Ovulation Induction in Women With Clomiphene Citrate Resistant PCOS

Cairo University (CU)

Status and phase: Completed; Early Phase 1

Conditions: Infertility; Polycystic Ovary Syndrome

Treatments: Other: blood urea and serum creatinine every month; Drug: induction of ovulation using letrozole-pioglitazone-metformin; Other: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone; Other: serum progesterone on day 21; Radiation: transvaginal ultrasound; Other: serum estradiol (E2) on day 12; Drug: induction of ovulation using clomiphene citrate-pioglitazone-metformin; Other: pretreatment blood urea and serum creatinine; Other: body mass index (BMI) calculation

Study type: Interventional

Funder types: Other

Identifiers

NCT01909141

fem2013

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 patients

Sex: Female

Ages: 20 to 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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100 participants in 2 patient groups

arm 1:letrozole-pioglitazone -metformin group

Active Comparator group

Description:

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.

Treatment:

Other: pretreatment blood urea and serum creatinine

Other: body mass index (BMI) calculation

Other: serum progesterone on day 21

Other: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone

Other: serum estradiol (E2) on day 12

Radiation: transvaginal ultrasound

Drug: induction of ovulation using letrozole-pioglitazone-metformin

Other: blood urea and serum creatinine every month

arm 2: clomiphene citrate-pioglitazone-metformin

Active Comparator group

Description:

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.

Treatment:

Other: pretreatment blood urea and serum creatinine

Other: body mass index (BMI) calculation

Other: serum progesterone on day 21

Other: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone

Other: serum estradiol (E2) on day 12

Radiation: transvaginal ultrasound

Other: blood urea and serum creatinine every month

Drug: induction of ovulation using clomiphene citrate-pioglitazone-metformin