Effect of Treatment With Corifollitropin Alpha in Vitro Fertilization in Patients With Poor Ovarian Response.

Study Overview
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Brief Summary
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Patients who have had or are expected to have a poor ovarian response (POR), because they meet any of the criteria of Bologna, can benefit from ovarian stimulation with 150 mg of alpha Corifollitropin (CFA) (Elonva ®) as single dose for a week, in the cycles of in vitro fertilization (IVF). In this study aims to demonstrate non-inferiority of the Corifollitropin Alpha (CFA ) versus daily administration of Human Menopausal Gonadotropin (hMG) (Menopur ®) during the first seven days of ovarian stimulation, in a protocol with gonadotropin-releasing hormone ( GnRH) antagonists

Detailed Description
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One of the most significant problems in fertilization treatments is Controlled Ovarian Stimulation low responsiveness . The incidence of low ovarian response is estimated at around 10-25%.The wide range of prevalence reported in the literature can be explained by the lack of consensus existed as to the criteria for the low response. The ovarian response to gonadotropin stimulation is crucial for successful assisted reproduction techniques .Cycles with low rates response was obtained and increased cancellation rate and worst pregnancy rates . Different criteria for the definition of low response, different tests to assess ovarian reserve and different threshold values for each has been used. In 2010 a group of experts from the ESHRE ,achieved consensus on the criteria for low ovarian response to homogenize the study groups and reach meaningful conclusions, are known as The Bologna criteria ,they defined the Poor Ovarian Response (POR). There is not sufficient to recommend most of the proposed treatments to improve pregnancy rates in poor responders evidence. Taking into account the profile of equivalence and safety of CFA (Corifollitropin Alpha , active of ELONVA ® ) , different studies had been concluded that CFA can be an alternative to daily injections of recombinant follicle stimulating hormone ( rFSH) in normal responders patients in vitro fertilization cycle with ovarian stimulation.But more research is needed to determine whether long-acting recombinant follicle stimulating hormone ( rFSH) is safe and effective for use in women with low and high response. The ovarian controlled stimulation with Alpha Corifollitropin produces significantly more oocytes compared to recombinant follicle stimulating hormone (r FSH ) administrated daily in normal responders patients, For this reason , the use of Alpha Corifollitropin may be beneficial in patients with poor response which the number of oocytes retrieved is crucial for successful treatment There have been two studies in which the results are compared after ovarian stimulation with daily rFSH vs CFA . In both shows , retrospectively and prospectively , the CFA seems to be at least as effective as hMG recombinant follicle stimulating hormone ( rFSH) daily. There are scientific publications showing that the association of luteinizing hormone ( LH) to recombinant follicle stimulating hormone ( rFSH) can improve embryos quality and achieved better pregnancy rate . The pregnancy rate was not statistically significant , in normal responders patients. Recently reported the beneficial effect in POR patients treated with CFA and hMG. The IVF treatment is known to affects the physical and mental condition in patients with infertility , being the excess emotional stress one of the most important reasons for discontinuation of treatment. The ovarian stimulation with CFA simplifies treatment , reducing the administration of multiple daily injections ,and may reduce the emotional burden on patients.

Official Title
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Prospective Randomized Study for the Evaluation of Controlled Ovarian Stimulation With Corifollitropin Alpha in Patients With Expected or Poor Ovarian Response in IVF Cycles

Conditions
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Infertility

Intervention / Treatment
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* Drug: Ganirelix 0.25 mg.
* Drug: Recombinant choriogonadotropin alfa
* Drug: Micronized natural progesterone.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Age ≥ 18 years old. - Signed informed consent to perform IVF and participation in this study. - Due to characteristics of our center not perform treatments in patients 40 years old ,and being one of the Bologna criteria that we will not be able to consider ,we decided to include patients affected subsidiary infertility treatment by IVF or intracytoplasmatic sperm injection (ICSI), present one of the following factors Have a history of surgical or medical treatment as a risk factor for POR. Patients witch had have a poor ovarian response in response to the ovarian controlled stimulation (previous cycle after conventional stimulation with ≤ 3 oocytes) Patients with ovarian reserve test anti-mullerian hormone(AMH ) <1.1 ng / ml (<8 pM) or antral follicle count (AFC)<7 Exclusion Criteria: -Anovulation. -Patient with tubal factor, untreated -Patient with uterine pathology untreated - Couples with severe male factor, fresh count <5 million / ml, and azoospermia in which the patient's sperm, epididymal or testicular is used

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: CFA , hMG,Ganirelix,choriogonadotropin alfa,progesterone.<br>Corifollitropin Alfa (CFA) 150 ug from the 2nd day of the cycle for 7 days. hMG 300 IU/24h, if required from the 8th day of the Controlled Ovarian Stimulation , until the day human chorionic gonadotropin ( hCG.) Ganirelix 0.25 mg,Dose: 250μg/24h since the day observe a follicle> 14mm. Recombinant choriogonadotropin alfa,Dose: 6,500 IU, pods, when follicles> 17 mm are observed. Micronized natural progesterone. Route of administration: vaginal. Dose: 400mg/24, from embryo transfer until the day of b-hCG. | Drug: Ganirelix 0.25 mg.<br>* Ganirelix 0.25 mg. Route of administration: Subcutaneous use. Dose: 250μg/24h since the day observe a follicle> 14mm.<br>* Other names: ORGALUTRAN®.;Drug: Recombinant choriogonadotropin alfa<br>* Recombinant choriogonadotropin alfa. Route of administration: Subcutaneous use. Dose: 6,500 IU, pods, when follicles> 17 mm are observed<br>* Other names: OVITRELLE®.;Drug: Micronized natural progesterone.<br>* Micronized natural progesterone. Route of administration: vaginal . Dose: 400mg/24, from embryo transfer until the day of b-hCG.<br>* Other names: PROGEFFIK®.;|
| Active Comparator: hMG ,Ganirelix,choriogonadotropin alfa,progesterone<br>Human Menopausal Gonadotropin (hMG). Dose: 300 IU/24h from the 2nd day of the cycle throughout the stimulation. Ganirelix 0.25 mg,Dose: 250μg/24h since the day observe a follicle> 14mm. Recombinant choriogonadotropin alfa,Dose: 6,500 IU, pods, when follicles> 17 mm are observed. Micronized natural progesterone. Route of administration: vaginal. Dose: 400mg/24, from embryo transfer until the day of b-hCG. | Drug: Ganirelix 0.25 mg.<br>* Ganirelix 0.25 mg. Route of administration: Subcutaneous use. Dose: 250μg/24h since the day observe a follicle> 14mm.<br>* Other names: ORGALUTRAN®.;Drug: Recombinant choriogonadotropin alfa<br>* Recombinant choriogonadotropin alfa. Route of administration: Subcutaneous use. Dose: 6,500 IU, pods, when follicles> 17 mm are observed<br>* Other names: OVITRELLE®.;Drug: Micronized natural progesterone.<br>* Micronized natural progesterone. Route of administration: vaginal . Dose: 400mg/24, from embryo transfer until the day of b-hCG.<br>* Other names: PROGEFFIK®.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of evolutionary gestation in each cycle | Evolutionary pregnancy has been defined as gestation of at least 1 fetus reaches 20 weeks of gestation diagnosed by normal ultrasound or confirmed by live birth | 20 week of gestation | 
| oocytes (MII) rate by patient | When follicular puncture occurs, we value the number of punctured follicles, total oocytes and MII oocytes | participants will be followed for the duration of the cycle,an expected average of 8-16 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events |  | participants will be followed for the duration of the cycle,an expected average of 16 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF, Infertility, Corifollitropin Alfa treatment, Ovarian stimulation