title: A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate-resistant polycystic ovary syndrome.
abstract: OBJECTIVE
  To examine the efficacy of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone among women with polycystic ovary syndrome (PCOS) resistant to clomifene citrate.
  
  
  METHODS
  A prospective double-blind randomized controlled trial of women younger than 40 years who had primary/secondary infertility associated with PCOS and had not ovulated in response to clomifene citrate regimens previously was conducted at a center in Cairo, Egypt, between August 1, 2013, and December 31, 2014. Computer-generated random number tables and opaque envelopes were used to assign participants to group A or group B. Participants allocated to group A received 100mg clomifene citrate daily for 5 days from the third day of the menstrual cycle, whereas those in group B received 5mg letrozole daily in the same regimen. All patients received 850 mg metformin and 15 mg pioglitazone for 10 days from the first day of the menstrual cycle. The primary outcome was cumulative ovulation rate. Analyses were by intention to treat.
  
  
  RESULTS
  Fifty women were assigned to each group. Ovulation occurred in 108 (92.3%) of 117 cycles in group A and 93 (86.9%) of 107 cycles in Group B (P=0.184).
  
  
  CONCLUSIONS
  Combined treatment with letrozole, metformin, and pioglitazone was efficacious among women with PCOS resistant to clomifene citrate. ClinicalTrials.gov: NCT01909141.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt. Electronic address: waleed_elkhyat@yahoo.com.
authors.forename: Waleed
authors.initials: W
authors.lastname: El-khayat
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Ghada
authors.initials: G
authors.lastname: Abdel Moety
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Maged
authors.initials: M
authors.lastname: Al Mohammady
authors.affiliation: Department of Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Dalia
authors.initials: D
authors.lastname: Hamed
mesh_terms: D000328:Adult; D002996:Clomiphene / Q000008:administration & dosage*; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004534:Egypt; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology; D057194:Intention to Treat Analysis; D000077289:Letrozole; D008687:Metformin / Q000008:administration & dosage*; D009570:Nitriles / Q000008:administration & dosage*; D010060:Ovulation / Q000187:drug effects; D010062:Ovulation Induction / Q000379:methods; D000077205:Pioglitazone; D011085:Polycystic Ovary Syndrome / Q000150:complications*; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D005300:Fertility Agents, Female; D009570:Nitriles; D045162:Thiazolidinediones; D014230:Triazoles; D002996:Clomiphene; D000077289:Letrozole; D008687:Metformin; D000077205:Pioglitazone
keywords: Clomifene citrate; Clomifene citrate resistance; Letrozole; Metformin; Pioglitazone; Polycystic ovary syndrome