Predicting Endometrial Receptivity for Optimal Reproductive Management

NCT ID: NCT04107129

Last Updated: 2024-08-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

76 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-07-01

Study Completion Date

2024-07-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Infertility, Female Endometriosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Known Endometriosis

Known Endometriosis undergoing IVF with PGTA

Endometrial Biopsy

Intervention Type 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

Euploid embryo transfer

Intervention Type OTHER

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

Blood sample

Intervention Type DIAGNOSTIC_TEST

Estradiol and Progesterone levels in the blood will be checked

Unexplained Infertility

Unexplained Infertility undergoing IVF with PGTA

Endometrial Biopsy

Intervention Type 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

Euploid embryo transfer

Intervention Type OTHER

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

Blood sample

Intervention Type DIAGNOSTIC_TEST

Estradiol and Progesterone levels in the blood will be checked

Low Risk Controls

Low Risk Controls undergoing IVF with PGTA

Endometrial Biopsy

Intervention Type 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

Euploid embryo transfer

Intervention Type OTHER

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

Blood sample

Intervention Type DIAGNOSTIC_TEST

Estradiol and Progesterone levels in the blood will be checked

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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

Intervention Type PROCEDURE

Euploid embryo transfer

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

Intervention Type OTHER

Blood sample

Estradiol and Progesterone levels in the blood will be checked

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

42 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

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

NIH

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Ruth Bunker Lathi

Professor, Obstetrics and Gynecology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ruth B Lathi, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Stanford Fertility and Reproductive Health

Sunnyvale, California, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 3756890 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22422778 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22819144 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 27222232 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26945096 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30673547 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2646155 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17118173 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30610661 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16359945 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9389833 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9595616 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9130884 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18546601 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16306079 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30196966 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28754906 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

4R44HD097750-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

51702

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Endometrial Rejuvenation Study
NCT04045821 TERMINATED NA
Surgery and ART For Endometrioma
NCT03717870 NOT_YET_RECRUITING NA