Ovulation Induction in Clomiphene Citrate Resistant PCO Women

NCT ID: NCT02341703

Last Updated: 2015-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2015-07-31

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

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.

Conditions

Polycystic Ovary Syndrome; Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

letrozole-metformin

Intervention Type: DRUG

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

transvaginal ultrasound

Intervention Type: RADIATION

transvaginal ultrasound will be done from day 10 of the cycle and every other day for monitoring of follicular enlargement.

laboratory investigations

Intervention Type: OTHER

day 3: FSH, LH, TSH, and total testosterone day 12 serum E2 day 21 serum progesterone

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

Group Type: ACTIVE_COMPARATOR

letrozole-metformin-pioglitazone

Intervention Type: DRUG

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.

transvaginal ultrasound

Intervention Type: RADIATION

transvaginal ultrasound will be done from day 10 of the cycle and every other day for monitoring of follicular enlargement.

laboratory investigations

Intervention Type: OTHER

day 3: FSH, LH, TSH, and total testosterone day 12 serum E2 day 21 serum progesterone

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

transvaginal ultrasound

transvaginal ultrasound will be done from day 10 of the cycle and every other day for monitoring of follicular enlargement.

Intervention Type: RADIATION

laboratory investigations

day 3: FSH, LH, TSH, and total testosterone day 12 serum E2 day 21 serum progesterone

Intervention Type: OTHER

Other Intervention Names

femara-cidophage; femara- bioglita plus

Eligibility 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Ghada Abdel Fattah

assistant professor of Obstetrics and Gynecology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ghada Abdel Fattah Abdel Moety, lecturer

Role: PRINCIPAL_INVESTIGATOR

Cairo University

Locations

faculty of medicine, Cairo University

Cairo, Cairo Governorate, Egypt

Countries

Egypt

Other Identifiers

University Hospital

Identifier Type: -

Identifier Source: org_study_id