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Objective To compare the effectiveness of two stimulation protocols in non-polycystic ovary (PCO) high responders undergoing in vitro fertilization (IVF). Design Prospective randomized trial. Setting A Reproductive Medicine and IVF Unit of a University Hospital and a private IVF Clinic. Methods Four hundred-and-twelve normoovulatory women with good ovarian responsiveness were randomized to receive either the "mild" (FSH 150 IU/day from day 4 of a spontaneous cycle followed by GnRH-antagonist from day 8; n=205) or the "long" (FSH 150 IU/day; n=207) stimulation protocol. The outcome of these two regimens was compared including "fresh" and thawing cycles. Results The total FSH dose and the peak estradiol level were significantly lower in the "mild" protocol, whereas the retrieved oocytes, fertilization rate, number and quality of embryos, pregnancy and implantation rates, cumulative "fresh plus thaw" success rate, and incidence of severe ovarian hyperstimulation syndrome were comparable with the two regimens. Conclusions In young, normoovulatory patients with good ovarian responsiveness undergoing IVF the "mild" stimulation protocol has effectiveness and risks comparable to the "long" protocol with low FSH starting dose, even when thawing cycles are included in the comparison.

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The cyclical arrival of endometrial cells into the abdominal cavity through retrograde flux at menstruation represents the etiopathogenetic basis of endometriosis. The endometrium has peculiar regenerative properties linked to the presence of adult stem cells similar to mesenchymal stem cells (MSCs). Once in the abdominal cavity, these MSCs could proliferate, invade, and differentiate into endometrial cells, finally generating ectopic implants. As only differentiated endometrial cells, and not endometrial MSCs, possess steroid hormone receptors, MSCs could be responsible for the high rate of persistence/recurrence of the disease after hypoestrogenism-inducing therapies. Even angiogenesis promoted by MSCs could play an important role, as survival and proliferation of endometriotic tissue depend on the formation of new blood vessels. Inhibition of angiogenesis represents, in fact, a new, promising therapeutic approach for the disease. Further, medications directly targeting endometriosis MSCs could be effective, alone or in association with hormonal treatments, in increasing the success of medical treatment.