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Steps involved in pre-implantation genetic testing 1 by Prof. Oladapo Ashiru

We continue to receive enquires from concerned members of the public concerning genetic diagnosis. Many questions centre on whether or not it is possible, and the processes involved. It is for this reason and more that I deem it fit to give a simplified detail of the processes involved in pre-implantation genetic testing.

This presentation should create the awareness of the use of PGT for helping couples with the sickle cell trait. We employ the technique of trophectoderm biopsy, which is an improvement over our earlier publication centring on biopsied embryos on day three with one single blastomere taken out of the eight blastomere cells for analysis. In comparison, trophectoderm biopsy is performed on a day five embryo called a “blastocyst”.

We remove about four to five cells from the external layer of the embryo and the extracted cells are analysed for abnormalities. This new process has a higher degree of specificity with a significant percentage increase in the pregnancy success, making it more acceptable and accessible. It is therefore noteworthy to bring this into the public domain for those who may require such therapy.

The technique of PGT is applied in conjunction with Assisted Reproductive Technology. ART refers to conception requiring the complex handling or manipulation of both the male and female gametes in-vitro to facilitate pregnancy.

  • What is IVF?

IVF means fertilisation achieved outside of the body. It involves ovulation induction, oocyte retrieval, sperm preparation, oocyte stripping, insemination and fertilisation in a culture dish and finally embryo transfer. Oocyte retrieval and embryo transfer processes are done under ultrasound guidance. It is also important to know that gamete handling is done under strict temperature control. Without the development of IVF, pre-implantation genetic testing will not be possible.

  • What is PGT?

Pre-implantation genetic testing, as the name implies, involves testing for specific genetic defects in the DNA code before embryo implantation. A targeted screening of a known genetic abnormality in the couple, PGT was first performed in the early 1990’s as a way for couples to prevent the pregnancy of a child with a genetic disease.

Currently at Medical Art Center, we offer PGT for genetic conditions including sickle cell anemia and chromosome aneuploidies. We work in collaboration with Genesis Genetics, a world-renowned genetics institute, and pioneers of PGT, for inherited genetic abnormalities.

  • Does PGT replace prenatal testing?

No, PGT does not. PGT is a research-based test allowing for a similar diagnosis to those available by prenatal testing. However, prenatal testing such as chorionic villus sampling or amniocentesis remain the gold-standard of modern obstetrics and are necessary for this setting should a pregnancy ensue.

  • History of PGT

In humans, PGT was developed in the United Kingdom in the mid-1980s as an alternative to current prenatal diagnoses. Initially, PGT revolved around the determination of gender as an indirect means of avoiding an X-linked disorder. In 1989 in London, the first unaffected child born following PGT performed for an X-linked disorder was reported. PGT became increasingly popular during the 1990s when it was used to determine a handful of severe genetic disorders, such as sickle-cell anemia, Tay Sachs disease, Duchenne’s muscular dystrophy and Beta-thalassemia.

In 2010 Oladapo Ashiru et al. used PGT with FISH (Fluorescent in situ Hybridisation) for chromosomal abnormalities and family balancing and in 2013 published their first success with the use of PGT to deliver a sickle cell-free baby boy. (Nigerian Medical Journal 2014). As of 2006, more than 15,000 PGT cycles have been reported. PGT is currently available for most known genetic mutations. Although the indications for PGT are well established, it is a relatively new and evolving technique in Africa.

  • Indications in  Nigeria

Autosomal dominant disorders: This is the situation where one of the partners is a carrier of the genetic defect (e.g., dwarfism)

Autosomal recessive disorders: This is a situation whereby couples are carriers of the genetic defect (e.g., Sickle Cell Disease)

X-linked disorder (Disorder associated with the X chromosome of XX or XY): This is a situation whereby one partner is a carrier of an x-linked genetic defect (e.g., Hemophilia)

Structural chromosomal abnormality: One partner is a carrier of a chromosome abnormality (translocation, inversion, deletion, insertion)

Human leukocyte antigen  matching: Allogeneic hematopoietic stem cell transplantation is a treatment for some acquired and congenital diseases. An essential factor in the outcome of the procedure is the degree of human leukocyte antigen compatibility between patient and donor. The more compatible the donor is to the recipient, the higher the chances of success. HLA identical siblings, therefore, provide the best opportunity for the recipient. PGT can be used to select HLA-compatible embryos if there is no HLA-compatible sibling in the family. It can be used for bone marrow transplant in sickle-cell affected children.

  • Sickle cell anaemia?

Sickle cell anaemia is a hereditary genetic condition in which a mutated form of hemoglobin distorts the red blood cells from a healthy disc shape into a crescent one. The disease is associated with some acute and chronic health problems, such as severe infections, attacks of severe pain (“sickle-cell crisis”) and an increased risk of death. 70 per cent of the world’s children with sickle cell disease are born in sub-Saharan Africa.

According to the World Health Organisation, in Africa, the highest prevalence of sickle-cell trait occurs between latitudes 15° north and 20° south, ranging between 10 per cent and 40 per cent of the population in some areas. In countries such as Cameroon, Republic of Congo, Gabon, Ghana and Nigeria, the prevalence is between 20 per cent and 30 per cent while in some parts of Uganda it is as high as 45 per cent. In countries where the trait prevalence is above 20 per cent, the disease affects about 2 per cent of the population. The geographic distribution of the sickle-cell trait is very similar to that of malaria.