Recurrent implantation failure and the microbiome

Joop Laven

Recurrent implantation failure and the microbiome

Joop S.E. Laven, M.D., Ph.D., Xu Shan Gao, M.D., S. Schoenmakers, M.D., Ph.D., Yvonne V. Louwers, M.D., Ph.D., Div. Reproductive Endocrinology & Infertility, Dept OBGYN, Erasmus MC, Rotterdam, The Netherlands

Abstract:

Repeated Implantation Failure (RIF) has been described as an iatrogenic condition resulting from three unsuccessful fresh in vitro fertilization (IVF) cycles, failing to achieve a pregnancy after three completed fresh IVF-cycles with their resulting embryo transfers (ET) or failure after the transfer of at least four good-quality embryo within a minimum of three fresh or frozen cycles. The prevalence varies depending on the definition of RIF used. A recent evaluation showed that up to 15% of the women undergoing an IVF treatment suffer from RIF which is defined as the failure to obtain a clinical pregnancy after at least three embryo transfer attempts.

Recent studies have investigated if and how the vaginal and endometrial microbiome affects endometrial receptivity and reproductive health. Although there is no consensus on the existence of a core uterine microbiome yet, evidence showed that the dominance of Lactobacillus spp. in the female reproductive tract is generally associated with eubiosis and improved chances of successful implantation and ongoing pregnancy. Conversely, vaginal and endometrial dysbiosis can cause local inflammation and an increase of pro-inflammatory cytokines compromising the integrity and receptivity of the endometrium mucosa and potentially hampering successful embryonic implantation. This review provides a critical appraisal of the influence of the microbiome on the different parts of the female reproductive tract and its impact on fertility outcomes, focusing on RIF. It seems that RIF as well as RPL are mainly both associated with an increase in microbiome diversity and a loss of Lactobacillus dominance in the urogenital system.

This presentation provides an updated overview of the vaginal and endometrial bacterial communities and interaction with the local immune system in RIF and RPL. A state of microbiota dysbiosis with overabundance of pathogenic species or absence of Lactobacillus-dominated vaginal and endometrial microbiome might trigger inflammation and hinder the process of embryonic implantation and interfere with early pregnancy.

Key Words: Repeated Implantation Failure (RIF), IVF, Lactobacillus, Diversity, Dominance

Joop Laven

Professor Joop S.E. Laven is professor in Reproductive Endocrinology and Infertility based at Erasmus Medical Centre, Rotterdam in the Netherlands and was initially trained at the University of Utrecht in the same country. After Medical school he completed his Ph.D. thesis on clinical and experimental aspects of varicocele at Utrecht University in 1991. From 1991 till 1997 he continued his training at the University Medical Center St. Radboud in Nijmegen. In 1997 he became board certified in OBGYN (FRCOG) and moved to the Erasmus Medical Center in Rotterdam. In 2000 he became certified subspecialist Reproductive Medicine. He is a member of ESHRE, ASRM, the Endocrine Society, the Society of Gynecological Investigation (SGI) and the Royal Dutch College of Obstetrics and Gynecology. He is the past president of the Dutch Society of Reproductive Medicine. He is the president-elect of AE-PCOS society For many years he had a particular interest in the management of polycystic ovary syndrome covering the full spectrum from the effects of the syndrome during adolescence and adult life on the menstrual cycle, fertility, body weight and cosmetic aspects. During the last decade the research focussed on more fundamental effects that PCOS may have on quality of life and long-term health risks as well as the genetic basis of the disease. More recently he was also involved in Genome Wide Association Studies (GWAS) exploring the genetic basis of PCOS, premature ovarian insufficiency, menarche and menopause. He has published over 350 peer-reviewed papers and several reviews as well as chapters in books, and has delivered over 400 lectures to international scientific audiences. He is a past member of the editorial board of Human Reproduction Update, Human Reproduction and the Journal of Endocrine Society. He is a visiting professor at the University of Shandong, Shandong, China and the University of Adelaide, Australia. He is also a member of the international guideline groups for PCOS, POI and unexplained infertility within the Center of Research Excellence (WHIRL) Monash University, Melbourne, Australia.