Predicting Endometrial Receptivity for Optimal Reproductive Management

Completed

• Conditions: Infertility, Female; Endometriosis
• Interventions: Procedure: Endometrial Biopsy; Other: Euploid embryo transfer; Diagnostic Test: Blood sample

• Registration Number: NCT04107129
• Lead Sponsor: Stanford University

Brief Summary

The purpose of this study is to understand why some women are infertile (unable to conceive a child). The investigators hope to learn if an endometrial biopsy after egg retrieval is feasible for detecting biomarkers for endometriosis and predicting implantation and pregnancy rate after embryo transfer.

This study design will provide for the first time, an opportunity to compare endometrial biopsy material from hyperstimulated (gonadotropin treated) subjects after egg retrieval. If successful, it would provide a new protocol for women with unexplained infertility or those with known endometriosis to avoid poor IVF outcomes.

Detailed Description

The investigators will recruit 100 women who are undergoing IVF with egg retrieval and delayed embryo transfer to consent to endometrial biopsy 1 week after egg retrieval. Currently most women in the Stanford's IVF program undergo egg retrieval with delayed embryo transfer (ET) with preimplantation genetic testing of embryos. This delay allows most to avoid the condition known as ovarian hyperstimulation and allows time for genetic screening (PGT-A) performed on embryos. Such a delay also opens the window for endometrial assessment for proteins like SIRT1 and BCL6 that have been suggested to be associated with endometriosis. Endometriosis is thought to cause IVF failure (Littman et al., 2002); by treating endometriosis in the future, clinicians might avoid IVF failure due to an unexpected non-receptive endometrium (Littman et al., 2002). This study design will provide for the first time, an opportunity to compare endometrial biopsy material from hyperstimulated (gonadotropin treated) subjects after egg retrieval. If successful, it would provide a new protocol for women with unexplained infertility or those with known endometriosis to avoid poor IVF outcomes.

There is some evidence that endometrial scratching (biopsy) may enhance embryo attachment in future cycles (Vitagliano et al., 2018), although not all studies agree (Lensen et al., 2019). The endometrial biopsy taken in the secretory phase will be tested for BCL6 and SIRT1 expression, two proteins highly associated with the presence of endometriosis (Yoo et al., 2017). The samples of endometrium will be processed (put into formalin and paraffin blocks or saved in RNA later and not be analyzed until after completion of the ART cycle. Patients as well as the clinicians will be blinded to results and until the conclusion of the ART cycle following embryo transfer and subsequent pregnancy testing. This will be done to avoid interfering with the current ART cycle and to avoid the introduction of bias. Patients will be provided with test results after completion of the first embryo transfer if they wish to know.

Study Timeline

• Study First Submitted: 2019-09-17
• Study First Submitted QC: 2019-09-25
• Study First Posted: 2019-09-27
• Study Start: 2020-07-01
• Status Verified: 2023-07
• Primary Completion: 2023-07-01
• Study Completion: 2024-07-30
• Last Update Submitted: 2024-08-12
• Last Update Posted: 2024-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 76

Inclusion Criteria

1. Age - 18 to 42
2. AMH ≥ 1
3. Planning to undergo IVF with delayed embryo transfer
4. Must have blastocyst(s) by day 6 that were biopsied for PGT-A
5. BMI 18-35

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Exclusion Criteria

1. Uterine fibroids > 4 cm in size
2. Polycystic ovary syndrome (PCOS) according with the Rotterdam criteria.
3. Ovarian failure and subjects receiving donor oocytes/embryos
4. Anti-cardiolipid and/or lupus anti-coagulant abnormalities by history
5. Diabetes mellitus (Type I or Type II)
6. Untreated hypothyroidism
7. Hyperprolactinemia
8. Uncorrected uterine anomaly

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Known Endometriosis	Endometrial Biopsy	Known Endometriosis undergoing IVF with PGTA
Unexplained Infertility	Endometrial Biopsy	Unexplained Infertility undergoing IVF with PGTA
Unexplained Infertility	Euploid embryo transfer	Unexplained Infertility undergoing IVF with PGTA
Known Endometriosis	Euploid embryo transfer	Known Endometriosis undergoing IVF with PGTA
Known Endometriosis	Blood sample	Known Endometriosis undergoing IVF with PGTA
Low Risk Controls	Endometrial Biopsy	Low Risk Controls undergoing IVF with PGTA
Low Risk Controls	Euploid embryo transfer	Low Risk Controls undergoing IVF with PGTA
Unexplained Infertility	Blood sample	Unexplained Infertility undergoing IVF with PGTA
Low Risk Controls	Blood sample	Low Risk Controls undergoing IVF with PGTA

Primary Outcome Measures

Name	Time	Method
SIRT1 gene expression in the endometrium	2-3 years	Endometrial biopsy specimens will be stained for SIRT1 using immunostaining and Hscore assignment.

Secondary Outcome Measures

Name	Time	Method
Number of patients who have a positive pregnancy test (HCG level > 5) 9 days after embryo transfer	2-3 years	pregnancy rate
Number of embryo transfers that lead to live births	2-3 years	live birth rate
BCL6 expression in the endometrium	2-3 years	Endometrial biopsy specimens will be stained for BCL6 using immunostaining and Hscore assignment.

Trial Locations

Locations (1)

Stanford Fertility and Reproductive Health; 🇺🇸 Sunnyvale, California, United States