The benefit of individualized low-dose human chorionic gonadotropin support for high responders in gonadotropin-releasing hormone agonist-triggered in-vitro fertilization/intracytoplasmic sperm injection cycles

Ovarian hyperstimulation syndrome (OHSS) is one of the major complications in artificial reproductive technology, especially in high responders. Exogenous human chorionic gonadotropin (hCG) for triggering final oocyte maturation during controlled ovarian stimulation (COS) is primarily responsible for the pathogenesis of early-onset OHSS. Several strategies were offered to prevent OHSS, including reducing the gonadotropin dose, individualizing in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment protocols, using adjuvant metformin therapy, and further considering alternatives for triggering ovulation, coasting, cryopreservation of embryos, avoiding hCG for luteal phase support (LPS), cryopreservation of embryos, albumin infusion, cabergoline administration, and others. Recently, gonadotropin-releasing hormone agonist (GnRHa) used to induce final oocyte maturation and ovulation presented an alternative to hCG to effectively reduce OHSS risk in COS. The Cochrane Review revealed that GnRHa trigger was associated with a lower incidence of OHSS than was hCG [odds ratio (OR) 0.15, 95%, confidence interval (CI) 0.05e0.47]. However, the critical disadvantage of GnRHa trigger is early luteolysis and consequently luteal phase insufficiency, resulting in impaired endometrial receptivity and worse conception rates. The Cochrane Review indicated that GnRHa trigger was associated with a lower ongoing pregnancy rate (OR 0.70, 95% CI 0.54e0.91) and a higher early miscarriage rate (OR 1.74, 95% CI 1.10e2.75) than was seen with hCG. To improve reproductive outcomes in GnRHa trigger protocol, some strategies of modified LPS were suggested as follows: (1) intensive LPS with aggressive exogenous administration of estradiol (E2) and progesterone (P); (2) dual trigger with both GnRHa and low-dose hCG; and (3) hCG rescue after oocyte retrieval. All approaches have been shown to be effective in generating pregnancy rates similar to conventional hCG trigger and leading to a very low OHSS risk. However, combined modified LPS in GnRHa trigger protocol seems to be popular in Taiwan.