Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54.

CONTEXT: Loss of function of the G protein-coupled receptor of kisspeptins (GPR54) was recently described as a new cause of isolated hypogonadotropic hypogonadism. In vivo studies performed in several species have confirmed the major role of kisspeptins in neuroendocrine regulation of the gonadotropic axis and therefore sexual maturation. OBJECTIVE: The objective of this study was to specify the exact contribution of kisspeptins and GPR54 to the initiation of puberty in humans. DESIGN: Detailed neuroendocrine descriptions were performed in five patients with isolated hypogonadotropic hypogonadism bearing a new GPR54-inactivating mutation. RESULTS: A homozygous mutation (T305C) leading to a leucine substitution with proline (L102P) was found in the five affected patients. This substitution completely inhibited GPR54 signaling. Phenotypic analysis revealed variable expressivity in the same family, either partial or complete gonadotropic deficiency. LH pulsatility analysis showed peaks with normal frequency but low amplitude. Repeated GnRH tests performed between 12 and 21 yr of age in one affected male revealed progressive changes in pituitary response from an early pubertal to an almost full pubertal pattern. Double GnRH test stimulations performed at a 120-min interval showed reduced dynamic pituitary response in GPR54-mutated patients. CONCLUSION: GPR54 inactivation does not impede neuroendocrine onset of puberty; rather, it delays and slows down pubertal maturation of the gonadotropic axis. The L102P loss of function mutation in GPR54 results in a more quantitative than qualitative defect of gonadotropic axis activation.

Recombinant follicle-stimulating hormone versus human menopausal gonadotropin in the late follicular phase during ovarian hyperstimulation for in vitro fertilization.

OBJECTIVE: To study the effect of exogenous LH in the late follicular phase on ongoing pregnancies and at the different stages of IVF-ET (stimulation, fertilization, and implantation) in patients with low endogenous LH. DESIGN: Retrospective cohort study with modeling of the different phases of IVF-ET. SETTING: IVF center of the teaching hospital in Bordeaux, France. PATIENT(S): Women undergoing IVF and ICSI treatment. INTERVENTION(S): One group received recombinant FSH alone (FSH group) and the other received recombinant FSH and hMG in the late follicular phase (i.e., when the largest follicle reached 14 mm) (FSH/hMG group). MAIN OUTCOME MEASURE(S): Ongoing pregnancy, number of oocytes, and number of embryos. RESULT(S): The FSH/hMG group had a higher probability of having at least one oocyte (odds ratio [OR] = 2.75 [1.11-6.80]), of having at least one embryo after oocyte retrieval (OR = 2.84 [1.33-6.07]), and of ongoing pregnancy after ET (OR = 2.04 [0.83-5.01]), and globally had a higher probability of ongoing pregnancy (OR = 2.83 [1.19-6.71]). CONCLUSION(S): In ovarian hyperstimulation for IVF-ET, LH supplementation in the late follicular phase of women with low endogenous LH is beneficial for ongoing pregnancy by increasing the rate of success of all stages of the treatment.

Endometrial vascularity and ongoing pregnancy after IVF.

BACKGROUND: Embryo transfer is prone to failure. AIM: To investigate whether endometrial vascularity influences in vitro fertilization (IVF) outcome. METHODS: Total 144 patients receiving IVF (conventional or microinjection) were assessed with color and power Doppler on the day of embryo transfer: age, IVF type, number and quality of embryos, endometrial thickness and aspect, mean uterine PI, uterine notch, type of endometrial vascularity (peripheral or sub- and intra-endometrial), and pregnancy involving second trimester were recorded. RESULTS: 27 (18.7%) pregnancies were obtained. By univariate analysis, two parameters were significant: high frequency of uterine notch (P = 0.03) and peri-endometrial vascularity (P = 0.012) in the group of failures. Multivariate analysis by logistic regression clearly showed that the absence of sub- and intra-endometrial color signal decreased the chances of pregnancy eight-fold odds ratio (OR) = 0.14 [CI: 0.029-0.68]. CONCLUSION: In this limited series, the presence of sub- and intra-endometrial vascularity on the day of transfer seemed to be mandatory for obtaining an ongoing pregnancy.