Second-Line Treatments for Anovulatory Infertility in PCOS Patients

Study Overview
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Brief Summary
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To date, it is still unclear the potential role of laparoscopic ovarian diathermy (LOD) in the management of polycystic ovary syndrome (PCOS)-related anovulatory infertility. Metformin administration, alone or combined with clomiphene citrate (CC), has shown to be an effective and attractive second-line treatment for ovulation induction in women with polycystic ovary syndrome (PCOS) after failure of CC treatment. The aim of the present study will be to compare in a randomized controlled fashion the efficacy of LOD with metformin plus CC administration in the treatment of the CC-resistant PCOS patients.

Detailed Description
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A total of 50 primary infertile anovulatory PCOS patients with documented CC-resistance will be enrolled and randomized into two groups of treatment of 25 subjects each. Group A will undergo diagnostic laparoscopy followed by metformin plus CC, whereas group B will undergo LOD followed by observation. Anovulatory patients will receive IM progesterone. The treatment will be of six months followed by nine-month of observation for pregnant patients. The incidence of spontaneous menses, and the pregnancy, abortion, and live-birth rates will be recorded.

Official Title
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Laparoscopic Ovarian Diathermy or Metformin Plus Clomiphene Citrate Administration as Second-Line Treatment for Infertile Anovulatory Patients With Polycystic Ovary Syndrome: a Randomized Controlled Trial

Conditions
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Polycystic Ovary Syndrome, Infertility, Anovulation

Intervention / Treatment
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* Drug: Metformin plus clomiphene citrate
* Procedure: Laparoscopic ovarian drilling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PCOS Clomiphene citrate-resistance Anovulation Infertility Exclusion Criteria: Age < 18 or > 35 years Body mass index >35 Neoplastic, metabolic, endocrine, hepatic, renal, and cardiovascular disorders or other concurrent medical illnesses Current or previous use of oral contraceptives, glucocorticoids, antiandrogens, ovulation induction agents, antidiabetic and anti-obesity drugs or other drugs affecting hormone levels, carbohydrate metabolism, or appetite Pelvic diseases Previous pelvic surgery Suspected peritoneal factor infertility/subfertility 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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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: A<br>Metformin plus clomiphene citrate | Drug: Metformin plus clomiphene citrate<br>* Metformin administration will start from 3rd day of a P-induced withdrawal bleeding with a dose of 850 mg (1 tablet daily) and increasing the dosage after one week up to 1700 mg/day (two tablets daily). Clomiphene citrate CC will be administered for five days beginning on cycle day 3rd of a P-induced withdrawal bleeding using a starting dose of 50 mg daily. If ovulation will not occur, the dose will be increased by 50 mg in successive cycles until the ovulation will be achieved or up to a maximal dose of 150 mg daily.<br>|
| Active Comparator: B<br>Laparoscopic ovarian drilling | Procedure: Laparoscopic ovarian drilling<br>* Laparoscopic ovarian drilling will be performed as follows: according to ovary size three to six punctures will be performed at each ovary inserting an insulated needle cautery of 36 mm perpendicularly as possible to the ovarian surface with a cutting current of 100 watt power. Then, the needle will be activated for 2-3 seconds at each point using a coagulating current of 40 watt power. At completion of the procedure, the ovarian surface will be washed with a crystalloid solution and all injured areas will be completely covered with hyaluronic acid gel.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live-birth rate |  | fifteen months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spontaneous menses |  | six months | 
| Pregnancy rate |  | six months | 
| Abortion rate |  | fifteen months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anovulation, Clomiphene citrate, Fertility, Metformin, Ovulation induction, PCOS, Sterility, Treatment, Clomiphene citrate-resistance