Is it right to screen out embryos for cancers they may never get?
Paula did - and says it’s the only way she’d have children
HAVING watched her mother battle breast cancer and then ovarian cancer, only to learn that she, too, had inherited the faulty gene that dramatically increases the risk of both, Paula Macrae made a brave and selfless decision.
Determined not to pass on that risk, she decided she would not have children.
‘I’d always imagined having a family,’ she says. ‘But I didn’t want to pass on the faulty gene, like my mum had to me.
‘I know she feels terribly guilty about it, even though obviously it’s not her fault. But having seen her go through all that pain . . . I just thought: “I’ve got an option here: it can end with me.” ’
Paula, now 36, and her husband Andy, who’s 44, had only just married when, in July 2012, she found out she and her mother, Pauline, carried a faulty version of the BRCA2 gene. Mutations of this tumour-suppressing gene significantly raise the risk of breast and ovarian cancer.
Between 45 and 90 per cent of women with BRCA gene mutations will develop breast cancer. Men with faulty BRCA genes are at increased risk of breast and prostate cancer.
The rogue genes can be passed on from either parent — genes come in pairs, and we inherit one copy from our mother and one from our father.
But BRCA mutations are ‘dominant’, which means you need only one version to have an increased risk of cancer. If you do have a copy, there is a 50:50 chance that you will pass it on to a child.
It was in 2005 that Paula’s mother was diagnosed with breast cancer at the age of 59. She had a mastectomy, followed by a course of radiotherapy.
‘Five years later she found out she had ovarian cancer,’ says Paula, an analyst for an insurance company from Edinburgh.
‘I Googled it and found out that breast cancer and ovarian cancer are linked by these genes. I went to my doctor straight ThE away and asked if we could be tested.’
GP first referred Paula and her family for genetic counselling, to receive advice and support on inherited conditions. In 2012, Paula’s mother was tested and found to have the faulty BRCA2 gene, so Paula, her two sisters (she’s a triplet) and brother were all tested. Paula was the only one to have inherited it.
‘I have to have an MRI scan and a mammogram every year, but nothing’s happened to me yet, so there’s no point worrying,’ she says. ‘It’s different for Mum: she’s still going through it. She’s now on Avastin for the ovarian cancer.’
Paula decided children were no longer an option the day she got her results.
‘The genetic counsellor said: “You know, if you do look to have a family, we’d test you at 12 weeks or so, and if the baby was found to have the gene you could have a termination.”
‘I just thought: “No, I’m not interested. I couldn’t have a termination, knowing I wanted to have a baby.” ’
‘I thought: “That’s it, I’m not going to have children, then.” ’
In fact, there was another option — PGD, or pre-implantation genetic diagnosis, which Paula later read about. Pre- implantation genetic diagnosis is a technique that helps couples with a known inherited condition in their family to avoid passing it on to their children.
Couples have IVF treatment to create embryos, which are then checked for the faulty genes. Embryos found to be clear are implanted into the womb.
‘I was surprised it hadn’t been mentioned before,’ says Paula. ‘I didn’t want to hope too much, but when we moved house, I asked my new genetics counsellor if pre-implantation genetic diagnosis was available for people like me.’
It was. The technology has been available since the Nineties and the first condition it was used for was cystic fibrosis. Today, it is approved for more than 250 conditions.
‘Couples can get funding for the treatment only if there is a known, confirmed genetic condition in the family — and there is deemed to be a significant risk of it being passed on,’ says Alison Lashwood, a consultant genetic counsellor and clinical lead in PGD at Guy’s and St Thomas’ NhS Trust in London.
‘For NhS funding, the risk has to be more than 10 per cent.’
In 2013, the treatment was made availa- ble to any couple who meet NhS funding criteria (before then it was done on a case-by-case basis.)
There must be a significant risk of passing on a genetic condition that has been confirmed by tests. The woman has to be under 40 and have a BMI between 19 and 29, and the couple must be non-smokers.
It won’t be offered if a couple already have a child together who is unaffected by the condition.
The condition must also be approved by the human Fertilisation and Embryology Authority (hFEA).
The technique’s use for BRCA gene faults is unusual, because unlike conditions such as cystic fibrosis, it isn’t 100 per cent certain an embryo with the gene mutation will end up with the disease.
‘My position is a cautious one,’ says Dr Anna Smajdor, a lecturer in medical ethics at Norwich Medical School.
‘Pre-implantation genetic diagnosis was initially developed for very specific life-threatening conditions that a child would definitely get. But using it to avoid BRCA 1 and 2 mutations effectively screens out embryos that might never suffer from that disease.
‘When you’re offering it for the risk of disease rather than the disease itself, that becomes a more open-ended question.’
As henry Scowcroft of Cancer Research UK points out: ‘Nor is a child born with a “normal” copy of the BRCA 1 gene guaranteed to be cancer-free.’
If you want to avoid the risk of having a child with disease, it raises questions about how you define ‘risk’ and ‘ disease’, says Dr Smajdor. ‘It has become “good practice” to take into account the parents’ feelings on what risks they don’t want, so to some extent it’s in the eye of the beholder.
‘There’s a long list of conditions that pre-implantation genetic diagnosis is licensed for now and it’s growing all the time. But where’s the cut-off point?’
henry Scowcroft isn’t convinced this is a concern. ‘It’s not a “slippery slope”,’ he says, pointing out that like cystic fibrosis and other genetic diseases, BRCAdriven breast cancers are linked to a single, detectable genetic fault.
‘Things such as height, weight and intelligence are influenced by more subtle genetic mutations that we don’t really understand. So it’s hard to see how PGD techniques to weed out these variants could get approval,’ he adds.
As the hFEA puts i t: ‘These genetic tests can still be used only for a minority of people if there is a history of cancer across generations of a family.’
For this reason, couples considering the treatment must see a clinical genetics counsellor first.
Paula started treatment in August 2014. This involves a cycle of IVF, and starts with taking drugs to halt a woman’s natural egg production as well as drugs to stimulate the ovaries to produce a number of eggs at the same time. These are then collected in a minor operation around six weeks later.
On average, around 11 eggs are collected — for Paula, it was 19. The eggs are then fertilised with the partner’s sperm and the resulting AROUND embryos are left to develop.
the six-day mark, a small sample is taken from the embryos to test the genetic material. The embryos are then frozen until the results are ready.
One downside of preimplantation genetic diagnosis is that it might make it more difficult for affected couples to get pregnant, because there could be no ‘healthy’ embryos.
Although fertile, they have the same chance of getting pregnant as couples going through IVF because of fertility problems — around one in three treatment cycles results in pregnancy.
‘I think some patients think they’re going to have a better chance than normal IVF couples,’ says Alison Lashwood.
‘But it doesn’t work like that. If you don’t get many eggs, you may not get many embryos, and then once you’ve tested them, there could be nothing to transfer — particularly with a dominant condition such as BRCA mutations, where there’s a one in two chance the embryo will be affected.’
Paula and Andy had 16 embryos that made it to the testing stage — five were found to have the BRCA gene fault, and 11 were suitable for implantation.
If there is more than one, the best-quality embryo is selected. The embryo is implanted via a catheter (a fine tube) inserted through the neck of the womb, guided by ultrasound.
The remaining embryos can be frozen in case the first one doesn’t result in pregnancy. If treatment is successful, the embryos will be discarded or donated to medical research, according to whatever the couple decides.
Next comes a 12-day wait for an appointment to do a pregnancy test. ‘It felt like a really long time,’ says Paula.
Fortunately, to the couple’s delight, it was positive and on October 8, 2014, they had their first scan.
‘I was incredibly nervous,’ says Paula. ‘But it was all fine, I could see the heartbeat flickering away, and it was just unbelievable.’
Baby Owen Robert Macrae was born on June 5, 2015. ‘holding him for the first time was an amazing feeling — knowing he was finally here and that he won’t pass on the gene.’