Abstract

The segmentation of the in vitro fertilization (IVF) cycle, consisting of the freezing of all embryos and the postponement of embryo transfer (ET), has become popular in recent years, with the main purpose of preventing ovarian hyperstimulation syndrome (OHSS) in patients with high response to controlled ovarian stimulation (COS). Indeed cycle segmentation (CS), especially when coupled to a GnRH-agonist trigger, was shown to reduce the incidence of OHSS in high-risk patients. However, CS increases the economic costs and the work amount for IVF laboratories. An alternative strategy is to perform a fresh ET in association with intensive luteal phase pharmacological support, able to overcome the negative effects of the GnRH-agonist trigger on the luteal phase and on endometrial receptivity. In order to compare these two strategies, we performed a retrospective, real-life cohort study including 240 non-polycystic ovarian syndrome (PCO) women with expected high responsiveness to COS (AMH >2.5 ng/mL), who received either fresh ET plus 100 IU daily human chorionic gonadotropin (hCG) as luteal support (FRESH group, n = 133), or cycle segmentation with freezing of all embryos and postponed ET (CS group, n = 107). The primary outcomes were: implantation rate (IR), live birth rate (LBR) after the first ET, and incidence of OHSS. Overall, significantly higher IR and LBR were observed in the CS group than in the FRESH group (42.9% vs. 27.8%, p < 0.05 and 32.7% vs. 19.5%, p < 0.05, respectively); the superiority of CS strategy was particularly evident when 16–19 oocytes were retrieved (LBR 42.2% vs. 9.5%, p = 0.01). Mild OHSS appeared with the same incidence in the two groups, whereas moderate and severe OHSS forms were observed only in the FRESH group (1.5% and 0.8%, respectively). In conclusion, in non-PCO women, high responders submitted to COS with the GnRH-antagonist protocol and GnRH-agonist trigger, CS strategy was associated with higher IR and LBR than the strategy including fresh ET followed by luteal phase support with a low daily hCG dose. CS appears to be advisable, especially when >15 oocytes are retrieved.

Highlights

  • IntroductionAntagonists is required during controlled ovarian stimulation (COS) of multiple follicles in order to avoid a premature luteinizing hormone (LH) surge

  • In reproductive physiology, the luteinizing hormone (LH) is mandatory for maintaining corpus luteum function and promotes the secretion of progesterone and growth factors involved in embryo implantation and placentation [1,2].In in vitro fertilization (IVF), suppression of hypothalamic activity by GnRH analogs/antagonists is required during controlled ovarian stimulation (COS) of multiple follicles in order to avoid a premature LH surge

  • In women who have a large ovarian reserve, the administration of exogenous human chorionic gonadotropin (hCG) in the presence of supraphysiological estradiol levels is associated with an increased risk of ovarian hyperstimulation syndrome (OHSS) [8], partly caused by the stimulating effects of hCG on ovarian production of vasoactive factors [9,10]

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Summary

Introduction

Antagonists is required during controlled ovarian stimulation (COS) of multiple follicles in order to avoid a premature LH surge. In order to compensate for the supra-physiological pre-ovulatory levels of estradiol, observed during COS [4,5], the addition of progesterone is needed for optimal endometrial receptivity and to avoid early pregnancy loss [6,7]. In women who have a large ovarian reserve (defined as “high responders”), the administration of exogenous hCG in the presence of supraphysiological estradiol levels is associated with an increased risk of ovarian hyperstimulation syndrome (OHSS) [8], partly caused by the stimulating effects of hCG on ovarian production of vasoactive factors [9,10]

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