title: Factors associated with nonresponse to ovulation induction using letrozole among women with World Health Organization group II anovulation.
abstract: BACKGROUND
  Letrozole, a third generation aromatase inhibitor is gaining importance in ovulation induction. Some prefer to use it as a second line agent in women who fail to respond to clomifene citrate. However, our knowledge about the predictors of response to letrozole is limited.
  
  
  OBJECTIVE
  The study was aimed at identifying the factors associated with letrozole resistance among women with World Health Organization (WHO) group II anovulation.
  
  
  METHODS
  Study was conducted at the infertility clinic at a tertiary care hospital in Sri Lanka. A case-control study design was used and included 50 subjects with WHO group II anovulation (25 clomifene responsive and 25 clomifene resistant). After a treatment cycle of letrozole, the factors were compared between the subjects who responded and those who failed to respond to treatment.
  
  
  RESULTS
  Ovulation was achieved in 76% (n = 19) of subjects who had responded to clomifene previously and in 24% (n = 6) with clomifene resistance. The factors associated with letrozole resistance included the presence of hirsutism (odds ratio [OR]: 3.89; 95% confidence interval [CI]: 1.2-12.3) and clomifene resistance (OR: 10.03; 95% CI: 2.81-35.7). The early follicular phase mean (standard deviation) luteinizing hormone level was significantly higher among the nonresponders (9.75 [4.78] - 7.28 [2.3]; P = 0.02). Nonresponders showed significantly lower levels of oestradiol on the 5(th) and 9(th) days (28.50 [3.39] pg/mL vs. 7.49 [3.62] pg/mL; P = 0.0007 and 142.04 [76.22] pg/mL vs. 28.10 [12.8] pg/mL; P = 0.0001) of the menstrual cycle, respectively.
  
  
  CONCLUSIONS
  The features associated with resistance to Letrozole at a dose of 2.5 mg show some overlap with those associated with clomifene resistance. However, some features do not show similar association. The effectiveness of letrozole at a dose of 2.5 mg in induction of ovulation among women with clomifene resistance is low and it does not seem to be a suitable treatment at a dose of 2.5 mg for this indication.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Kelaniya, Kelaniya, Sri Lanka.
authors.forename: Thilina Sanjeewa
authors.initials: TS
authors.lastname: Palihawadana
authors.affiliation: Department of Obstetrics and Gynaecology, University of Kelaniya, Kelaniya, Sri Lanka.
authors.forename: Prasantha Sudehana
authors.initials: PS
authors.lastname: Wijesinghe
authors.affiliation: Vindana Reproductive Health Centre, Colombo, Sri Lanka.
authors.forename: Harshalal Rukka
authors.initials: HR
authors.lastname: Seneviratne
keywords: Anovulation; clomifene resistance; letrozole; letrozole resistance