PGD ​​- Preimplantation Genetic Diagnosis

In the past, when advanced scientific and technological tools were not available, couples who carried serious genetic diseases and wanted to have children had to take the risk that their children would also suffer from the disease. Other couples who had difficulty conceiving or suffered repeated miscarriages were often forced to give up their dream or adopt.

Today, advanced methods make it possible to perform genetic tests on fetuses before they have taken root in their mother’s womb, thus increasing the chances of getting pregnant and giving birth to a healthy baby. PGD ​​(Preimplantation Genetic Diagnosis) allows the detection of embryos that carry serious genetic diseases, while PGS (Preimplantation Genetic Screening) allows the detection of embryos that lack or excess chromosomes.

Selecting embryos in which no genetic defects have been found and returning them to the patient’s uterus increases the chances of getting pregnant and reduces the risk of miscarriages and diseases in the fetus. The PGD method may save couples carrying genetic diseases the need to have an abortion or termination of pregnancy at an advanced stage of pregnancy. The PGS method may increase the chances of couples undergoing IVF treatments to conceive and avoid recurrent miscarriages.

Working together – to fulfill your dream

The Assuta centers in Ramat Hachayal and Rishon Lezion have IVF units, among the most advanced and largest in the world, where thousands of treatment cycles are performed every year. The Preimplantation Center for Diagnosis and Genetic Survey in Assuta joins these units, providing an additional, advanced and complementary service to Assuta patients under one umbrella.

The Center for Preimplantation Diagnosis and Genetic screening was opened in 2016 and contains an advanced laboratory that uses sophisticated equipment and advanced scientific techniques. The center employs highly experienced doctors, scientists, genetics and laboratory staff, all of whom work collaboratively with each other as well as with the physicians of Assuta’s IVF units.

PGD Diagnosis – Questions and Answers

Dr. Baruch Feldman, Founder and Director of the PGD Service at Assuta, and Dr. Michal Naftali, Director of the PGD Laboratory, talk about technology that is changing the world but at the same time raising challenging ethical issues

What is the purpose of a PGD test?

Dr. Baruch Feldman, an expert in medical genetics, neonatology and gynecology and director of the PGD service in Assuta: “PGD is a practical option offered to couples who are at risk of having a baby with a genetic disease or genetic defect. “Our goal is to help couples avoid a situation where, at an advanced stage of pregnancy, they will find that their fetus carries a genetic disease, and then have to go through the difficult process of terminating a pregnancy – a process that is perceived by many as ethically, religiously and morally problematic.”

How does the PGD program fit in with the IVF unit?

Dr. Michal Naftali, who co-founded the laboratory with Dr. Feldman:

Couples who come to us and carry a known inherited genetic disease, seek to diagnose the fetus in order to increase the chance of having a healthy child, thus avoiding a situation where they will have to terminate the pregnancy due to a genetic problem in the fetus. In order to undergo the genetic diagnosis these couples have to go through a process of in vitro fertilization, during which a large number of embryos will be formed. Already in the preliminary meeting, the couple met with the genetic counseling team of the PGD Center and the staff of the IVF unit so that they could study the special case of the couple. After building a unique diagnostic plan for them, the couple will go through the IVF process. About 3 to 5 days after the fertilization is done we take the embryos that are in the initial developmental stage (6-8 cells) and remove a single cell from them, when in fact this cell represents the whole embryo genetically. Using advanced and accurate laboratory equipment, we diagnose the genetic composition of the cell and test whether the fetus has the specific genes that may cause the child to develop a disease in the future. We will repeat the operation with all the fetuses of the couple and only a healthy fetus will be returned to the uterus. If a number of normal embryos are formed – they will be frozen.

Can implantation of healthy fetuses reduce the risk of miscarriage?

Dr. Naftali: “It is estimated that 50% of miscarriages are due to a chromosomal imbalance. In cases where a woman experiences recurrent miscarriages we can perform a genetic scan of the fetus before implantation (PGS). Unlike genetic diagnosis (PGD), genetic scanning (PGS) allows us to check whether embryos have the correct number of chromosomes. In this way we help reduce the risk of miscarriage and various conditions resulting from a chromosomal imbalance. ”

Dr. Feldman: “Genetic screening before implantation helps fertility doctors and in vitro fertilization laboratories to select the fetus that has the best chance of implantation, while to date the embryonic appearance has determined which of them will be returned to the uterus( an embryo without fragmentation, with equal, normal and identical cells in size is now considered a suitable embryo for implantation). PGS helps fertility doctors know that the embryos they return are also chromosomally normal. ”

Ethical questions are an integral part of the essence of genetic testing, what do you think about it?

Dr. Feldman: “In every test we perform, we help people, but no less – we stumble. Clearly in the case of Tai Sachs there is no question, and the defective fetuses will not be returned to the uterus because the pregnancy will be terminated anyway. It is a very serious disease that causes the child a lot of suffering and always ends in the death of the child. But what happens when parents are carriers of diseases that are considered mild, such as deafness? There are those who would argue that deafness can be easily dealt with, there are treatments and means, but what if the couple already has a deaf child at home and the experience is not easy? And what about genes of older diseases, like Huntington, Creutzfeldt–Jakob disease, or diseases that are less rare and less serious, like Parkinson’s? One of the characteristics of diseases that appear in old age is that not all of them can be predicted or severe. So do I want to avoid them, or not?

Complex questions also arise when there are genes that increase the risk of cancer. Angelina Jolie, for example, revealed that she underwent a double mastectomy after discovering that she carries the BRCA gene, a gene that significantly increases the risk of developing breast and ovarian cancer. But imagine what would have happened if Angelina’s parents had been able to perform a genetic diagnosis before Angelina was born and found out she was carrying the gene? Would we have gotten to know Angelina? After all, the gene only increases the risk and does not necessarily cause the disease. There is no single answer to this question. Some parents will choose not to implant these embryos, even though the gene will not necessarily cause the disease.

The issue of a potential bone marrow donor to a sick sibling also raises difficult questions. In order for a fetus to serve in the future as a donor to its sibling we are looking for certain characteristics. In Israel, there have been a number of cases in which embryos that were genetically diagnosed before implantation were implanted and found to be suitable donors to a brother or sister who has a genetic disease. These and other cases are essentially a “gray area,” so these dilemmas often raise discussions between ethicists, geneticists, and fertility physicians. ”

And what about cases where couples want to choose the sex of the fetus?

Dr. Feldman: “PGD is a very advanced technology that makes it possible to determine in advance the sex of the fetus that will be returned to the uterus. Determining the sex of the fetus for a non-medical purpose is prohibited by law in many places in the world – and also in Israel. Determining the sex of the fetus is common in Israel to rule out diseases related to the sex of the fetus, for example the Hemophilia, in which the girls can be carriers of the disease – but it is expressed only in boys. In these cases the couples are allowed to decide whether they are willing to implant girls that are carriers. What happens when spouses who have an autistic son come to us? The chance that the next son will be on the autistic continuum is 20%, but if it is a girl, the chance drops to 8-6%. I believe that in these cases, if the couple requests that a fetus of the female sex be selected, it is appropriate to discuss this before an ethics committee.

Who decides in which cases to agree to perform a pre-implantation genetic diagnosis?

Dr. Feldman: “The decision involves a genetics consultant, the fertility doctor and of course the couple who performs the test. In addition, in 2013, the Ministry of Health issued recommendations for performing a PGD test, which helps in decision-making. This document certainly makes decisions easier, but there are complex cases that do not appear in the document. “I believe that in problematic cases the issues need to be brought up for discussion and there is a need for a multi-system decision, because one doctor or a couple of parents do not have the ability to make difficult decisions of this kind.”