title: Effects of Letrozole-HMG and Clomiphene-HMG on Incidence of Luteinized Unruptured Follicle Syndrome in Infertile Women Undergoing Induction Ovulation and Intrauterine Insemination: A Randomised Trial.
abstract: BACKGROUND
  Luteinized unruptured follicle (LUF) syndrome is considered a cause of ovulation failure and a subtle cause of infertility. Preovulatory injection of human chorionic gonadotropin (HCG) prevents or treats LUF syndrome, but it has also occurred after the induction of ovulation with clomiphene/HMG and HCG. This study was designed for evaluation and comparison of LUF incidence in eligible infertile women undergoing two stimulation protocols (clomiphene + HMG and letrozole + HMG) in addition to intrauterine insemination (IUI). Some related factors were compared between LUF and non-LUF cycles as secondary outcomes.
  
  
  METHODS
  The study was designed as a prospective randomized controlled trial. Patients were randomized using a table of random numbers into two equal protocol groups. For group A, (n = 90) clomiphene citrate was administrated orally in doses of 100 mg/day, and group B (n = 90) orally received letrozole 5 mg/day from day 3 to 7 of the menstrual cycle. Then HMG 75IU/day was administered intramuscularly in both groups on day 8 of the menstrual cycle and the dose was adjusted on the basis of ovarian response. The optimum size of preovulatory follicles for the injection of HCG (10,000 IU) was considered 18-23 mm. The number and size of preovulatory follicles were assessed by vaginal ultrasound 12 h before HCG (D0). Endometrial thickness was measured as well. IUI was performed on all patients 38-40 h after HCG. The second ultrasound examination was performed to observe the evidence of oocyte releasing at the time of IUI (D1). If the follicles were unruptured, a third sonography was performed on day 7 after HCG (D7) to observe LUF syndrome.
  
  
  RESULTS
  There was a significant difference between clomiphene-HMG and letrozole-HMG in LUF (p = 0.021) and pregnancy (p = 0.041). The complete LUF in letrozole-HMG was lower than the alternative group and the pregnancy rate was higher. The patients in the non-LUF group had higher midluteal progesterone and a thicker endometrium compared to LUF cycles (p = 0.039) and (p < 0.001). The results of our multivariate logistic regression indicate that size 18-19.9 mm leads to the complete LUF  less than ≥22 mm [AOR: 0.25, P = 0.005], and  in size 20- 21.9 mm  as well [AOR: 0.17, P = 0.002].
  
  
  CONCLUSIONS
  Letrozole, with lower incidences of LUF, is more effective than clomiphene citrate for the induction of ovulation in IUI cycles. In our study, we illustrated that larger follicles of ≥22 mm diameter were associated with higher incidences of LUF. We recommend that further studies investigate and focus on the relationship between follicular size and/or full hormonal profiles and LUF.
authors.affiliation: Department of Reproduction & Infertility, Mirza-kouchak Khan women Hospital, Tehran University of Medical Sciences, Tehran, Iran. Azmoodeh@yahoo.com.
authors.forename: Azra
authors.initials: A
authors.lastname: Azmoodeh
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Pejman Manesh
authors.forename: Firouzeh
authors.initials: F
authors.lastname: Akbari Asbagh
authors.forename: Azizeh
authors.initials: A
authors.lastname: Ghaseminejad
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Hamzehgardeshi
mesh_terms: D000328:Adult; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D002996:Clomiphene / Q000008:administration & dosage*; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage*; D005498:Follicular Phase / Q000187:drug effects*; D006801:Humans; D007247:Infertility, Female / Q000628:therapy*; D007315:Insemination, Artificial / Q000379:methods*; D000077289:Letrozole; D007986:Luteinizing Hormone / Q000378:metabolism*; D009570:Nitriles / Q000008:administration & dosage*; D006080:Ovarian Follicle / Q000187:drug effects*; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D011446:Prospective Studies; D013577:Syndrome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D047072:Aromatase Inhibitors; D005300:Fertility Agents, Female; D009570:Nitriles; D014230:Triazoles; D002996:Clomiphene; D000077289:Letrozole; D007986:Luteinizing Hormone