Strategies for Ovulation Induction in Anovulatory Infertile Patients With PCOS

Anovulatory Infertility Related to Polycystic Ovary Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00461643
• Other study ID #: 01/2007
• Status: Recruiting
• Phase: Phase 4
• First received: April 13, 2007
• Last updated: April 5, 2013
• Start date: January 2007

Study information

• Verified date: April 2013
• Source: University Magna Graecia
• Contact: Stefano Palomba, MD
• Phone: +39-0961.883234
• Email: stefanopalomba[@]tin.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 552
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anovulatory Infertility Related to Polycystic Ovary Syndrome
• Infertility
• Polycystic Ovary Syndrome

Intervention

Drug:
• Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins

Locations

Country	Name	City	State
Italy	"Pugliese" Hospital	Catanzaro
Italy	"Pugliese" Hospital	Catanzaro
Italy	Pugliese-Ciaccio Hospital	Catanzaro

Sponsors (1)

Lead Sponsor	Collaborator
University Magna Graecia

Country where clinical trial is conducted

Italy, 

References & Publications (3)

Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, Steinkampf MP, Coutifaris C, McGovern PG, Cataldo NA, Gosman GG, Nestler JE, Giudice LC, Leppert PC, Myers ER; Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007 Feb 8;356(6):551-66. — View Citation

Moll E, Bossuyt PM, Korevaar JC, Lambalk CB, van der Veen F. Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. BMJ. 2006 Jun 24;332(7556):1485. Epub 2006 Jun 12. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Multiple pregnancy rate		9 months	Yes
Secondary	Ovulation rate		15 months	No
Secondary	Pregnancy rate		15 months	No
Secondary	Abortion rate		15 months	Yes
Secondary	Live-birth rate		24 months	No
Secondary	Adverse-events		15	Yes