Clinical trial NCT04107129: Predicting Endometrial Receptivity for Optimal Reproductive Management
Official title: Predicting Endometrial Receptivity for Optimal Reproductive Management (PERFORM)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infertility, Female
Endometriosis
Keywords: Infertility
Endometriosis
BLC6
SIRT1
In Vitro Fertilization (IVF)
Embryo Transfer (ET)
Frozen Embryo Transfer (FET)
Assisted Reproductive Technology (ART)
PERFORM
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2019-09-27
Enrollment: 76
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: SIRT1 gene expression in the endometrium
timeFrame: 2-3 years
Secondary outcomes:
measure: BCL6 expression in the endometrium
timeFrame: 2-3 years
measure: Number of patients who have a positive pregnancy test (HCG level > 5) 9 days after embryo transfer
timeFrame: 2-3 years
measure: Number of embryo transfers that lead to live births
timeFrame: 2-3 years
Other outcomes:
Locations:
city: Sunnyvale
country: United States
facility: Stanford Fertility and Reproductive Health
state: California
Study officials:
affiliation: Stanford University
name: Ruth B Lathi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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