Multiple Sclerosis (MS) is a complex multifactorial autoimmune disease, whose sex- and age-adjusted prevalence in Sardinia (Italy) is among the highest worldwide. To date, 233 loci were associated with MS and almost 20% of risk heritability is attributable to common genetic variants, but many low-frequency and rare variants remain to be discovered. Here, we aimed to contribute to the understanding of the genetic basis of MS by investigating potentially functional rare variants. To this end, we analyzed thirteen multiplex Sardinian families with Immunochip genotyping data. For five families, Whole Exome Sequencing (WES) data were also available. Firstly, we performed a non-parametric Homozygosity Haplotype analysis for identifying the Region from Common Ancestor (RCA). Then, on these potential disease-linked RCA, we searched for the presence of rare variants shared by the affected individuals by analyzing WES data. We found: (i) a variant (43181034 T > G) in the splicing region on exon 27 of CUL9; (ii) a variant (50245517 A > C) in the splicing region on exon 16 of ATP9A; (iii) a non-synonymous variant (43223539 A > C), on exon 9 of TTBK1; (iv) a non-synonymous variant (42976917 A > C) on exon 9 of PPP2R5D; and v) a variant (109859349-109859354) in 3′UTR of MYO16.

Day 3 embryo quality is a predictor of in vitro fertilization (IVF) success rates in cleavage-stage embryo transfer. However, the association between day 3 embryo quality and clinical outcomes in blastocyst transfer policy is largely unknown. This retrospective study included 1074 frozen–thawed single day 5/6 blastocyst transfers between January 2019 and December 2022. Three groups were assessed depending on whether the transferred blastocyst derived from a top-quality, good-quality, or poor-quality embryo at day 3. The analysis was conducted independently for each blastocyst quality group (top, good, and poor) using multivariable logistic regression. We applied a Factorial Analysis of Mixed Data (FAMD) to reduce the potential collinearity between the covariates used in the model. All the blastocysts included in this study were obtained from the first ICSI freeze-all cycles. The cleavage and blastocysts stages were assessed between 67 ± 0.5 (day 3), 115 ± 0.5 (day 5), and 139 ± 0.5 (day 6) hours post-insemination (hpi), respectively. After adjusting for the day of transfer (day 5 or day 6) and FAMD dimensions, no statistical differences in a β-HCG, clinical pregnancy, and live birth were observed among the same-quality blastocysts derived from different day 3 embryo quality groups (top = A, good = B, and poor = C). Our findings showed that a day 3 embryo quality assessment may be unnecessary in planned freeze-all blastocyst cycles.

Chromosomal structural rearrangements (SR) can impair gametogenesis, increasing the risk of embryos carrying unbalanced chromosomal content (i.e., with a gain or loss of chromosomal material). In such cases, assisted reproduction technologies (ARTs) with preimplantation genetic testing for structural rearrangements (PGT-SR) is recommended to identify embryos with a normal or balanced karyotype. However, data on IVF laboratory outcomes in this context remain limited. This retrospective cohort study analyzed 548 ART cycles, comprising 129 with PGT-SR and 419 with PGT-A, conducted at a single university-affiliated center. Following propensity score matching, laboratory outcomes were compared using logistic regression. The fertilization rate was comparable between groups, but the PGT-SR group had significantly lower blastocyst development (36.7% vs. 47.1%) and top-quality blastocyst development rates (9.6% vs. 21.1%). No significant differences were found either in the blastocyst development rate on days 5, 6, 7, or in euploidy rates. In the PGT-SR cohort, the generalized linear mixed-effects model indicated no significant effect of carrier gender on the normal/balanced blastocyst rate, while the type of SR was strongly associated with it: non-reciprocal SRs yielded a higher rate of normal/balanced blastocysts (89.9%) compared to reciprocal translocations (45.7%). These findings indicate that patients undergoing PGT-SR generate fewer blastocysts available for biopsy, and that in cases involving reciprocal translocations, the proportion of normal/balanced blastocysts suitable for transfer is significantly reduced. These results underscore the importance of personalized counseling in managing expectations and supporting informed clinical decision-making.