Predicting Endometrial Receptivity for Optimal Reproductive Management

NCT04107129 | Completed

• 2 other identifiers: 517024R44HD097750-02
• Study Type: observational
• Target: 76
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• SIRT1 gene expression in the endometrium

  Endometrial biopsy specimens will be stained for SIRT1 using immunostaining and Hscore assignment.

  2-3 years

Secondary Outcomes (3)

• BCL6 expression in the endometrium

  2-3 years

• Number of patients who have a positive pregnancy test (HCG level > 5) 9 days after embryo transfer

  2-3 years

• Number of embryo transfers that lead to live births

  2-3 years

Study Arms (3)

Known Endometriosis

Known Endometriosis undergoing IVF with PGTA

Procedure: Endometrial Biopsy; Other: Euploid embryo transfer; Diagnostic Test: Blood sample

Unexplained Infertility

Unexplained Infertility undergoing IVF with PGTA

Procedure: Endometrial Biopsy; Other: Euploid embryo transfer; Diagnostic Test: Blood sample

Low Risk Controls

Low Risk Controls undergoing IVF with PGTA

Procedure: Endometrial Biopsy; Other: Euploid embryo transfer; Diagnostic Test: Blood sample

Interventions

Endometrial Biopsy PROCEDURE

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

Known Endometriosis; Low Risk Controls; Unexplained Infertility

Euploid embryo transfer OTHER

Patients undergoing IVF and Preimplantation genetic testing will undergo delayed euploid frozen embryo transfer per clinical protocol and standard of care.

Known Endometriosis; Low Risk Controls; Unexplained Infertility

Blood sample DIAGNOSTIC_TEST

Estradiol and Progesterone levels in the blood will be checked

Known Endometriosis; Low Risk Controls; Unexplained Infertility

Eligibility Criteria

• Age: 18 Years - 42 Years
• Gender Eligibility Details: Adult females of reproductive age.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Stanford University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Stanford Fertility and Reproductive Health

Sunnyvale, California, 94087, United States

Location

Related Publications (18)

• Budwit-Novotny DA, McCarty KS, Cox EB, Soper JT, Mutch DG, Creasman WT, Flowers JL, McCarty KS Jr. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res. 1986 Oct;46(10):5419-25.

  PMID: 3756890 BACKGROUND

• Simoens S, Dunselman G, Dirksen C, Hummelshoj L, Bokor A, Brandes I, Brodszky V, Canis M, Colombo GL, DeLeire T, Falcone T, Graham B, Halis G, Horne A, Kanj O, Kjer JJ, Kristensen J, Lebovic D, Mueller M, Vigano P, Wullschleger M, D'Hooghe T. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod. 2012 May;27(5):1292-9. doi: 10.1093/humrep/des073. Epub 2012 Mar 14.

  PMID: 22422778 BACKGROUND

• Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012 Sep;98(3):511-9. doi: 10.1016/j.fertnstert.2012.06.029. Epub 2012 Jul 20.

  PMID: 22819144 BACKGROUND

• Endometriosis exerts "profound" economic burden in the US. (2007). PharmacoEconomics & Outcomes News. https://doi.org/10.2165/00151234-200705230-00025

  BACKGROUND

• Evans-Hoeker E, Lessey BA, Jeong JW, Savaris RF, Palomino WA, Yuan L, Schammel DP, Young SL. Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis. Reprod Sci. 2016 Sep;23(9):1234-41. doi: 10.1177/1933719116649711. Epub 2016 May 24.

  PMID: 27222232 BACKGROUND

• Fox C, Morin S, Jeong JW, Scott RT Jr, Lessey BA. Local and systemic factors and implantation: what is the evidence? Fertil Steril. 2016 Apr;105(4):873-84. doi: 10.1016/j.fertnstert.2016.02.018. Epub 2016 Mar 3.

  PMID: 26945096 BACKGROUND

• Lensen S, Osavlyuk D, Armstrong S, Stadelmann C, Hennes A, Napier E, Wilkinson J, Sadler L, Gupta D, Strandell A, Bergh C, Vigneswaran K, Teh WT, Hamoda H, Webber L, Wakeman SA, Searle L, Bhide P, McDowell S, Peeraer K, Khalaf Y, Farquhar C. A Randomized Trial of Endometrial Scratching before In Vitro Fertilization. N Engl J Med. 2019 Jan 24;380(4):325-334. doi: 10.1056/NEJMoa1808737.

  PMID: 30673547 BACKGROUND

• Lessey BA, Metzger DA, Haney AF, McCarty KS Jr. Immunohistochemical analysis of estrogen and progesterone receptors in endometriosis: comparison with normal endometrium during the menstrual cycle and the effect of medical therapy. Fertil Steril. 1989 Mar;51(3):409-15. doi: 10.1016/s0015-0282(16)60545-9.

  PMID: 2646155 BACKGROUND

• Lessey BA, Palomino WA, Apparao KB, Young SL, Lininger RA. Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women. Reprod Biol Endocrinol. 2006;4 Suppl 1(Suppl 1):S9. doi: 10.1186/1477-7827-4-S1-S9.

  PMID: 17118173 BACKGROUND

• Likes CE, Cooper LJ, Efird J, Forstein DA, Miller PB, Savaris R, Lessey BA. Medical or surgical treatment before embryo transfer improves outcomes in women with abnormal endometrial BCL6 expression. J Assist Reprod Genet. 2019 Mar;36(3):483-490. doi: 10.1007/s10815-018-1388-x. Epub 2019 Jan 4.

  PMID: 30610661 BACKGROUND

• Littman E, Giudice L, Lathi R, Berker B, Milki A, Nezhat C. Role of laparoscopic treatment of endometriosis in patients with failed in vitro fertilization cycles. Fertil Steril. 2005 Dec;84(6):1574-8. doi: 10.1016/j.fertnstert.2005.02.059.

  PMID: 16359945 BACKGROUND

• Meyer WR, Lessey BA, Castelbaum AJ. Hydrosalpinx and altered uterine receptivity. Fertil Steril. 1997 Nov;68(5):944-5. doi: 10.1016/s0015-0282(97)90360-5. No abstract available.

  PMID: 9389833 BACKGROUND

• Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998 Apr 30;17(8):857-72. doi: 10.1002/(sici)1097-0258(19980430)17:83.0.co;2-e.

  PMID: 9595616 BACKGROUND

• Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997 May;67(5):817-21. doi: 10.1016/s0015-0282(97)81391-x. No abstract available.

  PMID: 9130884 BACKGROUND

• Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101-8. doi: 10.1038/nprot.2008.73.

  PMID: 18546601 BACKGROUND

• Talbi S, Hamilton AE, Vo KC, Tulac S, Overgaard MT, Dosiou C, Le Shay N, Nezhat CN, Kempson R, Lessey BA, Nayak NR, Giudice LC. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women. Endocrinology. 2006 Mar;147(3):1097-121. doi: 10.1210/en.2005-1076. Epub 2005 Nov 23.

  PMID: 16306079 BACKGROUND

• Vitagliano A, Di Spiezio Sardo A, Saccone G, Valenti G, Sapia F, Kamath MS, Blaganje M, Andrisani A, Ambrosini G. Endometrial scratch injury for women with one or more previous failed embryo transfers: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2018 Sep;110(4):687-702.e2. doi: 10.1016/j.fertnstert.2018.04.040.

  PMID: 30196966 BACKGROUND

• Yoo JY, Kim TH, Fazleabas AT, Palomino WA, Ahn SH, Tayade C, Schammel DP, Young SL, Jeong JW, Lessey BA. KRAS Activation and over-expression of SIRT1/BCL6 Contributes to the Pathogenesis of Endometriosis and Progesterone Resistance. Sci Rep. 2017 Jul 28;7(1):6765. doi: 10.1038/s41598-017-04577-w.

  PMID: 28754906 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Endometrial biopsy will be collected. Urine, saliva, and blood samples will also be collected for future studies

MeSH Terms

Conditions

Infertility, Female; Endometriosis; Infertility

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Ruth B Lathi, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Obstetrics and Gynecology

Study Record Dates

• First Submitted: September 17, 2019
• First Posted: September 27, 2019
• Study Start: July 1, 2020
• Primary Completion: July 1, 2023
• Study Completion: July 30, 2024
• Last Updated: August 14, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)