Role of genetic testing in in-vitro fertilization

Dr Shiva Murarka, Senior Scientist-Reproductive Genomics & Vishakha Mali, Genetic Counsellor, Neuberg Centre for Genomic Medicine explains that the usual IVF workup includes commonly recommended genetic tests like- couple karyotype, Y chromosome microdeletion, and sperm DNA fragmentation

Today, IVF or in-vitro fertilization, is a household name. It is the most common assisted conception for couples facing difficulty in achieving a successful pregnancy. IVF entails fusing sperm and eggs outside of the body in a laboratory. The uterus receives the embryo or embryos after they have been formed. This might sound easy theoretically, but there are a lot of complex biological processes that go on in an IVF procedure. Not all IVF cycles end in a successful pregnancy. Thus, many times, in the hope of a healthy pregnancy, couples have to undergo multiple IVF cycles. The usual IVF workup includes commonly recommended genetic tests like- couple karyotype, Y chromosome microdeletion, and sperm DNA fragmentation.

However, there are upcoming molecular/ genetic tests which are used increasingly in the modern day. Advent of genetic testing in an IVF clinic has increased the rate of healthy pregnancy outcomes. These tests include either testing the embryos or screening the intrauterine environment.

Couples facing infertility, recurrent pregnancy losses or couples who are known to be carriers of a genetic condition can be additionally benefitted from the following tests:

Screening of embryos:

Also termed as Preimplantation Genetic Testing (PGT). The embryos can be screened for the following:

• For chromosomal aneuploidies- PGT-A

Around 10-15 per cent of first trimester pregnancy losses are attributed to genetic causes, like chromosomal aneuploidies. PGT-A screens for chromosomal aneuploidies in the embryos thereby increasing the chances of a successful pregnancy.

Indications for PGT-A include advanced maternal age, recurrent implantation failure, severe male factor and couples with normal karyotypes who have experienced recurrent miscarriage.

• For structural aneuploidies- PGT-SR

For an individual known to be a carrier of a balanced chromosomal translocation (like inversion, reciprocal translocation or Robertsonian translocation), there is a risk of unbalanced chromosomal translocation in every pregnancy which might lead to pregnancy loss. The test-PGT SR aids in identifying the embryos with unbalanced chromosomal translocation, thereby filtering them out and increasing the chances of implantation of healthy embryos.

• For monogenic disorders- PGT-M

This test is useful in cases where a couple has an affected child/ a family history of genetic condition with a known genetic variant and now wants to have a healthy pregnancy. The genetic change present in the affected child/ carrier parents can be tested in the embryos to know their affection status. Based on this report, healthy embryos can then be implanted. The test must be accompanied with appropriate genetic counseling so that the patient makes a well informed decision.

Increasing the rate of implantation:

• Endometrial Receptivity Testing

The journey of a pregnancy from formation of an embryo followed by implantation, and ultimately leading to a live birth is an intricate process and involves synchronisation of multiple systems. One such parameter which is observed to play an important role in implantation is the timing or period of implantation. One third of couples faced with recurrent implantation failure are found to have a displaced Window of Implantation (WOI). WOI is the best suited timing for embryo implantation.

Endometrial Receptivity Testing analyses the transcriptomic signature to determine the best suited time for embryo implantation when the endometrium is most receptive.

• Endometrial Microbiota Testing

A normal endometrial microbiota is important for implantation. The test EndoBiome assesses the levels of endometrial Lactobacillus as well as presence of specific pathogens associated with poor reproductive outcomes. Based on the report, measures can be taken to improve the endometrial microbiota thereby increasing the rate of implantation.