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Resumen: La mejor comprensión de la fisiología reproductiva y la disponibilidad de más y mejores recursos diagnóstico/terapéuticos permiten individualizar la estimulación ovárica y hacerla más efectiva (mejores resultados), eficiente (en menos tiempo y con dosis más bajas), segura (con menos y más leves complicaciones), cómoda (menos molestias y autonomía) y accesible (para más personas, a menores costos). Con tecnología de ADN recombinante se dispone ahora de todas las gonadotrofinas e incluso algunas con formas moleculares modificadas para aumentar la duración de acción y disminuir el número de inyecciones. El esquema más utilizado es el de FSH recombinante junto con antagonistas de GnRH. Hay indicaciones específicas para agregar LH o coadyuvantes como hGH o andrógenos transdérmicos. La estimulación ovárica, además de infertilidad, se usa para la preservación de la fertilidad. Cada vez se implementan más estrategias como acumulación de óvulos, esquemas no convencionales (random start, DuoStim y otros) junto a vitrificación ovular, estudio genético preimplantatorio, transferencias embrionarias diferidas y la investigación continúa. Se pronostican mejoras en un futuro próximo, entre otras antagonistas por vía oral y estudio genético de pacientes para diagnosticar mutaciones o polimorfismos de gonadotrofinas y sus receptores. Aunque ya es factible individualizar la estimulación y volverla más efectiva, segura y amigable, así como ofrecer otras opciones a pacientes de mal pronóstico. Summary: Due to an increased understanding of reproductive physiology and to the availability of more and better diagnostic/therapeutic agents, ovarian stimulation through individualization, has become more effective (improved results), efficient (shorter span and lower doses), safe (less and milder complications), comfortable (less discomfort and dependance) and affordable (for more people at lower cost). All gonadotrophins are now available by recombinant DNA technology, including some modified compounds for specific purposes such as longer action and fewer injections. The most popular ovarian regime uses recombinant FSH and GnRH antagonist. There are precise indications for adding LH or adjuncts like hGH or transdermal androgens. Besides infertility, ovarian stimulation is also indicated for fertility preservation. Strategies like oocyte accumulation, non-conventional stimulation protocols (random start, DuoStim and others), oocyte vitrification, preimplantation genetic testing, freeze-all, deferred embryo transfer for particular cases are becoming popular, and the research still goes on. Future advances like oral GnRH antagonists, and the study of mutations and polymorphisms for gonadotropins and its receptors are foreseen. Today through individualization, ovarian stimulation is safe, effective and friendly, also we can offer good options to bad prognosis patients.

Research Question: Is the DuoStim strategy an effective alternative to two conventional ovarian stimulation cycles in poor-prognosis patients undergoing preimplantation genetic testing for aneuploidies (PGT-A) to improve euploidy rates and obtain the first euploid embryo in less time?, Design: This randomized controlled trial was performed at IVI Madrid between June 2017 and December 2020 and included 80 patients with a suboptimal profile aged 38 or older undergoing PGT-A cycles. Patients were blindly randomized into two groups: 39 women underwent two ovarian stimulations in consecutive cycles (control group), whereas the double stimulation strategy was applied to 41 women (DuoStim group). The main outcome was the euploidy rate in each group. The secondary outcomes were the time it took to obtain a euploid embryo and the main cycle outcomes., Results: The baseline characteristics of the patients were similar. No differences were found between the control group and the DuoStim group in the mean days of stimulation (21.3 ± 1.6 versus 23.0 ± 1.4, P = 0.10), total gonadotrophins (4005 ± 450 versus 4245 ± 430, P = 0.43), metaphase II oocytes (8.7 ± 1.8 versus 6.8 ± 1.7, P = 0.15) or euploid embryos obtained (0.8 ± 0.4 versus 0.6 ± 0.4, P = 0.45). The euploid rate per randomized patient (ITT) was 16.1% in the control group versus 22.7% in the DuoStim group, with P-values of 0.371, and the euploidy rate per patient treated was 39.0% versus 45.7% in the control versus DuoStim groups. However, there was a significant difference in the average number of days it took to obtain a euploid blastocyst, favouring the DuoStim group (44.1 ± 2.0 versus 23.3 ± 2.8, P < 0.001)., Conclusions: The use of the DuoStim strategy in poor-prognosis patients undergoing PGT-A cycles maintains a similar euploidy rate while reducing the time required to obtain a euploid blastocyst., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What are the reproductive outcomes of Bologna criteria poor responders undergoing dual stimulation (DuoStim) and subsequent cryopreserved embryo transfer?, Design: Case series of patients treated during the period August 2015 to March 2018 in a public fertility clinic. The study included 54 Bologna criteria poor responder IVF patients younger than 42 years receiving a follicular stimulation (DuoStim 1) followed by a luteal phase stimulation (DuoStim 2) within the same cycle, both stimulations being performed with corifollitropin alfa followed by a subsequent cryopreserved embryo transfer cycle. The primary endpoint was the number of oocytes retrieved in DuoStim 1 compared with DuoStim 2. The secondary endpoint was ongoing pregnancy rate (OPR) at 12 weeks of gestation., Results: The mean number of oocytes retrieved in DuoStim 1 and DuoStim 2 was 2.4 ± 2.1 versus 3.7 ± 2.6, respectively; thus, a total of 1.2 (95% CI, 0.46-1.96) more oocytes was retrieved in DuoStim 2 compared with DuoStim 1 (P = 0.002). The OPR at 12 weeks was 20% (11/54) in this poor ovarian response population with a mean age of 36.7 years., Conclusions: Luteal phase stimulation results in more oocytes in poor responders compared with follicular phase stimulation. DuoStim, using corifollitropin alfa followed by individualized FSH dosing, appears to be an alternative to conventional follicular phase stimulation, decreasing the risk of cycle cancellation., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)