Efficacy Study Comparing the Effect of Clomiphencitrate to an Antagonist Protocol

Study Overview
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Brief Summary
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The aim of this study is to assess the oocyte yield of infertile women with suspected or known poor ovarian reserve (POR) undergoing a GnRH antagonist protocol for IVF with Merional® starting either with a low (150 IU) or a high dose (450 IU) and adding 100mg of CC (Serophene®) in the early follicular phase of the stimulation (day 3 to 7). To date no RCT has been conducted to compare the reproductive outcome of patients with POR as defined by the ESHRE Bologna criteria after controlled ovarian hyperstimulation with HMG in an GnRH antagonist protocol using low doses versus high doses of HMG and adding CC versus placebo. We hypothesize that adding 100 mg of CC on day 3-7 to a HMG antagonist protocol will lead to an additional increment of endogenous GT thus increasing the oocytes yield after controlled ovarian stimulation due to higher endogenous gonadotropin secretion.

Official Title
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Prospective Randomized Phase IV Study Comparing the Effect of Adding Clomiphencitrate Versus Placebo to a High Dose Versus a Minimal Dose GnRH Antagonist Protocol on the Number of Oocytes Collected From Women That Are Poor Responders

Conditions
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Female Infertility, Ovarian Insufficiency

Intervention / Treatment
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* Drug: High Dose Clomiphencitrat
* Drug: Low Dose Clomiphencitrat
* Drug: High Dose Placebo
* Drug: Low dose Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: >18 years < 43 years BMI: ≥ 18 ≤ 32 kg/m2 Poor responder as defined by ESHRE working group Exclusion Criteria: Age < 18 und > 43 years Pregnancy Breast feeding Uterine conditions interfering with endometrial proliferation and embryo implantation (submucous fibroids or polyps) Women diagnosed with PCOS according to the Rotterdam criteria Hyperprolactinaemia - untreated Both ovaries not accessible transvaginally for oocyte pick up Ovarian cysts of unclear dignity Evidence of hydrosalpinx on ultrasound Clinically significant severe systemic disease that are incompatible with pregnancy Known or suspected hypersensitivity to the active substances (gonadotrophins, ganirelix, progesterone, clomiphencitrate) Untreated thyroid or adrenal disorders Bleeding disorders Cancer Severe renal or hepatic dysfunction Necessity to take medication that could influence ovarian stimulation History of OHSS in prior IVF cycle

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 43 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High Dose Clomiphencitrat<br>450 IU Merional® plus 100mg Serophene® | Drug: High Dose Clomiphencitrat<br>* 100mg of clomiphencitrate(Serophene®) are added to a high dose of HMG (450 IU of Merional®) in the early follicular phase of the stimulation (day 3 to 7).<br>|
| Active Comparator: Low Dose Clomiphencitrat<br>150 IU Merional® plus 100mg Serophene® | Drug: Low Dose Clomiphencitrat<br>* 100mg of clomiphencitrate(Serophene®) are added to a low dose of HMG (150 IU of Merional®) in the early follicular phase of the stimulation (day 3 to 7).<br>|
| Placebo Comparator: High Dose Placebo<br>450 IU Merional® plus Placebo | Drug: High Dose Placebo<br>* Placebo is added to a high dose of HMG (450 IU of Merional®) in the early follicular phase of the stimulation (day 3 to 7).<br>|
| Placebo Comparator: Low Dose Placebo<br>150 IU Merional® plus Placebo | Drug: Low dose Placebo<br>* Placebo is added to a low dose of HMG (150 IU of Merional®) in the early follicular phase of the stimulation (day 3 to 7).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of collected oocytes |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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female infertility, poor ovarian response, controlled ovarian hyperstimulation, IVF, Antagonist protocol