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Preimplantation Genetic Diagnosis in Sickle Cell Disease.

How can Preimplantation Genetic Diagnosis (PGD or PIGD) help reduce risk in Sickle Cell Disease? Couples in relationships where both are carriers for a genetic illness find themselves in a particularly challenging situation.


Gloved hand holding a culture dish in the laboratory



What Is Preimplantation Genetic Diagnosis?

Preimplantation Genetic Diagnosis is a procedure to assist parents at risk of passing a genetic condition to their children.

It has existed for several years (since the '90s), carried out in highly specialised centres by exceptionally well-trained staff. 

So PGD reduces the risk of transmitting a particular genetic condition from parent to child.

There may be options, but the choice can be difficult depending on one's attitudes, beliefs, culture or financial means.


How Can PGD Help With Sickle Cell Disease?

Sickle Cell Disease (SCD) is one of many conditions where this process could make a difference for families.

In Sickle Cell Disease, individuals have inherited the 'S' sickle gene which affects the protein haemoglobin.

The altered haemoglobin changes the shape of the red blood cell.

This leads to several problems within the body affecting the supply of oxygen - learn more.


Which Genotype gets the Most Severe Sickle Cell Disease?

People who have inherited 2 copies of the S gene (SS) suffer from Sickle Cell Anaemia.

They experience painful bone crisis and are more at risk of severe anaemia, problems like a stroke - read more.

Others who have inherited the S gene and another abnormal haemoglobin B-Thalassemia can also have quite severe disease (S-BThalassemia genotype).

In both these cases, each parent could potentially pass the abnormal gene to their child.

This is how these children develop the severe conditions; that is by inheritance.

In the group of all sickle cell diseases, these are the people who will most benefit from PGD.


What is the Preimplantation Genetic Diagnosis Process?

The process of PGD determines whether the chromosomes of the developing foetus or embryo have the gene in question.

This happens within the first few days of existence. 


Retrieving the Embryo

The embryo develops from both parents via IVF (In-vitro Fertilisation), a highly specialised and delicate process.

First, doctors stimulate a woman's ovaries to produce eggs.

Next, semen from the partner is obtained and the most viable sperm are selected.

These will be coupled with the eggs in a delicate procedure until fertilisation happens.

Fertilisation is when the sperm and egg combine to form the foetus or embryo.


Removing Cells from the Embryo

Early in the development of the embryo, some tissue is taken for analysis of its chromosomes.

This determines if it carries the affected gene and happens between the third to the sixth day after fertilisation.

(The timing only depends on the process used to obtain the sample cells) 

There are different methods that an embryologist could use to collect the tissue that have one advantage or the other.

The most commonly used method allows doctors to retrieve a single cell from the 3-day old embryo.

Another method allows the specialist to get more specific cells, but the embryo is older, risking its survival.


Photo of smiling baby of african background - preimplantation genetic diagnosis process could mean a health life for him.
Preimplantation genetic diagnosis - Photo by Chayene Rafaela on Unsplash


Laboratory Analysis in PGD

In the case of analysis of the cells taken from the embryo, there are also a number of methods.

A popular one is PCR - Polymerase Chain Reaction, which helps to diagnose gene conditions like Sickle Cell Disease.

In PCR, the cell's DNA is amplified or copied many times in order to help the analysis.

It is necessary to test the chromosomes in the couple (and sometimes other family members).

This helps determine if those chromosomes in the embryo have any sign of the abnormal gene.

And this is the analysis known as Pre Genetic Implantation Diagnosis.


Sometimes Testing may go Wrong

The analysis of the chromosome from the embryo is a still-evolving science.

There are some reasons why an embryo that appears healthy may still have an abnormal gene.

Sometimes, embryos possess more than one type of cells.

It is possible that when taking the sample cells to test, the sample may not be fully representative of the embryo.

There may be laboratory contamination, or the amplified cell contains part of the mother or father that could affect the result.


Embryo Transfer

If the PGD screening results in an embryo that appears free of the genetic abnormality, the next step is to plant it in the mother's womb to develop until maturity.

For the reasons above, even after PGD, specialists will recommend prenatal screening using either Chorionic Villus Sampling (CVS) or Amniocentesis to check that the foetus is free of the gene.

This happens around the time from 10 weeks to 16 weeks of pregnancy.

If all appears well, then pregnancy continues till delivery.


What are some issues around PGD? 

1. It requires specialist involvement - usually fertility experts for IVF and embryologists to collect the cells for testing from the embryo (embryo biopsy).

2. It requires specialist IVF facilities and laboratories for effective testing.

3. It takes considerable time - before, during and after the procedure.

4. There is still no guarantee after analysis that all abnormal chromosomes are detected and the selected embryo is free of the affected gene.

5. There is a possibility of damage to the embryo during the analysis.

6. There are risks around prenatal testing - CVS or Amniocentesis - womb infection or miscarriage may result.

7. There are challenges with the cost of the procedure in countries where people pay out of pocket.


What are the Safety Issues with Preimplantation Genetic Diagnosis?

In respect of safety, this will depend on some elements:

  • The age of the mother, 
  • the skill of the clinicians, 
  • the adequacy of the centres including aftercare nursing, availability of all the reagents, tools and other materials needed for the procedure.

Potential areas of concern for safety are:

  • The initial stage of IVF when the woman must take medication to stimulate her ovaries for eggs - she may develop side effects to the medicines
  • During retrieval of her eggs through the vagina when she must undergo general anaesthesia - she may react to the anaesthetic or suffer complications of surgery
  • Small chance (0.1%) of embryo injury during the biopsy to retrieve its cells for genetic testing
  • Procedures like embryo implantation may also carry complications
  • As most women may need a prenatal diagnosis as well to confirm the absence of genetic problems, safety issues to both Mum and baby may occur at that stage


Conclusion

The couple will need to understand that while Preimplantation Genetic Diagnosis can reduce the chance of having a child with SS genotype, it is not 100% certain.

This also applies to the S-Bthalassemia condition.

In a very good facility, and with skilled professionals, of course, the chances are better, and the safety profile of the procedure is better.

When accessible, it is an option that can reduce the distress of considering a therapeutic abortion at an advanced stage of pregnancy.

Preimplantation Genetic Diagnosis is a procedure that has shown success, but any couple wishing to undertake it should clearly understand its benefits and challenges - which is where Genetic Counselling comes in.

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More Reading

References

Editing by AskAwayHealth Team

Disclaimer

All AskAwayHealth articles are written by practising  Medical Practitioners on a wide range of health care conditions to provide evidence-based guidance and to help promote quality health care. The advice in our material is not meant to replace the management of your specific condition by a qualified health care practitioner.
To discuss your condition, please contact a health practitioner or reach us directly through info@askawayhealth.org

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