Twin delights after seven years and six rounds of IVF

New embryo screening process helps to beat the odds for couples who have had multiple failures

First twins born in Ireland as a result of the use of pre-implantation genetic screening. Photograph: Cyril Byrne

First twins born in Ireland as a result of the use of pre-implantation genetic screening. Photograph: Cyril Byrne

 

On the day of her first appointment at a Dublin fertility clinic, Linda saw a sign in the waiting room inviting those who had had three or more failed IVF cycles to take part in a survey.

She remembers turning to her husband, Steve, and saying “Could you imagine if you had to go three rounds?” Little did she know then that she would be that woman – and more.

From the day they married in 2008, keen to start a family straight away, it took Steve and Linda seven years, six rounds of IVF at two fertility clinics and four heartbreaking miscarriages to get to where they are today – staring in love and awe at their four-month-old twin boys and anticipating a “very special Christmas”.

They are also believed to be the first couple to have had babies after having one of the newest procedures in IVF treatment – Pre-implantation Genetic Screening (PGS) – carried out in Ireland. A baby girl was born in Cork at the end of October after her parents were recommended to use PGS, when they too had experienced a number of failed cycles (see sidebar).

Just two fertility clinics in the Republic are licensed to carry out biopsies on embryos here for PGS – the Beacon Care Fertility in Dublin and the Cork Fertility Centre. Both clinics send the samples to specialised labs in the UK for analysis.

While Steve and Linda asked that their names be changed to protect the family’s privacy, they agreed to share their experiences with The Irish Times in case it might help other couples.

“I do have a fabulous end to my story and I hope other people out there take hope,” says Linda. “I didn’t have just one thing wrong.”

Endometriosis

The first sign that there was anything untoward came less than a year after their wedding, when she had a bad haemorrhage and endometriosis was diagnosed.

“All the attention went on getting that sorted,” says Linda, who had an operation within a week of seeing a consultant. Aged 33 at the time, she was advised to carry on trying to conceive naturally for three months but then to consider assisted reproduction.

They started attending a Dublin fertility clinic in 2010 and continued there until 2014, during which time she became pregnant four times – twice naturally and twice as a result of IVF. But each time, there was bad news at the seven-week scan and each time Linda had to be treated in hospital.

“I would miscarry yet my body would continue to think I was pregnant, so I ended up having to have medication to get my body to miscarry fully,” she explains. “It was always months and months before we could start again.”

The clinic was unable to explain what was going wrong, as “my ovaries were fine; every time I got an egg collection, they got a lot. The big issue for them was the fact that I had endometriosis.”

By 2014 they had undergone five rounds of IVF and the clinic, it seemed, had gone as far as it could with them. They were advised to consider trying Beacon Care Fertility to observe the embryos and possibly biopsy them for PGS.

Steve and Linda were taking time out in Belfast in the spring of 2014, “getting our heads together”, when, over a cup of coffee, she picked up a newspaper that somebody had left on a nearby table. In it she read about a woman who had been through 10 miscarriages and couldn’t get beyond seven weeks, before attending Dr Simon Thornton at Beacon Care.

“It was like reading my own story,” says Linda. “She started talking about intralipid treatment, which is about dampening down your immune system, and that is what geared me to go to the Beacon.”

The results of a suite of tests at the clinic suggested that aspects of Linda’s immune system were considered to be hostile to implantation, explains the Beacon’s medical director, Dr Ahmed Omar, who took over after Thornton’s retirement.

“That doesn’t mean that her miscarriages were because of that, but it is a risk factor.” She was also found to have the MTFHR gene mutation, another risk factor, which means her body doesn’t activate folic acid and she needed to take a supplement containing an activated form.

“The other thing that they were telling us,” says Steve, “was that if we were lucky enough to get embryos, they would be able to test them to see if they were chromosomally perfect. Another reason for miscarriage is if there is a chromosome imperfection.”

For this, their sixth round of IVF, “we decided to throw the kitchen sink at it”, says Linda. PGS costs €3,000 on top of €4,500 for the treatment cycle, plus other costs. They started the cycle in June 2014 but didn’t get to embryo transfer until December 15th.

Linda describes how the cycle began with down regulation – “pushing my body into menopause”. After a bleed and a scan, to make sure the ovaries were quiet and the lining of the womb thin, “from that point on, they take over your body”.

Really tough

The medication to stimulate creation of follicles was, she says, “really tough; I got chronic headaches and was really tired”. She had three stimulation scans to look for follicles and check the womb lining, before being told when to take the “trigger” injection at home on July 19th. The egg collection was done on July 21st.

“We were thrilled because 20 eggs were collected, which is a phenomenal number, and the embryologist takes over then. She rang me that evening and said ‘I have injected 18 of them successfully [with Steve’s sperm]’.

“But the following day, I got a phone call to say they didn’t know what happened, but only four had fertilised. We lost all the rest.” When they had got to this point before in IVF, they usually had about 10 embryos.

“What happens then is your embryologist phones you every day to tell you if they are dividing. I have it my head that she was their very first babysitter,” Linda says.

“We were down to three on July 23rd and then one of them slackened off and our two little heroes carried on.”

They both looked good but the only way of being sure was to get them biopsied for PGS to check their chromosomes.

The clinic said normally you would do a biopsy only if you had three or more embryos, Linda explains, but she asked them to “biopsy these anyway”. All the couple wanted to know was were the embryos chromosomally compatible with life because they couldn’t face another miscarriage if they weren’t.

Results

The biopsy is usually done now at the blastocyst stage – five to seven days after fertilisation – and then the embryos were frozen while the couple waited for the results of the PGS, which take up to two weeks to come back from Beacon Care’s Nottingham lab. On August 12th they were told that both embryos were “euploids”.

“That is the word you want to hear”, says Steve, “two perfect embryos”. Then it was time to start prepping Linda’s body.

“That meant intralipid infusions, steroids, heparin [blood-thinning] injections – a whole concoction they put together as a result of those test results.” But still the womb lining was not thickening to the 9mm the Beacon requires before doing an embryo transfer.

“I got a call from Dr Omar to say ‘we’re stopping’ – so you can imagine, after going through all of that,” she says. “He explained the lining wasn’t thick enough and he didn’t want to risk the transfer.

“I understood but, to be honest . . . you don’t really function. You look okay on the outside but you’re not at all.”

She stopped all medications straight away and had to wean herself off the steroids, then waited for another bleed to start all over again.

This time the long protocol, involving down regulation before stimulation, was recommended and it started on November 11th. Finally, by mid-December, they got the go-ahead for embryo transfer.

Linda never contemplated anything but transferring both embryos and the clinic was happy to do that. “The two of them had survived together and I was a bit nervous if we separated them, they wouldn’t survive.”

Transfer

The morning of the transfer, on December 15th, was an anxious time because they knew the two embryos might not survive the thawing but all was fine.

The transfer “happened like that”, says Linda, clicking her fingers. “You can see them shooting in, it’s amazing.” Then came the long, two-week wait.

“There is nothing more you can do except eat really well, rest and just hope for the best,” says Linda who dreaded every visit to the toilet during that fortnight.

The clinic had given her a pregnancy test kit to keep at home and on day 14 they could hardly believe their eyes when they got a “really strong positive test”. But still they didn’t dare get their hopes up, as they waited for the seven-week scan.

“I was sort of looking forward to the day and not looking forward to the day,” she says. “We had gone in for seven-week scans before and it had always been the end of the road.”

Steve says the scan operator assured them beforehand that just because she might be quiet didn’t mean it was bad news, that scans are difficult to read and not to be worried.

“Then she quickly told us it was good news – and then that it was great news.” There were two, the right size and in their own sacs.

“Pretty much from that moment on, we got nothing but good news,” says Linda who had to be pushed by Steve into telling extended family at 14 weeks.

“I was just terrified that we had got all this good news and if we said it out loud, would it all go wrong?”

Linda enjoyed the pregnancy but couldn’t bear to go more than two weeks without the reassurance of a scan at the twin clinic in Holles Street hospital. Despite the PGS and all the scans, the couple didn’t want to be told the gender of the babies.

About week 30 she developed cholestasis, a condition that triggers intense itching and requires monitoring. She had been advised to have a scheduled C-section no later than week 37 but it was done at 34 weeks after her waters broke.

“They chose their birthday,” she says of the two boys who weighed in at 4.6lbs and 5.2lbs.

Linda stayed in hospital for five nights and, after two weeks in the high dependency unit, the twins came home together 10 days later. “And I haven’t stopped looking at them since,” she smiles.

Names have been changed in this piece. swayman@irishtimes.com

PGS and PSD explained

What is PGS? It’s Pre-implantation Genetic Screening and involves taking a few cells from an embryo, usually at the blastocyst stage (five to seven days after fertilisation in a lab) and checking it does not have any chromosomal abnormalities before it is transferred to the mother’s womb. Chromosomal abnormalities are the most common cause of miscarriage and IVF cycle failure.

What is PGD? That’s Pre-implantation Genetic Diagnosis and also involves the biopsy of embryos but this time to look for hereditary genetic abnormalities known to be carried by either the mother or the father or both, for example, cystic fibrosis. A couple who could conceive naturally may opt for IVF with PGD, to ensure they don’t have a(nother) child with that condition – they have often found out they are carriers of a genetic abnormality only after having one affected child.

Where can both procedures be done? The Health Products Regulatory Authority (HPRA) – formerly known as the Irish Medicines Board – has authorised the processes used to obtain samples for PGS and PGD at Beacon Care Fertility in Dublin and the Cork Fertility Centre.

Where are the samples analysed? At specialised labs outside Ireland – there are currently no labs here that can do it.

What about other clinics here offering a PGS/PGD service? This would involve referring patients to another assisted reproduction clinic outside Ireland, according to the HPRA, which confirms that only the two clinics mentioned above are authorised to do it here.

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