Second-Line Treatments for Anovulatory Infertility in PCOS Patients

NCT ID: NCT00558077

Last Updated: 2007-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-02-28
• Study Completion Date: 2005-10-31

Brief Summary

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

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.

Conditions

Polycystic Ovary Syndrome; Infertility; Anovulation

Keywords

Anovulation; Clomiphene citrate; Fertility; Metformin; Ovulation induction; PCOS; Sterility; Treatment; Clomiphene citrate-resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Metformin plus clomiphene citrate

Group Type: EXPERIMENTAL

Metformin plus clomiphene citrate

Intervention Type: DRUG

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.

B

Laparoscopic ovarian drilling

Group Type: ACTIVE_COMPARATOR

Laparoscopic ovarian drilling

Intervention Type: PROCEDURE

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.

Interventions

Metformin plus clomiphene citrate

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.

Intervention Type: DRUG

Laparoscopic ovarian drilling

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Magna Graecia

OTHER

Sponsor Role: lead

Principal Investigators

Stefano Palomba, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Obstetrics and Gynecology, University "Magna Graecia" of Catanzaro

Fulvio Zullo, MD

Role: STUDY_CHAIR

Department of Obstetrics and Gynecology, University "Magna Graecia" of Catanzaro

Locations

"Pugliese" Hospital

Catanzaro, Catanzaro/Italy, Italy

Countries

Italy

References

Palomba S, Orio F Jr, Falbo A, Manguso F, Russo T, Cascella T, Tolino A, Carmina E, Colao A, Zullo F. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 Jul;90(7):4068-74. doi: 10.1210/jc.2005-0110. Epub 2005 Apr 19.

Reference Type: BACKGROUND

PMID: 15840746 (View on PubMed)

Palomba S, Orio F Jr, Nardo LG, Falbo A, Russo T, Corea D, Doldo P, Lombardi G, Tolino A, Colao A, Zullo F. Metformin administration versus laparoscopic ovarian diathermy in clomiphene citrate-resistant women with polycystic ovary syndrome: a prospective parallel randomized double-blind placebo-controlled trial. J Clin Endocrinol Metab. 2004 Oct;89(10):4801-9. doi: 10.1210/jc.2004-0689.

Reference Type: BACKGROUND

PMID: 15472166 (View on PubMed)

Other Identifiers

01/2003

Identifier Type: -

Identifier Source: org_study_id