Patricia Díaz-Gimeno1, Maria Ruiz-Alonso2, Patricia Sebastian-Leon3, Antonio Pellicer4, Diana Valbuena2, Carlos Simón5. 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.
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.
Authors: Jenny N Fung; Sally Mortlock; Jane E Girling; Sarah J Holdsworth-Carson; Wan Tinn Teh; Zhihong Zhu; Samuel W Lukowski; Brett D McKinnon; Allan McRae; Jian Yang; Martin Healey; Joseph E Powell; Peter A W Rogers; Grant W Montgomery Journal: Sci Rep Date: 2018-07-30 Impact factor: 4.379
Authors: G Rozen; P Rogers; S Chander; R Anderson; O McNally; M Umstad; A Winship; K Hutt; W T Teh; A Dobrotwir; R Hart; W Ledger; K Stern Journal: Hum Reprod Open Date: 2020-10-25