Predicting Endometrial Receptivity for Optimal Reproductive Management (PERFORM)

July 26, 2023 updated by: Ruth Bunker Lathi, Stanford University

Predicting Endometrial Receptivity for Optimal Reproductive Management (PERFORM)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

76

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Sunnyvale, California, United States, 94087
        • Stanford Fertility and Reproductive Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 42 years (Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

These criteria are meant to define two populations of women (high and low risk for endometriosis) and not include confounding diagnoses including PCOS, autoimmune conditions and endocrine disorders such as hypothyroidism and hyperprolactinemia.

Description

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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Known Endometriosis
Known Endometriosis undergoing IVF with PGTA
Procedure: Endometrial Biopsy
An endometrial biopsy is the removal of a small piece of tissue from the endometrium, which is the lining of the uterus. Endometrial tissue will be tested for BCL6 and SIRT1 Biomarkers
Other: Euploid embryo transfer
Patients undergoing IVF and Preimplantation genetic testing will undergo delayed euploid frozen embryo transfer per clinical protocol and standard of care.
Diagnostic test: Blood sample
Estradiol and Progesterone levels in the blood will be checked
Unexplained Infertility
Unexplained Infertility undergoing IVF with PGTA
Procedure: Endometrial Biopsy
An endometrial biopsy is the removal of a small piece of tissue from the endometrium, which is the lining of the uterus. Endometrial tissue will be tested for BCL6 and SIRT1 Biomarkers
Other: Euploid embryo transfer
Patients undergoing IVF and Preimplantation genetic testing will undergo delayed euploid frozen embryo transfer per clinical protocol and standard of care.
Diagnostic test: Blood sample
Estradiol and Progesterone levels in the blood will be checked
Low Risk Controls
Low Risk Controls undergoing IVF with PGTA
Procedure: Endometrial Biopsy
An endometrial biopsy is the removal of a small piece of tissue from the endometrium, which is the lining of the uterus. Endometrial tissue will be tested for BCL6 and SIRT1 Biomarkers
Other: Euploid embryo transfer
Patients undergoing IVF and Preimplantation genetic testing will undergo delayed euploid frozen embryo transfer per clinical protocol and standard of care.
Diagnostic test: Blood sample
Estradiol and Progesterone levels in the blood will be checked

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SIRT1 gene expression in the endometrium
Time Frame: 2-3 years
Endometrial biopsy specimens will be stained for SIRT1 using immunostaining and Hscore assignment.
2-3 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

  • Principal Investigator: Ruth B Lathi, MD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2020

Primary Completion (Actual)

July 1, 2023

Study Completion (Estimated)

July 30, 2024

Study Registration Dates

First Submitted

September 17, 2019

First Submitted That Met QC Criteria

September 25, 2019

First Posted (Actual)

September 27, 2019

Study Record Updates

Last Update Posted (Actual)

July 28, 2023

Last Update Submitted That Met QC Criteria

July 26, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 51702
  • 4R44HD097750-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No PHI will be shared with collaborators. Collaborators will only have access to aggregate data by study group

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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