Chromosomal rearrangements have long been known to significantly impact fertility and miscarriage risk. Advancements in molecular diagnostics are challenging contemporary clinicians and patients in accurately characterizing the reproductive risk of a given abnormality. Initial attempts at preimplantation genetic diagnosis were limited by the inability to simultaneously evaluate aneuploidy and missed up to 70% of aneuploidy in chromosomes unrelated to the rearrangement. Contemporary platforms are more accurate and less susceptible to technical errors. These techniques also offer the ability to improve outcomes through diagnosis of uniparental disomy and may soon be able to consistently distinguish between normal and balanced translocation karyotypes. Although an accurate projection of the anticipated number of unbalanced embryos is not possible at present, confirmation of normal/balanced status results in high pregnancy rates (PRs) and diagnostic accuracy.

Glucocorticoid (GC) receptors (GRs) have profound anti-survival effects on human small cell lung cancer (SCLC). To explore the basis of these effects, protein partners for GRs were sought using a yeast two-hybrid screen. We discovered a novel gene, FAM33A, subsequently identified as a SKA1 partner and involved in mitosis, and so renamed Ska2. We produced an anti-peptide antibody that specifically recognized full-length human SKA2 to measure expression in human cell lines and tissues. There was a wide variation in expression across multiple cell lines, but none was detected in the liver cell line HepG2. A xenograft model of human SCLC had intense staining and archival tissue revealed SKA2 in several human lung and breast tumours. SKA2 was found in the cytoplasm, where it co-localized with GR, but nuclear expression of SKA2 was seen in breast tumours. SKA2 overexpression increased GC transactivation in HepG2 cells while SKA2 knockdown in A549 human lung epithelial cells decreased transactivation and prevented dexamethasone inhibition of proliferation. GC treatment decreased SKA2 protein levels in A549 cells, as did Staurosporine, phorbol ester and trichostatin A; all agents that inhibit cell proliferation. Overexpression of SKA2 potentiated the proliferative response to IGF-I exposure, and knockdown with shRNA caused cells to arrest in mitosis. SKA2 has recently been identified in HeLa S3 cells as part of a complex, which is critical for spindle checkpoint silencing and exit from mitosis. Our new data show involvement in cell proliferation and GC signalling, with implications for understanding how GCs impact on cell fate.

For over 2 decades preimplantation genetic testing (PGT) has been in clinical use to reduce the risk of miscarriage and genetic disease in patients with advanced maternal age and risk of transmitting disease. Recently developed methods of genome-wide genotyping and machine learning algorithms now offer the ability to genotype embryos for polygenic disease risk with accuracy equivalent to adults. In addition, contemporary studies on adults indicate the ability to predict polygenic disorders with risk equivalent to monogenic disorders. Existing biobanks provide opportunities to model the clinical utility of polygenic disease risk reduction among sibling adults. Here, we provide a mathematical model for the use of embryo screening to reduce the risk of type 1 diabetes. Results indicate a 45-72% reduced risk with blinded genetic selection of one sibling. The first clinical case of polygenic risk scoring in human preimplantation embryos from patients with a family history of complex disease is reported. In addition to these data, several common and accepted practices place PGT for polygenic disease risk in the applicable context of contemporary reproductive medicine. In addition, prediction of risk for PCOS, endometriosis, and aneuploidy are of particular interest and relevance to patients with infertility and represent an important focus of future research on polygenic risk scoring in embryos.

Summary At the onset of the global pandemic of COVID‐19 (SARS‐CoV‐2), guidelines recommended using regional anaesthesia for caesarean section in preference to general anaesthesia. National figures from the UK suggest that 8.75% of over 170,000 caesarean sections are performed under general anaesthetic. We explored whether general anaesthesia rates for caesarean section changed during the peak of the pandemic across six maternity units in the north‐west of England. We analysed anaesthetic information for 2480 caesarean sections across six maternity units from 1 April to 1 July 2020 (during the pandemic) and compared this information with data from 2555 caesarean sections performed at the same hospitals over a similar period in 2019. Primary outcome was change in general anaesthesia rate for caesarean section. Secondary outcomes included overall caesarean section rates, obstetric indications for caesarean section and regional to general anaesthesia conversion rates. A significant reduction (7.7 to 3.7%, p < 0.0001) in general anaesthetic rates, risk ratio (95%CI) 0.50 (0.39–0.93), was noted across hospitals during the pandemic. Regional to general anaesthesia conversion rates reduced (1.7 to 0.8%, p = 0.012), risk ratio (95%CI) 0.50 (0.29–0.86). Obstetric indications for caesarean sections did not change (p = 0.17) while the overall caesarean section rate increased (28.3 to 29.7%), risk ratio (95%CI) 1.02 (1.00–1.04), p = 0.052. Our analysis shows that general anaesthesia rates for caesarean section declined during the peak of the pandemic. Anaesthetic decision‐making, recommendations from anaesthetic guidelines and presence of an on‐site anaesthetic consultant in the delivery suite seem to be the key factors that influenced this decline.

Preimplantation genetic testing for polygenic disease risk (PGT-P) represents a new tool to aid in embryo selection. Previous studies demonstrated the ability to obtain necessary genotypes in the embryo with accuracy equivalent to in adults. When applied to select adult siblings with known type I diabetes status, a reduction in disease incidence of 45–72% compared to random selection was achieved. This study extends analysis to 11,883 sibling pairs to evaluate clinical utility of embryo selection with PGT-P. Results demonstrate simultaneous relative risk reduction of all diseases tested in parallel, which included diabetes, cancer, and heart disease, and indicate applicability beyond patients with a known family history of disease.