Premature ovarian insufficiency and rare oocyte abnormalities

POI is a heterogeneous syndrome, often leading to infertility and associated comorbidities. Its prevalence is 1-4%, making it a public health concern. It is clinically defined by amenorrhea or spaniomenorrhea > 4 months, with an FSH level > 25 IU/L in women under 40 years of age.

There is considerable genetic heterogeneity associated with this syndrome. Karyotyping rules out Turner syndrome or chromosomal rearrangements. Molecular biology testing rules out FMR1 premutation. Targeted high-throughput sequencing (panel) can rule out a pathogenic variant in known candidate genes. To date, more than 130 genes responsible for POI have been identified.

Rare oocyte abnormalities include oocyte maturation defects (OZEMA: Oocyte, Zygote, Embryo Maturation Arrest) and oocyte dysmorphies. To date, more than 30 genes have been implicated in the occurrence of this phenotype.

The subpopulation eligible for genome sequencing corresponds to patients with undiagnosed conditions. Accurate genetic diagnosis will enable appropriate genetic counseling based on the cause (patient and family), the implementation of monitoring to detect possible comorbidities, and appropriate prevention and treatment.