O-149 Personalized probiotics and food supplementation according to microbiome miRNA test improves the conception rate in multiple IVF failure patients

Abstract

Study question Can the microbiota play a role in the development of infertility by affecting the epigenetic, immunologic, and/or biochemical functions of the host? Summary answer The customization of diet and a nutraceutical and probiotic supplementation according microbiome miRNA signature could increase the pregnancy and live birth rates. What is known already The normal gut microbiota has an impact on the normal function of the male and female reproductive tract by regulating the immunological changes associated with conception. Several miRNAs -a class of small noncoding RNA molecules that control gene expression at the post-transcriptional level- have been described to be associated with dysbiosis and an immune imbalance. We previously demonstrated that women with unexplained infertility could have a gut and vaginal microbiome imbalance with increased intestinal permeability linked to an overexpression of miR-21 and miR-155. Study design, size, duration Observational study including 287 multiple IVF failure infertile patients. They had an average age of 40y and they performed 4 IVF-ET within 10 years on average. Swab samples were collected from the vagina and rectum. Participants/materials, setting, methods Microbial composition by NGS and miRNA expression by real time PCR of vaginal and rectal samples were measured. Immunometabolic markers from blood (TPO, vitamin D and B12, insulin, LDL) were analyzed. Patients followed a customized food supplementation, according to the tested biomarkers, for 90 days. Main results and the role of chance We found that 80% of women showed increased miRNA levels associated with gut and vaginal microbiome imbalances. Deficient values of Vitamin D and/or B were found in 73.2% of tested patients, whereas 56.1% showed high LDL and or insulin values and 19.9% showed positive anti thyroid TPO antibodies. Based upon the elevated levels of miRNAs and immunometabolic markers (insulin, vitamin D, autoantibodies, LDL cholesterol and secretory IgA), patients completed a 60-90 day therapy prior to their next IVF-ET attempt with no clinical side effects. BMI measurements before and after the therapy were not significantly different. After normalization of the blood biomarkers, each patient underwent a next IVF -ET attempt. The total pregnancy rate resulted in 75% (215/287) of positive chemical pregnancy (hCG) and 73% (157/215) of clinically confirmed pregnancy (ultrasound). The live birth rate per intended egg retrieval (all embryos transfers) was 60% (129/215); 27 pregnancies resulted in first trimester losses and one fetal death after a severe preeclampsia. Limitations, reasons for caution A future study should be performed testing miRNA expression before and after the food supplementation to achieve a direct correlation between the microRNA test and the supplementation in a placebo control study in order to evaluate the efficacy of the personalized supplementation on improving pregnancy and live birth rates. Wider implications of the findings Immune system and microbiome modulation could be adress by customizing different strains of probiotics and nutraceuticals selected for their immunomodulatory capacity. An anti-inflammatory dose-specific effect to maintain a delicate immune balance and favor endometrial mucous vascularization and the subsequent placentation, should be personalized to achieve a healthy pregnancy. Trial registration number CEI 1590