Controlled Ovarian Stimulation Versus Modified Natural Cycles in Poor Responders

Study Overview
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Brief Summary
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This is a prospective, randomized, single center, phase 4 controlled trial. The study will compare the efficacy of two different strategies for the management of predicted poor response patients under stimulation for IVF/ICSI: up to three MNC cycles (group 1) versus a single GnRH antagonist CFA (group 2).

Official Title
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A Randomized Comparison of One Controlled Ovarian Stimulation With Corifollitropin Alfa Versus up to Three Modified Natural Cycles in Expected and Established Poor Responders

Conditions
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Ovarian Reserve, Poor Responders, IVF

Intervention / Treatment
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* Drug: A single Gonadotropin-Releasing Hormone (GnRH) antagonist corifollitropin alfa (CFA) stimulation
* Drug: Up to three modified natural cycles with Follitropin beta.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent form (ICF) dated and signed. Age ≥18 and <45 years old. Body Mass Index (BMI) ≥18.5 Kg/m² and <35 Kg/m². Regular menstrual cycles (between 21 and 35 days). Two ovaries present. Current pregnancy wish. Poor responders as defined according to the POSEIDON criteria: POSEIDON Group 3: patients < 35 years with poor ovarian reserve pre-stimulation parameters (AFC <5 or AMH <1.2 ng/mL); POSEIDON Group 4: patients ≥35 years with poor ovarian reserve pre-stimulation parameters (AFC <5 or AMH <1.2 ng/mL). Exclusion Criteria: Simultaneous participation in another clinical study. Untreated and uncontrolled thyroid dysfunction. Tumors of the ovary, breast, uterus, pituitary or hypothalamus. Abnormal (not menstrual) vaginal bleeding without a known/diagnosed cause. Ovarian cysts or enlarged ovaries. Malformations of the reproductive organs. Current use of oral contraceptives, anti-psychotics, anti-epileptics or chemotherapy. Previous antibiotic hypersensitivity reactions (streptomycin and/or neomycin). Patients who undergo preimplantation genetic testing (PGT), fertility preservation or oocyte donation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 44 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 |
| --- | --- |
| Active Comparator: Up to 3 modified natural cycles<br> | Drug: Up to three modified natural cycles with Follitropin beta.<br>* Follitropin beta in a low dose will be given.<br>|
| Experimental: Controlled ovarian stimulation<br> | Drug: A single Gonadotropin-Releasing Hormone (GnRH) antagonist corifollitropin alfa (CFA) stimulation<br>* CFA will be administered in combination with Follitropin beta.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of good quality blastocysts after CFA stimulation vs. after a first MNC |  | On fifth day of embryonal development | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of good quality blastocysts after CFA stimulation vs. after a second or third MNC |  | On fifth day of embryonal development | 
| The relative number of blastocysts after ART, relative to the number of oocytes |  | On fifth day of embryonal development | 
| The probability of having at least one blastocyst of good quality after ART |  | On fifth day of embryonal development |