Abstract
Objective: To examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may improve conventional IVF/intracytoplasmic sperm injection (ICSI) cycle in poor ovarian response (POR) patients.Design: Cohort historical, proof of concept study.Setting: Tertiary, University affiliated Medical Center.Patient(s): Thirty POR patients, defined according to the Bologna criteria, who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle, were included. For the purposes of this study, we eliminated a bias in this selection by including only “genuine” poor responder patients, defined as those who yielded up to 3 oocytes following COH with a minimal gonadotropin daily dose of 300 IU.Main Outcome Measure(s): Number of oocytes retrieved, number of top-quality embryos, COH variables.Result(s): The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly higher numbers of follicles >13 mm on the day of hCG administration, higher numbers of oocytes retrieved, and top-quality embryos (TQE) with an acceptable clinical pregnancy rate (16.6%). Moreover, as expected, patients undergoing the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol required significantly higher doses and a longer duration of gonadotropins stimulation.Conclusion(s): The combined Stop GnRH-ag/GnRH-ant COH protocol is a valuable tool in the armamentarium for treating “genuine” poor ovarian responders. Further, large prospective studies are needed to elucidate its role in POR and to characterize the appropriate patients subgroup (before initiating ovarian stimulation) that may benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.
Highlights
Controlled ovarian hyperstimulation (COH) is a crucial step in the success of in vitro fertilization-embryo transfer (IVF-ET), enabling the recruitment of multiple oocytes and subsequently, the vitrification of all surplus embryos [1]
The controversy surrounding the diagnosis of patients with poor ovarian response (POR) to ovarian stimulation resulted in a systematic standardization of the definition by the European society of Human Reproduction and Endocrinology (ESHRE), known as the Bologna criteria
When considering the additional benefit of increasing the oocyte yield in POR, it has been demonstrated in all age groups, that the retrieval of merely one more oocyte (2 instead of 3 oocytes) increases the cumulative live birth rate (LBR) per cycle by ∼25% [16]
Summary
Controlled ovarian hyperstimulation (COH) is a crucial step in the success of in vitro fertilization-embryo transfer (IVF-ET), enabling the recruitment of multiple oocytes and subsequently, the vitrification of all surplus embryos [1]. Until 2011, there was no one single definition for patients with poor ovarian response, though the most accepted criterion was a decreased response to COH, which, in IVF cycles, correlates to the reduced quantity of oocytes retrieved. According to the Bologna criteria, in order to define POR, “at least two of the following three features must be present: (i) Advanced maternal age (≥40 years) or any other risk factor for POR; (ii) A previous POR (≤3 oocytes with a conventional stimulation protocol); and (iii) An abnormal ovarian reserve test [3]. In the absence of advanced maternal age or abnormal ovarian reserve tests, two previous maximal stimulation attempts with POR are sufficient to define a patient as a poor responder.”
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