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CompletedNCT05954962PRO_NATUpdated Mar 27, 2026

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

A Phase 4 interventional study of Progesterone 200 MG and Ganirelix Acetate in IVF, sponsored by Instituto Bernabeu. Completed at 1 site in Spain. Open to female participants aged 18 Years to 33 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-03-27.

Sponsored by Instituto Bernabeu · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
150
Allocation
Randomized
Ages
18 Years to 33 Years
Sex
Female
01

Study 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.

Read the detailed description

The study will aim to include 150 women (egg donors): 75 per group and the principal variable will be the number of retrieved mature (MII) oocytes. Randomized, prospective, controlled, single center, phase IV study.

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Conditions studied

  • IVF
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In context

Lead sponsor

Instituto Bernabeu is the lead sponsor of 18 studies on the registry; 3 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 33 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
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Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
150 participants (actual)

Study arms

  • Active comparator
    CONTROL GROUP

    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

  • Experimental
    STUDY GROUP

    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

  • DrugProgesterone 200 MG

    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.

  • DrugGanirelix Acetate

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

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What researchers measure

Primary outcomes

  1. MII oocytes

    number of mature (MII) oocytes in both stimulations.

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

Secondary outcomes

  1. Duration

    duration of ovarian stimulation under both protocols.

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

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Study locations

1 site
  • Instituto Bernabeu
    Elche, Alicante 03206, Spain
08

References and documents

Publications

  • 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. PubMed 9853849 ↗
  • 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. PubMed 7793300 ↗
  • 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. PubMed 30927417 ↗
  • 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. PubMed 32366146 ↗
  • 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. PubMed 15950626 ↗
  • 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. PubMed 33814126 ↗
  • 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. PubMed 16500366 ↗
  • 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. PubMed 30852654 ↗
  • 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. PubMed 25956370 ↗
  • 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. PubMed 16434510 ↗
  • 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. PubMed 3106404 ↗
  • 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. PubMed 6150318 ↗
  • 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. PubMed 29300975 ↗
  • 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. PubMed 28697910 ↗
  • 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. PubMed 38577571 ↗

Individual participant data

Plan to share: No — The information collected in the study will always be treated as grouped data and never as individual or personal data, thus maintaining anonymity and confidentiality.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 27, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT05954962
Lead sponsor
Instituto Bernabeu
Responsible party
Maria Martinez Moya (Principal Investigator, Instituto Bernabeu) — Principal investigator
First posted
Jul 20, 2023
Start date
Dec 23, 2023
Primary completion
Apr 3, 2025
Completion
Aug 30, 2025
Last update
Mar 27, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Nov 2024. You cannot join it, but the record below documents what was studied.

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