Reprod. Med., Volume 4, Issue 2 (June 2023) – 5 articles

For over 30 years, defects of the functional integrity of the sperm membrane, as evidenced by a low hypo-osmotic swelling test when evaluating the semen analysis, are not only associated with male infertility (even with sperm that otherwise seem normal), but unless corrected, successful intrauterine pregnancies will rarely ensue. This defect, interestingly, does not impair fertilization of the oocyte, but instead, prevents a normal-appearing embryo from successfully implanting. The frequency in infertile couples increases with advancing age of the male, ranging from 5% in younger males to 25% in men in their late forties or early fifties. It seems to be related to a toxic protein added to the sperm as they traverse the ejaculatory ducts. The defect is very correctable, either by treating the sperm with the protein digestive enzyme chymotrypsin prior to intrauterine insemination and avoidance of unprotected sex prior to ovulation, or in vitro fertilization with intracytoplasmic sperm injection. Unfortunately, this very inexpensive, easy-to-perform test is rarely performed by the large majority of physicians treating infertility. The purpose of this manuscript is to hopefully rekindle interest within the infertility community to add this test to the standard semen analysis. Full article

Psychomotor developmental delay in infants includes failure to acquire abilities such as sitting, walking, grasping objects and communication at the ages when most infants have acquired these abilities. Known risk factors include a large number of aspects of family environment, socioeconomic position, problems in pregnancy and birth and maternal health. It is clinically useful to be able to screen for developmental delay so that healthcare interventions can be considered. The present research used machine learning (random forest) to create an algorithm predicting psychomotor delay in 9-month-old infants using information ascertainable at birth and in early infancy. The dataset was the UK longitudinal Millennium Cohort study. In total, 53 predictors measuring socioeconomic indicators, paternal, family and social support for the mother, beliefs about good parenting, maternal health, pregnancy and birth were included in the initial algorithm. Feature reduction showed that of the 53 variables, birthweight, gestational age at birth, pre-pregnancy BMI, family income and parents’ ages had the highest feature importance scores and could alone correctly predict developmental delay with over 99% sensitivity and 100% specificity. No features measuring aspects of early infant care or environment meaningfully added to algorithm performance. The relationships between delay and some of the predictors, particularly income, were nonlinear and complex. The results suggest that the risk of psychomotor developmental delay can be identified in early infancy using machine learning, and that the best predictors are factors present prior to and at birth. Full article

Endometriosis-associated ovarian cancer (EAOC) is an evolving clinical entity believed to develop from ovarian endometriosis. Continuous efforts are nowadays invested in exploring its pathogenesis and causality. Since endometrioma is a widespread sub-type of the disease, malignant transformation to EAOC during reproductive age may cause much concern and affect its management. The summary relative risk of developing EAOC in women with endometriosis is 1.93-fold compared to women without endometriosis, but its lifetime risk is relatively low, equivalent to 2.1%. EAOC is an age-dependent disease with a mean age of 51.64 ± 3.24 years at diagnosis; 30.68% of patients are below 50, presumably premenopausal. Only 2.10% and 0.017% of cases are below 45 and 40 years, apparently in reproductive age. The evidence is reassuring and implies that managing an intact endometrioma should not be altered in most women of reproductive age. Particular attention should be focused on sporadic cases with an enlarging endometrioma, atypical findings on transvaginal ultrasound (TVUS), and characteristic magnetic resonance imaging (MRI) features. Full article

Infertility treatment is a possible factor in hypertensive disorders of pregnancy (HDP). Identifying the characteristics of pregnant women who have undergone infertility treatment and have a potential risk for HDP is valuable for its prevention and treatment. Using data from 12,456 pregnant Japanese women from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, the association between infertility treatment and HDP was analyzed. A multiple logistic regression model showed an association between infertility treatment and HDP (odds ratio, 1.34; 95% confidence interval, 1.05–1.72). In vitro fertilization/intracytoplasmic sperm injection were also associated with HDP. Moreover, these associations were observed even among women who were not overweight and did not smoke. The application of infertility treatment should be carefully considered, even among women with low modifiable risk factors. Full article

Endometrium, a highly dynamic tissue, is known for its remarkable ability to regenerate, differentiate, and degenerate in a non-conception cycle and transform into a specialized tissue to nurture and protect the embryo in a conception cycle. This plasticity of the endometrium endows the uterus to execute its major function, i.e., embryo implantation. However, this boon becomes a bane, when endometrium- or endometrium-like cells adhere, grow, and invade extrauterine sites, leading to endometriosis. Endometrial deposits at the extrauterine site lead to severe pelvic pain, painful menstruation, and infertility in endometriosis. Although benign, endometriotic lesions share several traits with cancerous cells, excessive proliferation, adhesion, invasion, and angiogenesis make endometriotic lesions analogous to cancer cells in certain aspects. There exists evidence to support that, akin to the cancer cell, endometriotic lesions harbor somatic mutations. These lesions are known to experience higher proliferative stress, oxidative stress, and inflammation, which may contribute to somatic mutations. However, it would be of more interest to establish whether in the eutopic endometriosis also, the mutational burden is higher or whether the DNA Damage Response (DDR) is compromised in the eutopic endometrium, in endometriosis. Such investigations may provide more insights into the pathobiology of endometriosis and may also unravel cellular events associated with the origin of the disease. This review compiles inferences from the studies conducted to assess DNA damage and DDR in endometriosis. Full article