Window of implantation transcriptomic stratification reveals different endometrial subsignatures associated with live birth and biochemical pregnancy

Window of implantation transcriptomic stratification reveals outcome-specific subsignatures associated with live birth and biochemical pregnancy, highlighting the translational value of this genomic approach to optimize the endometrial factor in infertility.

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Volume 108, Issue 4, Pages 703–710.e3

Authors:

Patricia Díaz-Gimeno, Maria Ruiz-Alonso, M.Sc., Patricia Sebastian-Leon, Ph.D., Antonio Pellicer, M.D., Ph.D., Diana Valbuena, M.D., Ph.D., Carlos Simón, M.D., Ph.D.

Abstract:

Objective

To refine the endometrial window of implantation (WOI) transcriptomic signature by defining new subsignatures associated to live birth and biochemical pregnancy.

Design

Retrospective cohort study.

Setting

University-affiliated in vitro fertilization clinic and reproductive genetics laboratory.

Patient(s)

Healthy fertile oocyte donors (n = 79) and patients with infertility diagnosed by Endometrial Receptivity Analysis (n = 771).

Intervention(s)

None.

Main Outcome Measure(s)

WOI transcriptomic signatures associated with specific reproductive outcomes.

Result(s)

The retrospective cohort study was designed to perform a prediction model based on transcriptomic clusters for endometrial classification (training set, n = 529). The clinical follow-up set in the expected WOI (n = 321) was tested with the transcriptomic predictor to detect WOI variability and the pregnancy outcomes associated with these subsignatures (n = 228). The endometrial receptivity signature was redefined into four WOI transcriptomic profiles. This stratification identified an optimal endometrial receptivity (RR) signature resulting in an ongoing pregnancy rate (OPR) of 80% in terms of live birth, as well as a late receptive-stage (LR) signature with a potential high risk of 50% biochemical pregnancy. Abnormal down-regulation of the cell cycle was the main dysregulated function among the 22 genes associated with biochemical pregnancy.

Conclusion(s)

The major differences between the WOI transcriptomic stratification were in the OPR and biochemical pregnancy rate. The OPR ranged from 76.9% and 80% in the late prereceptive (LPR) and RR signatures, respectively, versus 33.3% in the LR. The biochemical pregnancy rate was 7.7% and 6.6% in LPR and RR, respectively, but 50% in LR, which highlights the relevance of endometrial status in the progression of embryonic implantation.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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