Addition of Gonadotropin Releasing Hormone Agonist to Luteal Phase Support

Female Infertility Clinical Trial

Official title:

Impact of Addition of Gonadotropin Releasing Hormone Agonist to Luteal Phase Support on Antagonist ICSI Cycles

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05286554
• Other study ID #: 0201599
• Status: Completed
• Phase: Phase 4
• Start date: March 17, 2022
• Est. completion date: January 18, 2024

Study information

• Verified date: March 2022
• Source: Alexandria University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Hormonal milieu during implantation is crucial to embryo-endometrium interaction and to the viability of the conceptus. There are many protocols of luteal phase support (LPS) in assisted reproductive technology (ART) cycles. GnRH-agonist (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. If the GnRH-a is administered in the mid-luteal phase, an initial flare-up with increased levels of LH takes 3-4 days before receptor down-regulation kicks in. The increased luteinizing hormone (LH) results in increased support for the corpus luteum (CL), leading to higher output of P4 and providing stronger LPS. In earlier studies, the inadvertent administration of GnRH-a in the mid-luteal phase, did not compromise pregnancy outcomes but rather enhanced implantation rates. Therefore, the use of GnRH-a in LPS was investigated and found to enhance clinical outcomes after GnRH-a and GnRH antagonist- treated ovarian stimulation cycles, as well as, in recipients of donated oocytes. Several studies since then investigated the role of GnRHa for LPS, found that luteal support with GnRH-a could be used as the first choice in patients at high risk for ovarian hyperstimulation syndrome (OHSS), or even as the sole source of LPS in a GnRH-a-triggered antagonist ovarian stimulation cycle. Although many trials have showed substantial efficacy of GnRH-a addition for luteal support on pregnancy outcomes in women undergoing IVF/ICSI, others, found no benefit of its addition to the standard LPS. A meta-analysis concluded that there is benefit, however, this evidence is of very low quality. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: January 18, 2024
• Est. primary completion date: October 27, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 38 Years

Eligibility

Inclusion Criteria:

1. Patient age = 38 years.

2. BMI = 30.

3. Basal follicle stimulating hormone (FSH) level = 10 IU/L.

4. Anti-Müllerian hormone (AMH): = 5 ng/ml.

Exclusion Criteria:

1. Endometriosis.

2. Polycystic ovarian syndrome (PCOS).

3. Uterine pathology or anomaly.

4. Evidence of hydrosalpinx by hysterosalpingography or ultrasound.

5. Comorbidities: Diabetes mellitus, hypertension, immune diseases.

Related Conditions & MeSH terms

• Female Infertility
• Infertility
• Infertility, Female

Intervention

Drug:
• gonadotropin releasing hormone-agonist
subcutaneous injection
• Progesterone
vaginal suppositories (400 mg twice daily) starting on the day after oocyte retrieval and will be continued till pregnancy assessed by serum ß-HCG 15 days after ICSI, and if pregnant, for 10 weeks of gestation.

Locations

Country	Name	City	State
Egypt	Alexandria University	Alexandria

Sponsors (1)

Lead Sponsor	Collaborator
Alexandria University

Country where clinical trial is conducted

Egypt, 

References & Publications (13)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Implantation rate	the ratio of the number of gestational sacs detected by sonography to the total number of embryos transferred.	2 weeks after positive pregnancy test
Secondary	Multiple pregnancy rate	The percentage of pregnancies with more than one fetus	8 weeks of gestation
Secondary	Serum ß-human chorionic gonadotropin (ß-HCG) concentration	In milli-International unit/ml on day 15 after ICSI	15 days after ICSI