Machine Learning-Based Approach Highlights the Use of a Genomic Variant Profile for Precision Medicine in Ovarian Failure.

Ovarian failure (OF) is a common cause of infertility usually diagnosed as idiopathic, with genetic causes accounting for 10-25% of cases. Whole-exome sequencing (WES) may enable identifying contributing genes and variant profiles to stratify the population into subtypes of OF. This study sought to identify a blood-based gene variant profile using accumulation of rare variants to promote precision medicine in fertility preservation programs. A case-control (n = 118, n = 32, respectively) WES study was performed in which only non-synonymous rare variants <5% minor allele frequency (MAF; in the IGSR) and coverage ≥ 100× were considered. A profile of 66 variants of uncertain significance was used for training an unsupervised machine learning model to separate cases from controls (97.2% sensitivity, 99.2% specificity) and stratify the population into two subtypes of OF (A and B) (93.31% sensitivity, 96.67% specificity). Model testing within the IGSR female population predicted 0.5% of women as subtype A and 2.4% as subtype B. This is the first study linking OF to the accumulation of rare variants and generates a new potential taxonomy supporting application of this approach for precision medicine in fertility preservation.

[Twin pregnancy discordant for trisomy 13: three cases]. / Gestación gemelar con un feto con síndrome de Patau (trisomía 13): tres casos clínicos.

BACKGROUND: The association between Patau's syndrome and multiple pregnancy is extremely rare. This paper reports three cases with different obstetric treatment. CASE 1: Dichorionic diamniotic twin pregnancy with a fetus affected by trisomy 13 diagnosed at 16 weeks of gestation. The pregnancy was managed conservatively resulting in the delivery of twins at 38 weeks. The structurally normal twin was male survived without sequelae, but the female fetus with trisomy 13 died shortly after delivery. CASE 2: Dichorionic diamniotic twin pregnancy. At 14 weeks of pregnancy, one of the fetus affected by trisomy 13 showed an early intrauterine growth restriction and a cystic hygroma. At 16 weeks of pregnancy the abnormal twin died spontaneously. Avaginal delivery occurred at 38 weeks being born a healthy male. CASE 3: Dichorionic diamniotic twin pregnancy. The trisomy 13 fetus had been diagnosed at 17 weeks of pregnancy and showed a cardiopathy. At 32 weeks of gestation a selective fetal reduction was performed. Vaginal delivery occurred at 35 weeks and a healthy newborn was born. CONCLUSION: Patau's syndrome has an unfortunate fetal and neonatal outcome. It is important an early diagnosis to establish the best strategy to minimize the risk of the healthy twin.