title: Minimum ovarian stimulation involving combined clomiphene citrate and estradiol treatment for in vitro fertilization of Bologna-criteria poor ovarian responders.
abstract: OBJECTIVE
  The aim of this study was to assess the efficacy of a minimal ovarian stimulation involving combined clomiphene citrate (CC) and estradiol (E2) administration for poor responders with diminished ovarian reserve (DOR).
  
  
  METHODS
  In this case-control study, we recruited 41 consecutive hypergonadotropic poor responders (69 cycles) who met Bologna-criteria and had experienced cancellation of oocyte retrieval. In 10 (20 cycles), 11 (21 cycles) and 20 patients (28 cycles) between 2012 and 2014, follicular development was induced using an E2 cycle, CC cycle and CC + E2 cycle, respectively. After confirmation of high follicle-stimulating hormone levels (15-40 mIU/ml) at menstrual day 3, DOR patients were treated with oral E2 of 1.0 mg/day, CC of 100 mg/day, or both CC and E2 continuously, until ovulation induction. Two days later, we transvaginally aspirated the follicles, performed in vitro fertilization, and cryopreserved the cleavage embryos. One warmed embryo was transferred into the uterus during the hormone replacement cycles.
  
  
  RESULTS
  For the E2, CC, and CC + E2 cycles, the median patient age was 41 years in all groups, and the serum anti-Müllerian hormone levels were 0.2 ± 0.3, 0.4 ± 0.4, and 0.2 ± 0.3 ng/mL, respectively (P = 0.258); follicular development failure rates were 50.0%, 19.0%, and 3.6%, respectively (P < 0.001); numbers of retrieved oocytes (/cycle) were 0.5 ± 0.6, 0.8 ± 0.7, and 1.2 ± 1.1, respectively (P = 0.033); and clinical pregnancy rates (/cycle) were 5.0%, 4.8%, and 10.7%, respectively (P = 0.725).
  
  
  CONCLUSIONS
  CC + E2 administration for the patients with DOR was effective with a lower cancellation rate of oocyte retrieval and a higher number of retrieved oocytes.
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Kuroda
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Kitade
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kumakiri
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Jinushi
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Shinjo
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Ozaki
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ikemoto
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Katoh
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000328:Adult; D002996:Clomiphene / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004624:Embryo Transfer; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy*; D008875:Middle Aged; D054315:Oocyte Retrieval; D009865:Oocytes / Q000187:drug effects; D065851:Ovarian Reserve; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy
chemical_list: D002996:Clomiphene; D004958:Estradiol
keywords: clomiphene citrate; diminished ovarian reserve; estrogen replacement; in vitro fertilization; minimal ovarian stimulation