Ovulation Induction in Women With Clomiphene Citrate Resistant PCOS
Condition: Polycystic Ovary Syndrome; Infertility
MeSH terms: Polycystic Ovary Syndrome; Infertility; Syndrome
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-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.
    

Intervention name(s): induction of ovulation using letrozole-pioglitazone-metformin; induction of ovulation using clomiphene citrate-pioglitazone-metformin; transvaginal ultrasound; body mass index (BMI) calculation; day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone; pretreatment blood urea and serum creatinine; serum estradiol (E2) on day 12; serum progesterone on day 21; blood urea and serum creatinine every month
Intervention type(s): Drug; Drug; Radiation; Other; Other; Other; Other; Other; Other
Intervention description(s): induction of ovulation will be done for arm 1 for 3 consecutive cycles unless pregnancy occured.; induction of ovulation for arm 2 will be done in 3 consecutive cycles unless pregnancy occured.; 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; BMI will be calculated for all women by dividing the weight in kilograms by the height in meters squared; baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) will be done for all women.; blood urea and serum creatinine will be assayed before stating induction of ovulation to have baseline levels.; serum E2 will be assayed on day 12 of the cycle for all women.; serum progesterone will be assayed on day 21 for all women to monitor ovulation.; blood urea and serum creatinine will be assayed every month during the treatment period to find out any hazards on kidney functions
Intervention MeSH terms: Metformin; Pioglitazone; Carbamide Peroxide; Letrozole; Clomiphene; Enclomiphene; Zuclomiphene; Hormones; Estradiol; Testosterone; Progesterone; Follicle Stimulating Hormone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: letrozole; clomiphene citrate; pioglitazone; metformin; ovulation induction; PCOS