Genetic Glitches: How chromosomal aberrations can disrupt pregnancy

Recurrent miscarriage or Recurrent Pregnancy Loss (RPL) is the spontaneous loss of two to three, or more consecutive pregnancies. It is estimated to affect up to 10-15% of all clinically recognized pregnancies. The most common causes of RPL include uterine problems, hormonal disorders and genetic abnormalities. The focus of this article will be about the genetic abnormalities in parents, that may cause RPL.

Majority of RPL cases have been noted due to abnormal chromosomal segregation during parental gametogenesis and balanced reciprocal translocation. A balanced reciprocal translocation is a chromosomal abnormality where two non-homologous chromosomes exchange DNA segments without losing or gaining any genetic material. Around 1% of miscarriages are also found to be due to unbalanced translocations. An unbalanced translocation occurs when a fetus inherits a chromosome with extra or missing genetic material, from a parent with a balanced translocation. In cases of RPL, one of the parent is a carrier having balanced chromosomal rearrangement, leading to unbalanced translocations in the offspring, which increases chances of recurrent abortion, malformed baby, or sterility in a couple.

Chromosomal aneuploidy in the embryo is another common cause of miscarriages. Aneuploidy is a genetic error that occurs when the number of chromosome copies in a cell is altered. It's primarily caused by chromosome non-disjunction, which is when chromosomes fail to separate during cell division. This can happen during sperm and egg production, or during embryo implantation. Trisomies of chromosome 13, 18, and 21 are the common chromosomal aneuploidies followed by X chromosome monosomy (45, X). 

Recurrent abortions make the couples feel guilty and mentally depressed. To this day, routine genetic counselling of couples has not been made a regular practice, for proper management of recurrent pregnancy loss cases. Cytogenetic analysis has been an essential tool for predicting the success of reproductive options, and parental karyotyping can help assess the cause of RPL. The genetic counseling and appropriate patient management can be made easily and accurately, thus helping lower many RPL cases.

REFERENCES:

Pal AK, Ambulkar PS, Waghmare JE, Wankhede V, Shende MR, Tarnekar AM. Chromosomal aberrations in couples with pregnancy loss: A retrospective study. J Hum Reprod Sci 2018;11:247-53.