More genetic conditions approved by MOH for testing before embryos are implanted for IVF

SINGAPORE – Thirteen severe genetic conditions have been added to a list of conditions approved for testing before couples decide to go ahead with the implantation of embryos in in-vitro fertilisation (IVF).

Of these, six are single gene defects that can put a person at greater risk of conditions like breast cancer and mild brittle bone disease.

The remaining seven are chromosomal abnormalities that carry an increased risk of miscarriage, which would likely make the embryos unsuitable for IVF.

In response to queries from The Straits Times, the Ministry of Health (MOH) said it allows pre-implantation genetic testing (PGT) of embryos for severe genetic conditions “that are highly likely to develop in individuals and have limited treatment options available”.

An MOH spokeswoman confirmed that the 13 conditions were added on Oct 31.

They bring the total number of conditions approved for PGT to 169, including those previously approved for testing, such as Huntington’s disease, spinal muscular atrophy, sickle cell anaemia, and haemophilia A and B.

The MOH spokeswoman said financial support for pre-implantation testing of approved conditions is available to eligible couples who would like to conceive but are at risk of transmitting serious inheritable diseases to their newborns.

Since July 1, 2022, couples where at least one spouse is a Singapore citizen and who are assessed to meet a set of clinical criteria

can receive up to 75 per cent in co-funding

from the Government, subject to caps, to cover part of their PGT costs if they visit a public assisted reproduction (AR) centre.

They can also use their own or their spouse’s MediSave, subject to withdrawal limits, regardless of whether they seek care at a public or private AR centre.

There are 11 AR centres that provide pre-implantation testing, with three in the public healthcare sector – KK Women’s and Children’s Hospital (KKH), the National University Hospital (NUH) and Singapore General Hospital (SGH).

Associate Professor Tan Ee Shien, head and senior consultant at KKH’s genetics service, said all 13 conditions are considered rare.

One of them involves mutations in the RAD51D gene, which is estimated to occur in 0.3 per cent to 0.5 per cent of the population.

An individual who inherits the RAD51D gene mutation is born healthy, but faces a significantly higher lifetime risk of developing certain cancers, particularly breast and ovarian cancer, usually in adulthood, said Prof Tan.

Research has shown that mutations in the RAD51D gene accounted for 0.3 per cent of patients with breast cancer, and 1 per cent of patients with ovarian cancer, said Dr Nur Azleen Sidek, an associate consultant at NUH’s reproductive endocrinology and infertility division.

Mutations of other genes such as BRCA1 and BRCA2 similarly lead to higher risks of breast and ovarian cancers, and are already in the list of approved conditions for PGT.

Another newly approved condition is the type 1 form of osteogenesis imperfecta, which affects about one in 10,000 to 20,000 live births worldwide. This is due to mutations in the COL1A1 gene.

Prof Tan said it is the mildest form of “brittle bone disease”, with the individual suffering from bone fragility, leading to frequent fractures, often from minimal trauma. Other possible problems include early hearing loss and brittle teeth.

Seven of the conditions newly approved for testing have to do with chromosomal structural rearrangements, or structural abnormalities in the chromosomes – the cell structures that contain DNA.

Sometimes, rearrangements or translocations, where parts of the chromosomes break off and swop places, may affect pregnancy by increasing the risk of recurrent miscarriages, said Dr Hemashree Rajesh, a senior consultant at SGH’s department of obstetrics and gynaecology.

They could also result in the child having developmental issues, she added.

MOH said in its licensing conditions that PGT cannot be carried out for social reasons, such as gender selection for non-medical reasons; or with the intention to alter the genetic make-up of an embryo.

Couples where either spouse has a known inheritable condition or abnormal chromosome number or structure may be at a high risk of having a child with a specific genetic disorder. When seeking options to conceive, they would be assessed for their suitability for IVF treatment, and also referred for genetic counselling on PGT.

Embryos which contain gene mutations or chromosomal rearrangements may not necessarily be no longer fit for implantation.

For conditions like osteogenesis imperfecta, which needs only a defective gene from one parent to be passed on, only an unaffected embryo carrying two normal copies of the gene will be suitable for implantation, said Dr Azleen.

An embryo with one abnormal copy of the gene would not be suitable for transfer.

For autosomal recessive conditions requiring abnormal genes from both parents to be passed on, embryos with two affected genes will not be recommended for transfer, said Dr Liu Shuling, director of the KKIVF Centre at KKH.

Depending on the gene and condition, embryos with one affected gene may still result in the child developing a milder form of the disease, and parents can decide whether to transfer these embryos after additional genetic counselling.

Affected embryos will not be kept, said Dr Rajesh.