What is the prognosis for a live birth after unexplained recurrent implantation failure following IVF/ICSI?

Abstract

STUDY QUESTION What is the cumulative incidence of live birth and mean time to pregnancy (by conception after IVF/ICSI or natural conception) in women experiencing unexplained recurrent implantation failure (RIF) following IVF/ICSI treatment? SUMMARY ANSWER In 118 women who had experienced RIF, the reported cumulative incidence of live birth during a maximum of 5.5 years follow-up period was 49%, with a calculated median time to pregnancy leading to live birth of 9 months after diagnosis of RIF. WHAT IS KNOWN ALREADY Current definitions of RIF include failure to achieve a pregnancy following IVF/ICSI and undergoing three or more fresh embryo transfer procedures of one or two high quality embryos or more than 10 embryos transferred in fresh or frozen cycles. The causes and optimal management of this distressing condition remain uncertain and a range of empirical and often expensive adjuvant therapies is often advocated. Little information is available regarding the long-term prognosis for achieving a pregnancy. STUDY DESIGN, SIZE, DURATION Two hundred and twenty-three women under 39 years of age who had experienced RIF without a known cause after IVF/ICSI treatment in two tertiary referral university hospitals between January 2008 and December 2012 were invited to participate in this retrospective cohort follow up study. PARTICIPANTS/MATERIALS, SETTING, METHODS All eligible women were sent a letter requesting their consent to the anonymous use of their medical file data and were asked to complete a questionnaire enquiring about treatments and pregnancies subsequent to experiencing RIF. Medical files and questionnaires were examined and results were analysed to determine the subsequent cumulative incidence of live birth and time to pregnancy within a maximum 5.5 year follow-up period using Kaplan Meier analysis. Clinical predictors for achieving a live birth were investigated using a Cox hazard model. MAIN RESULTS AND THE ROLE OF CHANCE One hundred and twenty-seven women responded (57%) and data from 118 women (53%) were available for analysis. During the maximum 5.5 year follow up period the overall cumulative incidence of live birth was 49% (95% CI 39–59%). Among women who gave birth, the calculated median time to pregnancy was 9 months after experiencing RIF, where 18% arose from natural conceptions. LIMITATIONS, REASONS FOR CAUTION Since only 57% of the eligible study cohort completed the questionnaire, the risk of response bias limits the applicability of the study findings. WIDER IMPLICATIONS OF THE FINDINGS This study reports a favorable overall prognosis for achieving live birth in women who have previously experienced RIF, especially in those who continue with further IVF/ICSI treatments. However since 51% did not achieve a live birth during the follow-up period, there is a need to distinguish those most likely to benefit from further treatment. In this study, no clinical factors were found to be predictive of those achieving a subsequent live birth. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the University Medical Center Utrecht, in Utrecht and the Academic Medical Centre, in Amsterdam. NSM has received consultancy and speaking fees and research funding from Ferring, MSD, Merck Serono, Abbott, IBSA, Gedion Richter, and Clearblue. During the most recent 5-year period BCJMF has received fees or grant support from the following organizations (in alphabetic order); Actavis/Watson/Uteron, Controversies in Obstetrics & Gynecology (COGI), Dutch Heart Foundation, Dutch Medical Research Counsel (ZonMW), Euroscreen/Ogeda, Ferring, London Womens Clinic (LWC), Merck Serono, Myovant, Netherland Genomic Initiative (NGI), OvaScience, Pantharei Bioscience, PregLem/Gedeon Richter/Finox, Reproductive Biomedicine Online (RBMO), Roche, Teva, World Health Organisation (WHO). None of the authors have disclosures to make in relation to this manuscript.

Live Birth Rates after Active Immunization with Partner Lymphocytes

“…Table 3 summarizes studies addressing live birth rates in patients with RIF in relation to the number of previous ART cycles who did not undergo LIT [18][19][20]. Although the live birth rates reported by Koot et al were significantly higher than those registered in our study (49% vs. 33%) [19], a comparison of these two analyses is limited by the following factors. First, 7 of 75 patients with RIF in our study (9%) were older than 39 years.…”

Loss of CDYL Results in Suppression of CTNNB1 and Decreased Endometrial Receptivity

“…Embryo implantation is a profound process composing of embryo apposition, adhesion, penetration, and invasion (Singh et al, 2011). Recurrent implantation failure (RIF) is defined as the absence of implantation after either transfer of three or more morphologically good quality embryos or placement of 10 or more embryos in several transfers (Koot et al, 2019). RIF has become an obstacle in assisted reproductive techniques and accounts for approximately 10% of women who fail to achieve a clinical pregnancy during their in vitro fertilization-embryo transfer (IVF-ET) treatment (Polanski et al, 2014;Macklon, 2017;Nowak et al, 2017).…”

Determining Diagnostic Criteria of Unexplained Recurrent Implantation Failure: A Retrospective Study of Two vs Three or More Implantation Failure

“…However, based on the results of this study, it seemed that it was inappropriate to include two implantation failure in the RIF definition. The date of RIF diagnosis was determined, defined as the first day of the menstrual period after the last failed IVF/ICSI/FET treatment ( 21 ). So, if a patient was under 40 years old and had failed to achieve a clinical pregnancy after transferring at least four cleavage embryos or two blastocysts, we could classify her at the second or third failed ET cycles (the hypothetical RIF definition: at least two failed ET cycles vs generally accepted RIF definition: at least three failed ET cycles).…”

“…But the other side of this results suggested that women’s fertility was damaged seriously and we should pay more attention to the biological age. A recent study of 118 women who had experienced RIF showed that the median pregnancy time was just 9 months after the diagnosis of RIF ( 21 ). And for RIF patients, the live birth rate decreased significantly with age.…”