DuoStim – a reproducible strategy to obtain more oocytes and competent embryos in a short time-frame aimed at fertility preservation and IVF purposes. A systematic review

Abstract

Recent evidence suggests that follicular development occurs in a wave-like model during the ovarian cycle, where up to three cohorts of follicles are recruited to complete folliculogenesis. This understanding overtakes the previous dogma stating that follicles grow only during the follicular phase of the menstrual cycle. Therefore, in in vitro fertilization (IVF), novel protocols regarding ovarian stimulation have been theorized based on the use of gonadotrophins to prompt the growth of antral follicles at any stage of the menstrual cycle. These unconventional protocols for ovarian stimulation aim at a more efficient management of poor-prognosis patients, otherwise exposed to conflicting outcomes after conventional approaches. DuoStim appears among these unconventional stimulation protocols as one of the most promising. It combines two consecutive stimulations in the follicular and luteal phases of the same ovarian cycle, aimed at increasing the number of oocytes retrieved and embryos produced in the short time-frame. This protocol has been suggested for the treatment of all conditions requiring a maximal and urgent exploitation of the ovarian reserve, such as oncological patients and poor responders at an advanced maternal age. At present, data from independent studies have outlined the consistency and reproducibility of this approach, which might also reduce the drop-out between consecutive failed IVF cycles in poor-prognosis patients. However, the protocol must be standardized, and more robust studies and cost-benefit analyses are needed to highlight the true clinical pros and cons deriving from DuoStim implementation in IVF.

The best execution of the DuoStim strategy (double stimulation in the follicular and luteal phase of the same ovarian cycle) in patients who are poor ovarian responders

“…The adverse reactions and complications of the accumulation of a high number of oocytes in a relatively narrow cycle time during the DuoStim protocol [48], and the short-term and long-term effects on the patient and the embryos require additional research. The length of time between the two stimulation schemes is very short, and the biological markers and microenvironment stability of the twice-obtained oocytes remain to be studied.…”

The effect of dual stimulation on ploidy rates in patients with poor ovarian response

“…The advantage of dual stimulation is obtaining more eggs and embryos in a single cycle. Especially in LS, higher blastocyst and euploidy rates compared to those obtained in FS supported the use of the dual protocol in patients who will experience ovarian failure due to medical reasons and who have time constraints [25]. However, more research is needed on this subject.…”

“…Selection of the right stimulation agent, the use of agonists or antagonists to reduce LH (luteal hormone) peak, hCG or agonist trigger use to obtain a mature oocyte, fresh or frozen embryo transfer, and whether the embryo is selected with pregenetic diagnosis or morphological characteristics are the key steps. The main goal in all is to keep the ovarian response at a maximum in patients with a weak response [25].…”

Oocyte cryopreservation - current scenario and future perspectives: A narrative review

“…Dual stimulation (Duo stim) is another novel protocol which can be used in such patients to increase the frozen oocyte pool in a short period, thus increasing the cumulative live birth rates, later on in life. [ 10 11 ] Retrieval of immature oocytes followed by in-vitro maturation is an effective alternative to further shorten this delay. [ 12 13 ] Embryos can be formed later on with thawed oocytes whenever the women are in remission and are planning pregnancy.…”