Pasado presente y futuro de la estimulación ovárica en el tratamiento de la infertilidad / Past, present and future of ovarian stimulation in infertility treatment

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.

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

Gonadotropin therapy in assisted reproduction: an evolutionary perspective from biologics to biotech

Gonadotropin therapy plays an integral role in ovarian stimulation for infertility treatments. Efforts have been made over the last century to improve gonadotropin preparations. Undoubtedly, current gonadotropins have better quality and safety profiles as well as clinical efficacy than earlier ones. A major achievement has been introducing recombinant technology in the manufacturing processes for follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. Recombinant gonadotropins are purer than urine-derived gonadotropins, and incorporating vial filling by mass virtually eliminated batch-to-batch variations and enabled accurate dosing. Recombinant and fill-by-mass technologies have been the driving forces for launching of prefilled pen devices for more patient-friendly ovarian stimulation. The most recent developments include the fixed combination of follitropin alfa + lutropin alfa, long-acting FSH gonadotropin, and a new family of prefilled pen injector devices for administration of recombinant gonadotropins. The next step would be the production of orally bioactive molecules with selective follicle-stimulating hormone and luteinizing hormone activity.

Estimulação ovariana para reprodução assistida: a evolução / Ovarian stimulation for assisted reproduction: evolution

estimulação ovariana controlada (EOC) convencional para reprodução assistida, há mais de 25 anos, é realizada predominantemente com o bloqueio hipofisário longo com análogos agonistasdo GnRH, estimulação com gonadotropinas urinárias e, recentemente, recombinantes, e maturação folicular final com hCG. Esse ainda é o protocolo mais utilizado e com o qual os especialistas em medicina reprodutiva estão mais familiarizados. No entanto, alguns inconvenientes devem ser salientados: o tempo de tratamento é relativamente longo (podendo ser maior que um mês) e a incidência de síndrome de hiperestimulação ovariana grave (OHSS) é relevante. Pode-se argumentar que, em termos percentuais, o risco não é grande, mas em um serviço que realiza 500 aspirações foliculares por ano, a incidência de 1% significa 5 pacientes com quadro de OHSS – quase uma a cada dois meses. Podemos consideraresse fato aceitável?(...).