics, and multidimensional data analysis has opened the window of implantation to a greater level of scrutiny. It is time to further investigate the endometrial microbiome and expand research to its virome, fungome, epigenome, and metabolome to increase our understanding the biology of this dynamic tissue and to develop targeted therapies of endometrial disorders that underlie infertility and poor pregnancy outcomes and affect women’s health more broadly. We are indeed on the threshold to transform clinical reproductive medicine and improve reproductive outcomes with precision and personalization for individual patients.”






[2] Moreno, I., CodoƱer, F.M., Vilella, F. et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016; 215: 684–703

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