Letrozole or Combined Clomiphene Citrate Metformin as a First Line Treatment in Women With Polycystic Ovarian Syndrome
Condition: Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Syndrome
Study type: Interventional

Summary: 
      The purpose of this study is to compare and determine the efficacy of letrozole
      administration to that of combined metformin and Clomiphene in infertile women with
      polycystic ovary syndrome (PCOS) not treated before with any ovulation induction agent
    

Detailed description: 
      The study will be in 200 patient diagnosed to have PCOS among those attending the Fertility
      Outpatient Clinic at the Women's Health Center, Assiut University Hospitals.

      The present study was prospective randomized controlled trial conducted over a period of 3
      years from 1st of January 2009 to 1st of January 2012, at the Women's Health Center, Assiut
      University hospital, Assiut, Egypt, after approval was received from the Ethics Committee of
      faculty of medicine , Assiut University. Women referred to the infertility clinic in women's
      health center were screened for PCO using Rotterdam consensus criteria for the diagnosis of
      PCOS. The patients who were newly diagnosed as PCO and not treated previously were invited to
      participate in our study. Written informed consent was obtained from each participant after
      an information sheet had been provided. The patients had the right to refuse participation in
      the study or to withdraw at any time without being denied their full regular clinical care.
      All personal information and medical data were confidential and were not made available to
      third parties. All participants met the Rotterdam consensus criteria for the diagnosis of
      PCOS. At admission, a thorough medical history was taken and all women underwent physical
      examination, which included anthropometric measurements and after spontaneous menstruation or
      progestin induced withdrawal bleeding, basal endocrine evaluation on day 3 of the cycle
      included measurement of the serum concentrations of luteinizing hormone (LH),
      follicle-stimulating hormone (FSH),thyroid stimulating hormone(TSH ) and prolactin. Then
      vaginal sonographic examination were done to measure endometrial thickness and exclude cases
      endometrial pathology or baseline ovarian cysts.

      The participants were randomized to receive letrozole or clomiphene citrate plus metformin.
      Randomization was performed using a computer-generated random numbers table, and allocation
      concealment was achieved using serially numbered opaque envelopes that were only opened once
      the interventions were assigned.

      In the letrozole group, the ovaries were stimulated using 2.5mg/day letrozole (Femara;
      Novartis Pharma, Basel, Switzerland) for 5 days,in the form of one tablet( 2.5 mg) per day
      for 5 days from day 3 to day 7 of the menstrual cycle and if ovulation has occurred with no
      pregnancy continue on the same dose for another 2 consecutive cycles ,but if no ovulation
      increase the dose to 2 tablets per day(5 mg) for another 2 consecutive cycles in the same
      manner .

      The patients in the second group will take metformin (Cidophage tablets,500 mg per tablet;
      CID, ARE, in an oral dose of 1,500 mg/d) 500mg three times daily for 3 months Plus
      clomid(50-mg tablets twice daily; Global Napi Pharmaceuticals, Cairo, Egypt , Arab Republic
      of Egypt) In the form of 50 mg twice daily (100mg /day) for 5 days from day 3 to day 7 of
      menstrual cycle and to be repeated for 3 consecutive cycles in the same manner if no
      pregnancy occur.

      In both groups, endometrial thickness and mean follicular diameter were assessed by the same
      investigator using transvaginal ultrasound on days 2 ,10, 12, and 14 of the menstrual cycle,
      and 10 000 IU of human chorionic gonadotropin (hCG) (Pregnyl; Organon, Oss, The Netherlands)
      were injected intramuscularly if there was at least 1 leading follicle measuring 18 mm or
      more in diameter and endometrial thickness detected at that time(endometrial thickness was
      determined at the greatest diameter perpendicular to the midsagittal plane in the fundal
      region, including both layers of the endometrium). All participants were advised to have
      intercourse 24-36 hours after the hCG injection. Two days after being given Human chorionic
      gonadotropin, the patients were assessed for signs of ovulation (disappearance of
      preovulatory follicle, fluid in the cul-de-sac, and/or corpus luteum formation). Pregnancy
      will be diagnosed when positive pregnancy test in urine done or a gestational sac was
      detected on transvaginal ultrasound examination 1week after the missed period or serum β-hCG
      concentration 14 days after HCG injection if menses had not occurred. A biochemical pregnancy
      was considered when the serum β-hCG concentration was 50 mIU/mL or more in the absence of
      menstruation. All study medication were stopped when there was positive pregnancy
      test.Pregnant patients then will be followed up until an ultrasound could document the
      viability of pregnancy. A clinical pregnancy was defined as the presence of a gestational sac
      with a beating fetal heart on transvaginal ultrasound. A spontaneous abortion was defined as
      the spontaneous loss of a pregnancy before the end of the 20th week.
    

Intervention name(s): Letrozole; Clomiphene; Metformin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): •Drug: Letrozole tablets (Femara; Novartis Pharma, Switzerland) 2.5 mg letrozole daily from day 3 of the menses for 5 days; •Drug: CC (Clomid®; Global Napi Pharmaceuticals, Cairo, Egypt) 100 mg CC for 5 days starting from day 3 of menstruation; •Drug: metformin HCl (Cidophage®; CID,Cairo, Egypt) metformin HCl 1500 daily for 3 months
Other intervention name(s): Femara; Novartis Pharma, Switzerland; clomid; Cidophage
Intervention MeSH terms: Metformin; Letrozole; Clomiphene
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: PCO