Low dose clomiphene citrate as a mild stimulation protocol in women with unsuspected poor in vitro fertilization result can generate more oocytes with optimal cumulative pregnancy rate

J Ovarian Res. 2018 May 4;11(1):37. doi: 10.1186/s13048-018-0408-x.


Background: The use of long protocol during controlled ovarian stimulation for assisted reproduction attracts high dosage of gonadotropins. High dose of gonadotropins can be detrimental to oocyte development, which affects its quality and compromises the treatment outcome. Mild stimulation protocols that attract low dose gonadotropins could be useful alternative regimen to address such problems. This study evaluated the efficacy of low dose clomiphene citrate based protocol plus low dose gonadotropins on predicted normal responder patients who had unsuspected poor in vitro fertilization (IVF) result, following an initial stimulation with long gonadotropin-releasing hormone (GnRH) agonist protocol.

Methods: This a retrospective study of 65 infertile women who underwent 130 cycles in our center from January 2011 to December 2014. The initial IVF cycle (Group 1) was treated with long GnRH-a protocol plus a high dose of gonadotropins (≥150 IU/d), while second IVF cycle (Group 2) had low dose clomiphene citrate based protocol plus low dose gonadotropins (75-112.5 IU/d).

Results: The rate of cumulative pregnancy/started cycle (9.2% [6/65] vs. 51% [33/65]; P < 0001) was significantly better in CC protocol than the long GnRH agonist protocol. The number of oocytes retrieved was also higher in CC protocol compared to the long protocol (7.26 ± 1.95 vs. 5.98 ± 1.31; P = 0.03). There was a lower number of patients without embryos (12.31% vs. 33.85%; p < 0.0001) in CC protocol than long protocol.

Conclusions: This study showed a better cumulative pregnancy rate in the low dose CC based protocol. There was a higher number of oocytes retrieved after using a lower total dose of recombinant FSH in CC protocol. Thus, clomiphene treatment plus low dose rFSH can be an alternative option for such patients in second cycle stimulation instead of repeating long protocol regimen. Randomized controlled studies with larger number of patients will be needed for more accurate evidence.

Keywords: Clomiphene citrate; Long GnRH-a protocol; Mild ovarian stimulation; Unsuspected poor IVF results.

MeSH terms

  • Adult
  • Clomiphene / administration & dosage*
  • Female
  • Fertility Agents, Female / administration & dosage
  • Fertilization in Vitro*
  • Follicle Stimulating Hormone / administration & dosage
  • Gonadotropin-Releasing Hormone / agonists
  • Gonadotropins / administration & dosage
  • Humans
  • Infertility, Female / drug therapy*
  • Infertility, Female / pathology
  • Live Birth
  • Oocytes / drug effects
  • Oocytes / growth & development
  • Ovarian Hyperstimulation Syndrome / drug therapy*
  • Ovulation Induction / methods
  • Pregnancy
  • Pregnancy Rate
  • Sperm Injections, Intracytoplasmic / methods


  • Fertility Agents, Female
  • Gonadotropins
  • Clomiphene
  • Gonadotropin-Releasing Hormone
  • Follicle Stimulating Hormone