GnRH antagonist administered twice the day before hCG trigger combined with a step-down protocol may prevent OHSS in IVF/ICSI antagonist cycles at risk for OHSS without affecting the reproductive outcomes: a prospective randomized control trial

J Assist Reprod Genet. 2017 Nov;34(11):1537-1545. doi: 10.1007/s10815-017-1010-7. Epub 2017 Aug 3.

Abstract

Purpose: The purpose this study is to investigate whether a double antagonist dose (0.25 mg/12 h) administered the day before hCG trigger is effective in preventing ovarian hyperstimulation syndrome (OHSS) in GnRH antagonist IVF/intracytoplasmic sperm injection (ICSI) cycles at risk for OHSS.

Methods: This is a prospective randomized control study, conducted from November 2012 to January 2016. A total of 194 patients undergoing a IVF/ICSI GnRH antagonist cycle that were at risk of OHSS and chose to proceed with embryo transfer and avoid cycle cancellation or embryo cryopreservation were allocated into two groups. The inclusion criteria consisted of a rapid rise of oestradiol ≥ 3500 pg/ml combined with ≥ 18 follicles > 11 mm in diameter without any mature follicle > 16 mm, in any day of stimulation. Overall, 97 patients (intervention group A) received a double dose of GnRH antagonist (0.25 mg/12 h) the day before hCG while 97 patients (control group B) did not. Recombinant FSH administration was tapered to 100 IU/24 h the day of the allocation in both groups.

Results: Incidence of early-onset moderate/severe OHSS was significantly lower in intervention group A compared to control group B (0 vs 12.37%, P < 0.001). Clinical pregnancy rate per cycle (50.52 vs 42.27%, P = 0.249) was not significantly different between the two groups. Oestradiol (3263.471 ± 1271.53 vs 5233 ± 1425.17, P < 0.001), progesterone (0.93 ± 0.12 vs 1.29 ± 0.14, P < 0.001) and luteinizing hormone (1.42 ± 0.31 vs 1.91 ± 0.33, P < 0.001) were significantly lower in group A the day of the hCG triggering.

Conclusion: The administration of a rescue double GnRH antagonist dose the day before hCG trigger may represent a safe alternative preventive strategy for early OHSS without affecting the reproductive outcomes.

Trial registration number: ISRCTN02750360.

Keywords: GnRH antagonists; IVF-ICSI; Implantation; OHSS; Ovarian stimulation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Chorionic Gonadotropin / administration & dosage*
  • Embryo Implantation / drug effects
  • Embryo Transfer / methods
  • Estradiol / administration & dosage
  • Female
  • Fertilization in Vitro / methods*
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors*
  • Hormone Antagonists / administration & dosage*
  • Humans
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / growth & development
  • Ovarian Hyperstimulation Syndrome / drug therapy
  • Ovarian Hyperstimulation Syndrome / pathology
  • Ovarian Hyperstimulation Syndrome / prevention & control*
  • Ovulation Induction / methods
  • Pregnancy
  • Pregnancy Rate
  • Sperm Injections, Intracytoplasmic / methods

Substances

  • Chorionic Gonadotropin
  • Hormone Antagonists
  • Gonadotropin-Releasing Hormone
  • Estradiol