Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous inherited disorders characterized by impaired neuromuscular transmission. Mutations in the acetylcholinesterase (AChE) collagen-like tail subunit gene (COLQ) cause synaptic basal-lamina associated CMS with end-plate AChE deficiency. Here we present the clinical and molecular genetic findings of 22 COLQ-mutant CMS patients, carrying a total of 20 different COLQ mutations, 11 of them had not previously been reported. Typically, patients with esterase deficiency suffer from a severe, progressive weakness with onset at birth or in early infancy. In addition, patients with a late onset showing a mild course of disease are described. AChE inhibitor therapy, beneficial for other forms of CMS, is of no effect in cases of esterase deficiency. The large cohort of COLQ patients studied here enabled us to define additional clinical presentations associated with COLQ mutations that differ from the 'classical' phenotypes: several patients with disease onset at birth or in early infancy presented an unexpected, mild disease course without significant progression of weakness. Moreover, many patients had clinical features reminiscent of limb-girdle CMS with mutations in the recently discovered DOK7 gene, including sparing of eye movements and a predominantly proximal muscle weakness. There was no long-term objective benefit from esterase inhibitors treatment in COLQ patients. Surprisingly, a short-term beneficial effect was observed in four patients and a Tensilon test was positive in two. Treatment with ephedrine was efficient in all five cases where it was administered. The variability of phenotypes caused by COLQ mutations, the divergence from the previously published classical clinical features and an initial positive response to esterase inhibitors in some patients may obscure AChE deficiency as the molecular cause of the disease and delay the start of appropriate therapy. Moreover, overlap with other CMS subtypes and potentially absence of a repetitive compound muscle action potential should be considered in the diagnosis of COLQ-mutated patients.

Tubal factor infertility (TFI) accounts for more than 30% of the cases of female infertility and mostly resides from an inflammatory process triggered by an infection. Clinical appearances largely differ, and very often infections are not recognized or remain completely asymptomatic over time. Here, we characterized the microbial pattern in females diagnosed with infectious infertility (ININF) in comparison to females with non-infectious infertility (nININF), female sex workers (FSW) and healthy controls (fertile). Females diagnosed with infectious infertility differed significantly in the seroprevalence of IgG antibodies against the C. trachomatis proteins MOMP, OMP2, CPAF and HSP60 when compared to fertile females. Microbiota analysis using 16S amplicon sequencing of cervical swabs revealed significant differences between ININF and fertile controls in the relative read count of Gardnerella (10.08% vs. 5.43%). Alpha diversity varies among groups, which are characterized by community state types including Lactobacillus-dominated communities in fertile females, an increase in diversity in all the other groups and Gardnerella-dominated communities occurring more often in ININF. While all single parameters did not allow predicting infections as the cause of infertility, including C. trachomatis IgG/IgA status together with 16S rRNA gene analysis of the ten most frequent taxa a total of 93.8% of the females were correctly classified. Further studies are needed to unravel the impact of the cervical microbiota in the pathogenesis of infectious infertility and its potential for identifying females at risk earlier in life.

Laparoscopic myomectomy is regarded as the gold standard for women with symptomatic fibroids who wish to become pregnant. High-intensity focused ultrasound (HIFU or MRgFUS) ablation of uterine fibroids is also being discussed as a non-surgical, minimally invasive, therapeutic option. This review examines the available data on the impact of HIFU/MRgFUS on fertility and pregnancy, focusing particularly on potential direct side-effects of this type of intervention on ovaries, fallopian tubes and uterus and potential late effects on pregnancy and birth, based on the current literature. All pregnancies after HIFU/MRgFUS published to date (around 100 cases) were evaluated. The published case series suggest that HIFU/MRgFUS ablation has no impact on the rate of miscarriages or other obstetrical outcome parameters. Because no prospective studies exist which permit firm conclusions to be drawn on the impact of HIFU/MRgFUS on fertility and pregnancy outcome in women with symptomatic fibroids, this approach is currently only recommended for women with suspected fertility problems due to uterine fibroids who either decline surgery or who have an unacceptably high surgical risk.

Objective: To elaborate the antenatal sonographic findings of fetuses with the suspicion of fetal akinesia, thereby focusing on the accuracy of prenatal differentiation between subtypes of fetal akinesia, namely Pena-Shokeir phenotype (PSP) and arthrogryposis multiplex congenita (AMC). Methods: We herein present our experience of 21 patients with PSP and AMC diagnosed antenatally at a tertiary prenatal referral center. During the study period 30,485 consecutive high- and low-risk pregnancies were examined. The prenatal sonograms, pediatric charts and autopsy data of affected individuals were reviewed. Our findings were analyzed together with findings retrieved from the literature. Results: The diagnosis of AMC has been established between 12+0 and 30+1 gestational weeks, whereas cases found to have PSP were all diagnosed in advanced pregnancy. In accordance to previous findings, our data suggest that pulmonary hypoplasia is obligatory in PSP and cannot be found in AMC. Therefore, all pregnancies (9/9) affected by PSP were terminated on parental request. Of those fetuses with AMC, 3/12 were liveborn, 2 of which have neuromotoric disabilities. Conclusions: Establishing the correct prenatal diagnosis of PSP and AMC at an early stage and its diligent prognostic evaluation play a crucial role in order to provide adequate advice to the afflicted parents and to enable appropriate intervention at an early stage.