PGD/PGS Research & The Future


It has now been over 20 years since the procedure involving embryo biopsy and subsequent genetic testing has been available. Initially, testing was accomplished by a procedure called Fluorescent In Situ Hybridization (FISH)*. The limitation of this particular technology was that it wasn’t possible to test for all 23 chromosome pairs due to technical limitations. At first, only 5 chromosomes could be tested. With time, this was increased to 7, then 9 and ultimately 12. Even though at best only half of the chromosomes from a biopsied embryo could be tested, several interesting findings emerged. First, in women over 40, 90 % of the embryos biopsied were found to be genetically abnormal. This finding lent support to our assumptions regarding the cause of the decrease in fertility rate and the increase in miscarriage and genetic abnormality rates of older women. Second, It was also found that morphological criteria currently used for assessment of embryo quality might in some cases be misleading. In other words, some of the embryos that appeared perfect in form were found to be genetically abnormal while some very unattractive embryos were in fact normal. Yet the inability of FISH to provide complete genetic information for each embryo biopsied limited its effectiveness. In fact, there was little data supporting the use of FISH to improve the success of IVF and only limited data supporting its use to improve outcome in women with recurrent miscarriages.

Recently, a newer technology has emerged that has appears much more promising in its ability to deliver complete genetic information about an embryo in question. This technique is referred to as Comparative Genomic Hybridization (CGH). In contrast to FISH, CGH is able to provide information about all 23 chromosome pairs from a single cell which has been removed from a 3 day old embryo or from several cells removed from a 5 day old embryo. CGH has replaced FISH for this reason and hopefully will actually be able to improve the efficiency of IVF while limiting the occurence of miscarriages.


It is well known that women experience an age related decline fertility starting in their early 30′s. Ultimately, the decline in fertility observed in women over 40 years of age results in less than one half the fertility rate compared to women under 40 as a group. At the same time, the incidence of miscarriage increases from about 25% at age 35, to 33% at age 40 and 50% at age 45. Better known are the statistics related to genetic abnormality of pregnancies as women age. At age 35, the total risk for chromosomal abnormality as demonstrated by amniocentesis is 1/132; at age 40 it is 1/38, and by age 45 has increased to 1/12. Until recently, we could only assume that these were related occurrences, resulting from an increase in the percentage of genetically abnormal oocytes with increasing age.


This has tremendous implications for the future of ART. In the same way that ICSI was first performed only in a few fertility clinics worldwide and after dissemination of expertise and experience has now become routine in nearly every ART laboratory, embryo biopsy and PGS may become routine in the next few years. This would mean that for a particular individual, if it was found that the majority of her embryos were abnormal for instance, that individual would have powerful objective information that could lead her to seek an egg donor, thus sparing the expense and disappointment of repeated IVF failures. It would also allow physicians to transfer only normal embryos, which would maximize the chances of a successful outcome irrespective of age. Clearly, this is one of the most exciting developments in the field of reproductive medicine

PGD, the testing of an embryo for the presence of an abnormal gene causing a specific disease, is now applicable to over 1000 different disorders. Probably the most common disorders are Cystic Fibrosis, Hemophilia, Sickle Cell disease and Tay-Sachs but there are many more lesser known ones that we can test for as well. PGD can be performed along with PGS for chromosome screening on the same single cell.