Addition of Gonadotropin Releasing Hormone Agonist to Luteal Phase Support

NCT05286554 | Completed Phase 4

• 1 other identifier: 0201599
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Hormonal milieu during implantation is crucial to embryo-endometrium interaction and to the viability of the conceptus. Alterations in the peri-implantation environment are considered to impair perinatal outcomes in intracytoplasmic sperm injection (ICSI) therapy. GnRH-a is a new and promising modality for LPS. Regimens for using GnRH-a in LPS, including single mid-luteal bolus or the addition of a GnRH-a to progesterone supplementation, have been recently suggested. The aim of this study is to evaluate the impact of addition of mid-luteal single-dose or multiple-dose GnRH agonist to the routine luteal phase support in patients undergoing ICSI cycles using GnRH antagonist protocol.

Conditions

Female Infertility

Keywords

luteal phase support, ICSI, gonadotropin releasing hormone agonist

Outcome Measures

Primary Outcomes (1)

• Clinical pregnancy rate

  Calculated as the number of clinical pregnancies (Presence of an intrauterine gestational sac with embryonic cardiac activity observed by vaginal ultrasound) divided by the number of embryo transfer procedures.

  2 weeks after positive pregnancy test

Secondary Outcomes (3)

• Implantation rate

  2 weeks after positive pregnancy test

• Multiple pregnancy rate

  8 weeks of gestation

• Serum β-human chorionic gonadotropin (β-HCG) concentration

  15 days after ICSI

Study Arms (3)

Group 1

EXPERIMENTAL

Will receive routine LPS and additional single GnRH-a bolus, triptorelin 0.1 mg subcutaneous injection on the 6th day after oocyte retrieval.

Drug: gonadotropin releasing hormone-agonist; Drug: Progesterone

Group 2

EXPERIMENTAL

Will receive routine LPS and additional multiple mid-luteal GnRH-a, triptorelin 0.1 mg subcutaneous injection on the 5th, 7th and 9th days after oocyte retrieval.

Drug: gonadotropin releasing hormone-agonist; Drug: Progesterone

Group 3 (Control)

ACTIVE COMPARATOR

Will receive the routine LPS without GnRH-a

Drug: Progesterone

Interventions

gonadotropin releasing hormone-agonist DRUG

subcutaneous injection

Also known as: triptorelin 0.1 mg

Group 1; Group 2

Progesterone DRUG

vaginal suppositories (400 mg twice daily) starting on the day after oocyte retrieval and will be continued till pregnancy assessed by serum β-HCG 15 days after ICSI, and if pregnant, for 10 weeks of gestation.

Also known as: cyclogest

Group 1; Group 2; Group 3 (Control)

Eligibility Criteria

• Age: 20 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient age ≤ 38 years.
• BMI ≤ 30.
• Basal follicle stimulating hormone (FSH) level ≤ 10 IU/L.
• Anti-Müllerian hormone (AMH): ≤ 5 ng/ml.

You may not qualify if:

• Endometriosis.
• Polycystic ovarian syndrome (PCOS).
• Uterine pathology or anomaly.
• Evidence of hydrosalpinx by hysterosalpingography or ultrasound.
• Comorbidities: Diabetes mellitus, hypertension, immune diseases.

Sponsors & Collaborators

• Alexandria University: lead

Study Sites (1)

Alexandria University

Alexandria, Alexandria Governorate, 21526, Egypt

Location

Related Publications (13)

• de Ziegler D, Pirtea P, Andersen CY, Ayoubi JM. Role of gonadotropin-releasing hormone agonists, human chorionic gonadotropin (hCG), progesterone, and estrogen in luteal phase support after hCG triggering, and when in pregnancy hormonal support can be stopped. Fertil Steril. 2018 May;109(5):749-755. doi: 10.1016/j.fertnstert.2018.03.006.

  PMID: 29778367 BACKGROUND

• Thomsen LH, Kesmodel US, Andersen CY, Humaidan P. Daytime Variation in Serum Progesterone During the Mid-Luteal Phase in Women Undergoing In Vitro Fertilization Treatment. Front Endocrinol (Lausanne). 2018 Mar 19;9:92. doi: 10.3389/fendo.2018.00092. eCollection 2018.

  PMID: 29615975 BACKGROUND

• Shoham G, Leong M, Weissman A. A 10-year follow-up on the practice of luteal phase support using worldwide web-based surveys. Reprod Biol Endocrinol. 2021 Jan 26;19(1):15. doi: 10.1186/s12958-021-00696-2.

  PMID: 33499875 BACKGROUND

• Wang NF, Bungum L, Skouby SO. What is the optimal luteal support in assisted reproductive technology? Horm Mol Biol Clin Investig. 2021 Feb 22;43(2):225-233. doi: 10.1515/hmbci-2020-0081.

  PMID: 33609426 BACKGROUND

• Balasch J, Martinez F, Jove I, Cabre L, Coroleu B, Barri PN, Vanrell JA. Inadvertent gonadotrophin-releasing hormone agonist (GnRHa) administration in the luteal phase may improve fecundity in in-vitro fertilization patients. Hum Reprod. 1993 Jul;8(7):1148-51. doi: 10.1093/oxfordjournals.humrep.a138210.

  PMID: 8408503 BACKGROUND

• Tesarik J, Hazout A, Mendoza C. Enhancement of embryo developmental potential by a single administration of GnRH agonist at the time of implantation. Hum Reprod. 2004 May;19(5):1176-80. doi: 10.1093/humrep/deh235. Epub 2004 Apr 7.

  PMID: 15070873 BACKGROUND

• Tesarik J, Hazout A, Mendoza-Tesarik R, Mendoza N, Mendoza C. Beneficial effect of luteal-phase GnRH agonist administration on embryo implantation after ICSI in both GnRH agonist- and antagonist-treated ovarian stimulation cycles. Hum Reprod. 2006 Oct;21(10):2572-9. doi: 10.1093/humrep/del173. Epub 2006 Aug 22.

  PMID: 16926261 BACKGROUND

• Fusi FM, Arnoldi M, Bosisio C, Lombardo G, Ferrario M, Zanga L, Galimberti A, Capitanio E. Ovulation induction and luteal support with GnRH agonist in patients at high risk for hyperstimulation syndrome. Gynecol Endocrinol. 2015;31(9):693-7. doi: 10.3109/09513590.2015.1025379. Epub 2015 Aug 31.

  PMID: 26527503 BACKGROUND

• Ma X, Du W, Hu J, Yang Y, Zhang X. Effect of Gonadotrophin-Releasing Hormone Agonist Addition for Luteal Support on Pregnancy Outcome in vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Meta-Analysis Based on Randomized Controlled Trials. Gynecol Obstet Invest. 2020;85(1):13-25. doi: 10.1159/000501204. Epub 2019 Aug 16.

  PMID: 31422404 BACKGROUND

• Aboulghar MA, Marie H, Amin YM, Aboulghar MM, Nasr A, Serour GI, Mansour RT. GnRH agonist plus vaginal progesterone for luteal phase support in ICSI cycles: a randomized study. Reprod Biomed Online. 2015 Jan;30(1):52-6. doi: 10.1016/j.rbmo.2014.09.017. Epub 2014 Oct 13.

  PMID: 25456166 BACKGROUND

• Isikoglu M, Ozgur K, Oehninger S. Extension of GnRH agonist through the luteal phase to improve the outcome of intracytoplasmic sperm injection. J Reprod Med. 2007 Jul;52(7):639-44.

  PMID: 17847764 BACKGROUND

• Martins WP, Ferriani RA, Navarro PA, Nastri CO. GnRH agonist during luteal phase in women undergoing assisted reproductive techniques: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2016 Feb;47(2):144-51. doi: 10.1002/uog.14874. Epub 2015 Dec 30.

  PMID: 25854891 BACKGROUND

• Qu D, Li Y. Multiple-dose versus single-dose gonadotropin-releasing hormone agonist after first in vitro fertilization failure associated with luteal phase deficiency: A randomized controlled trial. J Int Med Res. 2020 Jun;48(6):300060520926026. doi: 10.1177/0300060520926026.

  PMID: 32495663 BACKGROUND

MeSH Terms

Conditions

Infertility, Female

Interventions

Gonadotropin-Releasing Hormone; Triptorelin Pamoate; Progesterone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Progesterone Congeners; Gonadal Steroid Hormones

Study Officials

• Mervat Sheikh El-arab, PhD

  Alexandria Univsersity

  PRINCIPAL INVESTIGATOR

• Ahmed Abdel Aziz, PhD

  Alexandria Univsersity

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2022
• First Posted: March 18, 2022
• Study Start: March 17, 2022
• Primary Completion: October 27, 2023
• Study Completion: January 18, 2024
• Last Updated: January 29, 2025

Record last verified: 2022-03

Locations

EG (1)