Prospective Study of an Human Endometrial Receptivity Test (Win-Test)

Prospective Study of the 'Win Test', a New Diagnostic Tool to Assess Human Endometrial Receptivity Under Natural Cycle or Hormone Replacement Therapy

Evaluation of endometrial receptivity is a crucial step in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) programs. Using "Omic technologies", such as transcriptomic and proteomic analyses, the investigators previously identified a specific molecular signature of human endometrial receptivity during the embryo implantation window. After validation of this signature in fertile women and in an ex vivo model (i.e., stromal and epithelial endometrium cells),the investigatorsdeveloped a diagnostic tool called Win-Test (Window Implantation Test) to evaluate the expression level of a set of endometrial receptivity-specific genes during the implantation window by quantitative RT-PCR. Based on their expression, each endometrial biopsy sample can be classified as receptive, partially receptive or non-receptive. Then, after the identification of the right cycle day within the implantation window where endometrium is considered as receptive, a customized timing for embryo transfer with respect of the synchronization of the embryo-maternal dialogue must be performed. A prospective study to validate the relevance of the Win-Test, is a necessary step to gauge its effectiveness. In this objective, patients with multiple implantation failures will be recruited. Embryo transfers were performed in double-arm: the intervention group had a customized timing of embryo transfer according to the Win-Test strategy and recommendation, the control group had their embryos transferred in a classical timing. Pregnancy and live birth rates (LBR) were compared between groups.

Study Overview

• Status: Completed
• Conditions: Infertile

• Study Type: Observational
• Enrollment (Actual): 217

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Uhmontpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 27 years to 48 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women were recruited after written informed consent. All of them had a severe history of repeated implantation failures (RIFs). A classical infertility evaluation was performed including transvaginal sonography and uterine cavity was assessed by hysteroscopy. All patients were scheduled for replacement of cryopreserved embryos under hormone replacement therapy (HRT) or natural cycle. A mock frozen embryo transfer cycle, using a natural cycle or a HRT protocol, was monitored. Patients had endometrial biopsies performed through the presumed implantation window, 6 to 9 days after the LH (luteinizing hormone) surge for those on natural cycle or 5 to 9 days after the progesterone administration under HRT. Each biopsy was assessed for endometrial receptivity status using the Win-Test and assessment was stopped when appropriate endometrial receptivity was found. The clinical suitability of the Win-Test was performed in RIF patients who subsequently received Win-Test's guided embryo transfer.

Description

Inclusion criteria :

• Infertile patients associated with multiple implantation failures.
• Signatures consent and non-opposition letter.
• Patients with a standard infertility assessment.
• Patients with a monitored cycle (ultrasound, hormonal markers) during the mock frozen embryo transfer cycle to perform the Win-test and during the embryo transfer cycle.
• Patients with complete treatment information during the mock frozen embryo transfer cycle to perform the Win-test and during the embryo transfer cycle.
• Patients with accurate transfer day information.
• Patients for whom we have the outcome (pregnancy, live birth).

Exclusion criteria:

More than 24 weeks of amenorrhea

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
RIF patients; Repeated implantation failure patients
Oocyte/embryo donation program; Patients awaiting for oocyte/embryo-donation recipient patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate	Clinical pregnancy was defined as ultrasound visualization of a gestational sac with a positive embryo heartbeat	At 7-8 weeks of amenorrhea after customized timing of embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate	Live birth rate was defined as a delivery with at least one live born baby of more than 24 weeks of amenorrhea	More than 24 weeks of amenorrhea

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Merck Serono (GFI)
• Investigators: Principal Investigator: Samir Hamamah, University Hospital, Montpellier

Publications and helpful links

General Publications

• Haouzi D, Entezami F, Torre A, Innocenti C, Antoine Y, Mauries C, Vincens C, Bringer-Deutsch S, Gala A, Ferrieres-Hoa A, Ohl J, Gonzalez Marti B, Brouillet S, Hamamah S. Customized Frozen Embryo Transfer after Identification of the Receptivity Window with a Transcriptomic Approach Improves the Implantation and Live Birth Rates in Patients with Repeated Implantation Failure. Reprod Sci. 2021 Jan;28(1):69-78. doi: 10.1007/s43032-020-00252-0. Epub 2020 Jul 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2012
• Primary Completion (ACTUAL): May 1, 2019
• Study Completion (ACTUAL): May 25, 2019

Study Registration Dates

• First Submitted: December 5, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (ACTUAL): December 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 11, 2019
• Last Update Submitted That Met QC Criteria: December 10, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: ART; Endometrial receptivity; Endometrial receptivity assessment for customized embryo transfer; Human Reproduction
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: RECHMPL19_0590

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: NC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No