Single-Gene Causes: Why Second-Trimester Losses Need a Different Genetic Workup

I will not be able to give you details about specific sperm selection procedures, as in our hospital this is a multidisciplinary process involving the IVF specialist and the andrology laboratory. But in terms of the genetic implications: above the age of 50, there is a high chance that sperm quality is reduced, and the sperm DNA fragmentation index is likely to be elevated. Unless we specifically test for it, we do not know the exact level, but even without testing, there is a significant chance that sperm DNA quality is impaired, which can result in recurrent pregnancy loss or implantation failure. Testing the sperm DNA fragmentation index in men above 50 with a history of recurrent pregnancy loss or implantation failure would be worthwhile.

Metformin should be started at least 2 to 3 months before conception. It is safe to continue in pregnancy and is generally continued through the first trimester and sometimes beyond. It should be monitored with GTT as well as regular HbA1c and blood sugar checks throughout.

A recurring structural finding on ultrasound in the second trimester should prompt consideration of a single-gene cause rather than a chromosomal one.

Arthrogryposis or fetal akinesia, polyhydramnios, recurrent hydrops fetalis, recurrent renal anomalies, or repeatedly short long bones.

Long QT syndrome or another cardiac arrhythmia may be at play in cases of stillbirth or sudden intrauterine death.

Whether a condition is autosomal dominant, autosomal recessive, or X-linked determines both the inheritance pattern and the recurrence risk; sickle cell disease is an example of an autosomal recessive condition, where unaffected carrier parents face a 25% chance per pregnancy of an affected child.

Some women carry gene variants specifically linked to uterine receptivity or embryo implantation failure, which independently predispose to recurrent loss.