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Fertil Steril. 2017 Oct;108(4):703-710.e3. doi: 10.1016/j.fertnstert.2017.07.007. Epub 2017 Aug 30.

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

Author information

1
Fundacion IVI-Instituto Universitario IVI, University of Valencia, Valencia, Spain; Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain. Electronic address: patricia.diaz@ivi.es.
2
IGENOMIX, Parque Tecnológico, Paterna, Valencia, Spain.
3
Fundacion IVI-Instituto Universitario IVI, University of Valencia, Valencia, Spain; Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.
4
Fundacion IVI-Instituto Universitario IVI, University of Valencia, Valencia, Spain; Instituto de Investigación Sanitaria Hospital Universitario y Politécnico La Fe, Valencia, Spain.
5
Fundacion IVI-Instituto Universitario IVI, University of Valencia, Valencia, Spain; Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain; IGENOMIX, Parque Tecnológico, Paterna, Valencia, Spain; Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, California; Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.

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.

KEYWORDS:

Biochemical pregnancy signature; endometrial genomic medicine; endometrial receptivity; endometrial transcriptomic predictors; transcriptomic stratification of uterine receptivity

[Indexed for MEDLINE]

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