Strategies for Ovulation Induction in Anovulatory Infertile Patients With PCOS

Study Overview
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Brief Summary
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Anovulatory infertility is a common feature of the polycystic ovary syndrome (PCOS). Even if several first-step treatments have been proposed for anovulatory infertile PCOS patients, very few data are available in literature regarding the best integrated strategy. In fact, a single compound could be effective as first-step approach but not or less useful when integrated in a more complex strategy. The goal of the current protocol will be to compare three different strategies for treating anovulatory infertility in PCOS patients having as primary end-point the multiple pregnancy rate.

Detailed Description
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All patients eligible will undergo baseline assessment consisting of antropometric, hormonal, and ultrasonographic assessments. Successively, patients enrolled will be allocated in three different strategies (strategy A, B, and C). A total of 184 infertile PCOS patients per arm will be enrolled and treated with three different integrated strategies: clomiphene followed by clomiphene plus metformin followed by gonadotropins (strategy A); metformin followed by metformin plus clomiphene followed by gonadotropins(strategy B); and metformin plus clomiphene followed by gonadotropins(strategy C). In all patients, the same regimen will be used to administered clomiphene, metformin, and gonadotropins.Both clomiphene and metformin will be administered at incremental doses in each case.Gonadotropins will be administrated to obtain a controlled ovarian stimulation using highly purified urinary FSH in a low-dose step-up protocol. During the study, the clinical and reproductive outcomes, and adverse experiences will be evaluated in each woman.

Official Title
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Comparison of Three Different Strategies for Treating Infertility in Anovulatory Women With Polycystic Ovary Syndrome: a Multicentre Randomized Controlled Clinical Trial

Conditions
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Anovulatory Infertility Related to Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Polycystic ovary syndrome (using ESHRE/ARSM 2004 criteria) Exclusion Criteria: Age <18 or >35 years Severe obesity (BMI >35) Neoplastic, metabolic, hepatic, and cardiovascular disorders or other concurrent medical illnesses Hypothyroidism, hyperprolactinemia, Cushing's syndrome, and non-classical congenital adrenal hyperplasia Current or previous (within the last six months) use of oral contraceptives, glucocorticoids, antiandrogens, antidiabetic and anti-obesity drugs or other hormonal drugs Previous use of ovulation induction agents Intention to start a diet or a specific program of physical activity No uterine bleeding after progesterone challenge test Organic pelvic diseases Previous pelvic surgery Suspected peritoneal factor infertility Tubal or male factor infertility or sub-fertility

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Strategy A<br>clomiphene followed by clomiphene plus metformin followed by gonadotropins | Drug: Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins<br> <br> |
| Active Comparator: Strategy B<br>metformin followed by metformin plus clomiphene followed by gonadotropins | Drug: Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins<br> <br> |
| Active Comparator: Strategy C<br>metformin plus clomiphene followed by gonadotropins | Drug: Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple pregnancy rate |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ovulation rate |  | 15 months | 
| Pregnancy rate |  | 15 months | 
| Abortion rate |  | 15 months | 
| Live-birth rate |  | 24 months | 
| Adverse-events |  | 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anovulation, Clomiphene citrate, Infertility, Metformin, PCOS, RCT, Treatment