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Comitê: Embriologia

Ovarian manipulation in ART: going beyond physiological standards to provide best clinical outcomes

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Throughout much of recent medical history, illness and treatment have been considered in terms of a profoundly simple model in which physiological knowledge should be applied and either medical treatment or surgical repair performed when a vital organ begins to lose some function. When reproductive organs begin to function abnormally, in vitro fertilization (IVF) has classically been proposed as a clinical approach to help infertile couples achieve a pregnancy. Since the birth of the first Btest-tube baby,^ ovarian stimulation (OS) protocols have been based on the administration of exogenous gonadotropins to induce the growth of multiple follicles during the follicular phase of the menstrual cycle, increasing the numberof mature oocytes fertilized by a sperm sample.

However, the latest research in IVF has moved physicians away from the classical physiology, allowing the development of new strategies to decouple organ functions from the female reproductive system in an attempt to achieve the best clinical outcomes for patients, and challenging the traditional concept of IVF.

The Bfreeze-all^ strategy based on vitrification represents one of the biggest breakthroughs in reproductive
edicine, allowing embryos to be transferred in a subsequent cycle and emerging as an alternative to fresh embryo transfer during IVF. Compared to slow freezing, current oocyte and embryo vitrification protocols yield excellent survival rates, up to 97% in young women [10, 43], and implantation and pregnancy rates for oocytes derived from vitrification/warming cycles are not different from those of fresh oocytes [11].

Establishment of the vitrification technique has dramatically changed routine clinical practice in reproductive centers; contrary to previous belief, ovarian function does not necessarily go hand in hand with the uterus, enabling a decoupling of both organs in assisted reproductive technologies (ARTs).

Such a dissociation of the uterus and ovarian function may occur in several clinical scenarios. First, the egg donation program allows a pregnancy to be established after manipulation of the recipient’s uterus with proper hormonal replacement therapy using donor oocytes. Second, the ovary may be stimulated in a progesterone-enriched milieu, raising the possibility of starting OS in a phase other than the follicular phase.

A report published in 1987 described multiple follicular development after IVF in the presence of a viable intrauterine pregnancy [16], challenging the previously held notion that a single cohort of antral follicles grows only during the follicular phase of the menstrual cycle. Similarly, recent studies on oncology patients and low responders have demonstrated that OS can be initiated in the luteal phase of the menstrual cycle with optimal
reproductive outcomes [62, 84].

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