Current partner codePEPTIDESDE
NCT06378268·Not applicable·INTERVENTIONAL

PPOS vs GnRH Antagonist in Ovarian Stimulation (ProGanOS Study)

Status

Active, not recruiting

Phase

Not applicable

Enrollment

626

Locations

1

Results

Not posted

Publications

12

Study summary

What the protocol is testing.

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.

Full detailed description

Study Procedures Participants will be randomized into two arms: * 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. * 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. Follicular monitoring will start on the fifth or sixth day of ovarian stimulation and was performed every 3-5 days thereafter using transvaginal ultrasound to record the number of developing follicles. Measuring LH, estradiol, and progesterone serum levels will be performed on the fifth or sixth day of ovarian stimulation and oocyte maturation day (before the trigger injection). The FSH dosage will be fixed during ovarian stimulation. When more than two dominant follicles reach a diameter of at least 17mm, \>= 50% diameter of remaining follicles cohort \>=12 mm, the final stage of oocyte maturation will trigger using human chorionic gonadotropin (hCG; IVF-C 10.000 IU, LG Chem, Ltd., Korea or Ovitrelle Pen 250µg, Merck Serono S.p.A., Italy). In individuals who are at high risk for OHSS, GnRH agonist trigger 0.2mg (Diphereline 0.2mg, Ipsen Pharma, France) will given subcutaneously. Transvaginal ultrasound-guided oocyte retrieval will be performed 34-36 hours after trigger, with the retrieval of all follicles exceeding 10mm in diameter. Oocyte fertilization will be carried out in vitro using ICSI. On the third day after fertilization, embryos will be evaluated for the degree of embryonic fragmentation, regularity, and number of blastomeres in accordance with the Istanbul consensus (Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011). Day 3 embryos will be cryopreserved or cultured until the blastocyst stage based on physician recommendation or patient references; viable blastocysts will then be cryopreserved on day 5 or day 6. Endometrial preparation for frozen embryo transfer (FET) will be given using an exogenous steroid regimen from day 2 to day 4 of the menstrual cycle. Oral estradiol valerate (Progynova, Bayer Schering Pharma, Germany) 8mg/day will be given for 10-12 days. When endometrial thickness reaches ≥ 7mm, along with a triple-line pattern, micronized progesterone 800mg will be administered. FET will be performed three to five days after progesterone administration. There will be no more than 2 embryo(s) transfers each FET cycle. After FET, estradiol and progesterone supplementation will be continued for all participants until the day of taking the pregnancy test. Participants with a positive pregnancy test continued to receive oral estradiol valerate 8mg/day and micronized progesterone 800mg/day until the fetal heart appeared, and then only micronized progesterone 800mg will be used until 12 weeks of gestation. All participants will be followed up per local protocol until outcomes are achieved.

Interventions

Treatment arms and agents.

DRUG

Dydrogesterone 10 mg

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

DRUG

Cetrorelix 0.25 mg

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.

Timeline

From registration to results.

  1. First posted

    Apr 22, 2024

  2. Study start

    Apr 24, 2024

  3. Primary completion

    Jun 30, 2026

  4. Study completion

    Sep 30, 2026

  5. Results posted

    Not reported

  6. Registry updated

    Mar 20, 2026

Outcomes

What the study measures.

Primary outcomes

Ongoing pregnancy

Time frame · At 10 weeks after embryo(s) placement

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

Secondary outcomes

The incidence of premature LH surge

Time frame · On the day having indication of oocyte maturation

LH level of ≥ 10 mIU/mL occurring before the criteria of oocyte maturation administration is met

The incidence of premature progesterone elevation

Time frame · On the day having indication of oocyte maturation

A progesterone level of ≥1.0 ng/mL occurring before the criteria of oocyte maturation administration is met

Number of oocytes retrieved

Time frame · On the oocyte(s) retrieval day

The number of oocyte retrieved

Number of mature oocytes

Time frame · On the oocyte(s) retrieval day

The number of MII oocytes

Number of day 3 embryos

Time frame · At 62-66 hours after ICSI

The number of day 3 embryos

Number of day 5 embryos

Time frame · At 112-116 hours after ICSI

The number of day 5 embryos

Number of good quality day 3 embryos

Time frame · At 62-66 hours after ICSI

Number of grade 1 and grade 2 day 3 embryos (acccording to Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011)

Number of good quality day 5 embryos

Time frame · At 112-116 hours after ICSI

Number of grade 1 and grade 2 day 5 blastocysts (acccording to Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011)

Number of frozen embryos

Time frame · at 112-116 hours after ICSI

the number of frozen embryos/blastocysts

Incidence of Ovarian hyperstimulation syndrome

Time frame · At 2 weeks after trigger

Ovarian hyperstimulation syndrome (OHSS) is a potentially lethal iatrogenic complication of the early luteal phase or/and early pregnancy after ovulation induction (OI) or ovarian stimulation (OS). OHSS was evaluated if symptoms were reported by the patient. OHSS was classified using the flow diagram developed by (Humaidan et al., 2016)

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
40 Years
Sex
FEMALE
Healthy volunteers
No

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Study locations

1 registered sites.

Vietnam. Showing up to 24 locations stored in the fast local snapshot.

My Duc Hospital

Ho Chi Minh City, Ho Chi Minh City, Vietnam

Publications

Results and literature.

PMID 16672246Messinis 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 17555751Papanikolaou 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 21273126Van 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 2492234Droesch 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 12536358van 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 21563131Al-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 27060174Toftager 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 21371705Griesinger 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 25956370Kuang 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 26945402Wang 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 27428219Zhu 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 28062551Massin 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.

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