PGD is much complicated than originally thought: the concept that a single cell would be representative of the rest of the embryo has been confused and compounded by the discovery of high levels of chromosomal mosaicism in human embryos, as well as by an increased understanding of the numerous complexities surrounding preimplantation development.
Although techniques and technology have significantly reduced the incidence of misdiagnosis, unfortunately this can still occur, due to chromosomal mosaicism, allele dropout or contamination (possible from cumulus or sperm cells).
Cost of PGD is also an important consideration, as some single-cell diagnoses are expensive techniques, and array technology is currently very expensive. For example, the cost of diagnostic technology can equal the cost of an IVF treatment cycle, which makes PGD a very expensive technique. If patients have to cover the cost themselves, they would be better to opt for prenatal diagnosis testing.
Data shows that the delivery rate per cycle for PGD is similar to that seen in IVF, even though PGD patients are normally fertile. Therefore, any center or patient embarking on PGD has to be aware that the diagnosis may not be 100% accurate due to mosaicism and technical problems, and that the chance of an unaffected baby after one cycle is low. The patients also have to decide whether undertaking an IVF cycle is more or less traumatic than natural conception and prenatal diagnosis testing. The natural pregnancy rate for patients registered for PGD may be high, as most of them have the alternative of prenatal diagnosis testing.
Patients who carry chromosome abnormalities are one of the most difficult groups of patients to treat, due to the high levels of abnormal embryos they produce.
Many couples around the world opt for PGD as an alternative to prenatal diagnosis testing. Although it is a demanding technique that requires a fully equipped molecular biology laboratory, highly skilled molecular biologists and close collaboration with clinical geneticists, technical breakthroughs over the past decade continue to make PGD a very real alternative for couples at risk. Hopefully, improvements in IVF and single cell diagnosis will increase the range of diseases that can be diagnosed at the single-cell level in order to help as many couples who carry genetic disease as possible.
Ethics and Laws
The law governing PGD varies worldwide. Some countries (like Ukraine) have legislation regulating PGD, or PGD and embryo research, and others have no legislation. Although a few countries banned cleavage stage biopsy, blastocyst biopsy means that this is no longer of any relevance. Some of the arguments against PGD include the fact that it may be abused, as in the case of embryos sex selection for family balancing, or for choosing certain characteristics, the so-called Designer Baby. Prenatal diagnosis testing has been abused for fetal sex selection in several countries for many years, but, as with all medical practices, the good should outweigh the bad: such practices should not be banned just because they could be abused.
Legislation governing the use of PGD should eliminate such problems. In Ukraine, the Ministry of Health of Ukraine, which regulates all IVF procedures, regulates PGD practices too. Thus, as per the Order of the Ministry of Health of Ukraine from September 09, 2013 No 787 “Order manual of appliances of assisted reproductive technologies”:
PGD of monogenic and chromosomal defects in oocytes and embryos at the stage before embryo transfer, and determination of sex of embryos to prevent inherited diseases related to sex, developed as an alternative method, have a high risk of having children with hereditary pathology. The main benefit of PGD is to reduce the risk of hereditary diseases and increase the incidence of pregnancy (in some cases), the ability to refuse invasive interventions on the fetal egg and to terminate pregnancy in the event of a pathology. Diagnostic can be performed on polar oocyte cells, individual embryonic blastomeres, and trophectoderm cells.
Indications for PGD are the risk of birth of children with a mutation of any isolated gene or with chromosomal abnormalities revealed as a result of a genetic examination (clinical-genetic examination, karyotyping).
PGD may be performed at the will of the patient (s) at their request for the preimplantation genetic study.
PGD is performed using fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) methods and the like.
In order of pregnancy achieved after PGD, prenatal diagnosis testing is recommended.
It must be remembered that undertaking PGD is a significant ordeal for couples, as the IVF procedure is so invasive, and the pregnancy rate is low. If couples want to select a gender of their baby, a cheaper and simpler way would be prenatal diagnosis testing, where many diseases could be diagnosed at one time.