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Controlled Ovarian HyperstimulationNCT06812559

Progesterone Primed Ovarian Stimulation Versus GnRH Antagonist Protocols in Women With Polycystic Ovarian Syndrome

An observational study of Controlled Ovarian Hyperstimulation and Polycystic Ovarian Syndrome, run by El Shatby University Hospital for Obstetrics and Gynecology at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to compare the use of the progesterone-primed ovarian stimulation protocol versus GnRH antagonist protocol in women with polycystic ovarian syndrome (PCOS) regarding the number of oocytes retrieved, percentage of MII oocytes, and the rate of good quality blastocysts available for… Read more about this study

Who is it for?
Ages Up to 37 years, women only
What is being tested?
Progesterone and GnRH antagonist (Cetrorelix)
How many people
100 participants
Where
1 siteEgypt
Study dates
1 Dec 2023to 1 Feb 2025
How long will I take part?
2 Months
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 37 years
  • Women only
  • No healthy volunteers
  • Child, Adult

Study population: History taking and examination: * Basal ultrasound scanning includes 3D assessment of the uterine cavity and a basal hormonal profile. * Semen analysis. Ovarian stimulation: * Will be on day 2 or 3 of the menstrual cycle * Using rFSH SC injections with a dose of 150 to 225 IU per day and highly purified hMG with a dose of 75 IU per day. These patients will be divided into two equal groups: Group 1 (Fixed GnRH antagonist protocol) (n= 50): • GnRH antagonist (Cetrotide 0.25 mg) SC injection will be added daily from the 6th day of COH and will be continued till the day of the GnRH agonist trigger. Group 2 (Progesterone-primed ovarian stimulation) (n= 50): • A daily dose of 20 mg dydrogesterone (2 Duphastone 10 mg tablets) will be added from day 1 or 2 of the menstrual cycle till day of trigger

Who may be able to join

  • Female age <37 years.
  • Body mass index (BMI) between (≥18 kg/m2 and ≤35 kg/m2).
  • Polycystic ovarian syndrome patients (according to Rotterdam criteria).
  • Patients suffering from primary or secondary infertility who are candidates for ICSI.

Who cannot join

  • Uncorrected Uterine factor of infertility: intrauterine adhesions, submucosal fibroids, and septate uterus.
  • Severe male factor infertility

Trial locations and contacts

1 site in 1 country.

Egypt1 site
  • ELShatby University Hospital

    Alexandria, Alexandria Governorate, 21648

Other trials in Egypt

About this study

Official title: Progesterone Primed Ovarian Stimulation Versus Gonadotrophin-Releasing Hormone Antagonist in Women With Polycystic Ovarian Syndrome

The purpose of this study is to compare the use of the progesterone-primed ovarian stimulation protocol versus GnRH antagonist protocol in women with polycystic ovarian syndrome (PCOS) regarding the number of oocytes retrieved, percentage of MII oocytes, and the rate of good quality blastocysts available for cryopreservation.

Read the detailed description

The syndrome of polycystic ovary (PCOS) is a common endocrine disease. It accounts for about 80% of women with anovulatory infertility. In vitro fertilization (IVF) is a commonly used infertility treatment for PCOS patients who fail to conceive with ovulation induction or if there are concomitant infertility factors such as tubal damage or male subfertility.

Patients with polycystic ovary syndrome (PCOS) are at high risk of ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) treatment which may lead to cycle cancellation to prevent their high morbidity or death rates. Increasing evidence has confirmed that frozen embryo transfer (FET) is related to a lower risk of OHSS. The 'freeze-all' strategy is recommended for PCOS patients to reduce the potential of moderate/severe OHSS.

Controlled ovarian stimulation (COS) is a key step in assisted reproductive technology (ART). In addition to the use of gonadotropins to recruit multiple follicles, it is mandatory to use a drug to prevent luteinizing hormone (LH) surge and premature ovulation.

Early LH surge is a main cause of cycle cancellation during controlled ovarian stimulation (COH) for women receiving IVF/ICSI therapy. The release of LH causes ovulation in response to rapidly increasing levels of E2 in the normal cycle, and a premature LH increase may impair IVF/ICSI egg production.

Gonadotropin-releasing hormone (GnRH) antagonist protocol has emerged as a routine ovulation stimulation protocol in recent decades due to its comparable convenience, safety, and efficacy compared to GnRH agonists. GnRH antagonist protocol is now the most commonly used COS protocol in PCOS patients due to the significantly reduced risk of OHSS especially when gonadotropin-releasing hormone agonist (GnRHa) was used for ovulation trigger. The GnRH antagonists were used primarily to reduce the incidence of the early LH surge. However, GnRH antagonists are expensive and sometimes difficult to manage with high rates of cycle cancellation and premature LH surges.

In past decades, when IVF relied on fresh embryo transfer, progesterone could not be considered during COS as early exposure to progesterone could lead to embryo-endometrium asynchrony. Advances in vitrification have made cryopreservation and thawing of embryos in a reliable manner, which has eliminated concerns about the deleterious effects of progesterone exposure on endometrial receptivity. Although controversies remain regarding the selection of when to choose FET, the ''freeze-all'' strategy could make the use of P formulations for the suppression of premature LH surge during COH feasible regardless of the effects of P on endometrial receptivity. Therefore, the PPOS protocol may be a suitable option when fresh embryo transfer is not required.

Progesterone-primed ovarian stimulation is a recent stimulation protocol, which was first suggested in 2015 by Dr. Yanping Kuang of China, it is a novel ovarian stimulation system utilizing progestin coupled with exogenous gonadotrophin, and ovulation triggered by a GnRH agonist, via 'freeze-all' methods. Oral progestin are used as an alternative to GnRH antagonist to prevent premature LH surges during ovarian stimulation. This novel ovarian stimulation regimen has shown successful prevention of a premature LH surge in cycles followed by embryo cryopreservation. In addition, oral progestin has the advantage of being convenient, given orally, cheap, and available readily.

The mechanism of LH suppression using GnRH-ant or progestin is distinct. GnRH-ant administration could lead to rapid suppression of pituitary LH secretion by competitively blocking the GnRH receptor, with an obvious dose-dependent suppression effect. In contrast, the inhibition of LH levels with progestin is indirect by regulating the hypothalamus GnRH secretion and requires sufficient duration before estrogen priming.

Being tested
Progesterone, GnRH antagonist (Cetrorelix)
Keywords
PPOS versus antagonist protocol in PCOS
Medical subject headings
Polycystic Ovary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ProgesteroneDrug

    Also called Duphaston 10mg Tablets

    compare the use of the progesterone-primed ovarian stimulation protocol versus GnRH antagonist protocol in women with polycystic ovarian syndrome (PCOS) regarding the number of oocytes retrieved, percentage of MII oocytes, and the rate of good quality blastocysts available for cryopreservation.

  • GnRH antagonist (Cetrorelix)Drug

    Also called Cetrotide 0.25mg

    Subcutaneous injection

Study groups in NCT06812559
Study groupRoleWhat they receive
Progesterone-primed ovarian stimulation Group• A daily dose of 20 mg dydrogesterone (2 Duphastone 10 mg tablets) will be added from day 1 or 2 of the menstrual cycle and will be continued till the day of the GnRH agonist trigger.
Receives: Drug: Progesterone
Antagonist protocol• GnRH antagonist (Cetrotide 0.25 mg) subcutaneous injection will be added daily from the 6th day of ovarian stimulation and will be continued till the day of the GnRH agonist trigger.
Receives: Drug: GnRH antagonist (Cetrorelix)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of oocytes retrieved (ovarian response).

    Total number of oocytes retrieved (in both groups)

    Measured: Baseline

  2. Percentage of MII oocytes.

    Number of MII oocytes to the total number of oocytes retrieved (in both groups)

    Measured: Baseline

  3. Rate of good-quality blastocysts available for cryopreservation

    percentage of the number of good-quality blastocysts to the number of 2PN fertilized oocytes cultured

    Measured: Baseline

Secondary outcomes (3)
  1. Fertilization rate

    Percentage of the number of MII oocytes microinjected which transform into 2PN

    Measured: Baseline

  2. Rate of blastocyst formation

    percentage of the number of blastocysts formed to the number of 2PN fertilized oocytes cultured

    Measured: Baseline

  3. Clinical pregnancy rate after 1st FET

    defined as elevated serum β-HCG (+) the presence of gestational sac(s) or fetal heartbeats (fetal pole) by ultrasonography

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2025
  2. Study start1 Dec 2023
  3. Primary completion1 Feb 2025
  4. Study completion1 Feb 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
100 participants (actual)
Target duration
2 Months
IDs, dates and publications
ClinicalTrials.gov ID
NCT06812559
Sponsor's protocol ID
PPOS vs Antagonist Protocols
Status last verified
Feb 2025
First submitted
2 Feb 2025
Last updated
25 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Lainas TG, Sfontouris IA, Zorzovilis IZ, Petsas GK, Lainas GT, Alexopoulou E, Kolibianakis EM. Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT). Hum Reprod. 2010 Mar;25(3):683-9. doi: 10.1093/humrep/dep436. Epub 2009 Dec 15.

    PubMed 20008886
  • Griesinger G, Diedrich K, Tarlatzis BC, Kolibianakis EM. GnRH-antagonists in ovarian stimulation for IVF in patients with poor response to gonadotrophins, polycystic ovary syndrome, and risk of ovarian hyperstimulation: a meta-analysis. Reprod Biomed Online. 2006 Nov;13(5):628-38. doi: 10.1016/s1472-6483(10)60652-9.

    PubMed 17169171
  • Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2016 Apr 29;4(4):CD001750. doi: 10.1002/14651858.CD001750.pub4.

    PubMed 27126581
  • Toftager M, Bogstad J, Lossl K, Praetorius L, Zedeler A, Bryndorf T, Nilas L, Pinborg A. Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols. Hum Reprod. 2017 Mar 1;32(3):556-567. doi: 10.1093/humrep/dew358.

    PubMed 28130435
  • Depalo R, Jayakrishan K, Garruti G, Totaro I, Panzarino M, Giorgino F, Selvaggi LE. GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET). Reprod Biol Endocrinol. 2012 Apr 13;10:26. doi: 10.1186/1477-7827-10-26.

    PubMed 22500852
  • 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.

    PubMed 16672246
  • Zhou R, Dong M, Huang L, Wang S, Fan L, Liang X, Zhang X, Liu F. Comparison of cumulative live birth rates between progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol in different populations. Front Endocrinol (Lausanne). 2023 Apr 18;14:1117513. doi: 10.3389/fendo.2023.1117513. eCollection 2023.

    PubMed 37143731
  • Pirtea P, de Ziegler D, Poulain M, Ayoubi JM. New Twists in Ovarian Stimulation and Their Practical Implications. Front Med (Lausanne). 2019 Sep 4;6:197. doi: 10.3389/fmed.2019.00197. eCollection 2019.

    PubMed 31555650
  • Zhu X, Ye H, Ye J, Fu Y. Progesterone protocol versus gonadotropin-releasing hormone antagonist protocol in women with polycystic ovarian syndrome undergoing in vitro fertilization treatments with frozen-thawed embryo transfer: a prospective randomized controlled trial. Ann Transl Med. 2021 Mar;9(5):387. doi: 10.21037/atm-20-1592.

    PubMed 33842608
  • Chen ZJ, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, Yang J, Liu J, Wei D, Weng N, Tian L, Hao C, Yang D, Zhou F, Shi J, Xu Y, Li J, Yan J, Qin Y, Zhao H, Zhang H, Legro RS. Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome. N Engl J Med. 2016 Aug 11;375(6):523-33. doi: 10.1056/NEJMoa1513873.

    PubMed 27509101
  • Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002 Nov-Dec;8(6):559-77. doi: 10.1093/humupd/8.6.559.

    PubMed 12498425
  • Sultan C, Paris F. Clinical expression of polycystic ovary syndrome in adolescent girls. Fertil Steril. 2006 Jul;86 Suppl 1:S6. doi: 10.1016/j.fertnstert.2006.04.015.

    PubMed 16798287
  • Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008 Mar;23(3):462-77. doi: 10.1093/humrep/dem426.

    PubMed 18308833
  • 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.

    PubMed 27428219

Questions about this trial

What is this clinical trial studying?

An observational study of Controlled Ovarian Hyperstimulation and Polycystic Ovarian Syndrome, run by El Shatby University Hospital for Obstetrics and Gynecology at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of oocytes retrieved (ovarian response). (time frame: Baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06812559, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2025.

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