Double or dual stimulation in poor ovarian responders: where do we stand?

Abstract

Recent advances in our recognition of two to three follicular waves of development in a single menstrual cycle has challenged the dogmatic approach of ovarian stimulation for in vitro fertilization starting in the early follicular phase. First shown in veterinary medicine and thereafter in women, luteal phase stimulation–derived oocytes are at least as competent as those retrieved following follicular phase stimulation. Poor ovarian responders still remain a challenge for many decades simply because they do not respond to ovarian stimulation. Performing follicular phase stimulation and luteal phase stimulation in the same menstrual cycle, named as double stimulation/dual stimulation, clearly increases the number of oocytes, which is a robust surrogate marker of live birth rate in in vitro fertilization across all female ages. Of interest, apart from one study, the bulk of evidence reports significantly higher number of oocytes following luteal phase stimulation when compared with follicular phase stimulation; hence, performing double stimulation/dual stimulation doubles the number of oocytes leading to a marked decrease in patient drop-out rate which is one of the major factors limiting cumulative live birth rates in such poor prognosis patients. The limited data with double stimulation/dual stimulation-derived embryos is reassuring for obstetric and neonatal outcome. The mandatory requirement of freeze-all and lack of cost-effectiveness data are limitations of this novel approach. Double stimulation/dual stimulation is an effective strategy when the need to obtain oocytes is urgent, including patients with malignant diseases undergoing oocyte cryopreservation and patients of advanced maternal age or with reduced ovarian reserve.

Fertility Preservation: How to Preserve Ovarian Function in Children, Adolescents and Adults

“…Protocols have even been developed for double stimulation (follicular and luteal phase ovarian stimulation) during the same menstrual cycle, known as DuoStim [19]. The goal is to maximize the number of gametes obtained, improving cumulative live birth rates without postponing cancer therapy [20][21][22].…”

The BISTIM study: a randomized controlled trial comparing dual ovarian stimulation (duostim) with two conventional ovarian stimulations in poor ovarian responders undergoing IVF

“…In fact, until recently, only retrospective, and non-randomized prospective studies have been performed to evaluate the increase of the number of oocytes in the second stimulation for women with POR. Most of the studies in the more recent review from Polat et al (2021) tend to show a slight increase in the number of oocytes in the luteal phase after a follicular stimulation ( Kuang et al , 2014a ; Vaiarelli et al , 2018 ). Only one small observational study reported more oocytes in the follicular than in the luteal phase with duostim (5.3 versus 3.8, respectively) ( Bourdon et al , 2020 ).…”

Retrospective study of influencing factors on the outcomes of luteal phase stimulation in patients with dual stimulation

“…With the understanding of multiple follicular waves within one menstrual cycle, double or triple ovarian stimulation and subsequent oocyte retrieval are being increasingly adopted by reproductive clinics ( Lu et al, 2021 ; Polat et al, 2021 ; Vaiarelli et al, 2020a ). Among them, dual/double stimulation (DS) is widely studied and performed, especially for women with poor ovarian responders (POR) and those in urgent need of fertility preservation.…”

“…Among them, dual/double stimulation (DS) is widely studied and performed, especially for women with poor ovarian responders (POR) and those in urgent need of fertility preservation. For POR with DS, patients got a better chance of getting more oocytes and subsequently more embryos for transfer ( Polat et al, 2021 ; Sighinolfi, Sunkara & La Marca, 2018 ). And the cumulative live birth rate (CLBR) also doubled when compared to FPS in these patients ( Vaiarelli et al, 2020a ).…”