Clinical trial NCT02341703: Ovulation Induction in Clomiphene Citrate Resistant PCO Women
Official title: Letrozole-metformin Versus Letrozole-metformin-pioglitazone in PCO Clomiphene Citrate Resistant Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Polycystic Ovary Syndrome
Infertility
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2015-01-19
Enrollment: 100
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: ovulation rate
timeFrame: 6 months
Secondary outcomes:
measure: pregnancy rate
timeFrame: 6 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: faculty of medicine, Cairo University
Study officials:
affiliation: Cairo University
name: Ghada Abdel Fattah Abdel Moety, lecturer
role: PRINCIPAL_INVESTIGATOR
References: