Ovarian Hyperstimulation Syndrome Prevention Strategies: Reducing the Human Chorionic Gonadotropin Trigger Dose

Abstract

This article reviews the biological plausibility and evidence for the use of a low triggering dose of human chorionic gonadotropin (hCG) in the prevention of ovarian hyperstimulation syndrome (OHSS). A systematic search of the literature revealed very little published data for or against the use of low-dose hCG in the prevention of OHSS after assisted reproductive technology. We have had success at avoiding OHSS as a result of gentle stimulation and low-dose sliding scale hCG trigger based on estradiol (E₂) levels. We therefore present the biological plausibility for such an approach by reviewing the relationship between OHSS, vascular endothelial growth factor, and hCG; the physiology of hCG; the relationship between risk of OHSS and E₂ at trigger; and the physiology of alternative methods of triggering such as recombinant luteinizing hormone and gonadotropin-releasing hormone agonist. We also present the results of a quasi-experimental before and after study of the sliding scale protocol for hCG trigger dose in in vitro fertilization with or without intracytoplasmic sperm injection cycles.

Sliding scale HCG trigger yields equivalent pregnancy outcomes and reduces ovarian hyperstimulation syndrome: Analysis of 10,427 IVF-ICSI cycles

“…The potential impact of lowering hCG trigger doses was supported by Kashyap et al, who reported on their incidence of OHSS in 2,625 cases prior to and after instituting a similar hCG sliding scale to the one described here. Specifically, they reported a reduction of early and severe OHSS by factors of 7 and 4 respectively, solely as a result of lowering the hCG dose according to E2 levels at trigger [1]. …”

“…While minimizing the risk of OHSS remains a perennial challenge of ART even in the era of the GnRH agonist trigger, modifiable risk factors associated with the development of OHSS include the rate of estradiol (E2) rise, the maximal E2 level reached, and number of small and intermediate size follicles on the day of trigger. [1]. While attentiveness to these risk factors will not eliminate OHSS altogether, they may minimize its incidence.…”

The Difficult In Vitro Fertilization Patient: An Individualized Approach

“…16 Since 2004, we have used a sliding scale for hCG administration (see ►Table 1 for dosing scheme), with some adjustment according to patient BMI (we find that 3,300 IU of hCG is typically not sufficient for patients with elevated BMI; a serum β-hCG level of less than 50 mIU/mL on the day after the trigger is associated with a lower percentage of mature oocytes and poorer IVF outcomes [unpublished data]). 17 Increasingly, in antagonist cycles we have moved away from dosing 3,300 IU and instead prefer to administer a GnRH agonist trigger (leuprolide acetate 2 mg) either alone or in conjunction with a very low hCG dose (1,500 IU); hCG is not given specifically for luteal support, but rather as a backup trigger if an appropriate LH surge does not occur in response to the GnRH agonist. In our experience, risk factors for nonresponse to GnRH agonist trigger, outside from a known history of hypothalamic dysfunction, are long-term use of OCPs and a trigger-day LH level of less than 0.5 mIU/mL.…”

In vitro fertilization for Orthodox Jewish couples: antagonist cycle modifications allowing for mikveh attendance before oocyte retrieval

“…Human chorionic gonadotropin (Profasi, EMD-Serono; Novarel, Ferring Pharmaceuticals; or Pregnyl, Schering-Plough) was administered when at least two follicles had attained a mean diameter of 17 mm, according to a flexible hCG-dosing regimen previously described elsewhere (10). Alternatively, in patients with E 2 >3,000 pg/mL, a 2 mg subcutaneous GnRH-agonist trigger was administered.…”