Ovulation Induction in Clomiphene Citrate Resistant PCO Women

Infertility Clinical Trial

Official title:

Letrozole-metformin Versus Letrozole-metformin-pioglitazone in PCO Clomiphene Citrate Resistant Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02341703
• Other study ID #: University Hospital
• Status: Completed
• Phase: Phase 0
• First received: January 14, 2015
• Last updated: July 27, 2015
• Start date: February 2015
• Est. completion date: July 2015

Study information

• Verified date: July 2015
• Source: Cairo University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Institutional Review Board
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Infertility
• Polycystic Ovary Syndrome

Intervention

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
• 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.

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

Locations

Country	Name	City	State
Egypt	faculty of medicine, Cairo University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ovulation rate		6 months	No
Secondary	pregnancy rate		6 months	No