Sickel cell and pre-implantation genetic testing by Prof. Oladapo Ashiru

Sickle cell anaemia is a hereditary genetic condition in which a mutated form of haemoglobin distorts the red blood cells from a normal disc shape into a crescent shape.

The disease is associated with a number of acute and chronic health problems, such as severe infections, attacks of severe pain (sickle-cell crisis), and an increased risk of death.

About 70 per cent of the world’s children with sickle cell disease are born in sub-Saharan Africa.

According to 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 rate 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 two per cent of the population. Basically, the geographic distribution of the sickle-cell trait is very similar to that of malaria.

 

The role of pre implantation genetic diagnosis

Pre-implantation genetic diagnosis, as the name implies, involves testing for specific genetic defects in the DNA code prior to embryo implantation. Usually, there is targeted testing of a known genetic abnormality in the couple. Simply put, it is the diagnosis of a genetic condition prior to achievement of a pregnancy.

Edwards and Gardner successfully performed the first known embryo biopsy on rabbit embryos in 1968.  The PGD was first developed in human beings in the United Kingdom as an alternative to current prenatal diagnosis in the mid-1980s. Initially, it revolved around the determination of gender as an indirect means of avoiding an X-linked disorder.

In 1989 in London, Handyside and his colleagues reported the first unaffected child born following PGD performed for an X-linked disorder.

The PGD was first performed in the early 1990s as a way for couples to prevent the pregnancy of a child with a genetic disease. Currently at Medical Art Centre, we are able to offer PGD testing to detect genetic conditions, including sickle cell anaemia and chromosome aneuploidies.

The PGD became increasingly popular during the 1990s when it was used to determine a handful of severe genetic disorders, such as sickle-cell anaemia, Tay Sachs disease, Duchenne’s muscular dystrophy and Beta-thalassemia.

As of 2006, more than 15,000 PGD cycles were reported. The PGD is currently available for most known genetic mutations. Although the indications for the diagnosis are well established, it is a relatively new and evolving technique.

We work in collaboration with Genesis Genetics, a renowned genetics institute. They pioneered PGD testing of embryos for inherited genetic abnormalities.

Pre-implantation genetic testing is able to distinguish between genetically normal or affected embryos. Currently, this is the only way to determine the genetic condition of an embryo prior to pregnancy.

How it is done

To go through PGD for sickle cell anaemia, DNA samples from family members must be obtained to build the probe. However, samples from only direct family members are required and so, there is no need to involve extended relatives.

Usually the siblings or the parents of the two partners are required. The probe that is built will be used to test the cells biopsied from the embryos. Traditional PGD probe preparation takes between 14 and 16 weeks, while the newer Ultra PGD takes between eight and 10 weeks to accomplish.

Oocyte retrieval: The female partner is given medications to create multiple follicular development and ovulation. Once these follicles are well developed, they are retrieved from the patient under conscious sedation, using a special ultrasound guided technique. The oocytes are then isolated from the follicles. The oocytes are allowed to rest in the incubator for about three or four hours before insemination. This time it is used to prepare the sperm for IVF.

In-vitro fertilisation: In IVF, each isolated oocyte is inseminated with approximately three drops of sperm solution from the male partner. It can also be fertilised by ICSI technology.

The inseminated eggs are kept in the incubator in the IVF laboratory for about three days. The fertilised embryo will rapidly divide into the two-cell, four-cell and eight-cell stages at which point about  one or two good embryos are selected and transferred into the uterus through the cervix.

IVF is a good treatment option when the fallopian tubes are blocked or in endometriosis and when the male partner has low sperm count.

Without the development of IVF, pre-implantation genetic diagnosis would not have been possible.

Today, in Nigeria and West Africa, sickle cell carrier couples now have the ability to screen their embryos before conception thereby avoiding a sickle cell baby.

Today we have been able to help more than 15 couples who are carriers of the sickle-cell gene have babies that are free of the disease.

The cost of this process even though quite high, compensates for all the stress of dealing with sickle cell babies. It is hoped that various groups including the government can come to the aid of couples in need of this technique but cannot afford it. In the long run, it will save a lot of money on the health management of complications of this disease.

More research is required to improve the speed of diagnosis and make the process less expensive. Another major area that deserves research and if possible a noble prize nomination is the study of the understanding of the window of implantation.

The reason is that this is the only major gap in knowledge for us to achieve close to 95 per cent success in IVF. Many scientists have predicted that by 2025 the success rate of IVF should approach 90 per cent, if not 95 per cent,  if more research is conducted in this field.

Finally, in our experience, we have preliminary evidence to suggest that environmental toxins and diet play a major role in reducing fertility and possible IVF success.

Most of these stem from my earlier basic research in reproductive toxicology. The use of Mayr therapy to detoxify the body and get rid of toxins such as heavy metals like mercury, arsenic, antimony, and lead as well as such toxin and allergies from bad eating have in general enhanced our success in IVF and PGD. Elimination of these factors helps in increasing the pregnancy rate.

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