Vaginal Microbiome & IVF: Associated with Higher Risk for Miscarriage and Reduced Pregnancy Rates
Imagine there were a condition, which affected approximately 1 out of every 5 patients, and it was associated with a 71% higher risk of miscarriage and a 45% decreased chance for a positive clinical pregnancy with IVF. Now also imagine that this condition was not checked for in the majority of patients going for fertility treatments. Imagine going for a 3rd, 4th, or 5th IVF with no success or your 3rd, 4th, or 5th early pregnancy miscarriage without any investigation in to this condition. This is the reality for many patients.
The reproductive microbiome has been investigated over the last several years and we have come a long way in our understanding of the differences in the vaginal and reproductive microbiome when we compare patients with recurring fertility challenges. While all of the studies are small or of low-quality, all of the studies have painted a very similar picture. Patients that have vaginal dysbiosis (VD) are more likely to experience early pregnancy loss or potentially have a lower chance of becoming pregnant with IVF.
A newly published paper performed a systematic review and meta-analysis on available studies evaluating for the impact of the reproductive and vaginal microbiome on pregnancy rates and miscarriage rates. And they found that approximately 19% of patients included in their studies have vaginal dysbiosis.
What is Vaginal Dysbiosis?
Normally the reproductive microbiome should be composed of >90% lactobacillus spp. If it falls below 90% it can be diagnosed as vaginal dysbiosis. There can be various microbes that may overgrow in the reproductive microbiome, such as, gardnerella, trichomonas, prevotella to name a few.
It is also important to mention that not all forms of lactobacillus are considered the same, in fact, overgrowth of specific forms of lactobacillus may actually be associated with a decrease in reproductive outcomes. Lactobacillus strains that usually are dominant in the reproductive tract include Lactobacillus jensenii, L. crispatus, L. gasseri, and L. iners. As an example, a microbiome with > 60% L. cripatus has been associated with decreased positive outcomes in one study.
How is Vaginal Dysbiosis Diagnosed?
The vaginal microbiome can be evaluated from a variety of techniques. The following are the most common methods:
Nugent Score (NS): this requires a vaginal swab and microscopy to analyze for lactobacillus spp. and pathogens associated with bacterial vaginosis.
Quantitative Polymerase Chain Reaction (qPCR): monitoring for targeted gene amplification
Amsel Criteria: checking for discharge, specific characteristics on microscopy, a vaginal pH > 4.5 and fishy odour when the sample is mixed with 10% potassium hydroxide solution
Limitations of the Research
The studies mostly establish correlation and not causation. There are other factors, such as, the use of antibiotics prior to the microbiome swab test that may also impact results. Also, hormone levels can cause growth of certain microbes. In pregnant patients, increasing estrogen levels also stimulate the growth of lactobacillus spp. and therefore may increase its dominance in the reproductive microbiome compared to patients that are not pregnant. However, most of the studies are finding similar associations where the presence of vaginal dysbiosis seems to be much more likely in patients that are experiencing miscarriages or recurrent implantation failure.
Skafte-Holm, A., Humaidan, P., Bernabeu, A., Lledo, B., Jensen, J. S., & Haahr, T. (2021). The Association BETWEEN VAGINAL DYSBIOSIS and Reproductive outcomes in Sub-Fertile women Undergoing ivf-treatment: A Systematic PRISMA review and meta-analysis. Pathogens, 10(3), 295.