Clinical trial NCT01816321: Corifollitropin Alfa Followed by Menotropin for Poor Ovarian Responders Trial
Official title: Corifollitropin Alfa Followed by Hp-HMG Versus Recombinant FSH in Young Poor Ovarian Responders. A Multicentre Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility
Poor Ovarian Response
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
Collaborators: name: University of Medicine and Pharmacy at Ho Chi Minh City
First posted: 2013-03-22
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In combination with the existing literature, previous work indicates that 1) women with poor ovarian response fulfilling the "Bologna criteria" have very low pregnancy rates, irrespective of age 2) current treatment protocols demonstrate ongoing pregnancy rates that do not exceed 8.5% and 3) corifollitropin alfa followed by hpHMG might increase ongoing pregnancy rates in young patients (\<40years old) fulfilling the criteria. These findings provide a strong rationale for a definitive large RCT. The COMPORT study will provide conclusive evidence regarding the superiority or not of this novel protocol with corifollitropin alfa followed by hpHMG for the treatment of young poor ovarian responders fulfilling the Bologna criteria.

Detailed description: Recently, the European Society of Human Reproduction and Embryology developed a new definition in order to select patients suitable for inclusion in future clinical trials as poor ovarian responders, the so-called "Bologna criteria". However, a limited number of studies has been published to date including patients with poor ovarian response according to the "Bologna criteria", whereas no randomized trial is published or ongoing for this population.

Preliminary reports in "Bologna poor responders" highlight the limited prospects for these women. Natural cycle IVF has been shown to result in disappointingly low live birth rates, regardless of patients' age and ovarian stimulation with widely accepted treatment modalities, e.g. short agonist protocol, did not appear demonstrate substantial benefits.

Nonetheless, despite the disappointing results from the vast majority of the preliminary studies in this population, a recent pilot study by our group has shown that a specific protocol may indeed be a promising option for women of younger age fulfilling the "Bologna criteria". Corifollitropin alfa followed by highly purified hMG in an antagonist protocol demonstrated an ongoing pregnancy rate of 28% in women \<40years, strongly suggesting the conduction of a future randomized trial testing this novel treatment protocol

Eligibility criteria: Inclusion Criteria:

* Age less than 40 years
* Fulfillment of the "Bologna criteria" for poor ovarian response.

Based on inclusion criteria two patients' categories are eligible:

1. Women \< 40 years old AND ≤3 oocytes in one of the previous cycles AND (Antral follicle count \<7 or antimullerian hormone serum values \<1.1 ng/ml)
2. Women \<40 years old and ≤3 oocytes in two the previous cycles with maximum ovarian stimulation

In addition women less than 40 years old will be considered eligible if they had undergone previous ovarian surgery or chemotherapy (risk factors for poor ovarian response) and have an AMH\<1.1ng/ml or an AFC\<7, as suggested by the Bologna criteria

Exclusion Criteria:

* Uterine abnormalities
* Recent history of any current untreated endocrine abnormality
* Unilateral or bilateral hydrosalpinx (visible on transvaginal ultrasound, unless clipped)
* Contraindications for the use of gonadotropins
* Recent history of severe disease requiring regular treatment

Primary outcomes:
measure: Ongoing pregnancy
timeFrame: 9-10 weeks of gestation
Secondary outcomes:
measure: Clinical pregnancy
timeFrame: 7 weeks of gestation
measure: Biochemical pregnancy
timeFrame: 2 weeks after embryo transfer
measure: Number of oocytes retrieved
timeFrame: 9 -20 days from initiation of ovarian stimulation
Other outcomes:
measure: Cycle cancellation due to poor ovarian response
timeFrame: Day 8-10 of ovarian stimulation
measure: Number of cycles reaching the stage of embryo transfer
timeFrame: 9 -20 days from initiation of ovarian stimulation
measure: Number and quality of embryos
timeFrame: Day of embryo transfer
measure: Number of cycles with frozen supernumerary embryos
timeFrame: 9 -20 days from initiation of ovarian stimulation
measure: Endocrine parameters (LH,FSH, E2, Progesterone) during ovarian stimulation
timeFrame: Days 1,6,8,10 of stimulation and day of ovulation triggering
measure: Cycle cancellation due to serious adverse effects of medication
timeFrame: 20-25 days after initiation of stimulation
Locations:
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Ho Chi Minh City
country: Vietnam
facility: University of Medicine and Pharmacy of Ho Chi Minh City
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Nikolaos P Polyzos, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Polyzos NP, De Vos M, Corona R, Vloeberghs V, Ortega-Hrepich C, Stoop D, Tournaye H. Addition of highly purified HMG after corifollitropin alfa in antagonist-treated poor ovarian responders: a pilot study. Hum Reprod. 2013 May;28(5):1254-60. doi: 10.1093/humrep/det045. Epub 2013 Feb 26.
citation: Polyzos NP, Devos M, Humaidan P, Stoop D, Ortega-Hrepich C, Devroey P, Tournaye H. Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients: an observational pilot study. Fertil Steril. 2013 Feb;99(2):422-6. doi: 10.1016/j.fertnstert.2012.09.043. Epub 2012 Oct 16.
citation: Polyzos NP, Blockeel C, Verpoest W, De Vos M, Stoop D, Vloeberghs V, Camus M, Devroey P, Tournaye H. Live birth rates following natural cycle IVF in women with poor ovarian response according to the Bologna criteria. Hum Reprod. 2012 Dec;27(12):3481-6. doi: 10.1093/humrep/des318. Epub 2012 Aug 30.
citation: Polyzos NP, Devroey P. A systematic review of randomized trials for the treatment of poor ovarian responders: is there any light at the end of the tunnel? Fertil Steril. 2011 Nov;96(5):1058-61.e7. doi: 10.1016/j.fertnstert.2011.09.048.
citation: Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
citation: Drakopoulos P, Vuong TNL, Ho NAV, Vaiarelli A, Ho MT, Blockeel C, Camus M, Lam AT, van de Vijver A, Humaidan P, Tournaye H, Polyzos NP. Corifollitropin alfa followed by highly purified HMG versus recombinant FSH in young poor ovarian responders: a multicentre randomized controlled clinical trial. Hum Reprod. 2017 Nov 1;32(11):2225-2233. doi: 10.1093/humrep/dex296.