Abstract

A drawback of gonadotropin-releasing hormone (GnRH) antagonist protocols in in vitro fertilization (IVF) is that they have limited flexibility in cycle programming. This proof of concept study explored the efficacy of a single-dose, long-acting GnRH antagonist IVF protocol. Trial registration number is NCT03240159, retrospectively registered on March 08, 2017. The efficacy of a single-dose long-acting antagonist, degarelix, was explored initially in healthy donors and subsequently in infertile patients. In the first part, five healthy oocyte donors underwent ovarian stimulation with this new protocol: in the late luteal phase, at day 24, a bolus injection of degarelix was administered subcutaneously to control the LH surge in the follicular phase. Ovarian stimulation with gonadotropins was initiated subsequently from day 7 to day 10. End points were first to inhibit the LH surge later in the follicular phase and, second, to retrieve mature oocytes for IVF. In the second part, five infertile women received the same bolus injection of degarelix administered during the luteal phase at day 24. Different gonadotropin starting days (day 2 through day 8) were tested in order to observe possible differences in ovarian stimulation. In these infertile patients, fresh embryo transfers were performed to assess the pregnancy efficacy of this protocol on pregnancy outcomes and to address any possible negative effects on endometrium receptivity. In the first part of the study, all donors were effectively downregulated with a single luteal dose of 0.5 ml of degarelix for up to 22 days until the final oocyte maturation triggering day. Mature oocytes were retrieved after 36 h from all patients and all produced 2-7 blastocysts. In the second part, all five infertile patients achieved sufficient LH downregulation and completed ovarian stimulation without any LH surge. All patients (except one with freeze all strategy) had blastocysts transferred and pregnancy occurred in three out of five women. A single dose of the long-acting antagonist degarelix during the luteal phase appears to be effective in downregulating hypophysis during ovarian stimulation. This represents a possible new protocol for IVF, which should be further elucidated in RCTs.

Highlights

  • A drawback of gonadotropin-releasing hormone (GnRH) antagonist protocols in in vitro fertilization (IVF) is that they have limited flexibility in cycle programming

  • There is solid evidence that the use of a GnRH antagonist is associated with a substantial reduction in ovarian hyperstimulation syndrome (OHSS) risk compared with long-course GnRH agonist protocols [3], without reducing the likelihood of achieving live birth [4]

  • Despite the clear benefits associated with GnRH antagonist pro­ tocols, GnRH agonists are still the treatment of choice in the majority of assisted reproductive technology clinics (5, survey 2010)

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Summary

Introduction

A drawback of gonadotropin-releasing hormone (GnRH) antagonist protocols in in vitro fertilization (IVF) is that they have limited flexibility in cycle programming. In contrast to gonadotropin-releasing hormone (GnRH) agonist treatment, GnRH antagonists block GnRH receptors by competitive binding, resulting in immediate gonadotrophin suppression This enables a short treatment regimen for ovarian stimulation as well as immediate recovery from hypophysis within hours after the antagonist injection. Despite the clear benefits associated with GnRH antagonist pro­ tocols (resulting in a steady increase in their use), GnRH agonists are still the treatment of choice in the majority of assisted reproductive technology clinics (5, survey 2010). It seems that the major reason for favoring a GnRH agonist protocol is primarily that GnRH antagonists offer less flexibility in cycle programming. A secondary factor is the asynchrony of the follicular cohort compared with the long GnRH agonist protocol [6]

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