Preimplantation Genetic Diagnosis and Chromosomal Abnormalities: The Scientific and Ethical Issues Surrounding PGD-A
In France, unlike in other countries, the conditions for using preimplantation genetic diagnosis are strictly regulated. It cannot be used for general genetic screening and must be limited to addressing a known risk. This is a situation that some would like to see change.
Valérie Depadt, Sorbonne Paris Nord University and Marjolaine Willems, University of Montpellier
While infertility is currently the main reason for seeking assisted reproductive technology (ART), it is not the only one. In some cases, these techniques are used to prevent the transmission of particularly serious genetic diseases to the child.
For the families involved, the issue goes beyond mere conception: the goal is to give birth to a child free of the condition identified in at least one of the parents. In this context, preimplantation genetic diagnosis (PGD)—which allows for the analysis of the genetic makeup of embryos resulting from in vitro fertilization before their transfer to the uterus—has been authorized in France since 1999.
PGD therefore applies to only a limited number of people. According to the French Biomedicine Agency, approximately 1,000 PGD applications are reviewed each year, of which about two-thirds are approved. Nevertheless, it raises major scientific, ethical, and political questions, which are all the more pressing given that legal frameworks and practices differ significantly from one country to another.
PGD in France: A Strictly Regulated Practice
PGD involves analyzing one to a few cells taken from the embryo to screen for a genetic abnormality. When performed simultaneously on several embryos obtained during the same fertilization cycle, it makes it possible to exclude embryos carrying that abnormality from transfer into the uterus.
In France, PGD is permitted when an abnormality causing a severely disabling disease—one that may not manifest until later in life or that may pose an immediate threat to life —has been previously and precisely identified in one of the parents or one of their immediate ancestors.
However, the law imposes a major restriction on the purpose of the test: the diagnosis may have no other purpose than to detect the previously identified genetic abnormality and to determine how to prevent or treat it. PGD is therefore in no way a general genetic screening test; it is a targeted test aimed at addressing a known risk.
This legal framework reflects a medical approach to PGD: it is an alternative to medical termination of pregnancy when the risk of disease is high. As such, the procedure is covered by health insurance for up to four IVF cycles. Due to the high level of technical expertise required and a desire for centralization, only five specialized centers are accredited: Paris, Strasbourg, Montpellier, Nantes, and Grenoble.
French law also explains the technological limitations observed in our country. In France, since only testing for the specific condition being diagnosed is permitted, the use of modern sequencing methods—known as “pan-genomic” (because they allow the entire genome to be sequenced)—remains limited.
The situation is different abroad, where such techniques are widely used.
Abroad: Advances in Screening for Chromosomal Abnormalities
In several countries, including the United States, the United Kingdom, and Spain, advances in genetic sequencing have led to a different use of preimplantation genetic testing. It is used for the general screening of chromosomal abnormalities in embryos.
This type of PGD is called PGD-A, which stands for aneuploidies. Aneuploidies are abnormalities in the number of chromosomes, such as trisomies or monosomies (one of the best-known examples of aneuploidy is trisomy 21, which is characterized by the presence of an extra chromosome in the21stchromosome pair).
PGD-A therefore no longer—or at least not exclusively—involves screening for a specific identified hereditary disease. It involves examining all the chromosomes of embryos produced through in vitro fertilization before transferring them to the uterus, in order to identify those with a normal chromosome number. These embryos are believed to have a better chance of implantation and live birth.
Abroad, this technique is widely offered at certain clinics—particularly in the private sector—sometimes even beyond strict medical indications. In some European countries, the United States, and Canada, where PGD-A is presented as a factor that increases the chances of success, it is used in a significant proportion of IVF cycles.
Why is this practice banned in France?
This situation stems from the desire to limit any expansion of the diagnostic process toward broader embryo selection, which is perceived as likely to pave the way for eugenic abuses.
However, some French ethics bodies have recently helped reignite the debate by recommending that the medical benefits of these techniques be evaluated within a strictly regulated framework.
The National Consultative Committee on Ethics for Life and Health Sciences (CCNE), in its Opinion No. 129 of 2017, supported authorizing screening for aneuploidies during in vitro fertilization for couples undergoing PGD and certain infertile couples.
According to the French Biomedicine Agency, it is also important to consider the implications of whole-genome sequencing, including its implications for prenatal diagnosis.
Unfortunately, at this time, the data needed to make an informed decision is still lacking.
PGD-A: Scientific Benefits Still a Matter of Debate
PGD-A is based on a biologically sound hypothesis: since chromosomal abnormalities are common in human embryos (occurring in 30 to 60 percent of embryos routinely screened during preimplantation genetic diagnosis, their identification could theoretically improve IVF outcomes and reduce the risk of implantation failure, miscarriage, medical termination of pregnancy, or the birth of a child with a serious genetic disorder.)
However, the scientific data appear less convincing than expected in light of the anticipated benefits.
It is important to note that an IVF cycle refers to a complete treatment attempt, including ovarian stimulation, egg retrieval, and embryo transfer(s), with multiple transfers sometimes resulting from a single cycle. In France, the live birth rate is approximately 25% per initiated cycle. In practice, patients undergo an average of two to three cycles to achieve a live birth, with the chances increasing cumulatively with the number of attempts. The distinction between the rate per transfer and the rate per initiated cycle is essential, as the observed benefit of PGD-A relates primarily to the former indicator.
In practice, during in vitro fertilization (IVF), several oocytes are fertilized in the laboratory to produce a limited number of embryos (often between five and ten). Without A-PGD, one or more embryos are selected based on morphological criteria and transferred, while the others may be frozen. With A-PGD, each embryo undergoes a biopsy, and only those considered euploid (with the correct number of chromosomes) are selected for transfer.
This selection process effectively reduces the number of available embryos. Data from IVF cohorts show that, on average, 30 to 60% of blastocyst-stage embryos (five to six days of development) are aneuploid, a proportion that increases with maternal age. For example, in a patient who produces eight blastocysts, PGD-A may result in the identification of only two to three euploid embryos—or even none, depending on the patient’s age—thereby reducing the number of embryos available for transfer.
The systematic exclusion of mosaic embryos—that is, those containing both euploid and aneuploid cells—may exacerbate this decline, even though live births of healthy children have been reported following the transfer of such embryos.
This selection process has multiple consequences: a reduction in the number of possible transfers per cycle, an increase in the number of cycles needed to achieve a pregnancy, and the risk of losing potentially viable embryos.
Studies have shown, in a large number of cases, an increase in pregnancy rates per embryo transfer in certain situations, such as implantation failure or recurrent miscarriages.
However, this does not appear to be consistently the case for the live birth rate per initiated cycle, even though this is the most relevant indicator for couples. PGD-A could even lead to a lower birth rate among women under 40.
How can these results be explained?
Several biological limitations explain these contrasting results. Embryonic biopsy relies on the analysis of a limited number of cells, which can lead to errors in interpretation due to a lack of representativeness.
In cases of embryonic mosaicism—that is, when the embryo contains both normal and aneuploid cells—the cells collected for analysis may not reflect the chromosomal makeup of the entire embryo, leading to discordant results or classification errors.
In addition, there is sometimes a capacity for self-correction. This phenomenon is a major factor limiting the accuracy of A-DPI. Furthermore, variability in sample collection conditions and the analytical limitations of sequencing techniques can contribute to false positives or false negatives, particularly in the detection of mosaicism.
Finally, not all miscarriages are related to chromosomal abnormalities, which inherently limits the potential impact of aneuploidy screening on live birth rates.
Given these uncertainties, international academic societies—particularly those in Europe (EHRE) and the United States—remain cautious and do not recommend the routine use of PGD-A in standard clinical practice for all couples undergoing IVF. There may be a benefit for certain subgroups of patients, particularly older women or those who have experienced multiple spontaneous miscarriages.
Current knowledge gaps underscore the need for rigorous studies—including those that address medico-economic aspects—to assess the actual benefits of PGD-A across different patient populations and clinical settings. Indeed, performing PGD-A doubles the cost of conventional IVF.
To address these gaps, the French National Agency for Medicines and Health Products Safety (ANSM) authorized Assistance publique – Hôpitaux de Paris (AP-HP) in 2021 to conduct a clinical trial (the DEVIT trial) to collect data on these issues. The objective of this study was to evaluate the benefits and risks.
But on February 7, 2024, the Montreuil Administrative Court (Montreuil Administrative Court,8thChamber, February 7, 2024,No.2206833), to which the conservative Jérôme-Lejeune Foundation had appealed, overturned the ANSM’s authorization, citing the legal ban on PGD-A, including at the research stage.
In a ruling dated July 10, 2025, the Paris Administrative Court of Appeals upheld the decision of the administrative court.
The study has therefore been halted, even though an objective assessment of the benefits and risks requires, precisely, methodologically sound research.
DPI-A: A Highly Polarized Debate in France
In France, the issue of assisted reproductive technology (ART) has sparked a particularly polarized debate.
Some patient advocacy groups, such as the BAMP! collective, point out an inconsistency: screening for Down syndrome is widely offered during pregnancy, with the option of medical termination in the event of an abnormality, while preimplantation screening remains prohibited.
Isn’t the risk of eugenics lower when it comes to selecting viable embryos than when it comes to routinely screening for trisomy 21 in a fetus a few months into pregnancy?
This situation effectively creates inequalities in access, since only couples with the necessary financial resources have the option of traveling abroad.
Conversely, opponents, such as the Jérôme-Lejeune Foundation, believe that extending PGD to include chromosomal screening could reinforce a culture of embryo selection and raise major ethical questions, particularly with regard to disability.
Put science back at the center of the discussion
In this context, the debate cannot easily be reduced to a dichotomy between a supposedly neutral scientific assessment and positions based on ethical and societal considerations.
The available scientific data on PGD-A remain controversial: while some studies suggest a benefit in specific indications (repeated implantation failure, recurrent miscarriages), others highlight the lack of a significant improvement in live birth rates for all patients undergoing ART, as well as limitations related to embryonic mosaicism, the representativeness of the biopsy, and variability in clinical practices.
Scientific assessment itself is therefore characterized by uncertainties, methodological choices, and differing interpretations.
At the same time, the use of assisted reproductive technology (ART) raises issues that go beyond the biomedical field alone, particularly with regard to the representation of disability, embryo selection, equitable access to care, and the purposes assigned to reproductive medicine. These dimensions involve collective choices and ethical frameworks that cannot be determined by scientific data alone.
Paradoxically, the lack of a legal framework for research on assisted reproductive technology (ART) in France has hindered the generation of national scientific data, as demonstrated by the decision of the Montreuil Administrative Court.
France views the development of authorized biomedical technologies only in accordance with the fundamental principles governing the human body, as set forth in Articles 16 and following of the Civil Code, to the exclusion of any commercial considerations.
The history of PGD illustrates the ongoing tension between biomedical progress, patient expectations, and ethical concerns. Today, PGD-A embodies high hopes for improving IVF outcomes, but also raises concerns about its societal implications.
In this context, the challenge may be less about immediately deciding “for” or “against” than about consolidating the available knowledge. De-escalating the debate, better informing the public, supporting research, and clarifying the uncertainties appear to be essential conditions for guiding future public health decisions.
In a field characterized by rapid innovation and far-reaching ethical issues, the quality of scientific data must play a decisive role in how our society defines and will define future collective choices.
Valérie Depadt, Associate Professor of Law, Sorbonne Paris Nord University and Marjolaine Willems, Clinical Geneticist, University of Montpellier
This article is republished from The Conversation under a Creative Commons license. Readthe original article.