Healthy birth in a case of total globozoospermia after intracytoplasmic sperm injection and assisted oocyte activation.

Globozoospermia is a rare (incidence <0.1%) and very severe disorder, with major implications in male fertility. Total globozoospermia is represented by the presence of spermatozoa with 100% rounded heads and a lack of acrosomes. These specific morphological modifications seem to be connected to defects occurring in the last stage of spermatogenesis, spermiogenesis, and will result in anomalies of the acrosomal reaction and a defective adherence of the spermatozoa to the oocytes zona pellucida. This will result in a failure of natural fertilization. This article aims to present the case of a couple diagnosed and successfully treated for primary male infertility. The 26-year-old male partner underwent two semen analyses that revealed the presence of fully rounded spermatozoa heads (morphological abnormality) and consequently was proposed for in vitro fertilization treatment. Semen preparation and the use of assisted reproductive techniques, intracytoplasmic injection of sperm cells into the assisted oocyte activation, have resulted in the conceivement of a healthy child. The particularities of this case lie in the early recognition of the total abnormal globozoospermia morphology. This is the first case reported in Romania where specific assisted reproductive techniques and treatments have resulted in a successful pregnancy for a couple with male total globozoospermia.

Longitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA Vaccination.

The host epigenetic landscape rapidly changes during SARS-CoV-2 infection, and evidence suggest that severe COVID-19 is associated with durable scars to the epigenome. Specifically, aberrant DNA methylation changes in immune cells and alterations to epigenetic clocks in blood relate to severe COVID-19. However, a longitudinal assessment of DNA methylation states and epigenetic clocks in blood from healthy individuals prior to and following test-confirmed non-hospitalized COVID-19 has not been performed. Moreover, the impact of mRNA COVID-19 vaccines upon the host epigenome remains understudied. Here, we first examined DNA methylation states in the blood of 21 participants prior to and following test-confirmed COVID-19 diagnosis at a median time frame of 8.35 weeks; 756 CpGs were identified as differentially methylated following COVID-19 diagnosis in blood at an FDR adjusted p-value < 0.05. These CpGs were enriched in the gene body, and the northern and southern shelf regions of genes involved in metabolic pathways. Integrative analysis revealed overlap among genes identified in transcriptional SARS-CoV-2 infection datasets. Principal component-based epigenetic clock estimates of PhenoAge and GrimAge significantly increased in people over 50 following infection by an average of 2.1 and 0.84 years. In contrast, PCPhenoAge significantly decreased in people fewer than 50 following infection by an average of 2.06 years. This observed divergence in epigenetic clocks following COVID-19 was related to age and immune cell-type compositional changes in CD4+ T cells, B cells, granulocytes, plasmablasts, exhausted T cells, and naïve T cells. Complementary longitudinal epigenetic clock analyses of 36 participants prior to and following Pfizer and Moderna mRNA-based COVID-19 vaccination revealed that vaccination significantly reduced principal component-based Horvath epigenetic clock estimates in people over 50 by an average of 3.91 years for those who received Moderna. This reduction in epigenetic clock estimates was significantly related to chronological age and immune cell-type compositional changes in B cells and plasmablasts pre- and post-vaccination. These findings suggest the potential utility of epigenetic clocks as a biomarker of COVID-19 vaccine responses. Future research will need to unravel the significance and durability of short-term changes in epigenetic age related to COVID-19 exposure and mRNA vaccination.