Double Stimulation in the Same Ovarian Cycle (DuoStim) to Maximize the Number of Oocytes Retrieved From Poor Prognosis Patients: A Multicenter Experience and SWOT Analysis

Abstract

A panel of experts known as the POSEIDON group has recently redefined the spectrum of poor responder patients and introduced the concept of suboptimal response. Since an ideal management for these patients is still missing, they highlighted the importance of tailoring the ovarian stimulation based on the chance of each woman to obtain an euploid blastocyst. Interestingly, a novel pattern of follicle recruitment has been defined: multiple waves may arise during a single ovarian cycle. This evidence opened important clinical implications for the treatment of poor responders. For instance, double stimulation in the follicular (FPS) and luteal phase (LPS) of the same ovarian cycle (DuoStim) is an intriguing option to perform two oocyte retrievals in the shortest possible time. Here, we reported our 2-year experience of DuoStim application in four private IVF centers. To date, 310 poor prognosis patients completed a DuoStim protocol and underwent IVF with blastocyst-stage preimplantation-genetic-testing. LPS resulted into a higher mean number of oocytes collected than FPS; however, their competence (i.e., fertilization, blastocyst, euploidy rates, and clinical outcomes after euploid single-embryo-transfer) was comparable. Importantly, the rate of patients obtaining at least one euploid blastocyst increased from 42.3% (n = 131/310) after FPS to 65.5% (n = 203/310) with the contribution of LPS. A summary of the putative advantages and disadvantages of DuoStim was reported here through a Strengths–Weaknesses–Opportunities–Threats analysis. The strengths of this approach make it very promising. However, more studies are needed in the future to limit its weaknesses, shed light on its putative threats, and realize its opportunities.

Outcomes in poor responders treated with in vitro fertilization/intracytoplasmic sperm injection according to bologna criteria

“…The question of how to calculate the results remains open: according to ICMART (Committee for Monitoring Assisted Reproductive Technology) criteria [25] or only for the embryo transfer/initiated cycle?…”

Novel Physiology and Definition of Poor Ovarian Response; Clinical Recommendations

“…The aim of DuoStim is to maximize the number of oocytes obtained per cycle. A large multicenter study has shown comparable fertilization, blastocyst, euploidy, and pregnancy rates from follicular phase stimulation and luteal phase stimulation [57]. Moreover, the rate of patients obtaining at least on euploid blastocyst significantly increased from 42.3% after follicular phase stimulation only to 65.5% with DuoStim [57].…”

“…In contrast, an 11% live birth rate per cycle was reported in the until now largest RCT including Bologna POR patients, using a GnRH agonist long protocol and 300 IU rFSH in combination with 150 IU rLH daily from day one of stimulation [67]. Furthermore, recently, a 20% ongoing pregnancy rate was reported in poor ovarian reserve patients using follicular as well as luteal phase stimulation (DuoStim) [57,58]. To conclude, ovarian stimulation with exogenous gonadotropin stimulation at a maximum of 300 rFSH should be used rather than natural cycle IVF in POSEIDON groups 3 and 4 patients.…”

“…Moreover, double stimulation (DuoStim) might be considered to accumulate the number of blastocysts needed to increase the probability of having at least one euploid blastocyst for subsequent frozen thaw embryo transfer. Vaiarelli et al [57] reported that a single DuoStim cycle in poor prognosis patients, essentially POSEIDON group 4 patients, resulted in 65.5% of patients having at least one euploid blastocyst for transfer [57]. Moreover, there was no difference in the ongoing pregnancy rate per single euploid blastocyst transfer between blastocysts obtained from the follicular phase and those obtained from the luteal phase stimulation, which were 39.5% and 49.4%, respectively [57].…”

“…A large multicenter study has shown comparable fertilization, blastocyst, euploidy, and pregnancy rates from follicular phase stimulation and luteal phase stimulation [57]. Moreover, the rate of patients obtaining at least on euploid blastocyst significantly increased from 42.3% after follicular phase stimulation only to 65.5% with DuoStim [57]. However, it should be noted that results from studies performed using the DuoStim protocol should be interpreted with caution, since most patients included in these studies do not explicitly fulfill the criteria of POSEIDON groups 1 and 2 but rather POSEIDON groups 3 and 4.…”