Abstract

The aim of this prospective study was to evaluate outcome benefits expected in repeated implantation failure (RIF) patients (n = 217) after customized embryo transfer based upon identification of the receptivity window by transcriptomic approach using the Win-Test. In this test, the expression of 11 endometrial genes known to be predictive of endometrial receptivity is assessed by RT-PCR in biopsies collected during the implantation window (6–9 days after the spontaneous luteinizing hormone surge during natural cycles, 5–9 days after progesterone administration during hormone replacement therapy cycles). Then, patients underwent either customized embryo transfer (cET, n = 157 patients) according to the Win-Test results or embryo transfer according to the classical procedure (control group, n = 60). Pregnancy and live birth rates were compared in the two groups. The Win-Test showed that in 78.5% of women, the receptivity window lasted less than 48 h, although it could be shorter (< 24 h, 9.5%) or longer (> 48 h, 12%). This highlighted that only in 20% of patients with RIF the endometrium would have been receptive if the classical embryo transfer protocol was followed. In the other 80% of patients, the receptivity window was delayed by 1–3 days relative to the classical timing. This suggests that implantation failure could be linked to inadequate timing of embryo transfer. In agreement, both implantation (22.7% vs. 7.2%) and live birth rates per patient (31.8% vs. 8.3%) were significantly higher in the cET group than in the control group. cET on the basis of the Win-Test results could be proposed to improve pregnancy and live birth rates.ClinicalTrials.gov ID: NCT04192396; December 5, 2019, retrospectively registered.

Highlights

  • Materials and MethodsInfertility is a major public health problem that affects more than one in six couples of childbearing age

  • We previously identified a set of genes (BCL2L10, CD68, TRPC4, SORCS1, FST, KRT18, LAMB3, MFAP5, ANGPTL1, PROK1, and C2CD4B) that are overexpressed in the endometrium during the implantation window and that seem to be relevant candidate biomarkers of human endometrial receptivity [7, 10,11,12,13,14]

  • Whatever the receptivity window duration, the analysis of the endometrial receptivity status at different time points within the same cycle or in subsequent cycles in the same patient showed that endometrial receptivity acquisition was a progressive process, as revealed by the mean expression levels of the Win-Test genes, during both natural and hormone replacement therapy (HRT) ± GnRH analogue (GnRHa) cycles with a tendency for a more progressive process under HRT

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Summary

Introduction

Materials and MethodsInfertility is a major public health problem that affects more than one in six couples of childbearing age. We previously identified a set of genes (BCL2L10, CD68, TRPC4, SORCS1, FST, KRT18, LAMB3, MFAP5, ANGPTL1, PROK1, and C2CD4B) that are overexpressed in the endometrium during the implantation window and that seem to be relevant candidate biomarkers of human endometrial receptivity [7, 10,11,12,13,14]. After validation of these transcriptomic results by reverse transcription-quantitative PCR (RTqPCR), we tested these candidate endometrial receptivity biomarkers in fertile patients and in an ex vivo model (i.e., stromal and epithelial endometrium cells) [10, 14, 15]. The aim of this prospective interventional multicenter study was to determine the ART outcomes (pregnancy and live birth rates) after frozen embryo transfer according to the Win-Test results compared with the usual procedure

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