Category Archives: Genetics Awareness

Preimplantation Genetic Diagnosis (PGD)

We live in an incredible age. With modern technology, we have the ability to virtually eradicate the occurrence of many genetic illnesses. We encourage premarital genetic testing to preempt this problem, when possible. However, a major tool in achieving this goal is the use of Pre-implantation Genetic Diagnosis (PGD).
What is PGD?
First off, PGD can only be performed in conjunction with In Vitro Fertilization (IVF).  As in all IVF, an egg is fertilized in the laboratory and allowed to grow for a few days. Before the fertilized egg is reintroduced into the mother, one or more cells are removed from the egg.
The genetic material (DNA) of the extracted cell contains information about the way the egg will continue to grow and develop. In PGD, the DNA of the extracted cell is expanded and analyzed to see if this specific egg has the characteristic we are trying to find.
If the fertilized egg contains the desired characteristics, the IVF procedure resumes and the egg is reintroduced/implanted in the mother with the hope that she will become pregnant and carry her child to birth.
PGD can be used as a tool to identify thousands of characteristics. If the DNA marker for a characteristic has been identified, we can search for that specific marker to “guarantee” a desired outcome. As such, we can not only use PGD to prevent genetic illnesses, we can also use it to determine the gender or eye color of the future baby as well.
You said you can get rid of the occurrence of many genetic illness with PGD. How does that work?
Before we talk about PGD, we need to present a simplified overview of basic genetics.
  • A baby receives half of his genetic identity from his mother and half from his father.
  • A person who carries a genetic abnormality within his DNA but will never be affected by that abnormality is generally called a “carrier” of the abnormality.
  • The exact nature of an abnormality will determine if the child is affected by the disorder or if he is unaffected and (like his parents) remains a carrier of the abnormality.
  • In recessive genetic disorders (such as Tay Sachs disease), a child will only be ill with the disorder if he inherits the abnormality from BOTH parents.  If he inherits the abnormality from only one parent, he will be a carrier of the gene. If both parents are carriers and he does not inherit the abnormality from either parent, he will be unaffected and cannot pass it on to his children.
  • In dominant genetic disorders (such as Marfan’s Syndrome), a child can be ill even if he only inherits the abnormality from one parent. Whether or not the child is ill from the disorder depends on the nature of the abnormality. Some dominant disorders are gender linked, while others are not. Other dominant disorders are passed on by an affected parent with ALL of that parent’s offspring being affected by the abnormality as well.
When a couple is aware that they have a genetic abnormality, PGD can help. Until recently a couple in this situation had few options.  They could decide to not have children, or to have children who would likely be affected.  Or, they could consider prenatal testing and the possible termination of a pregnancy, with the attendant halachic problems. With the onset of PGD we can now offer a better solution.
With PGD, the couple undergoes an IVF treatment, with PGD performed as described above. The DNA is examined for evidence of the abnormality and only those eggs that will not result in an ill child are used for implantation.
Are there genetic disorders that cannot be prevented via PGD?
Unfortunately, there are some rare dominant genetic disorders in which the affected parent passes the disorder on to ALL of their offspring. Since every single fertilized egg from this couple will contain the abnormality and disorder, PGD will not be effective.
In such a case, the couple needs to turn to their medical professional and their PUAH counselor (as well as possibly their personal Rabbi) to explore and discuss their options.
You said before that I can use PGD to choose the gender, eye color or other characteristics of my child. Can this really be done?
Yes, the technology for this is available via PGD. Any characteristic that is genetic and has been identified can be selected for using PGD. However, just because we can do something doesn’t mean that we should do it. On the other hand, there are some instances in which gender selection is critical, which we will discuss later.
Aside from the ethical and moral issues, PGD involves tampering with the fertilized egg, which may raise the chance of birth defects. Additionally, IVF requires the introduction of hormones and other medications to the female body, which may result in unwanted side affects as well. Finally, IVF treatments are not always successful and the financial expense of IVF and emotional cost of failed treatments may be a deterrent from embarking on PGD for gender selection or some other superficial characteristic unless it is specifically indicated.
Anyone considering undergoing PGD should consult with their medical professional and PUAH counselor to determine if the treatment is indeed indicated in their case.
Are there any risks or other reasons not to do PGD?
As noted above, any performance of PGD is invasive and can raise the risks for defects and other undesirable side effects.
There are also no guarantees that the procedure will work. IVF success rates are certainly less than 50% in most cases. Additionally, PGD technology is not 100% effective. This can be attributed either to the limits of the technology or to something called “mosaicism”.
Mosaicism is an occasional occurrence where not all of the cells of the fertilized egg have the same genetic makeup. The PGD sample may therefore not have same characteristics as the egg, leading to a misleading result.
Another impediment to the use of PGD is financial. The cost of PGD can be prohibitive and in most cases the chance that the couple will not have a sick child exceeds the probability that their child will be ill.
Are there other applications of PGD? 
There are definitely other applications of this technology. For example, a couple with a cancer stricken child who has no genetic donor match could use PGD to create a sibling for the child who could serve as the older child’s life-saving donor. The only limit to what we can do with PGD is the extent to which we have mapped the genetic markers used to identify genetic characteristics.
There is also a new technology known as Pre-implantation Genetic Screening (PGS). In PGS, a fertilized egg is screened for a variety of the most common genetic abnormalities without any prior indication that there may be a problem with the egg. If a genetic marker is identified, the egg can be discarded.
This application is highly controversial. Embryologists claim to have seen embryos that seem to have an abnormality, but when left to develop, result in healthy pregnancies and live births. This suggests that a natural mechanism exists that sometimes addresses and repairs a potentially problematic embryo. Excluding these embryos may actually limit, not enhance the couple’s ability to become pregnant.
PGS is currently most often used in cases of advanced maternal age. It is recommended because the eggs of a woman of advanced maternal age have a higher incidence of genetic abnormalities. However, many of these women cannot produce a high volume of eggs. As such, we may be better served to rely on standard IVF without PGS, unless there is reasonable concern for a specific abnormality. Each specific case needs to be reviewed with a medical professional and PUAH counselor to determine the recommended action.
Halachic considerations
PGD technology is truly remarkable. We have been given the tools to engender profound and significant changes in the fabric of our society. Issues and factors that once created severe stigmas in some portions of our communities can be dealt with in a responsible and effective manner. Still, great care must be made to use this tool in an ethical and moral manner for the good of society.
PGD also raises several distinct halachic issues that require clarification. Some issues may be universal to all cases of PGD, while others must be adjudicated based upon the criterion of the case involved.
Since PGD involves the use of only those eggs that we select as “good”, what should be done with the undesired eggs? Can we destroy them?
The Gemara states that an embryo is considered to be halachically equivalent to water (fluid) for the first forty days after conception. This should not be construed as a lack of concern for the value and sanctity of life itself. It should also not be misunderstood to mean that up until that time it is not really a pregnancy.
However, an embryo is not capable of growing past a certain point outside the body. The poskim ruled that early pregnancy cannot be terminated since it will eventually become life if left alone, but unused embryos may be destroyed since they will not.
Doesn’t PGD involve interference with nature? Is that permissible?
One might express the worry about interference with nature. However, we do not believe that once someone has a medical condition we are prohibited in intervening in a Divine plan and should therefore leave them to suffer. Rather, the Gemara interprets the verse ‘and he will heal him’ to mean that the doctor is given permission, and even obliged, to heal the sick. Thus we are commanded to heal others, even if as a result we “interfere” with nature.
We do distinguish between life-threatening conditions and elective procedures. This applies in this case as well. A fertility challenged couple is considered to be sick with a non life-threatening illness. Furthermore, people dealing with the prevention of genetic illnesses would also be classified as ill. As such, we are certainly permitted to act in a manner that would heal their illness.
The matter becomes a bit less clear when we are talking about adding additional criteria to an existing PGD. There is a clear difference between a couple who are undergoing PGD for a genetic disorder and want to utilize the analysis which is already being done to perform gender selection or some other elective selection and a couple for whom there is no medical indication for PGD or even IVF.
How far does this extend? Are we obligated to use PGD?
This question only arises when we are talking about life-threatening genetic disorders. All other cases are considered to be elective and we cannot obligate someone to undergo an elective treatment.
The real question is not simply the use of PGD, but in forcing a couple who might have children with genetic disorders to use ONLY PGD to have children. They must practice birth control against natural conception (excluding the IVF procedure) and perform PGD any time they wish to have a child.
At the heart of the issue is the obligation one has to save another person’s life. Using PGD to prevent the birth of a child with a genetic disorder falls into this category. Therefore, the question being raised involves how far this obligation extends?
Some rabbinic authorities maintain that our obligation to save others extends even to a person who is not yet alive and thus obligates the use of PGD to prevent potential life threatening illness. Others maintain that our obligation to save a life does not extend to a person who is not alive.
That does not mean that they recommend against it – quite the contrary. Yet they cannot require it.
Each couple considering PGD should consult with their Rabbi and their PUAH counselor to determine their best course of action as well as the halachic obligations of their particular case.
Examples of permitted elective PGD
Most poskim recommend against the performance of elective PGD. However, there can be instances where elective PGD is beneficial and thus has been allowed. In order to understand the depth of halacha and using halacha to solve problems and benefit people, we will present two sample cases where elective PGD was recommended. The cases being discussed are anecdotal in nature and not an indication that a procedure is halachically permitted. In each case, the couple’s Rabbi and PUAH counselor reviewed the particular circumstances involved and the couples were given an answer appropriate to their circumstances. Any couple with similar issues must consult with their Rabbi and PUAH counselor for a halachic decision for their particular circumstances.
The Kohein
A Kohein (member of the priestly class; descendent of Aaron) who could not produce sperm and his wife had gotten a halachic ruling that they were allowed to use a sperm donor to become pregnant. However, the husband did not want to explain why his son could not be called to the Torah as a Kohein nor why his son does not perform the Birkat Kohanim. They were permitted to use PGD to select only female eggs and today have two wonderful daughters.
The Depressed Father
A family with 5 children of one gender consulted PUAH. The father was under psychological care because of severe depression at having single gendered offspring. The depression was so severe that it prevented him from interacting with his children and functioning as a parent to them and husband to his wife. While extended psychological treatment was a viable option, the psychologist also felt that having a gender selected child could also treat the problem. After consulting with the psychologist and PUAH counselor, their Rabbi determined that the incapacity in this case was so severe that it permitted gender selection for their 6th pregnancy. The treatment was successful and the father is fully participant as a parent for ALL his children and no longer requires psychological care.
The IVF parts of PGD certainly require halachic supervision. However, since the PGD cells will not be reintroduced to the body, there is no need for special supervision in the PGD lab. However, supervision will be required for the removal of the cells, in order to maintain the integrity of the IVF supervision of the egg.
PGD technologies have been given to us as a tool to provide unbelievable benefits to couples whose options for having children used to be extremely limited.
  • PGD is performed as part of IVF
  • Among other applications, PGD technology is being used to eradicate the occurrence of genetic disorders
  • PGD is not only permissible in such instances, it is seen by some as an obligation to perform
  • Elective uses of PGD require analysis and specific Rabbinical guidance
  • PGD can sometimes even help avoid complex halachic issues

How Preimplantation Genetic Testing Has Revolutionized the Treatment of Patients with Recurrent Pregnancy Loss

Of the known causes of recurrent pregnancy loss, chromosomal abnormalities account for the majority of miscarriages. Biopsying an embryo for preimplantation genetic testing has revolutionized the treatment of recurrent pregnancy loss, by improving the embryologist’s ability to choose the healthiest and most chromosomally normal embryo for transfer.
Miscarriages can be emotionally and physically challenging for both women and couples. Recurrent pregnancy loss, which is defined by the American Society of Reproductive Medicine as two or more failed clinical pregnancies, can be devastating. Estimates vary, but at least 5% of women will suffer more than one miscarriage, and it is important that their evaluation be thorough, and their treatment be precise.
Recommendations vary regarding the evaluation and treatment of women with recurrent pregnancy loss, and debate exists about which treatments are most effective. Evaluation of a woman with multiple miscarriages includes a search for structural, hormonal, infectious, immunological, and genetic causes. Frustratingly, in up to 50% of women with recurrent pregnancy loss, a clear cause will not be identified. Of the known causes, chromosomal abnormalities account for the majority of miscarriages.
When a woman has a fibroid or abnormally shaped uterus (such as a uterine septum), surgical correction is usually indicated. When a woman suffers from recurrent miscarriages due to chromosomally abnormal eggs and embryos, we usually recommend that she undergo in vitro fertilization (IVF) so that we can analyze her embryos prior to implantation. Preimplantation genetic testing of embryos has revolutionized the treatment of recurrent pregnancy loss. Biopsying and sequencing an embryo allows us to choose the best embryo for transfer and to minimize the likelihood of miscarriage. More than half of embryos are chromosomally abnormal, and the percentage of abnormal eggs increases each year with maternal age. This is significant because up to 90% of chromosomally abnormal pregnancies abort spontaneously, compared to only 7% of chromosomally normal pregnancies. As such, selection of the healthiest embryo is integral to improving outcome in patients at risk for miscarriage.
As women age, natural fertility declines, and it becomes more difficult to find a normal embryo. In some women, it may even take more than one egg retrieval to find a healthy embryo for transfer. The good news is that available literature has found IVF with preimplantation genetic testing of embryos to be a safe and effective way of helping patients conceive and deliver a healthy baby.
We are fortunate to live in an era in which technology can be used to help prevent human disease and suffering. Preimplantation genetic screening using next-generation testing of embryos allows for selection of the healthiest embryos for transfer. Data continues to accumulating that by using the right technology, healthy outcomes are common, even in patients who previously suffered from recurrent pregnancy loss.
Dr. Alan B. Copperman
Medical Director of the Division of Reproductive Endocrinology and Infertility, RMA of NY