Comparison Elagolix vs Depot Leuprolide Prior to Frozen Embryo Transfers in Patients With Endometriosis

NCT04445025 | Completed Early Phase 1 FDA Drug

• 1 other identifier: elagolix
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Patients who have been previously surgically diagnosed with endometriosis and have embryos predicted to be euploid after in vitro fertilization will be divided into 2 groups via randomization. The test group will receive Elagolix for 60 days prior to starting frozen embryo transfer preparation. The control group will be given leuprolide acetate every 28 days x 2 prior to starting the frozen embryo transfer preparation. Comparative implantation rates between two groups of patients will be evaluated

Conditions

Infertility; Endometriosis

Outcome Measures

Primary Outcomes (1)

• Comparison of Implantation Rates

  Implantation rates of both groups will be compared (defined as number of intrauterine gestational sacs with visible cardiac activity noted on ultrasound examination performed 2-3 weeks after initial positive pregnancy test)

  2-3 weeks after initial positive pregnancy test (approx 14-15 weeks post initiation of treatment)

Secondary Outcomes (3)

• Comparison of Biochemical pregnancy rates

  2-3 weeks after initial positive pregnancy test (approx 14-15 weeks post initiation of treatment)

• Comparison of hormone levels between the two groups

  4 weeks and 8 weeks after initiation of treatment

• Comparison of live birth rates and pregnancy loss rates

  10-11 months after initiation of treatment

Study Arms (2)

Test group

EXPERIMENTAL

Subjects will receive the medication elagolix

Drug: Elagolix 200 MG; Diagnostic Test: Lab work

Control group

ACTIVE COMPARATOR

Subjects will receive leuprolide acetate

Drug: Leuprolide Acetate 3.75 MG/ML; Diagnostic Test: Lab work

Interventions

Elagolix 200 MG DRUG

Elagolix 200mg twice daily orally for 60 days prior to beginning frozen embryo transfer preparation

Test group

Leuprolide Acetate 3.75 MG/ML DRUG

Leuprolide Acetate intramuscularly every 28 days (twice) prior to beginning frozen embryo transfer preparation

Control group

Lab work DIAGNOSTIC_TEST

Serum follicle stimulating hormone (FSH), estradiol, luteinizing hormone (LH), progesterone, human chorionic gonadotropin (hCG), serum for microarray analysis, complete blood count, and chemistry panel with liver functions levels will be drawn via blood draw

Control group; Test group

Eligibility Criteria

• Age: 21 Years - 42 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of infertility who are candidate for IVF
• Surgical diagnosis of endometriosis within 10 years of study entry
• Willing to sign/give informed consent and adhere to parameters of study
• Normal endometrial cavity as diagnosed by 3D ultrasound and office hysteroscopy examinations at baseline or after correction of underlying clinically relevant cavity abnormalities
• Day 2-4 serum FSH level ≤ 12 mIu/mL and/or random serum AMH level ≥ 0.9 ng/mL and/or antral follicular phase follicle count obtained by trans-vaginal ultrasound examination ≥ 5
• No contraindication to GnRH agonist or GnRH antagonist use
• No prolonged use of GnRH agonist or antagonist (\> 30 consecutive days) or other treatment for endometriosis within 4 months of study entry
• Have at least one euploid embryo available for transfer
• Agrees to transfer best quality embryo as determined by CCRM physician and embryology team
• Regular menses ranging from 22-36 days
• Agrees to use barrier contraception throughout GnRH agonist or antagonist administration
• No evidence of untreated hydrosalpinx

You may not qualify if:

• Age \<21 or \> 42 years at time of initiation of IVF cycle
• Day 2-4 FSH level \>12 mIu/mL or random serum AMH level \<1.0 ng/mL and antral follicle count obtained by trans-vaginal ultrasound examination \< 5
• Planned use of donor oocytes or embryos
• Planned use of gestational carrier
• Use of GnRH agonist, GnRH antagonist or other approved medical therapy for endometriosis (with the exception of combination contraceptives) for \> 30 consecutive days prior to study entry
• Unwilling to abide by study parameters or sign informed consent
• No documentation of surgical diagnosis of endometriosis with study timeline (10 years of study entry)
• Absence of embryos predicted to be euploid available for transfer (embryos with no results may not be included in transfer)
• Prior adverse reaction to any GnRH agonist or antagonist
• Uncorrected or uncorrectable clinically relevant uterine cavity abnormalities or hydrosalpinx
• Acute or chronic renal, pulmonary, hepatic, or cardiac disease
• Prior diagnosis of pituitary adenoma or any other intracranial lesion
• Diagnosis of polycystic ovary syndrome (PCOS)
• Pregnancy prior to study initiation or initiation of endometrial preparation for embryo transfer.
• Undiagnosed vaginal bleeding

Sponsors & Collaborators

• Colorado Center for Reproductive Medicine: lead
• AbbVie: collaborator

Study Sites (1)

Colorado Center for Reproductive Medicine

Lone Tree, Colorado, 80124, United States

Location

Related Publications (8)

• Cosar E, Mamillapalli R, Ersoy GS, Cho S, Seifer B, Taylor HS. Serum microRNAs as diagnostic markers of endometriosis: a comprehensive array-based analysis. Fertil Steril. 2016 Aug;106(2):402-9. doi: 10.1016/j.fertnstert.2016.04.013. Epub 2016 May 11.

  PMID: 27179784 BACKGROUND

• Schoolcraft WB, Treff NR, Stevens JM, Ferry K, Katz-Jaffe M, Scott RT Jr. Live birth outcome with trophectoderm biopsy, blastocyst vitrification, and single-nucleotide polymorphism microarray-based comprehensive chromosome screening in infertile patients. Fertil Steril. 2011 Sep;96(3):638-40. doi: 10.1016/j.fertnstert.2011.06.049. Epub 2011 Jul 23.

  PMID: 21782169 BACKGROUND

• Surrey ES, Minjarez DA, Schoolcraft WB. The incidence of aberrant endometrial alphavbeta(3) vitronectin expression in a high risk infertility population: could prolonged GnRH agonist therapy play a role? J Assist Reprod Genet. 2007 Nov;24(11):553-6. doi: 10.1007/s10815-007-9164-3. Epub 2007 Nov 17.

  PMID: 18026832 BACKGROUND

• Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, Surrey E, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Rowan JP, Duan WR, Ng J, Schwefel B, Thomas JW, Jain RI, Chwalisz K. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. N Engl J Med. 2017 Jul 6;377(1):28-40. doi: 10.1056/NEJMoa1700089. Epub 2017 May 19.

  PMID: 28525302 BACKGROUND

• Surrey ES, Katz-Jaffe M, Kondapalli LV, Gustofson RL, Schoolcraft WB. GnRH agonist administration prior to embryo transfer in freeze-all cycles of patients with endometriosis or aberrant endometrial integrin expression. Reprod Biomed Online. 2017 Aug;35(2):145-151. doi: 10.1016/j.rbmo.2017.05.004. Epub 2017 May 17.

  PMID: 28601378 BACKGROUND

• Gardner DK, Surrey E, Minjarez D, Leitz A, Stevens J, Schoolcraft WB. Single blastocyst transfer: a prospective randomized trial. Fertil Steril. 2004 Mar;81(3):551-5. doi: 10.1016/j.fertnstert.2003.07.023.

  PMID: 15037401 BACKGROUND

• Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006 Jan 25;2006(1):CD004635. doi: 10.1002/14651858.CD004635.pub2.

  PMID: 16437491 BACKGROUND

• Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertil Steril. 2002 Oct;78(4):699-704. doi: 10.1016/s0015-0282(02)03373-3.

  PMID: 12372443 RESULT

MeSH Terms

Conditions

Infertility; Endometriosis

Interventions

elagolix; Leuprolide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Eric Surrey, MD

  Colorado Center for Reproductive Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Model Details: Test group will receive Elagolix 60 days prior to initiating frozen embryo transfer preparation. Control group will receive depot leuprolide twice (once every 28 days) prior to initiation frozen embryo transfer preparation.

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 24, 2020
• Study Start: September 1, 2020
• Primary Completion: September 30, 2024
• Study Completion: December 30, 2024
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)