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Pre-Implantation Genetic Diagnosis 
Vol.1 No.5 

The New Year

As children lost and wandering
In a wood take steps in circles
In vain attempts to find their home,
So time appears again today
On his elliptic path through space,
Persistent in the annual search
For life's controlling foci-Death and Birth.
Roy G. Pearce, M.D. 

 

 

Pre-Implantation Genetic Diagnosis

by Anuja Dokras, M.D.Ph.D.

Senior Resident


Department of Obstetrics and Gynecology 
Yale University School of Medicine 

Introduction

With recent advances in genetics, there are several inherited disorders which can now be diagnosed at a molecular level. For couples who are carriers or affected by any of these conditions and are at high risk for transmitting it to their offspring, it is currently possible to detect the disorder during pregnancy. This is done by one of two approaches: amniocentesis or chorionic villus sampling (which involves taking a small sample of the placenta at an early stage). However the couples have the dilemma of whether or not to terminate the pregnancy if the genetic abnormality is present. In some cases this may also not be a viable option for religious or moral reasons. An alternative would then be to diagnose the condition in embryos before the pregnancy is established. Only the unaffected embryos would then be transferred to the uterus. This technique is referred to as preimplantation genetic diagnosis and would obviate the need for screening during a pregnancy and hence prevent the physical and psychological trauma associated with possible termination. 

How can a diagnosis be made in the preimplantation period?

Research towards developing techniques for early genetic diagnosis in humans were initiated in the UK in the late 1980s (Handyside et al, 89, Lancet.347. and Dokras et al,90, Hum Reprod,5.821.). In vitro fertilization (IVF) techniques are used to obtain ova (eggs) from the mother which are then fertilized in the laboratory with sperm obtained from the father. One or more cells are then removed from the developing embryo 2 days to 4 days after fertilization. This highly sophisticated technique called micromanipulation does not adversely affect further development of the embryo. The cells removed are then used for analysis, and the results can be obtained within 12-24 hours. The embryos without the genetic defects are then transferred into the uterine cavity to develop into a normal pregnancy. 

What are the different conditions that can be screened?

Almost all genetically inherited conditions that are diagnosed in the prenatal period can also be detected in the preimplantation period. Diseases which have a high risk of transmission (25-50%) and are usually associated with significant morbidity and mortality can be screened for by this technique. The limiting factor however is that few cells (usually only 1-2) are available for diagnosis unlike following amniocentesis or chorionic villus sampling. Therefore the possibility of obtaining an accurate diagnosis has to be confirmed by laboratory experiments prior to the clinical application of this technique for a given disease. 

Are there babies born after application of this technique?

The first report of the successful application of this technique came from the Hammersmith Hospital, London, UK which currently is the center with the highest number of births following preimplantation diagnosis. Over 30 pregnancies have now been reported globally including the USA. The conditions screened for include cystic fibrosis, Tay Sachs disease, hemophilia, Fragile X syndrome, and rarer conditions such as Barth's syndrome and Rett's syndrome. 

Why does the technique involve IVF? 

Currently IVF is the only available method for obtaining an embryo in the very early stages of development . Therefore, although couples with a high risk of transmitting a genetic defect to their offspring may have normal fertility, they would need to go through the IVF procedure to provide embryos for screening. Not surprisingly, the pregnancy rate in this group has been shown to be higher than that seen in patients with documented infertility. 

Whom would this approach be applicable to? 

This technique is currently available to couples whose offspring are at a high risk (25-50%) for a specific genetic condition due to one or both parents being carriers or affected by the disease. Also the genetic code associated with the condition must be known in order to allow diagnosis. Currently it is not feasible to routinely screen women at lower risks, such as women over age 35 for Downs Syndrome, since the means of establishing a pregnancy is with the help of IVF. 

What Next? 

Only a few centers in the world today are offering preimplantation diagnosis to couples at high risk or those who have an already affected child. Efforts continue to be focused on improving methods to obtain an accurate diagnosis from only one or two cells. Techniques are now available to screen for more than one condition simultaneously, however the accuracy of these modifications need to be tested further. Although there is certainly a demand for this approach as shown by studies, it will continue to be available only in select specialized institutions with excellent IVF and molecular biology laboratories. To read ASRM guidelines for Pre-Implantation Genetic Diagnosis, Click here.

 
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