Mild Stimulation in In Vitro Fertilization

Abstract

Current approaches to ovarian stimulation for in vitro fertilization (IVF) are aimed at optimizing the number of oocytes retrieved in a treatment cycle. This approach is not without risks. Moreover, as the true costs of multiple pregnancy become clearer, the need to produce multiple embryos for transfer is increasingly questioned. Increasing knowledge of the physiological mechanisms involved in follicular development and dominance has led to new strategies in ovarian stimulation for IVF. The clinical availability of GnRH antagonists allows the normal cycle to be harnessed and manipulated by mild interventions to produce sufficient oocytes for successful IVF treatment. Recent evidence suggests that oocyte quality after mild stimulation may be superior to that after conventional stimulation regimens.

MILD ovarian stimulation with GnRH-antagonist vs. long protocol with low dose FSH for non-PCO high responders undergoing IVF: a prospective, randomized study including thawing cycles

“…The "mild" ovarian stimulation strategy, in which a low dose of exogenous gonadotropins is administered from day 4-7 of the menstrual cycle, allows initial follicle recruitment by endogenous FSH [1][2][3][4][5][6]. In women with abundant ovarian follicular reserve, starting FSH on cycle day 4 with a fixed daily dose of 150 IU is sufficient to overcome dominance and finally obtain an average number of 5-12 oocytes [16].…”

“…In human IVF, the protocol of ovarian stimulation in which gonadotropin administration is started at a low dose (100-150 IU/d) on day 4-7 of the menstrual cycle, thus allowing a "natural" recruitment of follicles by endogenous FSH in the early follicular phase, has been addressed as "mild" [1][2][3][4][5][6]. The "mild" stimulation strategy has been proposed as an alternative to the standard "long" stimulation protocol, in which pituitary suppression is obtained in the luteal phase of the run-in cycle and the recruitment of ovarian follicles is achieved by exogenous gonadotropins.…”

Stimulations ovariennes minimales : moins dangereuses mais rarement aussi efficaces

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La plupart des protocoles proposés repose sur une stimulation à faibles doses et/ou tardive, sans analogue de la GnRH, en protocole agoniste court [1] ou le plus souvent associée à l'introduction tardive d'un antagoniste de la GnRH [2][3][4][5][6].À la première question posée par J.-C. Emperaire -la stimulation minimale est-elle moins dangereuse ?-, il ne peut être répondu que par l'affirmative : bien entendu les stimulations ovariennes minimales réduisent largement tous les inconvénients du traitement, au premier rang desquels les syndromes d'hyperstimulation ovarienne [7] et les grossesses multiples. Elles sont indiscutablement plus confortables pour la femme, peuvent justifier un monitorage allégé, consomment moins d'ampoules de gonadotrophines, sont source d'économies par cycle traité et ont une réelle logique à l'époque du transfert de l'embryon unique.

La deuxième question posée par J.-C. Emperaire -la stimulation minimale est-elle efficace ?-, est la vraie bonne question, mais devrait plutôt être posée sous la forme : « les stimulations ovariennes minimales sont-elles aussi efficaces que les stimulations classiques ?

…”

“…La plupart des protocoles proposés repose sur une stimulation à faibles doses et/ou tardive, sans analogue de la GnRH, en protocole agoniste court [1] ou le plus souvent associée à l'introduction tardive d'un antagoniste de la GnRH [2][3][4][5][6].…”

Ultrassom para monitorização da estimulação ovariana controlada: revisão sistematizada e metanálise de estudos randomizados controlados

“…Na maioria dos protocolos é administrado agonista ou antagonista de GnRH (hormônio liberador de gonadotrofina -do inglês gonadotropin-releasing hormone) para a supressão da secreção endógena de hormônio folículo-estimulante (FSH) e hormônio luteinizante (LH), e em seguida, se administra FSH, visando o desenvolvimento multifolicular. Confirmado o crescimento de vários folículos por ultrassonografia (US) e/ou por dosagem hormonal (estradiol -E2) é, então, indicada uma única dose de hCG (gonadotrofina coriônica humana -do inglês human chorionic gonadotropin) para substituir o pico de LH na maturação oocitária final Fauser, 2003). Identificar o desenvolvimento adequado e avaliar o melhor momento para a administração do hCG não é uma tarefa simples.…”