Clinical trial NCT01909141
Conditions: Polycystic Ovary Syndrome Infertility
Keywords: letrozole clomiphene citrate pioglitazone metformin ovulation induction PCOS
Sponsor: Cairo University
Start date: 2013-08-01; Completion date: 2014-04-01
Enrollment: 100 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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: 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.
Interventions: intervention 1: induction of ovulation using letrozole-pioglitazone-metformin intervention 2: induction of ovulation using clomiphene citrate-pioglitazone-metformin intervention 3: transvaginal ultrasound intervention 4: body mass index (BMI) calculation intervention 5: day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone intervention 6: pretreatment blood urea and serum creatinine intervention 7: serum estradiol (E2) on day 12 intervention 8: serum progesterone on day 21 intervention 9: blood urea and serum creatinine every month
Intervention descriptions: intervention 1: induction of ovulation will be done for arm 1 for 3 consecutive cycles unless pregnancy occured. intervention 2: induction of ovulation for arm 2 will be done in 3 consecutive cycles unless pregnancy occured. intervention 3: transvaginal ultrasound will be done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle intervention 4: BMI will be calculated for all women by dividing the weight in kilograms by the height in meters squared intervention 5: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) will be done for all women. intervention 6: blood urea and serum creatinine will be assayed before stating induction of ovulation to have baseline levels. intervention 7: serum E2 will be assayed on day 12 of the cycle for all women. intervention 8: serum progesterone will be assayed on day 21 for all women to monitor ovulation. intervention 9: blood urea and serum creatinine will be assayed every month during the treatment period to find out any hazards on kidney functions

Protocol documents: