Advanced Paternal Age: A New Indicator for the Use of Microfluidic Devices for Sperm DNA Fragmentation Selection.

New social conditions and progress in ART have both contributed to the delay in parenthood in developed countries. While the effects of maternal age have been widely studied, paternal age is poorly understood, and there are no specific guides on ART techniques to treat its deleterious effects. It is known that there is an increase in sperm DNA fragmentation (SDF) in elderly men, and new sperm selection devices using microfluids have been developed. This study analyses 189 ICSI cycles with donor oocytes performed between January 2018 and February 2022. Spermatozoa were selected using an MSS device or density gradients, followed by ICSI fertilization and fresh/thawed embryo transfer. We assessed the association between the selection technique, paternal age (< or ≥45) and reproductive outcomes. Fertilization (FR), blastulation (BR), implantation (IR), live-birth (LBR) and miscarriage (MR) rates were calculated. The results showed significantly higher IR (57.7% vs. 42.5%) and LBR (42.9% vs. 30.3%) when applying MSS selection, and particularly higher BR, IR and LBR when the paternal age was equal to or over 45 years (BR: 64.4 ± 23% vs. 50.1 ± 25%, IR: 51.5% vs. 31.6% and LBR: 42.4% vs. 23.7%). We also found a negative correlation between BR and paternal age (r2 = 0.084). The findings show that MSS enhances success in assisted reproduction cycles with ICSI, especially in couples with advanced paternal age. We propose advanced paternal age as a new indicator for the application of sperm selection techniques that reduce fragmentation.

Novel Time-Lapse Parameters Correlate with Embryo Ploidy and Suggest an Improvement in Non-Invasive Embryo Selection.

Selecting the best embryo for transfer is key to success in assisted reproduction. The use of algorithms or artificial intelligence can already predict blastulation or implantation with good results. However, ploidy predictions still rely on invasive techniques. Embryologists are still essential, and improving their evaluation tools can enhance clinical outcomes. This study analyzed 374 blastocysts from preimplantation genetic testing cycles. Embryos were cultured in time-lapse incubators and tested for aneuploidies; images were then studied for morphokinetic parameters. We present a new parameter, "st2, start of t2", detected at the beginning of the first cell cleavage, as strongly implicated in ploidy status. We describe specific cytoplasmic movement patterns associated with ploidy status. Aneuploid embryos also present slower developmental rates (t3, t5, tSB, tB, cc3, and t5-t2). Our analysis demonstrates a positive correlation among them for euploid embryos, while aneuploids present non-sequential behaviors. A logistic regression study confirmed the implications of the described parameters, showing a ROC value of 0.69 for ploidy prediction (95% confidence interval (CI), 0.62 to 0.76). Our results show that optimizing the relevant indicators to select the most suitable blastocyst, such as by including st2, could reduce the time until the pregnancy of a euploid baby while avoiding invasive and expensive methods.

Meiotic chromosome abnormalities in fertile men: are they increasing?

OBJECTIVE: To determine the basal frequencies of meiotic chromosome abnormalities in fertile men. DESIGN: Descriptive design. SETTING: Research university laboratory and clinical andrology service. PATIENT(S): Seventeen fertile donors undergoing vasectomy. INTERVENTION(S): Analysis of testicular biopsies. MAIN OUTCOME MEASURE(S): Meiotic chromosome abnormalities in metaphase I spermatocytes. RESULT(S): A total of 1,407 spermatocytes I was analyzed. The main meiotic abnormality was absence or low chiasma number of individual bivalents (23.4%), followed by structural (3.3%) and numerical (0.7%) abnormalities. Sex chromosomes and G-group chromosomes were the most commonly found as univalents at metaphase I. Statistically significant heterogeneity was found for meiotic abnormalities among fertile men, caused by interindividual variation in the level of dissociated sex chromosomes (ranging from 3.2% to 43.7%). The mean total percentage of meiotic abnormalities in spermatocytes I from fertile men was 27.4%, 1.7 times higher than those described a few decades ago in fertile and even in infertile men. CONCLUSION(S): Fertile men are a heterogeneous group for meiotic errors, with individuals showing percentages of meiotic abnormalities as high as 50%. From these findings, caution is recommended when using meiotic studies to diagnose and provide genetic counselling to patients consulting for infertility.

Premature separation of sister chromatids in human male meiosis.

BACKGROUND: Meiotic disorders result in meiotic arrest and aneuploid spermatozoa, leading to male infertility, spontaneous abortions or affected offspring. We carried out meiotic studies in an infertile male to detect meiotic nondisjunction mechanisms leading to aneuploidy in spermatogenesis. METHODS AND RESULTS: Meiotic studies were performed in testicular and semen samples from a 38-year-old teratozoospermic male with normal somatic karyotype and a history of spontaneous abortions. We analysed 262 spermatocytes (69 pachytene cells, 106 metaphases I (MI), 87 metaphases II (MII)) by multiplex-fluorescence in situ hybridization and 20,193 spermatozoa by multicolour-FISH with probes for chromosomes 9, 10, 15, 21, X and Y. The results indicate high increase of 21 and XY disomies, as well as diploidy in both spermatocytes at MII and spermatozoa (P < 0.0001). Achiasmate segregation of sex chromosomes was found in 3.4% of spermatocytes II, preceded by early-dissociated XY bivalent at MI (41.5% of cells). We also detected premature separation of sister chromatids (PSSC) in 4.6% of MII. CONCLUSIONS: This individual presents high levels of numerical abnormalities in germ cells, caused by two different nondisjunction mechanisms during meiosis I. To our knowledge, this work represents the first time that PSSC has been demonstrated in human male germ cells.