Corifollitropin Alfa Followed by Menotropin for Poor Ovarian Responders Trial

Study Overview
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Brief Summary
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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
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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

Official Title
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Corifollitropin Alfa Followed by Hp-HMG Versus Recombinant FSH in Young Poor Ovarian Responders. A Multicentre Randomized Controlled Clinical Trial

Conditions
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Infertility, Poor Ovarian Response

Intervention / Treatment
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* Drug: Corifollitropin alfa
* Drug: recombinant FSH
* Drug: Ganirelix
* Drug: hp HMG


Participation Criteria
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Eligibility Criteria
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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: 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) 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Corifollitropin alfa followed by hpHMG<br> | Drug: Corifollitropin alfa<br>* Corifollitropin alfa 150μg on day 2 of the menstrual cycle (stimulation day 1)<br>Drug: Ganirelix<br>* Ganirelix 0.25mg/daily from day 7 of the cycle(stimulation day 6) until day of ovulation triggering<br>Drug: hp HMG<br>* hp HMG 300IU/daily from day 9 of the cycle (stimulation day 8)until day of ovulation triggering<br>|
| Active Comparator: recombinant FSH<br> | Drug: recombinant FSH<br>* recombinant FSH 300IU/daily from day 2 of the cycle (stimulation day 8)until day of ovulation triggering<br>Drug: Ganirelix<br>* Ganirelix 0.25mg/daily from day 7 of the cycle(stimulation day 6) until day of ovulation triggering<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy | The presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 9-10 weeks of gestation. | 9-10 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy | The presence of intrauterine gestational sac at 7 weeks of gestation | 7 weeks of gestation | 
| Biochemical pregnancy | Positive pregnancy test 2 weeks after embryo transfer | 2 weeks after embryo transfer | 
| Number of oocytes retrieved | The outcome will be evaluated on the day of oocyte retrieval | 9 -20 days from initiation of ovarian stimulation |