NATural Ovarian Stimulation

Controlled ovarian hyperstimulation (COH) seeks to improve IVF-ET results by increasing per-cycle oocyte and embryo availability. Yet, the coexistence of multiple preovulatory follicles engenders compulsory alterations in the endocrine milieu of the follicular phase. The most evident of them are the extremely high serum estradiol (E2) levels. The 10 to 15-fold increase in E2 levels as a result of COH has been shown to provoke unwanted consequences in both embryo quality and uterine receptivity.

Therefore, investigators elaborated an innovative COH protocol (NATural Ovarian Stimulation) that aimed at dissociating E2 production from multiple follicle development. To obtain this effect, they virtually curtailed endogenous LH production by using GnRH antagonist doses as strong and frequent enough to maintain E2 levels around the physiological range during standard exogenous FSH-only administration. Given that high E2 levels are commonly reached in patients having a normal follicle endowment, NATOS should target this group of good prognosis IVF-ET candidates. Indeed, this new COH approach was first tested in a pilot study that included 15 good prognosis IVF-ET candidates, aged 25-35 years, who volunteered to undergo NATOS. 11 out of 15 patients achieved a pregnancy. These pilot results spurred them to conduct a prospective, randomized trial to demonstrate that, in a good prognosis IVF-ET population, the physiological E2 environment resulting from NATOS significantly improves IVF-ET outcome when compared to the conventional GnRH antagonist protocol.

Inclusion criteria

• IVF-ET candidates (excluding PGD and oocyte donor);
• Body mass index from 18 to 30 kg/m2;
• Non smokers;
• Regular menstrual cycles (25-35 days);
• Presence of both ovaries;
• Antral follicle count (follicles measuring from 3 to 10 mm in diameter) ranging from 10 to 30 on cycle days 2 to 4;
• Serum AMH levels ranging from 0.5 to 5.0 ng/mL;
• Normal endometrium at ultrasound (US) and/or hysteroscopy;
• Informed consent signed

Exclusion criteria

• Iatrogenic ovarian insufficiency (surgery, radiotherapy, chemotherapy);
• Uterine abnormalities as demonstrated by pelvic US and/or hysteroscopy;
• Usual contra-indications for COH (cancer risk, blood coagulation disorders, etc)
• Renal insufficiency