IVF Centers Prof. Zech

Antibody‐drug conjugates (ADCs) and immunotherapy have changed the treatment landscape for locally advanced and metastatic urothelial carcinoma (la/mUC). Clinical trials have demonstrated the superiority of enfortumab vedotin (EV) combined with pembrolizumab (P) over chemotherapy. This retrospective, multicentre Austrian registry analysis evaluated the effectiveness and safety of EV + P in treatment‐naïve la/mUC patients in a real‐world setting. This study included 203 first‐line EV + P treated patients from 20 Austrian centres. The majority were male (77.3%), with a median age of 70 years (range, 26–92), while 33.5% were ≥75 years. Comorbidities were common, with 25.1% having a Charlson Comorbidity Index (CCI) ≥ 5, and 46.3% moderate to severe renal impairment. Among 195 evaluable patients, the objective response rate (ORR) was 63.6% (95% CI, 56.6–70.0), including 21.5% complete responses and 42.1% partial responses. Disease control was achieved in 75.4% (95% CI, 68.9–80.9). Median progression‐free survival (PFS) and overall survival (OS) were not reached after a median follow‐up of 5.8 months. Poor outcomes were associated with ECOG PS >2 (PFS, p = .003; OS, p< .001) and CCI ≥5 (PFS, p = .011; OS, p = .08). EV + P was generally well tolerated; grade ≥3 treatment‐related adverse events occurred in 38.4% of patients and immune‐related adverse events in 19.2%. Limitations of this study include its retrospective design and short follow‐up. These findings support the clinical use of EV + P as first‐line treatment for la/mUC, demonstrating substantial effectiveness and manageable toxicity in a large real‐world population, including elderly and comorbid patients. Extended follow‐up is warranted to determine long‐term survival and predictive markers of response.

Background and objectivesThe severity of the phenotype of spinal muscular atrophy (SMA) is highly variable, yet little is known about the phenotypic variation among siblings. We systematically investigated the phenotypic variability of therapy-naïve 5q-SMA siblings leveraging a large multicentre cohort from the SMArtCARE registry.ResultsClinical information was available from 132 siblings of 65 families. There were 24 (18.2%) type 1, 38 (28.7%) type 2, 54 (40.9%) type 3 patients, and 16 (12.1%) presymptomatic individuals. In 17 families (32.1%), there was discordance in the type of SMA among symptomatic siblings. We found no influence of gender on discordance in SMA type among siblings (p = 0.528). The median age at disease onset within all sibships varied by 6 months (interquartile range (IQR) = 1-30). There was no correlation in age of onset among siblings (r = 0.405; p = 0.052). Among siblings who lost ambulation, the median interval between the start of wheelchair use was 12 months, but the maximal interval was 18 years. In one pair of siblings, one sibling lost the ability to walk at the age of 13, whereas the other sibling was still ambulatory at the age of 54. In 6 sibling pairs (9.5%), only one of both siblings had a history of scoliosis surgery. Analysing SMN2 copy numbers, in one sibling pair (1.8%) 1 SMN2 gene copy was detected, while 10 (17.5%) had 2 copies, 23 (40.4%) had 3 copies, and 17 (29.8%) had 4 copies. Concordance in SMN2 copy numbers across siblings was observed in 90% of families. With increasing SMN2 copy number, the median differences in age of onset among siblings increased without reaching statistical significance.ConclusionThis study reports considerable phenotypic variability in therapy-naïve SMA sibships that cannot solely be explained by differences in SMN2 copy numbers.

In mammals, estrogens and progestogens are crucial for gestation, fetal development, and maternal preparation for parturition and lactation. Measuring these hormones allows for the diagnosis of pregnancy, estimation of pregnancy failures, and potentially prenatal sex determination. We evaluated urinary estrogen and progestogen metabolites as biomarkers for gestation detection and for their utility for fetal sex determination in wild Assamese macaques (Macaca assamensis) using 586 samples from 19 females, including 19 successful pregnancies. Four enzyme-immunoassays were tested for suitability in measuring urinary sex steroids using serial dilution: three assays targeting progestogen and one targeting estrogen metabolites (estrone conjugates, E1C). We performed a biological validation by measuring urinary hormone metabolites in one female across pre-, early-, late-, and post-gestation. None of the progestogen measurements reflected gestational status, while E1C levels showed the expected increases during gestation. Next, we measured urinary E1C across gestation in all females and investigated fetal sex effects on maternal E1C levels, expecting differences between females carrying male versus female fetuses. Urinary E1C levels increased as early as 9 days postconception and declined sharply at parturition, mirroring patterns in other primates. During late gestation, females carrying male fetuses had significantly higher E1C levels than those carrying female fetuses, yet overlapping values limit precision for prenatal sex determination. Urinary E1C offers a noninvasive marker for gestation monitoring in Assamese macaques, with application in ecological and conservation research. Additionally, results indicate intra- and inter-species-specific differences in steroid hormone metabolism and excretion, which need to be considered when selecting markers for reproductive monitoring.

Introduction: Partial cystectomy aims to preserve bladder function, yet its urodynamic impacts remain unclear. We investigate these effects using an ex vivo porcine model, evaluating bladder volume, compliance, and wall thickness, alongside with thermal damage after bi- and monopolar resection. Methods: Within an artificial human pelvis, we conducted partial bladder wall resections (5 cm2, 10 cm2). Urodynamic tests and sonography assessed volume, compliance, and thickness changes. Traction force for catheter retrieval and thermal collagen destruction were measured. Results: Bladder compliance decreased by 1.12 and 1.5 after 5 cm2 and 10 cm2 resections, respectively, with volume reductions of 3–6% and 10–18%. Wall thickness decreased by 20% and 30% post-resection. Comparable thermal damage was observed with mono- and bipolar resection methods. Conclusion: Our study outlines urodynamic impacts and technical considerations of partial cystectomy, affirming its endoscopic feasibility while highlighting potential bladder dysfunction risks.