Ovulation Induction in Women With Clomiphene Citrate Resistant PCOS

Early Phase 1

Completed

Conditions: Polycystic Ovary Syndrome
Infertility

Interventions: Drug: induction of ovulation using letrozole-pioglitazone-metformin
Drug: induction of ovulation using clomiphene citrate-pioglitazone-metformin
Radiation: transvaginal ultrasound
Other: body mass index (BMI) calculation
Other: pretreatment blood urea and serum creatinine
Other: serum estradiol (E2) on day 12
Other: serum progesterone on day 21
Other: blood urea and serum creatinine every month

Registration Number: NCT01909141

Lead Sponsor: Cairo University

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-pioglitazone with that of combined CC-metformin-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 we shall compare the effect of combined letrozole-metformin-pioglitazone with that of combined CC-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 (40 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 (40 women) will receive clomiphene citrate 100 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. Ovulation will be monitored by vaginal ultrasound and serum estrogen and progesterone.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 100

Inclusion Criteria

20-40 years old
PCOS infertile women resistant to CC for3 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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
arm 1:letrozole-pioglitazone -metformin group	induction of ovulation using letrozole-pioglitazone-metformin	Arm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 1:letrozole-pioglitazone -metformin group	transvaginal ultrasound	Arm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 1:letrozole-pioglitazone -metformin group	body mass index (BMI) calculation	Arm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 1:letrozole-pioglitazone -metformin group	pretreatment blood urea and serum creatinine	Arm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 1:letrozole-pioglitazone -metformin group	serum estradiol (E2) on day 12	Arm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 1:letrozole-pioglitazone -metformin group	serum progesterone on day 21	Arm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 1:letrozole-pioglitazone -metformin group	blood urea and serum creatinine every month	Arm 1 will receive letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 2: clomiphene citrate-pioglitazone-metformin	induction of ovulation using clomiphene citrate-pioglitazone-metformin	Arm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 2: clomiphene citrate-pioglitazone-metformin	serum estradiol (E2) on day 12	Arm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 2: clomiphene citrate-pioglitazone-metformin	serum progesterone on day 21	Arm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 2: clomiphene citrate-pioglitazone-metformin	blood urea and serum creatinine every month	Arm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 2: clomiphene citrate-pioglitazone-metformin	transvaginal ultrasound	Arm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 2: clomiphene citrate-pioglitazone-metformin	body mass index (BMI) calculation	Arm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
arm 2: clomiphene citrate-pioglitazone-metformin	pretreatment blood urea and serum creatinine	Arm 2 will receive clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.