IVF and pre-implantation genetic diagnosis in elimination of sickle cell disease by Prof. Oladapo Ashiru
Assisted Reproductive Technology development started after the breakthrough of Patrick Steptoe and Robert Edwards in the successful birth of a baby in 1978, after in-vitro fertilisation and embryo transfer. Increase knowledge in the Assisted Reproductive Technology was in the development of pre-implantation genetic diagnosis. We in Nigeria were also at the forefront of catching up with these technologies. We established and reported success with the PGT technique for sickle cell carriers. The utilisation of the procedure in our environment can eliminate sickle cell disease over a long time. As we all know, SCD is a group of disorders that affects haemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. SCD patients have a typical haemoglobin molecule called haemoglobin S, which distorts the red blood cell’s original biconcave disc to a sickle or crescent shape. This article discusses the roles of IVF procedures in curing SCD.
How does IVF relate to SCD?
In vitro fertilisation, popularly known as IVF, is an assisted reproductive technique that achieves fertilisation by retrieving oocytes from the female, collecting sperm from the male, and then combining them manually in a laboratory dish through a series of the procedure. From the first success in 1978, there have been upgrades in IVF procedures and newer techniques like ICSI, PGT, and PCR, among many others. The introduction of these procedures gave rise to exploring knowledge into the viability and quality of embryos both morphologically and genetically; one such is the Pre genetic implantation testing as both a preventive and corrective procedure for SCD.
According to the World Health Organisation, sickle cell disease is the most prevalent genetic disease in the African region. While 75 per cent of patients with SCD live in sub-Saharan Africa, Nigeria alone accounts for more than 100,000 births each year. It cannot but be overemphasised that sickle cell disease is fast becoming an African disease.
Nigeria experienced her first IVF success through Prof. Oladapo Ashiru, and Prof. Osato Giwa-Osagie, in 1989 at the Lagos University Teaching Hospital, making it the first in Sub-Saharan Africa. Since then, there has been a rise in the awareness of IVF among Nigerians and an increase in the number of fertility clinics in Nigeria, collectively working to solve the problems of infertility. A follow up to this development is establishing additional technologies in Assisted Reproductive Technology like pre-implantation genetic testing.
This acronym stands for pre-genetic implantation testing. It is defined as the technique used to identify genetic defects in embryos created through in vitro fertilization before it is transferred into the womb, thereby drastically reducing births with congenital abnormalities, miscarriages caused by chromosomal abnormalities and possible implantation failures. There are different forms of PGT, namely:
- PGT-M (Monogenic or single-gene disorders)
- PGT-A (Abnormal chromosomal number)
- PGT-SR (Structural mis-arrangement)
However, our focus is on PGT-M, which is used in conjunction with IVF treatment to test an embryo for single-gene disorders; this treatment is essential for couples with a history of genetic disorders. One significant use of PGT is the human leukocyte antigen matching (HLA), which has been instrumental in treating sickle cell disease in affected patients.
What is the relationship between PGT and SCD?
One of the proven answers to the question above is PGT- HLA typing for HLA matching for ‘cord blood stem cell transplant.’
HLA matching is a way to tell how closely the tissue of one person matches another person’s tissue. It is the name of the histocompatibility complex in humans; it is an integral part of the immune system that contains several genes that encode cell-surface antigen present proteins and is controlled by genes located on chromosome six.
PGT-HLA typing, on the other hand, is used to select the embryo of an HLA tissue type compatible with that of a child. Most likely, a sibling who requires a bone marrow transplant, especially in medical conditions like leukemia, thalassemia, and sickle cell disease, Fanconi Anemia, amongst many others. PGT-HLA typing has emerged as a tool for couples to select unaffected embryos of an HLA tissue type identical to an existing affected child.
Cord blood, otherwise known as umbilical cord blood, is the blood present in the umbilical cord, and it is an alternative source of hematopoietic progenitor stem cells. Yuri Verlinsky did the first successful cord blood transplant that in 1988 in a child with Fanconi Anaemia.
Since then, there have been advancements in PGT-HLA typing procedures, cord blood transplant conditioning, support system, and overall tissue engineering.
In the most basic term, PGT-HLA typing determines the embryo eligible for cord blood, which contains hematopoietic stem cells used for transplantation. The embryos with compatible HLA types are called “savior child.” At their birth, the cord blood is collected and then stored for present or future use as the case may be.
Through PGT, we are continually providing solutions to couples with a history or are carriers of the single-gene disorder. The article is particularly relevant as there is a need for more public awareness of this technology.