A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T)

Fertil Steril. 2014 Jun;101(6):1574-81.e1-2. doi: 10.1016/j.fertnstert.2014.03.012. Epub 2014 Apr 30.


Objective: To determine the optimal infertility therapy for women at the end of their reproductive potential.

Design: Randomized clinical trial.

Setting: Academic medical centers and private infertility center in a state with mandated insurance coverage.

Patient(s): Couples with ≥ 6 months of unexplained infertility; female partner aged 38-42 years.

Intervention(s): Randomized to treatment with two cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant.

Main outcome measure(s): Proportion with a clinically recognized pregnancy, number of treatment cycles, and time to conception after two treatment cycles and at the end of treatment.

Result(s): We randomized 154 couples to receive CC/IUI (N = 51), FSH/IUI (N = 52), or immediate IVF (N = 51); 140 (90.9%) couples initiated treatment. The cumulative clinical pregnancy rates per couple after the first two cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatments, 110 (71.4%) of 154 couples had conceived a clinically recognized pregnancy, and 46.1% had delivered at least one live-born baby; 84.2% of all live-born infants resulting from treatment were achieved via IVF. There were 36% fewer treatment cycles in the IVF arm compared with either COH/IUI arm, and the couples conceived a pregnancy leading to a live birth after fewer treatment cycles.

Conclusion(s): A randomized controlled trial in older women with unexplained infertility to compare treatment initiated with two cycles of controlled ovarian hyperstimulation/IUI versus immediate IVF demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group.

Clinical trial registration number: NCT00246506.

Keywords: Advanced reproductive age; FORT-T Trial; clomiphene citrate; controlled ovarian hyperstimulation; follicle-stimulating hormone; intrauterine insemination (IUI); in vitro fertilization; unexplained infertility.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Boston
  • Clomiphene / administration & dosage
  • Combined Modality Therapy
  • Drug Administration Schedule
  • Female
  • Fertility Agents, Female / administration & dosage
  • Fertility*
  • Fertilization in Vitro
  • Follicle Stimulating Hormone / administration & dosage
  • Humans
  • Infertility, Female / diagnosis
  • Infertility, Female / physiopathology
  • Infertility, Female / therapy*
  • Infertility, Male / diagnosis
  • Infertility, Male / physiopathology
  • Infertility, Male / therapy*
  • Insemination, Artificial
  • Live Birth
  • Male
  • Middle Aged
  • Patient Selection
  • Pregnancy
  • Pregnancy Rate
  • Reproductive Techniques, Assisted*
  • Risk Factors
  • Time Factors
  • Time-to-Pregnancy
  • Treatment Outcome


  • Fertility Agents, Female
  • Clomiphene
  • Follicle Stimulating Hormone

Associated data

  • ClinicalTrials.gov/NCT00246506