Determining the fertility benefit of controlled ovarian hyperstimulation with intrauterine insemination after operative laparoscopy in patients with endometriosis.

STUDY OBJECTIVE: To determine the fertility benefit of controlled ovarian hyperstimulation (COH) and intrauterine insemination (IUI) in surgically treated endometriosis. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Cleveland Clinic Foundation, tertiary care center. PATIENTS: Ninety-six women of reproductive age who underwent operative laparoscopy to treat endometriosis-related infertility (endometriosis stage I/II n = 67; stage III/IV n = 29) from 2001 to 2011 at the Cleveland Clinic Foundation. INTERVENTIONS: COH via letrozole, clomiphene, or gonadotropins, with or without IUI. MEASUREMENTS AND MAIN RESULTS: Kaplan-Meier estimations of cumulative pregnancy rates were compared by stage between COH/IUI and spontaneous cycles. Patients with stage I/II endometriosis attempted spontaneous pregnancy for 669 months and 216 COH + IUI cycles, and patients with stage III/IV endometriosis attempted spontaneous pregnancy for 379 months and 74 COH + IUI cycles. Crude pregnancy rates were 45.7% in stage I/II and 40.5% in stage III/IV. Twelve-month cumulative pregnancy rates in stage I/II were 45% for spontaneous attempts and 42% for COH + IUI, and in stage III/IV were 20% for spontaneous attempts and 10% for COH + IUI (not significant). Cumulative pregnancy rates for COH/IUI in stage I/II were significantly higher than in stage III/IV. Monthly fecundity rates were 3.81% for stage I/II spontaneous, 4.59% for COH/IUI, 3.05% for stage III/IV spontaneous, and 1.68% for COH/IUI (not significant). CONCLUSIONS: COH + IUI did not improve pregnancy rates in any stage of endometriosis. In stage III/IV we recommend postoperative in vitro fertilization.

Chronic desipramine treatment alters tyrosine hydroxylase but not norepinephrine transporter immunoreactivity in norepinephrine axons in the rat prefrontal cortex.

Pharmacological blockade of norepinephrine (NE) reuptake is clinically effective in treating several mental disorders. Drugs that bind to the NE transporter (NET) alter both protein levels and activity of NET and also the catecholamine synthetic enzyme tyrosine hydroxylase (TH). We examined the rat prefrontal cortex (PFC) by electron microscopy to determine whether the density and subcellular distribution of immunolabelling for NET and co-localization of NET with TH within individual NE axons were altered by chronic treatment with the selective NE uptake inhibitor desipramine (DMI). Following DMI treatment (21 d, 15 mg/kg.d), NET-immunoreactive (ir) axons were significantly less likely to co-localize TH. This finding is consistent with reports of reduced TH levels and activity in the locus coeruleus after chronic DMI and indicates a reduction of NE synthetic capacity in the PFC. Measures of NET expression and membrane localization, including the number of NET-ir profiles per tissue area sampled, the number of gold particles per NET-ir profile area, and the proportion of gold particles associated with the plasma membrane, were similar in DMI- and vehicle-treated rats. These findings were verified using two different antibodies directed against distinct epitopes of the NET protein. The results suggest that chronic DMI treatment does not reduce NET expression within individual NE axons in vivo or induce an overall translocation of NET protein away from the plasma membrane in the PFC as measured by ultrastructural immunogold labelling. Our findings encourage consideration of possible post-translational mechanisms for regulating NET activity in antidepressant-induced modulation of NE clearance.