Efficacy of Micronized Natural Progesterone vs GnRH Antagonist in the Prevention of LH Peak During Ovarian Stimulation.

NCT05954962 | Completed Phase 4

• 1 other identifier: IBMR43
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate if the use of oral micronized natural progesterone is not inferior to the use of subcutaneous antagonist in preventing LH peak in controlled ovarian stimulation.

Conditions

IVF

Outcome Measures

Primary Outcomes (1)

• MII oocytes

  number of mature (MII) oocytes in both stimulations.

  Egg collection day (between 8 and 14 days after starting of ovarian stimulation)

Secondary Outcomes (1)

• Duration

  Egg collection day (between 8 and 14 days after starting of ovarian stimulation)

Study Arms (2)

CONTROL GROUP

ACTIVE COMPARATOR

The patient will start to administer: (1) daily subcutaneous injections of gonadotropins on day 1 of ovarian stimulation (2) daily subcutenous injections of ganirelix ("antagonist") on day 5 or 6 of ovarian stimulation. Both medication will be stopped 1-2 days before egg retrieval.

Drug: Ganirelix Acetate

STUDY GROUP

EXPERIMENTAL

The patient will start to administer: (1) daily subcutaneous injections of gonadotropins on day 1 of ovarian stimulation (2) daily oral capsules of natural micronized progesterone on day 1 of ovarian stimulation. Both medication will be stopped 1-2 days before egg retrieval.

Drug: Progesterone 200 MG

Interventions

Progesterone 200 MG DRUG

The patients in the study group will administer oral natural micronized progesterone capsules from day 1 of ovarian stimulation instead of "antagonist" (ganirelix) subcutaneaous injections from day 5-6 of stimulation.

STUDY GROUP

Ganirelix Acetate DRUG

The patients in the control group will administer subcutaneaous injections of ganirelix from day 5-6 of stimulation as per currently used protocol.

CONTROL GROUP

Eligibility Criteria

• Age: 18 Years - 33 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Eligibility for the oocyte donation program at Instituto Bernabeu.
• Age between 18 and 33 years
• BMI \>18 and \<30
• Overall antral follicle count \>8
• Presence of both ovaries
• Ability to participate and comply with the study protocol
• Oral and written comprehension of Spanish
• Having given written consent

You may not qualify if:

• Endometriosis at any stage
• Any ovarian tumor whether benign or malignant
• Concurrent participation in another study
• Malabsorptive syndromes that may alter the efficacy of Seidigestan ® such as bariatric surgery, ulcerative colitis or Crohn's disease
• Irregular periods
• Hypogonadotropic hypogonadism
• Having received in the previous two months treatment with ovulation stimulators
• Having previously participated in the present study

Sponsors & Collaborators

• Instituto Bernabeu: lead

Study Sites (1)

Instituto Bernabeu

Elche, Alicante, 03206, Spain

Location

Related Publications (15)

• A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (Puregon). The ganirelix dose-finding study group. Hum Reprod. 1998 Nov;13(11):3023-31.

  PMID: 9853849 BACKGROUND

• Balasch J, Creus M, Fabregues F, Carmona F, Casamitjana R, Penarrubia J, Rivera F, Vanrell JA. Hormonal profiles in successful and unsuccessful implantation in IVF-ET after combined GnRH agonist/gonadotropin treatment for superovulation and hCG luteal support. Gynecol Endocrinol. 1995 Mar;9(1):51-8. doi: 10.3109/09513599509160191.

  PMID: 7793300 BACKGROUND

• Begueria R, Garcia D, Vassena R, Rodriguez A. Medroxyprogesterone acetate versus ganirelix in oocyte donation: a randomized controlled trial. Hum Reprod. 2019 May 1;34(5):872-880. doi: 10.1093/humrep/dez034.

  PMID: 30927417 BACKGROUND

• Castillo JC, Haahr T, Martinez-Moya M, Humaidan P. Gonadotropin-releasing hormone agonist for ovulation trigger - OHSS prevention and use of modified luteal phase support for fresh embryo transfer. Ups J Med Sci. 2020 May;125(2):131-137. doi: 10.1080/03009734.2020.1736696. Epub 2020 May 4.

  PMID: 32366146 BACKGROUND

• Fauser BC, Devroey P. Why is the clinical acceptance of gonadotropin-releasing hormone antagonist cotreatment during ovarian hyperstimulation for in vitro fertilization so slow? Fertil Steril. 2005 Jun;83(6):1607-11. doi: 10.1016/j.fertnstert.2005.02.011.

  PMID: 15950626 BACKGROUND

• Giles J, Alama P, Gamiz P, Vidal C, Badia P, Pellicer A, Bosch E. Medroxyprogesterone acetate is a useful alternative to a gonadotropin-releasing hormone antagonist in oocyte donation: a randomized, controlled trial. Fertil Steril. 2021 Aug;116(2):404-412. doi: 10.1016/j.fertnstert.2021.02.036. Epub 2021 Apr 2.

  PMID: 33814126 BACKGROUND

• Griesinger G, Dawson A, Schultze-Mosgau A, Finas D, Diedrich K, Felberbaum R. Assessment of luteinizing hormone level in the gonadotropin-releasing hormone antagonist protocol. Fertil Steril. 2006 Mar;85(3):791-3. doi: 10.1016/j.fertnstert.2005.08.048.

  PMID: 16500366 BACKGROUND

• Guo YC, Chen PY, Li TT, Jia L, Sun P, Zhu WS, Deng CC, Fang C, Liang XY. Different progestin-primed ovarian stimulation protocols in infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection: an analysis of 1188 cycles. Arch Gynecol Obstet. 2019 Apr;299(4):1201-1212. doi: 10.1007/s00404-019-05065-4. Epub 2019 Mar 9.

  PMID: 30852654 BACKGROUND

• Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.

  PMID: 25956370 BACKGROUND

• Macklon NS, Stouffer RL, Giudice LC, Fauser BC. The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev. 2006 Apr;27(2):170-207. doi: 10.1210/er.2005-0015. Epub 2006 Jan 24.

  PMID: 16434510 BACKGROUND

• Messinis IE, Templeton AA. Endocrine and follicle characteristics of cycles with and without endogenous luteinizing hormone surges during superovulation induction with pulsatile follicle-stimulating hormone. Hum Reprod. 1987 Jan;2(1):11-6. doi: 10.1093/oxfordjournals.humrep.a136481.

  PMID: 3106404 BACKGROUND

• Porter RN, Smith W, Craft IL, Abdulwahid NA, Jacobs HS. Induction of ovulation for in-vitro fertilisation using buserelin and gonadotropins. Lancet. 1984 Dec 1;2(8414):1284-5. doi: 10.1016/s0140-6736(84)92840-x. No abstract available.

  PMID: 6150318 BACKGROUND

• Yu S, Long H, Chang HY, Liu Y, Gao H, Zhu J, Quan X, Lyu Q, Kuang Y, Ai A. New application of dydrogesterone as a part of a progestin-primed ovarian stimulation protocol for IVF: a randomized controlled trial including 516 first IVF/ICSI cycles. Hum Reprod. 2018 Feb 1;33(2):229-237. doi: 10.1093/humrep/dex367.

  PMID: 29300975 BACKGROUND

• Zhu X, Ye H, Fu Y. Duphaston and human menopausal gonadotropin protocol in normally ovulatory women undergoing controlled ovarian hyperstimulation during in vitro fertilization/intracytoplasmic sperm injection treatments in combination with embryo cryopreservation. Fertil Steril. 2017 Sep;108(3):505-512.e2. doi: 10.1016/j.fertnstert.2017.06.017. Epub 2017 Jul 8.

  PMID: 28697910 BACKGROUND

• Martinez-Moya M, Guerrero J, Girela JL, Pitas A, Bernabeu A, Bernabeu R, Castillo JC. Micronized natural progesterone (Seidigestan(R)) vs GnRH antagonists for preventing the LH surge during controlled ovarian stimulation (PRO_NAT study): study protocol of a randomized clinical trial. Front Endocrinol (Lausanne). 2024 Mar 21;15:1350154. doi: 10.3389/fendo.2024.1350154. eCollection 2024.

  PMID: 38577571 DERIVED

MeSH Terms

Interventions

Progesterone; ganirelix

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 12, 2023
• First Posted: July 20, 2023
• Study Start: December 23, 2023
• Primary Completion: April 3, 2025
• Study Completion: August 30, 2025
• Last Updated: March 27, 2026

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)