Doble estimulación en el mismo ciclo ovárico (DuoStim) para aumentar la recuperación ovocitaria en pacientes bajas respondedoras: revisión sistemática de la evidencia científica actual.
Keywords:
Luteal phase stimulation, Follicular phase stimulation, Double stimulation, DuoStim, Poor ovarian responseAbstract
Objective
This review aims to investigate the efficacy of double stimulation in the same ovarian cycle (DuoStim), in terms of oocyte retrieval, cancellation rate, cycle length, miscarriage rate, and clinical and evolutionary pregnancy rate, in poor responders according to the Bologna criteria, comparing it with conventional stimulation in the follicular phase.
Methods
A systematic search of the literature of the last 10 years (2010-2020) was carried out in the PubMed database. Both randomized clinical trials and prospective and retrospective cohorts, meta-analyzes and systematic reviews of normal and hyporesponsive patients stimulated during the follicular phase and the luteal phase of the same ovarian cycle (DuoStim) are included. A detailed analysis of all the scientific evidence available on the subject as of April 2020 is carried out and the observational studies available in this regard that meet the inclusion and exclusion criteria that are defined are meta-analyzed, performing a first statistical comparison of the outcome variables between follicular versus luteal phase stimulation in patients with low response undergoing DuoStim and a second statistical comparison between the results obtained after DuoStim versus Conventional Stimulation. For the analysis of dichotomous variables, Odds ratio is used, while for the analysis of continuous variables the Difference of Means is used, both with 95% confidence intervals. The random effects model is used to combine the results according to their heterogeneity, applying the I2 statistical test to evaluate it. A total of 6 observational studies were included in the meta-analysis, 3 of them being randomized prospective and 3 retrospective. The first comparison includes a total of 549 cycles in the follicular phase and 455 in the luteal phase. In the second comparison, 237 patients undergoing a double stimulation cycle were considered compared to 408 patients with conventional stimulation.
Results
The meta-analysis carried out indicates that within a DuoStim protocol in women with poor ovarian response, oocyte recovery is greater after the luteal phase than after the follicular phase. On the other hand, no statistically significant differences were found in the rest of the parameters evaluated: duration of stimulation, cancellation rate, MII oocytes recovered, fertilization rate, clinical and ongoing clinical pregnancy rate, and early pregnancy loss rate. Regarding DuoStim versus Conventional Stimulation, there is scientific evidence that refers to greater recovery of MII oocytes after DuoStim. The meta-analysis carried out did not find statistically significant differences in the clinical pregnancy rate between the two protocols.
Conclusion
Luteal phase stimulation (LPS) increases oocyte retrieval compared to conventional follicular phase stimulation (FPS) in low responders, without significant differences in stimulation days or cycle cancellation rates with respect to FPS. There were also no differences in the number of mature oocytes retrieved or in clinical pregnancy rates between LPS and FPS, or between DuoStim and Conventional Stimulation. With this, more scientific evidence is needed in order to evaluate the cost-benefit ratio of DuoStim in improving reproductive results in poor responders, as well as the generalization of LPS as one more tool in ovarian stimulation protocols in patients a poor prognosis. In any case, it should be considered that the level of evidence of this meta-analysis is low or very low.
