title: Pregnancy and neonatal outcomes following letrozole use in frozen-thawed single embryo transfer cycles.
abstract: Are pregnancy and neonatal outcomes following letrozole use comparable with natural and HRT cycles in patients undergoing single frozen-thawed embryo transfer (FET)?
  
  
  
  Letrozole use was significantly associated with higher rates of clinical pregnancy, clinical pregnancy with fetal heart beat and live birth, and with a lower rate of miscarriage, compared with natural and HRT cycles.
  
  
  
  Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART. However, the effect of letrozole on pregnancy and neonatal outcomes in FET are not well known.
  
  
  
  A retrospective cohort study was conducted using data from the Japanese national ART registry between 2012 and 2013.
  
  
  
  A total of 110 722 single FET cycles with letrozole (n = 2409), natural (n = 41 470) or HRT cycles (n = 66 843) were included. The main outcomes were the rates of clinical pregnancy, clinical pregnancy with fetal heart beat, miscarriage and live birth. Adjusted odds ratios and relative risks (RRs) were calculated using a generalized estimating equation adjusting for correlations within clinics.
  
  
  
  The rates of clinical pregnancy, clinical pregnancy with fetal heart beat, and live birth were significantly higher, while the rate of miscarriage was significantly lower in the letrozole group compared with the natural and HRT groups. In blastocyst stage transfers, the adjusted RRs for clinical pregnancy with fetal heart beat of letrozole compared with natural and HRT cycles were 1.48 (95% CI: 1.41-1.55) and 1.62 (95% CI: 1.54-1.70), respectively. Similarly, the adjusted RRs of letrozole for miscarriage compared with natural and HRT cycles were 0.91 (95% CI: 0.88-0.93) and 0.84 (95% CI: 0.82-0.87), respectively. Neonatal outcomes were mostly similar in letrozole, natural and HRT cycles.
  
  
  
  Important limitations of this study included the lack of information concerning the reasons for selecting the specific FET method, parity, the number of previous ART failures, embryo quality and the dose and duration of letrozole intake.
  
  
  
  These results suggest that letrozole use may improve clinical pregnancy, clinical pregnancy with fetal heart beat, and live births and reduce the risk of miscarriage in patients undergoing single FET cycles.
  
  
  
  No external funding was used for this study. There are no conflicts of interest.
  
  
  
  Not applicable.
authors.affiliation: Division of Reproductive Medicine, Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo 157-8535, Japan.|Comprehensive Reproductive Medicine, Regulation of Internal Environment and Reproduction, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-0034, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tatsumi
authors.affiliation: Division of Reproductive Medicine, Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo 157-8535, Japan.|Sora no Mori Clinic, 229-1, Yagibaru, Yaese-cho, Shimajiri-gun, Okinawa 901-0406, Japan.
authors.forename: S C
authors.initials: SC
authors.lastname: Jwa
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of Tokushima, 3-18-15, Kuramoto-chou, Tokushima-shi, Tokushima 770-8503, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kuwahara
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of Tokushima, 3-18-15, Kuramoto-chou, Tokushima-shi, Tokushima 770-8503, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Irahara
authors.affiliation: Comprehensive Reproductive Medicine, Regulation of Internal Environment and Reproduction, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-0034, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Division of Reproductive Medicine, Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo 157-8535, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D000022:Abortion, Spontaneous / Q000453:epidemiology / Q000517:prevention & control*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001755:Blastocyst; D015331:Cohort Studies; D015925:Cryopreservation; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007231:Infant, Newborn; D007247:Infertility, Female / Q000628:therapy*; D007564:Japan / Q000453:epidemiology; D000077289:Letrozole; D050498:Live Birth; D008297:Male; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010062:Ovulation Induction / Q000009:adverse effects; D011247:Pregnancy; D018873:Pregnancy Rate; D012042:Registries; D012189:Retrospective Studies; D012306:Risk; D056826:Single Embryo Transfer / Q000009:adverse effects; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D005300:Fertility Agents, Female; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole
keywords: hormone replacement therapy; letrozole; natural cycle; neonatal outcome; pregnancy outcome