The confirmation of eubiotic vaginal flora may save us from reproductive failure and even preterm labor

By Marga Torres

Although the microbiome's role in human health has been well known for some time, in recent years there have been a growing number of studies that indicate that themicrobiome of the female genital tract may play a key role in reproduction.

In an increasing number of research studies, abnormal vaginal and endometrial microbiota are associated with lower pregnancy rates in In Vitro Fertilisation (IVF), as well as with unfavourable obstetric outcomes, including repeat miscarriages and preterm birth.

The presence of a Lactobacillus-dominated genital microbiota has been associatedwith significantly higher rates of implantation, pregnancy and clinical pregnancy in Assisted Reproductive Treatments (ART). In addition, the presence of a Lactobacillus Crispatus-dominated vaginal microbiota has been associated with higher live birthrates.

While there is no evidence to support routine microbiome testing in asymptomaticwomen prior to a spontaneous gestation cycle or when starting an assistedreproduction cycle, it is recommended when there are clinical symptoms such as heavy or foul-smelling vaginal discharge, frequent urinary tract infections, recurrentcandidiasis, a history of untreated male or female sexually transmitted diseases, and in patients with previous reproductive failures.

When genito-urinary microbiome alteration is suspected, confirming a eubiotic flora notonly improves success rates in assisted reproduction, but also reduces unfavourableobstetric outcomes such as preterm birth.

When this study is performed in asymptomatic women with no history of implantationfailure, repeat miscarriage or previous preterm birth and who are about to undergo IVF, it is an Add-on. In other words, it is an additional procedure to a standard protocol thatis used to increase the success rate in the absence of sufficient evidence with thecurrently available data.

The importance of accuracy in diagnosis

When studying the vaginal microbiota, we can use the microbiological culture and theclassic Nugent and Amsel criteria to diagnose bacterial vaginosis. However, thesetechniques may provide inaccurate results due to their inability to adequately measuremicrobial complexity.

In contrast, the new and more standardised molecular biology techniques are based onDNA and RNA analysis. They are more expensive but also more sensitive, therebyallowing for a more objective analysis and improving the ability to detect micro-organisms.

When diagnosing endometritis, the three traditional methods of endometrial culture, histology and hysteroscopy have been used. However, the Next GenerationSequencing (NGS) molecular study via bacterial RNA sequencing of the ribosomal S-subunit is similar in sensitivity and specificity to all three of the above methodscombined.  The most recently incorporated diagnostic technique is “culturomics” whichallows an even more detailed taxonomic evaluation.

It should be mentioned that all diagnostic techniques used, including hysteroscopy, microbiological culture, anatomo-pathological studies and NGS, together withimmunohistochemical techniques, are relatively simple and therefore easy to apply in AR centres.

Antibiotics, probiotics, anti-inflammatories and even transplants

The optimal treatment for women experiencing dysbiosis or recurrent vaginosis iscurrently unknown. While the standard treatment is to use antibiotics and vaginal probiotics, new treatments such as vaginal microbiome transplants are also beingstudied in patients with recurrent vaginosis who do not respond to standard treatment.

For chronic endometritis, broad-spectrum antibiotics have long been considered to be the standard treatment. However, whenever possible, antibiotics should be indicatedbased on the antibiogram. There have been demonstrated increases in pregnancyrates after treatment in women with chronic endometritis and implantation failure orrecurrent miscarriages.

Further research has also been carried out on adjuvant therapies such as anti-inflammatory drugs or probiotics that may act on the inflammatory process or regulatethe endometrial microbiome. While data available on the use of probiotics in patientswith dysbiosis show promising results, there is still no consensus regarding theeffectiveness of probiotic supplementation in modulating the vaginal and endometrial microbiota and reproductive outcomes.

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