Natural ovarian stimulation (NATOS): an innovative controlled ovarian hyperstimulation (COH) protocol that combines large oocyte availability and physiologic estrogenic environment

Abstract

Some compulsory endocrine alterations of COH such as extremely high E2 levels may alter the endometrial-myometrial readying for embryo implantation and are unwelcome in some malignant and benign gynecologic affections. We tested an innovative COH protocol that dissociates E2 production from multiple follicle development by the curtailing of endogenous LH levels using strong and sustained GnRH antagonist doses in combination with standard FSH administration. Prospective pilot study. We studied 4 IVF-ET candidates aged 25-33 years undergoing NATOS. On day 2 of their menstrual cycle, patients started daily recombinant FSH (doses fitting antral follicle counts) paralleled with daily GnRH antagonist (3 mg/day) administration. Ovarian, endometrial, and embryology data is shown in the Table. Despite the remarkable discrepancy between E2 levels on the day of hCG administration and oocyte-embryo availability, patients underwent ET and 3 of 4 achieved an ongoing pregnancy.Tabled 1Pat #1Pat #2Pat #3Pat #4Mean valuesE2 at hCG (pg/mL)239343579424396.2LH at hCG (mIU/mL)<0.1<0.1<0.1<0.1<0.1Endom. thick. (mm)6.911.09.29.79.2No. of mat. oocytes1111192516.5Fertil. rate (%)5464878071.2No. of embryos67192013.0No. of emb. transf.22222.0Outcomeno pregnancyong. pregnancyong. pregnancyong. pregnancy- Open table in a new tab 1. In NATOS, profound LH suppression by strong, sustained GnRH antagonist doses maintains E2 levels around the physiological range and normal endometrial growth; 2. NATOS led to multiple follicle development and normal oocyte retrieval, fertilization rates, and embryo morphology and early embryo development; 3. Encouraging embryo implantation rates with NATOS challenges the hypothesis that sizeable LH amounts are required for follicle-oocyte competence; 4. Whereas these results should be further confirmed, NATOS offers a new option for stimulating IVF-ET candidates, in particular, those seeking fertility preservation or suffering from repeated failures.