DuoStim Protocol for Egg and Embryo Freezing with Dr. Vitaly Kushnir

Double stimulation in the same ovarian cycle (DuoStim) is a newly developed protocol designed to maximize the number of oocytes retrieved in the shortest possible time. Unlike traditional protocols where patients undergo a single round of controlled ovarian hyperstimulation (COH) and oocyte retrieval in one menstrual cycle in a DuoStim protocol patients undergo two rounds of COH and two oocyte retrievals in the same menstrual cycle.The DuoStim protocol is designed to take advantage of the fact that the ovaries typically recruit multiple (2-5) waves of follicles each month. In a natural ovulatory cycle hormone signals from the brain allow only one follicle, containing one egg, to be selected for ovulation while multiple other follicles never reach maturity and the eggs inside of them die via atresia. During an IVF cycle fertility drugs are used to rescue some of those eggs which are otherwise destined to die, allowing collection of multiple mature eggs and creation of multiple embryos. A DuoStim protocol is an extension of this concept in that after the first egg retrieval a second round of stimulation with fertility drugs can be started during the luteal phase allowing a second egg collection in the same menstrual cycle.

The principal advantage of a DuoStim protocol is that it allows collection of more eggs than a traditional stimulation protocol in the same amount of time. This approach is thought to be practical in two clinical situations: 1. Women with low ovarian reserve who produce relatively few eggs in a given cycle and 2. Women undergoing fertility preservation via egg or embryo freezing who have limited time (ei. prior to starting chemotherapy for cancer).

A recent study conducted in Italy (Vaiarelli A, et al. Front Endocrinol. 2018;9:317.) included 310 poor prognosis patients undergoing a DuoStim IVF. The female age was 40.0 ± 3.0 years (33.0–44.0), the AFC was 5.3 ± 2.5 (3–13), the AMH was 1.0 ± 1.0 (0.1–2), and patients had previously underwent 1.0 ± 1.3 (0–6) previous IVF cycles collecting 4.0 ± 2.6 (0–14) MII oocytes. This study found that both stimulation phases yielded oocytes with equivalent quality based on (fertilization, blastocyst, euploidy rates, and clinical outcomes after euploid single-embryo-transfer). The second (luteal phase) stimulation helped increase the proportion of patients who had at least one euploid blastocyst from 42.3% to 65.5%.

There are several limitations to the DuoStim approach which are important to note. There is an increased cancellation risk during the second (luteal phase) stimulation. These protocols are designed for all eggs or embryos to be frozen for later usage. Finally, cost-effectiveness of this protocol has yet to be established.

DuoStim_EggFreezing_NewayFertilitySighinolfi G, et al. New strategies of ovarian stimulation based on the concept of ovarian follicular waves: From conventional to random and double stimulation. Reprod Biomed Online. 2018 Oct;37(4):489-497.