PPOS vs GnRH Antagonist in Ovarian Stimulation (ProGanOS Study)

NCT06378268 | Active Not Recruiting DMC

• 1 other identifier: 05/24/DD-BVMD
• Study Type: interventional
• Target: 626
• Locations: 1 country
• Sites: 1

Brief Summary

This non-inferiority randomized controlled trial will be conducted at My Duc Hospital, Ho Chi Minh City, Vietnam. This study compares the effectiveness of Progestin-Primed Ovarian stimulation versus GnRH protocol for ovarian stimulation in IVF treatment. Participants will be randomly assigned in a 1:1 ratio to receive Progestins or GnRH antagonists.

Conditions

Progestins Primed Ovarian Stimulation

Keywords

Progestins Primed Ovarian Stimulation; GnRH antagonist; ongoing pregnancy

Outcome Measures

Primary Outcomes (1)

• Ongoing pregnancy

  defined as pregnancy with a detectable heart rate at 12 weeks gestation or beyond

  At 10 weeks after embryo(s) placement

Secondary Outcomes (31)

• The incidence of premature LH surge

  On the day having indication of oocyte maturation

• The incidence of premature progesterone elevation

  On the day having indication of oocyte maturation

• Number of oocytes retrieved

  On the oocyte(s) retrieval day

• Number of mature oocytes

  On the oocyte(s) retrieval day

• Number of day 3 embryos

  At 62-66 hours after ICSI

Study Arms (2)

Progestins Primed Ovarian stimulation group

ACTIVE COMPARATOR

PPOS group: Recombinant FSH 150-300 IU/day will start from day 2 to day 4 of menstruation. The initial FSH dose will be chosen based on age, anti-Müllerian hormone (AMH) level, antral follicle count (AFC), and body mass index (BMI). The FSH dosage will be fixed during ovarian stimulation. Dydrogesterone (Duphaston, Abbott, USA) 20mg/day will start on the day of gonadotropin injection to the oocyte maturation trigger night.

Drug: Dydrogesterone 10 mg

GnRH antagonist group

ACTIVE COMPARATOR

GnRH antagonist group: Recombinant FSH 150-300 IU/day will be given from day 2 to day 4 of menstruation. The initial FSH dose will be chosen based on age, anti-Müllerian hormone (AMH) level, antral follicle count (AFC), and body mass index (BMI). The FSH dosage will be fixed during ovarian stimulation. Cetrorelix (Cetrotide, Merck, Germany) 0.25mg/day will be given from day 5 of stimulation by the oocyte maturation trigger day.

Drug: Cetrorelix 0.25 mg

Interventions

Dydrogesterone 10 mg DRUG

Dydrogesterone 10mg orally 2 times daily, starting on the day of gonadotropin injection to the oocyte maturation trigger night.

Also known as: Duphaston

Progestins Primed Ovarian stimulation group

Cetrorelix 0.25 mg DRUG

Cetrorelix 0.25mg is injected subcutaneously once a day. It is given from day 5 or day 6 of stimulation by the oocyte maturation trigger day.

Also known as: Cetrotide

GnRH antagonist group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Woman aged 18-40
• BMI ≤ 25kg/m2
• AMH \> 1.2ng/mL or AFC \>5
• Having indication for IVF treatment
• Agree to have frozen embryo(s) transfer
• Not participating in any other clinical trials
• Provision of written informed consent to participate

You may not qualify if:

• Undergoing IVF cycle with other protocols: Down-regulation, mild stimulation, Random start
• Oocyte donation cycles
• Undergoing vitrified oocyte accumulation
• Oocyte cryopreservation
• Cycle with PGT (Preimplatation genetic testing)
• Women with PCOS
• Women allergy to dydrogesterone, rFSH, GnRH antagonist

Sponsors & Collaborators

• Mỹ Đức Hospital: lead

Study Sites (1)

My Duc Hospital

Ho Chi Minh City, Ho Chi Minh City, 70000, Vietnam

Location

Related Publications (16)

• Messinis IE. Ovarian feedback, mechanism of action and possible clinical implications. Hum Reprod Update. 2006 Sep-Oct;12(5):557-71. doi: 10.1093/humupd/dml020. Epub 2006 May 3.

  PMID: 16672246 RESULT

• Papanikolaou EG, Kolibianakis EM, Pozzobon C, Tank P, Tournaye H, Bourgain C, Van Steirteghem A, Devroey P. Progesterone rise on the day of human chorionic gonadotropin administration impairs pregnancy outcome in day 3 single-embryo transfer, while has no effect on day 5 single blastocyst transfer. Fertil Steril. 2009 Mar;91(3):949-52. doi: 10.1016/j.fertnstert.2006.12.064. Epub 2007 Jun 6.

  PMID: 17555751 RESULT

• Van Vaerenbergh I, Fatemi HM, Blockeel C, Van Lommel L, In't Veld P, Schuit F, Kolibianakis EM, Devroey P, Bourgain C. Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression. Reprod Biomed Online. 2011 Mar;22(3):263-71. doi: 10.1016/j.rbmo.2010.11.002. Epub 2010 Nov 13.

  PMID: 21273126 RESULT

• Droesch K, Muasher SJ, Brzyski RG, Jones GS, Simonetti S, Liu HC, Rosenwaks Z. Value of suppression with a gonadotropin-releasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization. Fertil Steril. 1989 Feb;51(2):292-7. doi: 10.1016/s0015-0282(16)60493-4.

  PMID: 2492234 RESULT

• van Loenen AC, Huirne JA, Schats R, Hompes PG, Lambalk CB. GnRH agonists, antagonists, and assisted conception. Semin Reprod Med. 2002 Nov;20(4):349-64. doi: 10.1055/s-2002-36713.

  PMID: 12536358 RESULT

• Al-Inany HG, Youssef MA, Aboulghar M, Broekmans F, Sterrenburg M, Smit J, Abou-Setta AM. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2011 May 11;(5):CD001750. doi: 10.1002/14651858.CD001750.pub3.

  PMID: 21563131 RESULT

• Toftager M, Bogstad J, Bryndorf T, Lossl K, Roskaer J, Holland T, Praetorius L, Zedeler A, Nilas L, Pinborg A. Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles. Hum Reprod. 2016 Jun;31(6):1253-64. doi: 10.1093/humrep/dew051. Epub 2016 Apr 8.

  PMID: 27060174 RESULT

• Griesinger G, Schultz L, Bauer T, Broessner A, Frambach T, Kissler S. Ovarian hyperstimulation syndrome prevention by gonadotropin-releasing hormone agonist triggering of final oocyte maturation in a gonadotropin-releasing hormone antagonist protocol in combination with a "freeze-all" strategy: a prospective multicentric study. Fertil Steril. 2011 May;95(6):2029-33, 2033.e1. doi: 10.1016/j.fertnstert.2011.01.163. Epub 2011 Mar 2.

  PMID: 21371705 RESULT

• 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 RESULT

• Wang Y, Chen Q, Wang N, Chen H, Lyu Q, Kuang Y. Controlled Ovarian Stimulation Using Medroxyprogesterone Acetate and hMG in Patients With Polycystic Ovary Syndrome Treated for IVF: A Double-Blind Randomized Crossover Clinical Trial. Medicine (Baltimore). 2016 Mar;95(9):e2939. doi: 10.1097/MD.0000000000002939.

  PMID: 26945402 RESULT

• Zhu X, Ye H, Fu Y. The Utrogestan and hMG protocol in patients with polycystic ovarian syndrome undergoing controlled ovarian hyperstimulation during IVF/ICSI treatments. Medicine (Baltimore). 2016 Jul;95(28):e4193. doi: 10.1097/MD.0000000000004193.

  PMID: 27428219 RESULT

• Massin N. New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF. Hum Reprod Update. 2017 Mar 1;23(2):211-220. doi: 10.1093/humupd/dmw047.

  PMID: 28062551 RESULT

• Vuong LN, Dang VQ, Ho TM, Huynh BG, Ha DT, Pham TD, Nguyen LK, Norman RJ, Mol BW. IVF Transfer of Fresh or Frozen Embryos in Women without Polycystic Ovaries. N Engl J Med. 2018 Jan 11;378(2):137-147. doi: 10.1056/NEJMoa1703768.

  PMID: 29320655 RESULT

• Shrestha D, La X, Feng HL. Comparison of different stimulation protocols used in in vitro fertilization: a review. Ann Transl Med. 2015 Jun;3(10):137. doi: 10.3978/j.issn.2305-5839.2015.04.09.

  PMID: 26207230 RESULT

• Ferin M, Rosenblatt H, Carmel PW, Antunes JL, Vande Wiele RL. Estrogen-induced gonadotropin surges in female rhesus monkeys after pituitary stalk section. Endocrinology. 1979 Jan;104(1):50-2. doi: 10.1210/endo-104-1-50.

  PMID: 109276 RESULT

• Leroy I, d'Acremont M, Brailly-Tabard S, Frydman R, de Mouzon J, Bouchard P. A single injection of a gonadotropin-releasing hormone (GnRH) antagonist (Cetrorelix) postpones the luteinizing hormone (LH) surge: further evidence for the role of GnRH during the LH surge. Fertil Steril. 1994 Sep;62(3):461-7. doi: 10.1016/s0015-0282(16)56932-5.

  PMID: 8062939 RESULT

MeSH Terms

Interventions

Dydrogesterone; cetrorelix

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Lan N Vuong, MD, PhD

  University of Medicine and Pharmacy at Ho Chi Minh City

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2024
• First Posted: April 22, 2024
• Study Start: April 24, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

VN (1)