The role of Letrozole (LE) in controlled ovarian stimulation (COS) in patients at high risk to develop ovarian hyper stimulation syndrome (OHSS). A prospective randomized controlled pilot study

J Gynecol Obstet Hum Reprod. 2020 Feb;49(2):101643. doi: 10.1016/j.jogoh.2019.101643. Epub 2019 Sep 26.

Abstract

Background: Recently, it has been shown that PCOS patients with extremely high anti-Mullerian hormone (AMH) level are more likely to experience OHSS during IVF, compared to PCOS patients with lower AMH level. While recent data questioned the effect of Letrozole (LE) on the occurrence of OHSS in non-PCOS patients, it role in PCOS patients with very high AMH level was never investigated in a prospective manners. Hence, our main objective was to evaluate the clinical outcome of PCOS patients at very high risk for OHSS undergoing two different COS protocols (with or without LE).

Methods: A prospective randomized controlled study (RCT) of 51 patients with specifically high levels of AMH undergoing one of two COS protocols. The control group (group A) consisted of 24 PCOS women who received low-dose gonadotropins using the multiple-dose GnRH-antagonist protocol, GnRH agonist-triggered and "freeze all". The study group (group B) consisted of 24 women with PCOS who received the same protocol combined with LE. High risk criteria for OHSS were: PCOS patients with low BMI, young age, and extremely high level of serum AMH (inclusion criteria for AMH > 50 pmol/L).

Results: Cumulative live birth rates per retrieval were similar in both groups. While no single case of severe OHSS was observed in, in the study group (group B), the rate of moderate and mild OHSS was 5 times lower compared to the control group (P < 0.05).

Conclusion: In PCOS patients with extremely high AMH levels the LE co-administration to GnRH-Ant protocols results in reduced incidence of OHSS than conventional GnRH-Ant protocols. LE co-administration may prove to be highly effective in preventing OHSS, even in the women who are at high risk to these dangerous complications.

Keywords: AMH; IVF; Letrozole; OHSS; PCOS.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Mullerian Hormone / blood
  • Aromatase Inhibitors / therapeutic use*
  • Female
  • Fertilization in Vitro*
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Humans
  • Infertility, Female / etiology
  • Infertility, Female / therapy
  • Letrozole / therapeutic use*
  • Ovarian Hyperstimulation Syndrome / epidemiology
  • Ovarian Hyperstimulation Syndrome / etiology
  • Ovarian Hyperstimulation Syndrome / prevention & control*
  • Ovulation Induction / methods*
  • Pilot Projects
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / complications
  • Prospective Studies
  • Risk Assessment
  • Young Adult

Substances

  • Aromatase Inhibitors
  • Gonadotropin-Releasing Hormone
  • Letrozole
  • Anti-Mullerian Hormone