Second-Line Treatments for Anovulatory Infertility in PCOS Patients - Full Text View

Sponsored by:	University Magna Graecia
Information provided by:	University Magna Graecia
ClinicalTrials.gov Identifier:	NCT00558077

Purpose

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	Intervention	Phase
Polycystic Ovary Syndrome Infertility Anovulation	Drug: Metformin plus clomiphene citrate Procedure: Laparoscopic ovarian drilling	Phase IV

MedlinePlus related topics: Infertility

Drug Information available for: Metformin Metformin hydrochloride Citric acid Sodium Citrate Clomiphene citrate Clomiphene Enclomiphene Zuclomiphene Hyaluronate Sodium Hyaluronic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

Further study details as provided by University Magna Graecia:

Primary Outcome Measures:

Live-birth rate [ Time Frame: fifteen months ]

Secondary Outcome Measures:

Spontaneous menses [ Time Frame: six months ]
Pregnancy rate [ Time Frame: six months ]
Abortion rate [ Time Frame: fifteen months ]

Enrollment:	50
Study Start Date:	February 2003
Estimated Study Completion Date:	October 2005

Arms	Assigned Interventions
A: Experimental 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.
B: Active Comparator 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.

Arms

Assigned Interventions

A: Experimental

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.

B: Active Comparator

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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558077

Locations

Italy, Catanzaro/Italy
"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

More Information

Publications:

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. Epub 2005 Apr 19.

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. Erratum in: J Clin Endocrinol Metab. 2005 Jul;90(7):3945.

Study ID Numbers:	01/2003
Study First Received:	November 13, 2007
Last Updated:	November 13, 2007
ClinicalTrials.gov Identifier:	NCT00558077
Health Authority:	Italy: The Italian Medicines Agency

Keywords provided by University Magna Graecia:

Anovulation
Clomiphene citrate
Fertility
Metformin
Ovulation induction

PCOS
Sterility
Treatment
Clomiphene citrate-resistance

Study placed in the following topic categories:

Infertility
Hyaluronic Acid
Gonadal Disorders
Citric Acid
Metformin
Endocrine System Diseases
Clomiphene
Ovarian Diseases

Genital Diseases, Male
Cysts
Genital Diseases, Female
Polycystic Ovary Syndrome
Endocrinopathy
Anovulation
Ovarian Cysts

Additional relevant MeSH terms:

Estrogen Antagonists
Disease
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Reproductive Control Agents
Selective Estrogen Receptor Modulators
Pharmacologic Actions
Adnexal Diseases

Estrogen Receptor Modulators
Neoplasms
Hypoglycemic Agents
Pathologic Processes
Therapeutic Uses
Syndrome
Fertility Agents, Female
Fertility Agents

ClinicalTrials.gov processed this record on January 16, 2009