Effectiveness of recombinant human follicle-stimulating hormone (r-hFSH): recombinant human luteinizing hormone versus r-hFSH alone in assisted reproductive technology treatment cycles among women aged 35-40 years: A German database study.

This non-interventional study compared the effectiveness of recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) (2:1 ratio) versus r-hFSH alone for ovarian stimulation (OS) during assisted reproductive technology treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register (D·I·R). Numerically higher clinical pregnancy (29.8% [95% CI 28.2, 31.6] vs. 27.8% [26.5, 29.2]) and live birth (20.3% [18.7, 21.8] vs. 18.0% [16.6, 19.4]) rates were observed with r-hFSH:r-hLH versus r-hFSH alone. The treatment effect was consistently higher for r-hFSH:r-hLH compared with r-hFSH alone in terms of clinical pregnancy (relative risk [RR] 1.16 [1.05, 1.26]) and live birth (RR 1.16 [1.02, 1.31]) in a post-hoc analysis of women with 5-14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of r-hFSH:r-hLH for OS in women aged 35-40 years with normal ovarian reserve.

Comparative effectiveness of gonadotropins used for ovarian stimulation during assisted reproductive technologies (ART) in France: A real-world observational study from the French nationwide claims database (SNDS).

This comparative non-interventional study using data from the French National Health Database (Système National des Données de Santé) investigated real-world (cumulative) live birth outcomes following ovarian stimulation, leading to oocyte pickup with either originator recombinant human follicle-stimulating hormone (r-hFSH) products (alfa or beta), r-hFSH alfa biosimilars, or urinaries including mainly HP-hMG (menotropins), and marginally u-hFSH-HP (urofollitropin). Using data from 245,534 stimulations (153,600 women), biosimilars resulted in a 19% lower live birth (adjusted odds ratio (OR) 0.81, 95% confidence interval (CI) 0.76-0.86) and a 14% lower cumulative live birth (adjusted hazard ratio (HR) 0.86, 95% CI 0.82-0.89); and urinaries resulted in a 7% lower live birth (adjusted OR 0.93, 95% CI 0.90-0.96) and an 11% lower cumulative live birth (adjusted HR 0.89, 95% CI 0.87-0.91) versus originator r-hFSH alfa. Results were consistent across strata (age and ART strategy), sensitivity analysis using propensity score matching, and with r-hFSH alfa and beta as the reference group.

Rare metabolic disease mimicking COL4A1/COL4A2 fetal brain phenotype.

Pathogenic variants of collagen type IV alpha 1 and 2 (COL4A1/COL4A2) genes cause various phenotypic anomalies, including intracerebral hemorrhage and a wide spectrum of developmental anomalies. Only 20% of fetuses referred for COL4A1/COL4A2 molecular screening (fetuses with a suspected intracerebral hemorrhage) carry a pathogenic variant in these genes, raising questions regarding the causative anomaly in the remaining 80% of these fetuses. We examined, following termination of pregnancy or in-utero fetal death, a series of 113 unrelated fetuses referred for COL4A1/COL4A2 molecular screening, in which targeted sequencing was negative. Using exome sequencing data and a gene-based collapsing test, we searched for enrichment of rare qualifying variants in our fetal cohort in comparison to the Genome Aggregation Database (gnomAD) control cohort (n = 71 702). Qualifying variants in pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) were overrepresented in our cohort, reaching genome-wide significance (P = 2.11 × 10-7 ). Heterozygous PDHA1 loss-of-function variants were identified in three female fetuses. Among these three cases, we observed microcephaly, ventriculomegaly, germinolytic pseudocysts, agenesis/dysgenesis of the corpus callosum and white-matter anomalies that initially suggested cerebral hypoxic-ischemic and hemorrhagic lesions. However, a careful a-posteriori reanalysis of imaging and postmortem data showed that the observed lesions were also consistent with those observed in fetuses carrying PDHA1 pathogenic variants, strongly suggesting that these two phenotypes may overlap. Exome sequencing should therefore be performed in fetuses referred for COL4A1/COL4A2 molecular screening which are screen-negative, with particular attention paid to the PDHA1 gene. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

[Contribution of the pre-operative Mri-coloscan couple in the surgical planning of deep digestive pelvic endometriosis]. / Apport du couple IRM-coloscanner pré-opératoire dans la planification chirurgicale de l'endométriose digestive.

INTRODUCTION: The digestive involvement of endometriosis accounts for up to 20-25% of deep localisations. Precise mapping of digestive lesions is essential in order to plan surgery and specialized teams. The aim of this study is to assess the contribution of the MRI-coloscan couple in the preoperative assessment of digestive endometriosis. METHODS: We analyzed 45 files of patients referred for suspected digestive endometriosis. They had all undergone a preoperative MRI and coloscan associated with surgery throughout the year. We first compared the data collected in imaging, and then compared the synthesis of this data with the surgical procedure performed. RESULTS: 35 patients required digestive surgery. 24 of 45 files were concordant in MRI and coloscanner. Data from MRI alone matched with surgery in 69% of cases, against 84% for the coloscan. The synthesis allowed a concordance of 89%. 25 segmental resections, 2 discoid and 16 shaving were performed. The use of coloscan made up for nine extra cases: the detection of four additional cases of multifocality, a single undiagnosed case of a deep lesion, and allowed to specify the depth of the involvement in four cases. On the contrary, the MRI was correct compared to the CT in four cases. The presence of a digestive surgeon was necessary in 53% of cases. CONCLUSION: In the era of imaging staging, it would seem interesting to turn towards a subclassification of the digestive involvement of endometriosis in order to decide which surgery to perform. In our experience, the coloscan is a useful complement of MR, especially to assess the depth of involvement and the multifocality.

How reproducible are classical and new CT-pelvimetry measurements?

PURPOSE: The objective of this study was to assess the reliability and reproducibility of existing and new computed tomography (CT)-pelvimetry measurements. MATERIAL AND METHODS: A retrospective cohort study of 63 women with a mean age of 33.9±5.2 (SD) years (range: 19-49 years) was conducted. Classical pelvimetry measurements were collected including the obstetric conjugate (OC), median transverse diameter (MTD), and interspinous diameter (ISD). Additionally, we used multiplanar reconstruction (MPR) mode to define two oblique planes: inlet pelvic plane (IPP) and mid-pelvic plane (MPP) and measure new pelvic parameters, including anteroposterior (APD), transverse diameters and circumference of both IPP and MPP (inletAPD, inletMTD, inletCIRC and midAPD, ISD, midCIRC, respectively). The reproducibility (intra- and inter-observer) of our results were assessed. Multivariate analyses using principal component analysis and clustering methods were conducted to analyze the association between pelvimetry measurements and identify patient sub-groups. RESULTS: All linear measurements (OC, inletAPD, MTD, inletMTD, midAPD, and ISD) showed statistically "almost perfect" intra- and inter-observer correlation coefficients (range: 0.924-0.980). Circumferences (inletCIRC and midCIRC) showed statistically "almost perfect" intra- (range: 0.847-0.857) and inter-observer correlation coefficients (range: 0.923-0.957). The measurement of 6 pelvimetric parameters allowed determining three groups of pelvis size. CONCLUSION: New pelvic measurements have excellent reproducibility and are similar to the classical measurements, based on the MPR analysis of CT planes adjusted to the inner bony pelvis.

Prenatal diagnosis of esophageal atresia: A case of triple negative screening.

Esophageal atresia (EA) is prenatally diagnosed in less than one third of the cases and is usually only suspected. Recently, magnetic resonance imaging (MRI) with dynamic sequence and biochemistry of the amniotic fluid have been proposed to enhance prenatal diagnosis of EA. We report the case of a triple negative screening (ultrasound, MRI with dynamic sequence and biochemistry of the amniotic fluid) with a postnatal diagnosis of EA type III with a small defect. Even using second line tests, prenatal diagnosis of EA remains a challenge.

Contribution of fetal brain MRI in management of severe fetal anemia.

INTRODUCTION: Intrauterine transfusion (IUT) has changed fetal anemia prognosis. However, long-term neurodevelopmental outcome is altered in 5% of children. Our objective was to study the contribution of fetal MRI to diagnosis brain lesions in case of fetal anemia. MATERIAL AND METHODS: Retrospective monocentric descriptive study from 2005 to 2016, including all patients followed for fetal anemia requiring IUT. The indications for MRI were: hydrops fetalis and / or hemoglobin <5 g / dL and / or more than 3 IUTs and / or acute severe anemia and / or ultrasound abnormality. Fetal and neonatal outcome and pediatric neurological monitoring were studied. RESULTS: 89 patients were followed for fetal anemia with IUT and 28 (29.1%) had fetal MRI, 12 of which were abnormal. Two out of twelve had abnormal ultrasound. Seven out of twelve had poor neurological prognosis: 2 medical terminations of pregnancy were performed; 2 children had severe developmental delay and 3 children had schooling difficulties. Five out of twelve children had favorable neurological prognosis. CONCLUSION: MRI of the fetal brain makes it possible to better detect brain lesions than ultrasound does in the management of severe fetal anemia and seems particularly appropriate in cases of acute anemia.

Management of red blood cell alloimmunization in pregnancy.

The main cause of fetal anemia is maternal red blood cell alloimmunization (AI). The search of maternal antibodies by indirect antiglobulin test allows screening for AI during pregnancy. In case of AI, fetal genotyping (for Rh-D, Rh-c, Rh-E and Kell), quantification (for anti-rhesus antibodies) and antibody titration, as well as ultrasound monitoring, are performed. This surveillance aims at screening for severe anemia before hydrops fetalis occurs. Management of severe anemia is based on intrauterine transfusion (IUT) or labor induction depending on gestational age. After intrauterine transfusion, follow-up will focus on detecting recurrence of anemia and detecting fetal brain injury. With IUT, survival of fetuses with alloimmunization is greater than 90% but 4.8% of children with at least one IUT have neurodevelopmental impairment.

Radiological assessment of the placement of Essure® in order to reduce hysterosalpingography: Pelvic X-ray versus combined pelvic X-ray and ultrasound.

OBJECTIVE: Three months after hysteroscopic sterilisation with Essure®, a confirmation test is required to evaluate the correct location of the inserts. The test may be conducted using a pelvic ultrasound (2D or 3D) or an abdominal X-ray. Should the location not look satisfactory on these tests, a follow-up hysterosalpingography (HSG) would be required. The objective of our study is to assess whether the Essure® 3-month confirmation test using a single X-ray or a combination of X-ray and ultrasound could reduce the use of HSG. STUDY DESIGN: This retrospective study examined patients who underwent birth control Essure® procedure between 2009 and 2015 in the Gynaecological Surgery Department at the Regional University Hospital Centre (CHRU) in Lille. We divided patients into two groups based on the imaging tests performed: single X-ray (2009-2010) versus X-ray and pelvic ultrasound (2014-2015). We then compared the results of the imaging tests and the use of HSG between the two groups. RESULTS: One hundred and thirty-four patients were tested, of which 60 (44.8%) using a single X-ray and 74 (55.2%) using a combination of X-ray and ultrasound. We note that the combined X-ray/ultrasound test reduces significantly the number of HSG performed (26.7% versus 12.2%, P=0.04). CONCLUSION: Compared to a single X-ray, the combination of X-ray and ultrasound enables to significantly limit the use of HSG.

Deep infiltrating endometriosis: Should rectal and vaginal opacification be systematically used in MR imaging?

OBJECTIVES: To evaluate the interest of rectal and vaginal filling in vaginal and recto-sigmoid endometriosis with MR imaging. To compare the results between a senior and a junior radiologist review. METHODS: Sixty-seven patients with clinically suspected deep infiltrating endometriosis were included in our MRI protocol consisting of repeated T2-weigthed sequences (axial and sagittal) before and after rectal and vaginal marking with ultrasonography gel. Vaginal and recto-sigmoid endometriosis lesions were analyzed before and after opacification. The inter-reader agreement between senior and junior scores was studied. RESULTS: Concerning vaginal and muscularis and beyond colonic involvement, no significant difference (P=0.32) was observed and the inter-reader agreement was excellent (K=0.96 and 0.97 respectively). Concerning serosa colonic lesions, a significant difference was observed (P=0.01) and the inter-reader agreement was poor (K=0). CONCLUSIONS: Rectal and vaginal filling in endometriosis staging with MRI is not necessary no matter the reader experiment.

Transparency and Reproducibility of Observational Cohort Studies Using Large Healthcare Databases.

The scientific community and decision-makers are increasingly concerned about transparency and reproducibility of epidemiologic studies using longitudinal healthcare databases. We explored the extent to which published pharmacoepidemiologic studies using commercially available databases could be reproduced by other investigators. We identified a nonsystematic sample of 38 descriptive or comparative safety/effectiveness cohort studies. Seven studies were excluded from reproduction, five because of violation of fundamental design principles, and two because of grossly inadequate reporting. In the remaining studies, >1,000 patient characteristics and measures of association were reproduced with a high degree of accuracy (median differences between original and reproduction <2% and <0.1). An essential component of transparent and reproducible research with healthcare databases is more complete reporting of study implementation. Once reproducibility is achieved, the conversation can be elevated to assess whether suboptimal design choices led to avoidable bias and whether findings are replicable in other data sources.

The contribution of fetal MR imaging to the assessment of oesophageal atresia.

OBJECTIVE: Present challenges are to improve the diagnosis rate of oesophageal atresia (OA) and evaluate as completely as possible a fetus affected by OA, specifically the type of OA and the length of the gap. Our aim was to evaluate the accuracy of fetal MR imaging (fMRI) for diagnosis of OA. METHODS: We reviewed fMRI performed because of sonographic suspicion of an OA. The signs reviewed included stomach size, "pouch sign", bowing of the trachea and visualization of the lower oesophageal lumen. The fetuses were assigned by consensus as having or not having EA, as well as having a tracheaoesophageal fistula (TOF). All findings were correlated with postnatal data. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Se, Sp, PPV and NPV of the technique were respectively 91%, 100%, 100% and 88%. The presence of the pouch sign yielded corresponding values of 82%, 100%, 100% and 78%. Mid-tracheal bowing was correlated positively with EA. The type of atresia was correctly evaluated in 90% of patients. CONCLUSION: fMRI is useful for the diagnosis of EA through the visualization of the oesophageal pouch or through associated signs such as tracheal bowing. Visualization of the lower oesophageal lumen seems to be a good sign of TEF. KEY POINTS: • Challenges are to improve the prenatal diagnosis of EA and associated malformations. • fMRI is able to diagnose EA through demonstration of the pouch sign. • Tracheal bowing is a promising indirect sign of EA. • Tracheoesophageal fistula can also be suspected thanks to fMRI. • Obstetrical US, fMRI and fetal CT are complementary for assessing associated malformations.

Does a combination of ultrasound, MRI, and biochemical amniotic fluid analysis improve prenatal diagnosis of esophageal atresia?

OBJECTIVE: Prenatal diagnosis of esophageal atresia (EA) remains a challenge. Our objective was to evaluate the combination of sonography, magnetic resonance imaging (MRI), and amniotic fluid biochemical markers in prenatal diagnosis of EA. STUDY DESIGN: A retrospective study of all cases with prenatal suspicion of EA from January 2008 to May 2013 in our regional reference center was carried out. Patients were included if all the three tests were performed. For each test, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) were evaluated. Each test was compared using Fisher's exact test. RESULTS: Fifteen patients were referred at a median gestational age of 28(+5) weeks (24-36) for suspicion of EA on the basis of small or non-visualized fetal stomach bubble and/or polyhydramnios. Se, Sp, PPV, and NPV for sonographic pouch sign/MRI/biochemical amniotic fluid were respectively 40/100/100/45.5%, 80/100/100/71.4%, and 90/60/81.8/75%. MRI was the best predictive test (p = 0.007). CONCLUSION: In case of ultrasound prenatal suspicion of EA (with or without visualization of the pouch sign), an MRI at 30-32 weeks using fast imaging employing steady-state acquisition should be proposed. Biochemical amniotic fluid may be helpful and should be evaluated in a larger study.

[Esophageal atresia: prevalence, prenatal diagnosis and prognosis]. / Atrésie de l'œsophage : prévalence, diagnostic anténatal et pronostic.

Esophageal atresia (EA) is a rare congenital malformation (1 in 2,500 to 3,500 births). Prenatal diagnosis (PN) is particularly interesting allowing search for associated malformations related to worse prognosis forms (reference ultrasound, MRI and amniocentesis) and planning the birth in an adapted medico-surgical center. Diagnosis of EA is usually suspected because of indirect and non-specific signs: association of polyhydramnios and absent or small stomach bubble. The visualization in ultrasound or MRI of cervical or thoracic fluid image corresponding to the expansion of the bottom of upper esophageal ("pouch sign") increases the specificity of diagnosis. However, prenatal diagnosis remains difficult and less than 50 % of EA are diagnosed prenatally. Biochemical analysis could improve these results. If EA is confirmed at birth, surgical management consists in a primary end-to-end anastomosis in first days of life, or in two-steps surgery if the defect is too large. Although current prognosis of EA is good, frequency of surgical complications and esophageal lesions secondary to gastroesophageal reflux justify a systematic and multidisciplinary extended follow-up.

Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease.

BACKGROUND: Frontotemporal dementia associated with motor neuron disease (FTD-MND) is a rare neurodegenerative disorder that may be inherited by autosomal dominant trait. No major gene has been identified but a locus was mapped on chromosome 9 (9p21.3-p13.3). METHODS: Ten French families with FTD-MND were tested for linkage to the 9p21.3-p13.3 region. We report extensive mutation screening in 9p-linked families and their clinical characteristics. RESULTS: We identified six new families with evidence for linkage to the chromosome 9p. Cumulative multipoint LOD score values were positive between markers D9S1121 and D9S301, reaching a peak of 8.0 at marker D9S248. Haplotype reconstruction defined the telomeric boundary at marker AFM218xg11, slightly narrowing the candidate interval. We found no disease-causing mutations by sequencing 29 candidate genes including IFT74 and no copy number variations in the 9p region. The mean age at onset was 57.9 +/- 10.3 years (range, 41-84), with wide heterogeneity within and among families suggesting age-dependant penetrance. The patients presented isolated FTD (32%), isolated MND (29%), or both disorders (39%). The general characteristics of the disease did not differ, except for an older age at onset and shorter disease duration in the 9p-linked compared to nonlinked families. TDP-43-positive neuronal cytoplasmic inclusions were found in cortex and spinal cord in 3 patients. CONCLUSIONS: This study increases the number of 9p-linked families now reported and shows that this locus may have a major effect on frontotemporal dementia (FTD) and motor neuron disease (MND). Considering our results, the causative gene might be implicated in at least 60% of the families with FTD-MND disorder.

[Correlation between the presence of type-2 anti-pemphigoid antibodies and dementia in elderly subjects with no clinical signs of pemphigoid]. / Corrélation entre présence d'anticorps anti-antigène de type 2 de la pemphigoïde et démence chez les sujets âgés sans manifestation clinique de pemphigoïde.

BACKGROUND: Pemphigoid is a form of auto-immune bullous dermatosis characterised by the production of antibodies directed against components of hemidesmosomes in the basal membrane. The physiopathological process responsible for unmasking of these antigens is unknown. Pemphigoid is more common in elderly subjects and is most often seen in debilitated subjects. The prevalence of pemphigoid anti-pemphigoid antibodies (anti-PB) is not known in the elderly population presenting no dermatological signs evocative of the disease. We studied the prevalence of anti-PBAg2 antibodies in elderly subjects with no signs of pemphigoid as well as in the correlation between the presence of these antibodies and diagnosis of dementia. PATIENTS AND METHODS: Elderly subjects (aged over 69 years) with no signs of pemphigoid were recruited consecutively in dermatology and geriatrics departments (138 subjects). Details of concomitant medication were recorded for all subjects and clinical examination was performed with calculation of MMS (Mini Mental Score). The subjects were then divided into two groups based on MMS score. The first group comprised subjects without dementia (MMS > 24) while the second comprised subjects with dementia. Serum anti-PBAg2 antibodies were determined by ELISA and indirect immunofluorescence with confirmation by Western blot. Antinuclear antibodies, used as a control for non-specific immune response, were assayed in all serum samples. The prevalence of these antibodies was compared between the two groups. RESULTS: The two groups were comparable in terms of age, sex and presence of dermatological diseases (ulcers, bedsores, erysipelas). Each group comprised 69 subjects. The overall presence of anti-PBAg2 antibodies in subjects with no signs are suggestive of pemphigoid was 3.6%. Presence of anti-PBAg2 antibodies was associated with diagnosis of dementia (p=0.04; 0% and 7% in groups 1 and 2, respectively). No correlation was seen between the presence of anti-PBAg2 antibodies and concomitant medication or dermatological disease. The overall prevalence of antinuclear antibodies was 14.5% and the figure was similar between the two groups. DISCUSSION: The presence of anti-PBAg2 could be associated with the diagnosis of dementia in elderly subjects.

Efficacy of escitalopram in patients with severe depression: a pooled analysis.

Escitalopram is an effective, well-tolerated treatment for major depressive disorder in both primary and specialist settings. This analysis compared the efficacy of escitalopram with citalopram in the treatment of patients with severe depression [defined as a score of > or =30 Montgomery-Asberg Depression Rating Scale (MADRS)]. Data from three clinical trials were used for this pooled analysis. A total of 506 severely depressed patients were included (169 received escitalopram, 171 citalopram and 166 placebo). Mean change from baseline in MADRS total scores (primary efficacy parameter) was significantly higher in the escitalopram-treated group compared with the citalopram-treated group (p = 0.003). There was a significant difference in response between escitalopram and citalopram (56 vs. 41%, respectively, p = 0.007). Results from secondary efficacy parameters (Hamilton rating for depression and Clinical Global Impression of Improvement and Severity scales) were consistent with previous results. The benefits in severe depression of escitalopram vs. citalopram were so demonstrated.