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The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) has clinically validated that PGT-Plus, a newly integrated preimplantation genetic testing approach, can detect hidden genetic abnormalities that are missed by conventional tests. These include triploidy[1] and genome-wide uniparental disomy (gwUPD)[2], both of which can lead to miscarriage or severe maternal complications. This more comprehensive and precise one-stop testing solution enhances  the current preimplantation genetic testing (PGT) used in assisted reproductive treatment (ART). It enables earlier detection and reduction of risks to both the mother and fetus, while alleviating the physical and psychological burden on families preparing for pregnancy. The study has been published in the internationally recognised reproductive medicine journal Human Reproduction Open.

Conventional screening blind spots may lead to miscarriages in embryos assessed as normal

With increasing maternal age among couples in Hong Kong, more families are turning to ART. However, recurrent miscarriage and embryo implantation failure often impose substantial financial and psychological stress. PGT plays a pivotal role in safeguarding embryo health by screening embryos for chromosomal and monogenic abnormalities before implantation in ART.

Conventional tests include PGT-A, PGT-M and PGT-SR[3]. However, these approaches are typically designed to assess specific types of genetic risk and therefore might have limitations in detecting certain complex abnormalities. In cases of triploidy or gwUPD, certain conventional tests cannot fully distinguish such complex abnormalities and may classify affected embryos as normal. These undetected genetic abnormalities may lead to early pregnancy loss, unexplained termination or fetal anomalies. In some cases, they may even cause complications that pose direct health risks to the mother, including molar pregnancy[4] and gestational trophoblastic disease[5].

PGT-Plus detects hidden genetic abnormalities in a single test

To assess the accuracy and performance of PGT-Plus, the researchers first analysed cell samples with known genetic abnormalities using established embryo testing methods, followed by parallel comparative analyses with PGT-Plus results.

By integrating conventional PGT with single nucleotide polymorphism (SNP)-based genetic analysis, PGT-Plus offers the following:

• More streamlined and comprehensive testing: among 1,049 blastocysts analysed, PGT-Plus identified an additional 2.2% of abnormal cases beyond conventional tests – 0.8% with triploidy and 1.4% with gwUPD;
• Improved embryo selection: among 258 embryos previously assessed as normal by conventional methods but that did not result in successful pregnancies after transfer, PGT-Plus recognised over 3% as carrying triploidy or gwUPD;
• Addresses potential undetected abnormalities: among people carrying chromosomal structural abnormalities[6], PGT-Plus identified chromosomal translocations[7] in about one in two embryos previously classified as structurally normal by conventional tests.

PGT-Plus shows encouraging potential to support more precise selection of embryos by screening against genetic abnormalities in those at risk of inherited genetic disorders or chromosomal rearrangements, helping to reduce recurrent genetically mediated pregnancy loss.

Dr Matthew Chau Hoi-kin, Research Assistant Professor in the Department of Obstetrics and Gynaecology at CU Medicine, said: “Through PGT-Plus, prospective parents only need to undergo a single testing workflow. While routine screening for chromosomal numerical abnormalities, monogenic disorders or structural rearrangements is being conducted, the innovative method concurrently detects triploidy and gwUPD, broadening the scope of embryonic genetic screening to benefit more people planning for pregnancy.”

Professor Richard Choy Kwong-wai from the Department of Obstetrics and Gynaecology at CU Medicine said: “This next-generation technology enables more comprehensive identification of embryos that were previously validated as normal but in fact harbour hidden genetic abnormalities. Addressing conventional limitations, it reduces the frequency of failed embryo transfers. We will focus on streamlining the workflows of genetic data comparisons and continue to advance precision genetic diagnostics.”

Dr Jacqueline Chung Pui-wah, Acting Chairperson and Associate Professor (Clinical) in the Department of Obstetrics and Gynaecology at CU Medicine, said: “In ART cases of recurrent miscarriage or implantation failure, clinicians have often been unable to identify a definitive cause. PGT-Plus not only enables more accurate embryo selection for transfer in people with infertility but also facilitates early prevention of severe maternal complications. This novel approach helps advanced-age and high-risk people develop safer and more reliable birth plans.”

The research was funded by the Research Grant Council Collaborative Research Fund, the National Natural Science Foundation of China, and the Research Grant Council General Research Fund.

[1]Triploidy is a rare genetic condition in which an individual has three complete sets of chromosomes in their cells instead of the usual two. Most embryos with triploidy miscarry early in development.

[2]gwUPD is a rare genetic condition where an individual inherits both copies of all chromosomes from a single parent, rather than one set from each. Thise condition typically leads to severe pregnancy complications and prevents the embryo from developing normally.

[3]These tests aim to detect aneuploidy, monogenic disorders and structural rearrangements, respectively.

[4]Molar pregnancy is a rare abnormal pregnancy where placental cells grow uncontrollably. It cannot develop into a healthy baby and carries a long-term risk of turning into a malignant cancer.

[5]Gestational trophoblastic disease is a rare group of pregnancy-related conditions that can cause benign, precancerous lesions (such as molar pregnancy) or highly aggressive malignant tumors.

[6]Chromosomal structural abnormalities occur when segments of chromosomes break and rearrange, altering the sequence or number of genes. These variations often lead to developmental delays, intellectual disabilities, or a higher risk of miscarriage.

[7]Chromosomal translocation is a rearrangement where segments of non-homologous chromosomes break and reattach. This condition can result in infertility or miscarriage.