V. Gallot

Levels of follicular G-CSF and interleukin-15 appear as noninvasive biomarkers of subsequent successful birth in modified natural in vitro fertilization/ intracytoplasmic sperm injection cycles

OBJECTIVE To explore oocyte competence for subsequent birth. The modified natural IVF/intracytoplasmic sperm injection (ICSI) cycle was used as an experimental model by measuring levels of cytokines, chemokines, and growth factors in individual follicular fluids (FF). DESIGN A retrospective blinded study. SETTING European network of research, Embryo Implantation Control (EMBIC). PATIENT(S) Single FF from 83 women were analyzed during a modified natural IVF/ICSI cycle, and reproducibility of follicular composition was evaluated over two cycles for 15 patients. INTERVENTION(S) Each FF sample was blindly tested to assess levels of 26 factors by bead-based immunoassays. MAIN OUTCOME MEASURE(S) Each mediator was evaluated as a potential biomarker of subsequent birth by multivariate regression analysis. RESULT(S) A combination of both FF G-CSF and IL-15 was the optimal model to predict birth (AUC(ROC), 0.85). Birth rates per cycle were 48.9% (16/33) if two good-prognosis criteria were present (FF G-CSF>12 pg/mL and IL-15<7 pg/mL) and 8% (3/36) and 0% (0/14) if, respectively, one or none were present. FF G-CSF was significantly correlated over two cycles (r=.71), suggesting a possible prognostic value of its documentation. CONCLUSION(S) Combined follicular G-CSF and IL-15 quantification appears as an efficient and noninvasive method to define oocyte competence for subsequent successful conception in modified natural IVF/ICSI cycles.

Les stimulations ovariennes modérées pour fécondation in vitro constituent-elles un réel progrès en assistance médicale à la procréation ?

Growing evidence indicates that mild ovarian stimulation for in vitro-fertilization-embryo transfer may be an interesting approach to reduce the incidence and severity of complications, the number of treatment days, cost, patient discomfort and number of patient drop-outs. However, the heterogeneity of FSH-sensitive follicles, presumably requires multiple follicular growth to improve oocyte-embryo selection. In addition, whether the acceptability probably is similar between standard ovarian stimulation and mild stimulation, per-treatment pregnancy rates with conventional stimulation is superior to mild stimulation in unselected populations. Hence, some specific indications tend to emerge such as alterations of the ovarian follicular reserve in women of less than 38 years, bad embryo qualities and implantation failure after conventional stimulation, patients with previous history of hyperstimulation syndrome or contraindications to hyperoestrogenia (estrogeno-related cancers and thromboembolic diseases). However, no randomized trials have ever been performed to compare the results of mild versus conventional stimulation in young patients and good responders. Therefore, there is insufficient scientific evidence to shift from standard stimulation to mild stimulation for all patients. Cultural standards have to be considered in the choice of the type of stimulation.

Cancer, préservation de la fertilité et gonadotrophines

The recent emergence of oncofertility raises the question of ovarian stimulation and its risks when performed for oocyte or/and embryo cryopreservation in a fertility preservation program. The relation between ovarian stimulation and cancer has been marked by the possible direct or indirect tumorigenic role for pituitary gonadotrophins in the tumorogenesis. Although the growth of many gonadal and extragonadal tumors is stimulated by gonadal sex hormones, whose production is regulated by gonadotrophins, there is still a lack of data to consider FSH and LH as tumor promoters. The purpose of this brief review is to present on one hand, the questions raised by the administration of exogenous gonadotrophins in cancer patients and on the other, to evaluate both experimental and clinical data about the possible relation between gonadotrophins and tumorogenesis.