title: Antagonist protocol versus clomiphene in unexplained infertility: A randomized controlled study.
abstract: OBJECTIVE
  The primary purpose of this randomized controlled trial study was to compare clinical pregnancy rates and ovulation parameters in female patients of unexplained infertility undergoing intrauterine insemination (IUI) using an antagonist protocol versus a conventional clomiphene citrate protocol.
  
  
  METHODS
  This was a multicenter parallel randomized controlled, open-label trial. A central randomization center used computer generated tables to allocate treatments. We conducted the study in two centers: Saudi Center and Samir Abbas and Assisted Reproductive Techniques Center of Cairo University, Cairo, Egypt between January 2011 and January 2014. Six hundred and twenty-two couples with unexplained infertility were randomized into two equal groups with 27 excluded after randomization: the antagonist protocol group and the clomiphene group. Antagonist protocol: human menopausal gonadotropins were given to 298 patients from Day 2 to reach a dominant follicle of 18-22 mm, intramuscularly. Then, orgalutrone (0.25 mg) was subcutaneously started from Day 6 or Day 7 until the day of human chorionic gonadotropins (hCG; that was given in the dose of 10,000 IU, intramuscularly) when follicles reached 18-22 mm. Afterward, the IUI of 0.5 mL was done from 34 hours to 36 hours using IUI catheter without guidance of ultrasonography and with an empty urinary bladder. The clomiphene citrate protocol was clomiphene citrate given 100 mg/d to 297 patients from Day 2 to Day 6 and follow up until day of hCG. The clinical pregnancy rate detected with ultrasound confirmed fetal heart pulsations at 6-weeks' gestation (4 weeks after IUI). The number of dominant follicles, level of serum estradiol, and luteinizing hormone at the day of hCG injection and the incidence of twin or triplet pregnancies in both groups were secondary outcome measures.
  
  
  RESULTS
  The clinical pregnancy rate in the antagonist protocol group was significantly (p < 0.001) higher than in the clomiphene group. It was 80 patients (27%) in the antagonist protocol group versus 41 patients (14%) in the clomiphene group. The mean number of dominant follicles was significantly (p < 0.001) greater in the antagonist protocol group (4.36 ± 1.36 dominant follicles) compared with the clomiphene group (2.71 ± 0.96 dominant follicles). In addition, the rate of twin pregnancies was 15 cases in the antagonist protocol group versus six cases only in the clomiphene group (p = 0.047). The luteinizing hormone also was significantly lower in the antagonist group (2.1 ± 1.3) compared with that in the clomiphene group (9.5 ± 3.6).
  
  
  CONCLUSIONS
  IUI clinical pregnancy rates were significantly higher by antagonist protocol.
authors.affiliation: Faculty of Medicine, Department of Gynecology and Obstetrics, Cairo University, Cairo, Egypt.
authors.forename: Adel M
authors.initials: AM
authors.lastname: Nada
authors.affiliation: Faculty of Medicine, Department of Gynecology and Obstetrics, Cairo University, Cairo, Egypt. Electronic address: kelsetohy@gmail.com.
authors.forename: Khaled A
authors.initials: KA
authors.lastname: ElSetohy
authors.affiliation: Monash University, Melbourne, Australia.
authors.forename: Moh'd M
authors.initials: MM
authors.lastname: Banat
authors.affiliation: Faculty of Medicine, Department of Andrology, Beni Suef University, Egypt.
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Shaheen
mesh_terms: D000328:Adult; D002996:Clomiphene / Q000008:administration & dosage*; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006727:Hormone Antagonists / Q000008:administration & dosage*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy*; D007315:Insemination, Artificial; D007986:Luteinizing Hormone / Q000097:blood; D008596:Menotropins / Q000008:administration & dosage*; D006080:Ovarian Follicle / Q000187:drug effects; D011247:Pregnancy; D018873:Pregnancy Rate; D059285:Pregnancy, Twin / Q000187:drug effects; D055815:Young Adult
chemical_list: D005300:Fertility Agents, Female; D006727:Hormone Antagonists; D002996:Clomiphene; D007987:Gonadotropin-Releasing Hormone; D008596:Menotropins; D007986:Luteinizing Hormone; C061018:ganirelix
keywords: IUI; LH; antagonist protocol; clinical pregnancy rate; dominant follicles