What is preimplantation genetic diagnosis (PGD)? What information does it provide, and why is it controversial? Learn about different forms of PGD and the extent to which it is possible in Switzerland.

What is preimplantation genetic diagnosis (PGD) and how does it work? What information does it allow, and why is it controversial? In this article, we describe different forms of preimplantation genetic screening and explore to what extent PGD is possible in Switzerland.

What is preimplantation genetic diagnosis?

Preimplantation genetic diagnosis (PGD) is a prenatal testing procedure that can be performed as a part of in vitro fertilisation. The purpose of PGD is to allow couples or individuals who are at risk of passing on a genetic disease to find out if they may have a child with a serious genetic or chromosomal disorder, and make an informed decision about whether they want to proceed with the pregnancy.

PGD may be used when it is known or suspected that individuals may be a carrier of a genetic mutation or chromosomal abnormality. This means that one may have a hereditary genetic disease and/or a family history of a serious genetic disease. Such genetic conditions may include cystic fibrosis, muscular dystrophy, or hemophilia.

It may also be used when couples experience unexplained infertility, meaning that the reason for struggling to conceive is not clear. In this case, examining the genetics of an embryo may help determine whether the embryo will likely make it through pregnancy (viability). It may also be used in the case of recurrent miscarriages to determine if there is something related to genetics that continually disrupts the pregnancy. In fact, one of the main reasons for miscarriage is genetic abnormalities.

In PGD testing, an embryo that was created in a test tube via IVF or ICSI has some cells removed, and the genetic material is analysed. The purpose of this prenatal testing method is to identify embryos that do not have any disease-related mutations or chromosomal abnormalities. It is performed prior to embryo transfer, in which the embryo is placed into the gestational carrier’s uterus to hopefully develop into a successful pregnancy.

While the test has been found to be highly accurate identifying genetic defects, the results of the analysis cannot be guaranteed.

Who is eligible for preimplantation genetic diagnosis in Switzerland?

PGD has been legally permitted in Switzerland for in vitro fertilisation since September 1, 2017 under very strict conditions. It may be used by couples who have a family history of serious genetic disease and are at increased risk of certain genetic or chromosomal abnormalities. These can pass on serious illnesses to the offspring or cause miscarriages.

In Switzerland, the Reproductive Medicine Act allows the genetic material of embryos to be examined in vitro (in a test tube). Their selection according to sex or to demonstrate chromosomal characteristics is only permissible if:

  • the risk that an embryo with an inherited predisposition to a serious disease implants itself in the uterus cannot otherwise be averted;
  • it is likely that the serious illness will manifest before the age of 50;
  • no effective and appropriate therapy to combat the serious illness is available; and
  • the couple asserts in writing to the doctor that the risk is not reasonable for them.

Different methods of PGD

The methods used to check embryos have different names depending on what kind of genetic defect may be present.

  • PGT-M (preimplantation genetic testing for monogenetic diseases): method for detecting monogenic diseases, or diseases where there are issues with single genes. Common single gene disorders include Huntington's disease, Tay-Sachs disease, sickle cell anemia, and cystic fibrosis.
  • PGT-SR (preimplantation genetic testing for chromosomal structural rearrangements): Method for detecting changes in the structure of the chromosomes. This may include when part of a chromosome breaks off and moves to another chromosome (translocation), or when part of a chromosome breaks off, flips around, and reattaches (inversion). One example of a disorder that occurs due to chromosomal structural rearrangements is Williams-Beuren syndrome.
  • PGT-A (preimplantation genetic testing for aneuploidies): method for detecting changes in the number of chromosomes (e.g. Down syndrome or trisomy 21). In this test, the number of chromosomes is counted to determine if there are more or fewer chromosomes than the standard 46.

PGT-A genetic screening is mainly used in women over 35 years of age, since the quality of the oocytes decreases with age and the chromosomes of the embryos are more often affected by numerical deviations. Such aneuploidy also increases the likelihood of miscarriage or stillbirth.

While a PGT-M is used to detect issues with genes (which are segments of DNA), PGT-SR and PGT-A are used to determine issues in chromosomes, which are the structures that contain genes. Chromosomal disorders may result from issues with structure (i.e. the placement and position of chromosomes) or number (i.e. if there are more or fewer than 46 chromosomes).

The process of getting PGD testing

Anyone interested in pre-implantation diagnostics will first receive comprehensive advice in a fertility center. However, this not only involves a fertility center, but also an institute that has a license from the Swiss Federal Office of Public Health (BAG) to carry out genetic analyses. Due to the strict legal requirements, there are a few administrative steps before PGD and a treatment contract must be concluded with the institutes involved.

Once the formalities have been completed and a couple has been approved to perform PGD, the following process will unfold:

Fertility analysis: In this step, a review of your medical history, a gynecological examination (uterine check) and a fertility check are carried out in the fertility center. For this purpose, the egg cell reserve is checked with a vaginal ultrasound and the various hormone levels are measured with a blood sample. In the case of couples with unexplained infertility, this step takes place before the PGD approval; in the case of couples who could inherit a genetic disease, the fertility analysis is only carried out after approval.

Stimulation treatment: The next step of the IVF cycle is hormonal stimulation. During this time, the woman will take medication and inject herself with shots to boost egg production. Ovulation is triggered 36 hours before collection at the fertility center with another injection.

Egg retrieval & fertilisation: For the next step, the couple goes to the fertility center for egg retrieval. The specialist removes the matured egg cells from the uterus through the patient's vagina with a needle. In this outpatient operation, the patient is under anesthesia. A maximum of 12 egg cells may be fertilised in the laboratory with the man's sperm by means of in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).

Genetic examination & discussion of further steps: After about 5 days, when the embryos are in the blastocyst stage, several cells from the outer layer of the embryos (called the trophectoderm) are removed with a glass pipette. The cells are then analysed for their genetic material and the blastocyst is frozen in the meantime. As soon as the results of the examination are available, the couple goes to the fertility center to discuss how to proceed.

Ideally, no embryo will have an anomaly. However, it is also possible that anomalies are identified in all or only individual embryos. The couple can now decide which embryos they want to continue using and what to do with the rest. The options are to induce pregnancy with one or more affected or unaffected embryos, to freeze the embryos for later fertilisation, to donate them to research, or to destroy them.

If all the embryos show abnormalities and the couple therefore does not want to continue using them, they can opt for another treatment cycle. In this case, the procedure starts again.

Risks of PGD

The following risks have to be taken into account in the entire PGD process.

Risk of misdiagnosis: The analyses do not offer 100 percent certainty with regard to the results. In order to gain even more certainty, couples can also have a prenatal diagnosis carried out after the embryo implants and during pregnancy.

In prenatal diagnostics, a distinction is made between invasive and non-invasive methods. With invasive methods, an intervention in the mother's body takes place (e.g. placenta puncture, amniotic fluid collection (amniocentesis) or umbilical cord puncture). With non-invasive methods, blood tests or ultrasound examinations are carried out (e.g. non-invasive prenatal test (NIPT) or nuchal translucency test).

Risk for the embryo: If there is an anomaly, there is a risk that the embryo will not be used for implantation in the uterus and will therefore be disposed of.

Risk for emotional well-being: PGD is a very emotional process for the couples involved. There are many ethical decisions to be made, which can be very stressful. It is also possible, for example, that all the embryos produced have an anomaly or that only one healthy embryo is found, but all the others are disposed of.

Financial risk: No medical procedure can guarantee pregnancy or live birth; the financial costs are to be borne independent of the outcome.

Alternatives to PGD

If a couple does not meet the legal requirements for pre-implantation diagnosis, polar body diagnosis or preconception diagnosis (PCD) is an alternative. In a PCD, the polar bodies are examined. These are cellular components expelled from the egg cell, through which the physicians receive an image of the genetic composition of the egg cell. However, with this method, it is only possible to analyse hereditary diseases that originate in the mother.

Why are there ethical concerns about PGD?

While PGD is a hugely beneficial reproductive technology, it is also controversial. In general, the ability to evaluate whether an embryo may express certain genetic traits can pose questions related to disability, the right to abortion, and the rights of a developing embryo. Beyond this, ethical concerns have been raised about:

  • the analysis of the embryo for suitability as an organ and tissue donor for a sick sibling
  • the gender selection or selection of other physical traits
  • the analysis of the embryo for possible diseases (e.g. breast cancer), which may only break out in adulthood, can be recognised early and for which there are promising treatments.

Due to these ethically questionable possibilities, PGD is strictly regulated in Switzerland. Prior to the new law in 2017, the Swiss population debated the ethical implications of PGD with regards to whether it should only include couples who risked passing on serious genetic diseases, or if it should also include couples who remain unable to conceive despite going through all possible treatment methods. In the end, an amendment was made allowing PGD to be used in instances where chromosomal abnormalities may prevent an embryo from developing or where couples fear passing on a serious genetic disease. The counter-committees consisted of various representatives from parties from the left to the right as well as 18 social organisations. Part of their argument was that the amendment discriminates against people with disabilities by classifying embryos as ‘worth living’ and ‘not worth living’.

The National Ethics Committee (NEK) and the Swiss Academy of Medical Sciences (SAMW) have written their own statement on the subject, which has been incorporated into the current legislation.

Conclusion

Although PGD is not 100% accurate and cannot guarantee pregnancy or live birth, it does reduce the risk of serious genetic and familial diseases and miscarriages. There are many ethical decisions to be made during treatment. Not least because of this, the affected couple is exposed to emotional stress. We recommend that couples who undergo prenatal diagnosis of their embryos have therapeutic support.

Do you or your partner have a serious, hereditary disease or have you had multiple miscarriages? Contact us and let our empathetic specialists advise you on prenatal diagnostics. Secure your spot for a free consultation today!