Should Preimplantation Genetic Diagnosis be used to

reject embryos?
Sofia Edwards

The ethical discussion surrounding the use of Preimplantation Genetic Diagnosis (PGD)
centres on a fundamental question; Should PGD be used to selectively reject embryos
during the in vitro fertilisation process? PGD serves as a powerful tool for genetic screening
and enabling the identification of hereditary anomalies; potentially sparing prospective
children from debilitating genetic diseases. However, its use generates many ethical, societal
and legal dilemmas. Advocates of PGD argue that it provides parents with the means to
make informed decisions about their offspring's genetic well-being. Conversely, critics of the
process express concerns regarding the potential repercussions of selective embryo
rejection, including concerns about genetic discrimination and how the implementation of the
process gives man the ability to ‘play god’. This debate encourages us to explore questions
concerning reproductive autonomy and the societal values we maintain.

Biological concepts
Currently, three types of preimplantation genetic diagnosis exist; PGTa, PGTm and PGTsr.
PGTa; (standing for Preimplantation Genetic Testing for Aneuploidy), is used to assess the
chromosomal status of embryos before they are transferred to the uterus. PGT-A is primarily
employed to identify embryos with the correct number of chromosomes, reducing the risk of
implanting embryos with aneuploidy (an abnormal number of chromosomes), which is a
common cause of miscarriages and birth defects.
How PGTa Works; After fertilisation, the embryos develop in the laboratory for several days.
PGT-A is typically performed on embryos at the blastocyst stage, which is around day five or
six of development. After allowing the embryos to develop, a small biopsy is performed on
the outer layer of the embryo (typically removing 5 to 7 cells). The cells obtained by the
biopsy are then subjected to genetic analysis to determine the number of chromosomes in
each embryo. Some possible tests are next-generation sequencing (which determines the
sequence of nucleotides) or array comparative genomic hybridization (which determines the
number of variations in DNA). The genetic analysis identifies whether each embryo has the
correct number of chromosomes (euploidy) or an abnormal number (aneuploidy). Embryos
with aneuploidy may have extra or missing chromosomes, which can result in developmental
issues if implanted. Only embryos determined to be euploid are considered for transfer to the
uterus.
How PGTm works; PGTm (Preimplantation Genetic Testing for Monogenic (single gene)
Disorders) is used to identify embryos that carry a specific single-gene disorder, such as
cystic fibrosis, Huntington's disease, or sickle cell anaemia. Typically utilised when one or
both prospective parents are known carriers of a monogenic disorder and wish to reduce the
risk of passing the condition to their offspring. Procuring the cells takes the same process as
PGTa, once again allowing the embryo to develop to the blastocyst stage before performing
the biopsy. A technique known as Polymerase chain reaction (which enables the creation of
multiple copies of a DNA segment) is commonly used for genetic analysis. Only embryos
that are determined to be unaffected by the specific monogenic disorder are considered for
transfer to the uterus. This selection reduces the risk of passing on the disorder to the
offspring.
How PGTsr works; PGTsr (Preimplantation Genetic Testing for Structural Rearrangements)
is used to determine the structural rearrangements in one of both parent's chromosomes.
The rearrangements can include translocations (when a chromosome breaks and the
fragmented pieces reattach to different chromosomes) and inversions (when a segment of a
chromosome breaks off and reattaches to the same chromosome but in a different location).
Once the embryo reaches the blastocyst stage, the biopsy undergoes genetic analysis.
Techniques such as next-generation sequencing, fluorescence in situ hybridization (where a
full set of chromosomes are placed onto a glass slide and a small piece of purified DNA
tagged with a fluorescent dye, the fluorescently labelled probe finds and then binds to its
matching sequence within the set of chromosomes) or comparative genomic hybridization
are typically used for this. The genetic analysis determines which embryos have a normal
chromosomal structure and which ones carry the structural rearrangement. Only embryos
without the rearrangement are considered for transfer to the uterus.

Preimplantation Genetic Testing for Structural Rearrangements

Chromosomal Inversion

Chromosomal Translocation

Stakeholders
Prospective Parents: Couples or individuals seeking assisted reproductive technologies
like in vitro fertilisation and PGT are primary stakeholders. They make decisions about
whether to undergo PGT and are directly affected by the outcome. Depending on the
parent's individual beliefs, their opinions could range greatly in the support of PGD, however
it is highly likely, that as they have already invested in invitro fertilisation (which is not cheap
by any means), they may have a bias towards anything that could potentially help them
become pregnant with a healthy child, meaning they would be supportive of PDG.
Healthcare Professionals: As the individuals potentially performing these procedures, they
are also directly affected by the outcome, though not to the extent of parents. Fertility
specialists, genetic counsellors, embryologists, and clinicians play crucial roles in advising,
performing, and interpreting PGT procedures. Because of their scientific backgrounds, they
may have a bias in support of PGD in cases where the prospective child would have a low
quality of life or when there is a higher likelihood of miscarriage.
Ethicists and Bioethicists: These experts analyse the moral, ethical, and philosophical
aspects of PGT, helping society navigate complex ethical questions related to embryo
selection and genetic manipulation. Ethicists and bioethicists do not uniformly hold a single
viewpoint on PGD. Their perspectives can vary widely based on their ethical frameworks,
personal beliefs, and the specific ethical principles they prioritise. For example, ethicists who
place importance on freedom and reproductive autonomy may argue that PGD empowers
prospective parents to make informed choices about their reproductive options, whereas
critics of PGD may raise concerns about eugenics, the idea of enhancing the human gene
pool in ways that could be discriminatory or ethically problematic.

Social, Economic and Legal Factors of Preimplantation Genetic Diagnosis

Preimplantation Genetic Diagnosis (PGD) exists at the intersection of complex social,
economic, legal, and political factors.
Social
Ethics and morality: Different societies and cultures hold varying ethical and moral beliefs
about the acceptability of PGD, particularly in cases involving genetic selection for
non-medical traits or gender.
Access and equity: The underrepresentation of people from lower socioeconomic
backgrounds receiving PGD may raise concerns about equitable access to reproductive
technologies and genetic screening.
Economic
Cost and Accessibility: The high cost of PGD can limit access to those who can afford it,
potentially exacerbating health disparities. Economic factors can also impact insurance
coverage for PGD.
Legal
Regulatory Frameworks: The laws and regulations that regulate PGD vary greatly by nation
and area, influencing its availability, legal usage, and ethical issues.
Parental Rights and Consent: Legal frameworks frequently address concerns of informed
consent, parental rights, and the disposition of unused embryos.
Reproductive Rights: Legal issues extend to reproductive rights, including the freedom to
make reproductive health and family planning decisions individually

Case Study
A case study conducted by Takeshi Sato, Tomohiro Ishii, Yu Yamaguchi, Yosuke Ichihashi,
Daigo Ochiai, Hiroshi Asanuma, Tatsuo Kuroda, and Tomonobu Hasegawa centres on
prenatal genetic counselling provided to parents of foetuses suspected of having ambiguous
genitalia, shedding light on the emotional and psychological impact of such counselling. In
Case 1 “at 22 weeks of gestation, labia majora swelling and clitoris-like structures were
observed despite a 46,XY karyotype in amniotic fluid cells.”. In Case 2 “at 28 weeks of
gestation, presented with bladder exstrophy and scrotum-like structures”. In both cases
genetic counselling was offered, conveying the potential challenges of legal sex assignment
at birth and the need for extensive medical information before making such a decision. At
birth both babies displayed ambiguous genitalia with parents opting to assign the legal sex
as male after comprehensive medical evaluations.
Several months post-birth, parents from both cases reported feeling reassured and
well-informed throughout the process. In the context of the question "Should preimplantation
genetic diagnosis be used to reject embryos?” This case study emphasises the importance
of prenatal (in this case) genetic counselling as a crucial part of reproductive decision
making. The role of informed parental decision making is paramount when faced with
complex medical and ethical choices.
Legal, social and economic factors influence the potential accessibility and ethical
considerations surrounding prenatal genetic counselling and, in turn, the decisions made by
parents. Legislation has the ability to dictate the content of counselling, social factors include
societal attitudes towards prenatal genetic testing and economic considerations, including
healthcare costs and insurance can influence who has access to genetic counselling
services.

Bioethical Concepts
This case study, viewed through a consequences-based ethical lens, particularly
emphasises the concepts of respect and justice.
Respect: Prenatal genetic counselling respects reproductive autonomy and emotional
well-being. It empowers parents with comprehensive and accurate information, allowing
them to make informed decisions regarding their child's legal sex assignment. The
counselling process recognises and eases the emotional challenges parents may face,
promoting their sense of agency and respect for their choices.
Non-maleficence: The counselling prioritises the well-being of parents and the child, aiming
to reduce emotional distress. Delayed legal sex assignment displays a commitment to
safeguarding the child's physical and emotional health, aligning with the principle of
non-maleficence.

In summary, the discourse surrounding Preimplantation Genetic Diagnosis and its potential
use for selectively rejecting embryos during in vitro fertilisation is a multifaceted issue. It
involves various biological techniques and engages stakeholders with diverse perspectives.
Social, economic, and legal factors also influence its use. Ultimately there is no right or
wrong answer for a topic as nuanced as this and it will only grow more complex as science
of reproductive technology progresses.

Bibliography

Preimplantation Genetic Diagnosis Overview:

Preimplantation Genetic Diagnosis: Overview, Indications and Conditions, Process.
Molina B Dayal, MD, MPH Medical Director, STL Fertility, LLC
Dec 07, 2022

Translocation
https://www.genome.gov/genetics-glossary/Translocation
Daphne W. Bell Ph.D
Sept 09 2023

Inversion
https://www.genome.gov/genetics-glossary/Inversion
Ellen Sidransky M.D
Sept 09 2023

Fluorescence in Situ Hybridization (FISH)

Fluorescence In Situ Hybridization (FISH).
Amalia Dutra Ph.D
Sept 09 2023

Stakeholders Perspectives on the implementation of genetic carrier screening in a changing

landscape
https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-017-2083-9
Holtkamp, K.C., Vos, E.M., Rigter, T.
16 February 2017

Refining the ethics of preimplantation genetic diagnosis: A plea for contextualized

proportionality
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587504/
Wybo Dondorp and Guido de Wert
Feb 2019

Preimplantation genetic diagnosis: an overview of socio-ethical and legal considerations

https://pubmed.ncbi.nlm.nih.gov/16724879/
Knoppers BM, Bordet S, Isasi RM

Case Report: Prenatal Genetic Counseling to Parents of Fetuses Suspected of Having

Ambiguous Genitalia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838588/
Sato T, Ishii T, Yamaguchi Y, Ichihashi Y, Ochiai D, Asanuma H, Kuroda T, Hasegawa T.
Case Report:
Jan 2021

PGT-SR
https://fertility.coopersurgical.com/genomics/pgt-sr/
Author: unknown

PGT-A – Preimplantation Genetic Testing for Aneuploidy

https://monashivf.com/services/genetic-testing/pgt-a-pre-implantation-genetic-testing-for-ane
uploidy-screening/
Author: Unknown

Microarray-based Comparative Genomic Hybridization (aCGH)

Microarray-based Comparative Genomic Hybridization (aCGH) | Learn Science at Scitable.
Aaron Theisen Ph.D
2008

Polymerase chain reaction

https://www.genome.gov/genetics-glossary/Polymerase-Chain-Reaction
Mike Smith Ph.D
Sept 09 2023

What is next generation sequencing?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841808/
Behjati S, Tarpey PS.
Aug 28 2013