Subcutaneous progesterone versus vaginal progesterone gel for luteal phase support in in vitro fertilization: a noninferiority randomized controlled study

Fertil Steril. 2014 Jan;101(1):112-119.e3. doi: 10.1016/j.fertnstert.2013.09.010. Epub 2013 Oct 17.


Objective: To compare the safety, efficacy, and tolerability of subcutaneous progesterone (Prolutex, 25 mg; IBSA Institut Biochimique SA) with vaginal progesterone gel (Crinone, 8%; Merck Serono) for luteal phase support (LPS) in assisted reproduction technologies (ART) patients.

Design: Prospective, open-label, randomized, controlled, parallel-group, multicenter, two-arm, noninferiority study.

Setting: Thirteen European fertility clinics.

Patient(s): A total of 683 ART patients randomized to two groups: Prolutex, 25 mg subcutaneously daily (n = 339); and Crinone, 90 mg 8% gel daily (n = 344).

Intervention(s): In vitro fertilization and embryo transfer were performed according to site-specific protocols. On the day of oocyte retrieval, Prolutex or Crinone gel was begun for LPS and continued for up to 10 weeks.

Main outcome measure(s): Ongoing pregnancy rate.

Result(s): The primary end point, ongoing pregnancy rates at 10 weeks of treatment were 27.4% and 30.5% in the Prolutex and Crinone groups, respectively (intention to treat [ITT]). The nonsignificant difference between the groups was -3.09% (95% confidence interval [CI] -9.91-3.73), indicating noninferiority of Prolutex to Crinone. Delivery and live birth rates resulted to be equivalent between the two treatments (26.8% vs. 29.9% in the Prolutex and Crinone groups, respectively [ITT]; difference -3.10 [95% CI -9.87-3.68]). No statistically significant differences were reported for any of the other secondary efficacy endpoints, including comfort of usage and overall satisfaction.

Conclusion(s): Implantation rate, pregnancy rate, live birth rate, and early miscarriage rate for Prolutex were similar to those for Crinone. The adverse event profiles were similar and Prolutex was safe and well tolerated.

Clinical trial registration number: NCT00827983.

Keywords: Luteal phase support; intracytoplasmic sperm injection; in vitro fertilization; pregnancy; progesterone.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Adult
  • Female
  • Fertilization in Vitro / methods*
  • Gels
  • Humans
  • Infertility, Female / epidemiology
  • Infertility, Female / metabolism
  • Infertility, Female / therapy*
  • Injections, Subcutaneous
  • Live Birth / epidemiology
  • Luteal Phase / drug effects*
  • Luteal Phase / metabolism
  • Pregnancy
  • Progesterone / administration & dosage*
  • Treatment Outcome


  • Gels
  • Progesterone

Associated data