Ovulation Induction in Clomiphene Citrate Resistant PCO Women
Condition: Polycystic Ovary Syndrome; Infertility
MeSH terms: Polycystic Ovary Syndrome; Infertility
Study type: Interventional
Phase: Early Phase 1

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.
    

Intervention name(s): letrozole-metformin; letrozole-metformin-pioglitazone; transvaginal ultrasound; laboratory investigations
Intervention type(s): Drug; Drug; Radiation; Other
Intervention description(s): 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; 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 will be done from day 10 of the cycle and every other day for monitoring of follicular enlargement.; day 3: FSH, LH, TSH, and total testosterone day 12 serum E2 day 21 serum progesterone
Other intervention name(s): femara-cidophage; femara- bioglita plus
Intervention MeSH terms: Metformin; Pioglitazone; Letrozole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment