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

Abstract

BackgroundThe definition of recurrent implantation failure (RIF) differs clinically, one of the most controversial diagnostic criteria is the number of failed treatment cycles. We tried to investigate whether the two implantation failure could be included in the diagnostic criteria of RIF.MethodsA retrospective analysis of the clinical data of patients (N=1518) aged under 40 years with two or more implantation failure, recruited from the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University from January 2016 to June 2019.ResultsAfter adjusting for confounding factors by using binary logistic regression, the results showed that partial general information and: distribution of associated factors were significant differences such as maternal age (aOR=1.054, P=0.001), type of cycle (aOR=2.040, P<0.001), stage of embryos development (aOR=0.287, P<0.001), number of embryos transferred (aOR=0.184, P<0.001), female factor (tubal pathology) (aOR=0.432, P=0.031) and male factor (aOR=1.734, P=0.002) between the groups with two and three or more unexplained implantation failure. And further explored whether these differential factors had a significant negative impact on pregnancy outcome, the results showed that: for patients who had three unexplained implantation failure, in the fourth cycle of ET, the live birth rate decreased significantly with age (aOR=0.921, P<0.001), and the live birth rate of blastocyst transfer was significantly higher than that of cleavage embryo transfer (aOR=1.826, P=0.007). At their first assisted pregnancy treatment after the diagnosis of RIF according to these two different definitions, there were no significant difference in the biochemical pregnancy rate, clinical pregnancy rate, ectopic pregnancy rate and abortion rate (P>0.05), but the live birth rate (35.64% vs 42.95%, P=0.004) was significantly different. According to the definition of ‘two or more failed treatment cycles’, the live birth rate of the first ET treatment after RIF diagnosis was significantly lower than that of patients according to the definition of ‘three or more failed treatment cycles’.ConclusionFor patients with unexplained recurrent implantation failure, two implantation failure cannot be included in the diagnostic criteria of RIF. This study supports the generally accepted definition of three or more failed treatment cycles for RIF.

Biomolecular Markers of Recurrent Implantation Failure—A Review

“…Recurrent implantation failure (RIF) is defined as three or more consecutive failed in vitro attempts with at least four high-quality embryos in a minimum of three fresh or frozen cycles [1]. This serious complication refers to women younger than 40 [2,3].…”

The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature

“…Similar observations are also made in the context of assisted reproduction techniques (ART) management. The probability of implantation failure is approximately 70% as deduced from the fact that the implantation rate per embryo transfer reaches 30% [10,11]. Acknowledging these data, albeit implantation failure may entail a pathological condition, at the same time it constitutes, from an evolution standpoint, a physiological "barrier" leading to the establishment of a competent pregnancy.…”

“…This phenomenon is known as recurrent implantation failure (RIF) and affects approximately 10-15% of women undergoing IVF treatment, globally [12]. Recurrent implantation failure constitutes a multifactorial condition for which there is no consensus yet regarding its definition [11]. The controversial criteria, indicating its highly variable nature, include the number of failed IVF cycles, the number of embryos transferred as well as maternal age [10,13].…”

“…The controversial criteria, indicating its highly variable nature, include the number of failed IVF cycles, the number of embryos transferred as well as maternal age [10,13]. Despite the fact that several definitions have been proposed, the most widely accepted is the one described by the failure to achieve a positive pregnancy test following three or more consecutive transfers of good quality embryos [10,11,[13][14][15][16]. The discrepancies regarding RIF definition have led to a lack of a standardized, efficient, and universally accepted protocol for RIF management, making RIF one of the most challenging conditions reproductive scientists should deal with in daily clinical practice [16].…”

MEKK4-mediated Phosphorylation of HOXA10 at Threonine 362 facilitates embryo adhesion to the endometrial epithelium

“…Recurrent implantation failure (RIF) is a typical example of a situation in which where endometrial factors may be the main cause of implantation failure following high-quality embryo transfer [3][4][5] .…”