Unravelling the genetic landscape of cervical insufficiency: Insights into connective tissue dysfunction and hormonal pathways.

Background: The intricate molecular pathways and genetic factors that underlie the pathophysiology of cervical insufficiency (CI) remain largely unknown and understudied.

Methods: We sequenced exomes from 114 patients in Latvia and Lithuania, diagnosed with a short cervix, CI, or a history of CI in previous pregnancies. To probe the well-known link between CI and connective tissue dysfunction, we introduced a connective tissue dysfunction assessment questionnaire, incorporating Beighton and Brighton scores.

Management of Pregnancy with Cervical Shortening: Real-Life Clinical Challenges.

Preterm birth is the leading cause of neonatal mortality worldwide and may be responsible for lifelong morbidities in the survivors. Cervical shortening is one of the common pathways to preterm birth associated with its own diagnostic and management challenges. The preventive modalities that have been tested include progesterone supplementation and cervical cerclage and pessaries.

Whole Genome Amplification in Preimplantation Genetic Testing in the Era of Massively Parallel Sequencing.

Successful whole genome amplification (WGA) is a cornerstone of contemporary preimplantation genetic testing (PGT). Choosing the most suitable WGA technique for PGT can be particularly challenging because each WGA technique performs differently in combination with different downstream processing and detection methods. The aim of this review is to provide insight into the performance and drawbacks of DOP-PCR, MDA and MALBAC, as well as the hybrid WGA techniques most widely used in PGT.

A systematic review and standardized clinical validity assessment of genes involved in female reproductive failure.

Genetic testing is becoming increasingly required at almost every stage of failed female reproduction/infertility. Nonetheless, clinical evidence for the majority of identified gene-disease relationships is ill-defined, thus leading to difficult gene variant interpretation and poor translation of existing knowledge into clinics. We aimed to identify the genes that have ever been implicated in monogenic female reproductive failure in humans and to classify the identified gene-disease relationship pairs using a standardized clinical validity assessment.

Exome sequencing reveals variants in known and novel candidate genes for severe sperm motility disorders.

Study Question: What are the causative genetic variants in patients with male infertility due to severe sperm motility disorders?

Summary Answer: We identified high confidence disease-causing variants in multiple genes previously associated with severe sperm motility disorders in 10 out of 21 patients (48%) and variants in novel candidate genes in seven additional patients (33%).

What Is Known Already: Severe sperm motility disorders are a form of male infertility characterised by immotile sperm often in combination with a spectrum of structural abnormalities of the sperm flagellum that do not affect viability. Currently, depending on the clinical sub-categorisation, up to 50% of causality in patients with severe sperm motility disorders can be explained by pathogenic variants in at least 22 genes.