Ovulation Induction in Clomiphene Citrate Resistant PCO Women

• ClinicalTrials.gov Identifier: NCT02341703
• Recruitment Status: Completed
• First Posted: January 19, 2015
• Last Update Posted: July 28, 2015
• Sponsor: Cairo University
• Information provided by (Responsible Party): Ghada Abdel Fattah, Cairo University

Study Description

Brief Summary:

Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). In CC resistant cases, the American College of Obstetrics and Gynecology (ACOG) recommends the use of insulin sensitizer metformin. Other insulin sensitizing agents include rosiglitazone and pioglitazone. Pioglitazone is said to improve fertility and ovulation in patients with PCOS.CC may be associated with poor endometrial thickening due to its antiestrogenic effect. Letrozole may improve this condition. In this study we will compare the effect of combined letrozole-metformin with that of combined letrozole-pioglitazone in ovulation induction in CC-resistant PCOS women

Condition or disease	Intervention/treatment	Phase
Polycystic Ovary Syndrome; Infertility	Drug: letrozole-metformin; Drug: letrozole-metformin-pioglitazone; Radiation: transvaginal ultrasound; Other: laboratory investigations	Early Phase 1

Detailed Description:

Polycystic ovary syndrome (PCOS) affects 5-10% of women in childbearing age. Hyperinsulinemia contributes to chronic anovulation commonly encountered in women with PCOS. The first choice therapy is clomiphene citrate (CC). In CC resistant cases, the ACOG recommends the use of insulin sensitizer metformin. Other insulin sensitizing agents include rosiglitazone and pioglitazone. Pioglitazone is said to improve fertility and ovulation in patients with PCOS. CC has a long half-life (2 weeks), and this may have a negative effect on the cervical mucus and endometrium, leading to discrepancy between ovulation and conception rates. There has been a search for a compound capable of inducing ovulation but devoid of the adverse antiestrogenic effects of CC. recent studies have suggested that letrozole, an aromatase inhibitor, does not possess the adverse antiestrogenic effects of CC and is associated with higher pregnancy rates than CC treatment in patients with PCOS.

In this study the investigators shall compare the effect of combined letrozole-metformin with that of combined letrozole-metformin-pioglitazone in ovulation induction in CC-resistant PCOS women.This will be a prospective comparative clinical trial in which 2 groups of women will be generated (groups A and B) using the sealed envelopes randomization method.Group A (50 women) will receive: letrozole 2.5 mg/day from 3rd day of the cycle for 5 days and (pioglitazone 15 mg + metformin 850 mg) once daily from 1st day of the cycle for 10 days. Group B (50 women) will receive letrozole 2.5 mg/day from 3rd day of the cycle for 5 days and metformin 500 mg three times daily from continuously untill pregncy occurrs. Ovulation will be monitored by vaginal ultrasound and serum estrogen and progesterone.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Letrozole-metformin Versus Letrozole-metformin-pioglitazone in PCO Clomiphene Citrate Resistant Women
• Study Start Date: February 2015
• Actual Primary Completion Date: July 2015
• Actual Study Completion Date: July 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: letrozole-metformin group; this group will receive letrozole 2.5 mg daily from day 3 of the cycle and for 5 days + metformin 500 mg three times daily from the first day of the cycle and continuous for three months unless pregnancy occurred. treatment will continue for 3 cycles unless pregnancy occurred. for this group: transvaginal ultrasound will monitor follicular enlargement laboratory investigations in the form of day 3 FSH, LH, TSH and serum testosterone will be done day 12 E2 day 21 serum progesterone	Drug: letrozole-metformin; letrozole 2.5 mg will be given daily from day 3 of the cycle for 5 days + metformin 500 mg three times daily continuously for 3 months unless pregnancy occurred; Other Name: femara-cidophage; Radiation: transvaginal ultrasound; transvaginal ultrasound will be done from day 10 of the cycle and every other day for monitoring of follicular enlargement.; Other: laboratory investigations; day 3: FSH, LH, TSH, and total testosterone day 12 serum E2 day 21 serum progesterone
Active Comparator: letrozole-metformin-pioglitazone group; this group will receive letrozole 2.5 mg daily from day 3 of the cycle and for 5 days + (metformin 850 mg + pioglitazone 15 mg) once daily from the first day of the cycle and for 10 days. treatment will continue for 3 cycles unless pregnancy occurred. for this group: transvaginal ultrasound will monitor follicular enlargement laboratory investigations in the form of day 3 FSH, LH, TSH and serum testosterone will be done day 12 E2 day 21 serum progesterone	Drug: letrozole-metformin-pioglitazone; letrozole will be given daily from day 3 of the cycle for 5 days + (metformin 850 mg + pioglitazone 15 mg) from the first day of the cycle for 10 days.; Other Name: femara- bioglita plus; Radiation: transvaginal ultrasound; transvaginal ultrasound will be done from day 10 of the cycle and every other day for monitoring of follicular enlargement.; Other: laboratory investigations; day 3: FSH, LH, TSH, and total testosterone day 12 serum E2 day 21 serum progesterone

Outcome Measures

Primary Outcome Measures :

1. ovulation rate [ Time Frame: 6 months ]

Secondary Outcome Measures :

1. pregnancy rate [ Time Frame: 6 months ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 40 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 20-40 years old
• PCOS infertile women resistant to CC for 3 cycles

Exclusion Criteria:

• Presence of medical disorders as diabetes, hypertension, cardiac problems, liver or kidney diseases, hyperprolactinemia or thyroid dysfunction
• Use of gonadotropins before
• Previous ovarian drilling
• Presence of urinary symptoms especially bloody urine

Contacts and Locations

Locations

Egypt

faculty of medicine, Cairo University

Cairo, Egypt, 002

Sponsors and Collaborators

Cairo University

Investigators

• Principal Investigator: Ghada Abdel Fattah Abdel Moety, lecturer; Cairo University

More Information

• Responsible Party: Ghada Abdel Fattah, assistant professor of Obstetrics and Gynecology, Cairo University
• ClinicalTrials.gov Identifier: NCT02341703
• Other Study ID Numbers: University Hospital
• First Posted: January 19, 2015
• Last Update Posted: July 28, 2015
• Last Verified: July 2015

Additional relevant MeSH terms:

Polycystic Ovary Syndrome; Infertility; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine System Diseases; Metformin; Pioglitazone; Letrozole; Hypoglycemic Agents; Physiological Effects of Drugs; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists