“Short agonist stop” protocol, an ovarian stimulation for poor responders in in vitro fertilization (IVF): A pilot study

Abstract

IntroductionPoor responder patients remain a challenge in assisted reproductive technologies. The “short agonist stop” (SAS) stimulation protocol uses a double stimulation (flare up effect with the gonadotropin-releasing hormone (GnRH) agonist (GnRH-a) then gonadotropins) associated with a less strenuous blockage (discontinuation of GnRH-a) to favor follicular recruitment in order to obtain a better ovarian response. This study aims to compare the number of oocytes obtained after a SAS stimulation protocol with those obtained after the previous stimulation protocol, in the same women, with poor ovarian response (POR) diagnosed according to the POSEIDON criteria.DesignThis therapeutic observational retrospective cohort from 2018 to 2022, with a case-control evaluation compared with the same patients’ previous performance, included women with POR undergoing IVF with SAS stimulation protocol. The primary outcome was the number of total oocytes recovered and secondary outcomes were the numbers of mature oocytes, total embryos observed at day 2 and usable cleaved embryos and blastocysts (day 5/6).Results63 patients with SAS and previous cycles were included. In the SAS group, the mean number of oocytes was significantly higher: 7.3 vs 5.7, p=0.018 in comparison with the previous attempt. So was the number of mature oocytes (5.8 vs 4.1, p=0.032) and the total mean number of embryos obtained at day 2 (4.1 versus 2.7, p=0.016). The SAS stimulation generated 84 usable embryos: 57 cleaved embryos and 27 blastocysts. The mean number of usable embryos was similar in both groups (1.64 vs 1.31, respectively, p=0.178). In total, out of 63 patients, after the SAS protocol, and subsequent embryo transfers (fresh and frozen, n=54), 9 patients had ongoing pregnancies and no miscarriage occurred. The cumulative ongoing pregnancy rate (cOPR) after the SAS protocol was 14.3% (9/63) per oocyte pick-up and 16.7% (9/54) per transfer.ConclusionSAS stimulation is a short and original protocol strengthening the therapeutic arsenal of poor responders, that may offer promising results for those patients with low prognosis and previous failed IVF. Results must be confirmed with a randomized controlled trial.

Effect of Short Agonist Stop (SAS) Protocol in a Patient Having an Allergic Reaction From Conventional Ovarian Stimulating Hormone

“…The SAS stimulation protocol employs a dual-phase stimulation approach involving initial activation with a gonadotropin-releasing hormone agonist (GnRH-a) followed by gonadotropin administration, coupled with a less stringent blockade (cessation of GnRH-a), to promote follicular recruitment and enhance ovarian response. This investigation compares the yield of oocytes attained through the SAS stimulation protocol against those obtained using the preceding stimulation regimen in the same cohort of women diagnosed with poor ovarian response (POR), as per the Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) criteria [ 8 ]. Controlled ovarian hyperstimulation (COH) represents a pivotal stage in achieving favourable outcomes in vitro fertilization-embryo transfer (IVF-ET) procedures, facilitating the recruitment of multiple oocytes and subsequent vitrification of surplus embryos.…”

“…This protocol distinguishes itself from others by employing GnRH agonists for a relatively brief duration, leading to a streamlined and expedited treatment cycle. The concise agonist cessation strategy represents an efficacious approach in reproductive medicine, endeavouring to enhance the rates of favourable outcomes in IVF cycles through optimization of the stimulation process [ 8 ].…”

“…These interventions play a crucial role in stimulating male sperm production and promoting ovarian follicle development in females [ 7 ]. In vitro fertilization (IVF) procedures integrate ovarian stimulation, utilizing protocols such as the short agonist stop (SAS), to modulate ovulation and promote the development of numerous follicles containing eggs, thereby enhancing the likelihood of successful conception [ 8 ]. Treatment modalities involve the administration of medications to women throughout each menstrual cycle to synchronize ovulation.…”

Assessment of The Results of Short Agonist Stop Ovarian Stimulation Protocol in Poor Responder Patients Undergoing ICSI Cycles

“…Mauries et al [16] study has documented that SAS stimulation is a short and original protocol strengthening the therapeutic arsenal of poor responders, which may offer promising results for those patients with low prognosis and a record of failed IVF. This protocol resulted in a significantly higher number of oocytes, mature oocytes, and embryos obtained and a non-significantly higher number of usable embryos, in comparison with their previous IVF cycle.…”

“…The SAS protocol is not mentioned in recent literature about stimulation protocols and management of poor responders in ART, nor in ESHRE's guidelines about ovarian stimulation for IVF/ICSI. This type of stimulation was studied more often in the 2000s, but still, only one randomized controlled trial (RCT) used this protocol [15,16] .…”