Second-Line Treatments for Anovulatory Infertility in PCOS Patients

Sponsor

University Magna Graecia (Other)

Overall Status

Completed

CT.gov ID

NCT00558077

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome Infertility Anovulation	Drug: Metformin plus clomiphene citrate Procedure: Laparoscopic ovarian drilling	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2003

Study Completion Date :

Oct 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Metformin plus clomiphene citrate	Drug: 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.
Active Comparator: B Laparoscopic ovarian drilling	Procedure: 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.

Arm

Intervention/Treatment

Experimental: A

Metformin plus clomiphene citrate

Drug: 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.

Active Comparator: B

Laparoscopic ovarian drilling

Procedure: 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.

Outcome Measures

Primary Outcome Measures

Live-birth rate [fifteen months]

Secondary Outcome Measures

Spontaneous menses [six months]
Pregnancy rate [six months]
Abortion rate [fifteen months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	"Pugliese" Hospital	Catanzaro	Catanzaro/Italy	Italy	88100

Sponsors and Collaborators

University Magna Graecia

Investigators

Principal Investigator: Stefano Palomba, MD, Department of Obstetrics and Gynecology, University "Magna Graecia" of Catanzaro
Study Chair: Fulvio Zullo, MD, Department of Obstetrics and Gynecology, University "Magna Graecia" of Catanzaro