Prevalence of lifetime eating disorders in infertile women seeking pregnancy with pulsatile gonadotropin-releasing hormone therapy.

OBJECTIVES: Relationships between weight and fertility are well known. The aim of this study is to assess the prevalence of lifetime eating disorder (ED) in a sample of infertile women seeking a specific infertility treatment, pulsatile gonadotropin-releasing hormone (pGnRH) treatment, and to compare it to the prevalence of lifetime ED in a sample of infertile women seeking other types of assisted reproductive technology (ART) treatments. DESIGN: Non-randomized, observational study including infertile female patients. Two-group design including consecutive women treated with GnRH pump (pGnRH) or with other types of ART. SETTING: Multi-centric infertility centers, France METHODS: Twenty one consecutive women treated with pGnRH treatment were compared to 21 consecutive women receiving other types of infertility treatment. Diagnosis of ED was based on DSM-IV and the Composite International Diagnostic Interview (CIDI). RESULTS: Twenty patients (95.2%) from the sample of women treated with pulsatile GnRH treatment and 5 patients (23.8%) from the patients receiving other types of infertility treatment met the criteria of lifetime ED diagnosis (p < 0.000). CONCLUSION: This study highlights the fact that the prevalence of ED is considerably higher in women receiving GnRH pulsatile treatment, when compared to women receiving other kinds of infertility treatment. In our study population ED were under-diagnosed, particularly in women receiving pulsatile GnRH treatment. Fertility clinicians should use reliable diagnostic tools to identify promptly ED in women presenting with hypothalamic amenorrhea and difficulties in conceiving. Level III: Evidence obtained from well-designed cohort or case-control analytic studies.

Natural mutations of the anti-Mullerian hormone type II receptor found in persistent Mullerian duct syndrome affect ligand binding, signal transduction and cellular transport.

The anti-Müllerian hormone type II (AMHRII) receptor is the primary receptor for anti-Müllerian hormone (AMH), a protein produced by Sertoli cells and responsible for the regression of the Müllerian duct in males. AMHRII is a membrane protein containing an N-terminal extracellular domain (ECD) that binds AMH, a transmembrane domain, and an intracellular domain with serine/threonine kinase activity. Mutations in the AMHRII gene lead to persistent Müllerian duct syndrome in human males. In this paper, we have investigated the effects of 10 AMHRII mutations, namely 4 mutations in the ECD and 6 in the intracellular domain. Molecular models of the extra- and intracellular domains are presented and provide insight into how the structure and function of eight of the mutant receptors, which are still expressed at the cell surface, are affected by their mutations. Interestingly, two soluble receptors truncated upstream of the transmembrane domain are not secreted, unless the transforming growth factor beta type II receptor signal sequence is substituted for the endogenous one. This shows that the AMHRII signal sequence is defective and suggests that AMHRII uses its transmembrane domain instead of its signal sequence to translocate to the endoplasmic reticulum, a characteristic of type III membrane proteins.

Predictive factors for pregnancy after controlled ovarian stimulation and intrauterine insemination: A retrospective analysis of 4146 cycles.

BACKGROUND: The variability in indications and low rate of pregnancy compared to IVF have led many authors to dismiss IUI and offer IVF first-line instead. OBJECTIVES: To determine what are the predictive factors for clinical pregnancy (CP) and live birth (LB) in intrauterine insemination (IUI) cycles following controlled ovarian stimulation (COS). METHODS: Retrospective unicentric study, between January 2009 and December 2016. Patients aged 18 to <43 years who had an IUI following COS with gonadotropins. Statistical analysis was performed using Chi square and logistic regression. RESULTS: 4146 cycles (1312 couples) included. Mean age was 34.7 +/- 4years. LBR per couple was 39% for anovulatory infertility compared to (p < 0.05) unex-plained infertility (28.6%), mixed (23.4%), male factor (20.1%), unilateral tubal (14.2%), low ovarian reserve (13.2%), and endometriosis (stage I and II) (11.1%). Multivariate analysis showed the following factors were associated with CP: Cycle rank ≤3 (Odds ratio (OR) = 1.5, 95% CI: 1.2-1.9, p < 0.001), age <38 years (OR = 1.5, 95% CI: 1.2-2, p < 0.001), ≥2 preovulatory follicles (OR = 1.4, 95% CI: 1.1-1.8, p = 0.004), TMSC ≥ 5 millions (OR = 1.8, 95% CI: 1.3-2.4, p < 0.001). Endometriosis, low ovarian reserve, unilateral tubal and male factor had a negative impact on CPR (OR = 0.3, 95% CI: 0.1-0.5, p < 0.001; OR = 0.4, 95% CI: 0.3-0.7, p < 0.001; OR = 0.5 95% CI: 0.3-0.9, p = 0.01; OR = 0.6, 95% CI: 0.4-0.8, p = 0.002 respectively) compared to anovulatory infertility. CONCLUSION: We confirm that IUI can be an efficient treatment in selected indications. Young patients with anovulatory infertility seem to be the ideal candidates, with a 39% LBR per couple.

X chromosome-linked Kallmann syndrome: clinical heterogeneity in three siblings carrying an intragenic deletion of the KAL-1 gene.

Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia. The gene underlying the X chromosome-linked form of the disease, KAL-1, consists of 14 coding exons. It encodes a glycoprotein, anosmin-1, which is involved in the embryonic migration of GnRH-synthesizing neurons and the differentiation of the olfactory bulbs. We describe herein the clinical heterogeneity in three affected brothers who carry a large deletion (exons 3-13) in KAL-1. All three had a history of hypogonadotropic hypogonadism with delayed puberty. Although brain magnetic resonance imaging showed hypoplastic olfactory bulbs in the three siblings, variable degrees of anosmia/hyposmia were shown by olfactometry. In addition, these brothers had different phenotypic anomalies, i.e. unilateral renal aplasia (siblings B and C), high-arched palate (sibling A), brachymetacarpia (sibling A), mirror movements (siblings A and B), and abnormal eye movements (sibling C). Last but not least, sibling A suffered from a severe congenital hearing impairment, a feature that had been reported in KS but had not yet been ascribed unambiguously to the X-linked form of the disease. The variable phenotype, both qualitatively and quantitatively, in this family further emphasizes the role of putative modifier genes, and/or epigenetic factors, in the expressivity of the X-linked KS.