Bringing science into practice; latest thinking in Preimplantation Genetic Diagnosis (PGD)

DNA photoIt is clear that the PGD world is going through a significant revolution and IVFAustralia (with our partners in Melbourne IVF) is at the forefront of it.

I was delighted to give a lecture last month on PGD at the Asian conference ‘Learning Initiatives for Fertility Experts’ in Ho Chi Minh City in Vietnam. It gave me an opportunity to review our own data at IVFAustralia, and to compare our service with what is published and what is done elsewhere.

PGD (Preimplantation Genetic Diagnosis) involves biopsy of embryos to assess the presence of either a specific genetic abnormality (eg. Cystic fibrosis or Huntingtons disease) or, more commonly, chromosomal abnormalities (eg. Down’s syndrome). This information is used to determine which embryo to transfer back.

IVFAustralia has led the move to array technology, which enables analysis of all 23 pairs of chromosomes from a single cell within 36 hours. This has led to a significant increase in demand for array PGD over the last 2 years. While most studies so far have focused on young IVF patients, demonstrating over 50% increases in pregnancy rates, success rates for more difficult cases including older women (eg. Over 40) and women with histories of repeated miscarriage or multiple IVF attempts are more modest. Still good, but clearly other factors need to be considered carefully for them – such as sperm quality, cycle control, uterine cavity factors and immune factors (NK cells).

Keep in mind also what is quoted from any study.  Many women starting a potential PGD cycle do not create embryos of good enough quality for biopsy, and many embryos biopsied are abnormal and so are not transferred. The success rate quoted will vary enormously if based on the number of cycles started, or number of cases with embryo biopsy, or number of cases with a transfer. As a woman gets older, it is not uncommon for all embryos tested for chromosomes to be abnormal, and so many of those cases do not get a transfer. However, the diagnosis of such a problem is often very helpful in its own right: to consider why IVF isn’t working, to try different treatments, or to ultimately give up trying with her own eggs.

The debate over day 3 or day 5 biopsy is still very topical. Day 3 biopsy gives a couple more embryos to test (better overall diagnostically), and can be combined with fresh transfer on day 5 (all complete in the one cycle). Day 5 offers a more focused approach on fewer embryos. While appealing for laboratories (less embryos to test) and potentially safer for the embryos (this is still hotly debated), it also results in delayed transfer of frozen embryos (in the following month), and the possibility than some embryos that don’t make the grade for biopsy – but could still produce a baby – are discarded or not tested. IVFAustralia will soon be able to offer both, and we will then assess the pros and cons of each approach in more detail in a single unit.

The technology changes will soon be even more significant. Over the next few months IVFAustralia with Melbourne IVF are moving to Karyomapping for single gene testing which will provide a far faster process for preparation and treatment. And we will also soon be moving towards Next Generation Sequencing which will also be faster, hopefully cheaper, and enable even more comprehensive testing including chromosomes and single genes. This incredible technology is a spin-off from the Human Genome Project in which the entire genetic sequence of a human was first described in 2003. It took over 10 years and over $100,000,000 to do that work. We can now do it in 3 days at a cost of a few thousand dollars.

Now that is progress!

Dr Gavin Sacks is a specialist with IVFAustralia and writes regularly about the latest technological advances in fertility treatment and practice.  For further information about Gavin click here.

Ngaire and Shannon’s story

We never thought it would happen for us! After over 4 years of trying to conceive and numerous IVF attempts later, we were giving up hope of a successful conception. As we approached our 16th treatment cycle with IVF Australia, my husband and I decided that this was going to be our last attempt, after trying pretty much every cycle variation over the years.

This last cycle was with Dr Gavin Sacks, and we tried the ‘Bondi Protocol’, which targets Natural Killer cells as a possible cause of infertility. As we were categorised as ‘unexplained infertility’, we were willing to try anything. After a long treatment cycle, we finally received a positive blood test result and were actually pregnant! This cycle was a true team effort – Dr Gavin Sacks’ work with the ‘Bondi Protocol’, Professor Bill Ledger with the egg collection and Dr Juliette Koch with the embryo transfer. All excellent doctors.

However, we do feel that our success this time around specifically is because of the treatment program for NK cells. We can’t thank Dr Sacks enough for pioneering the investigation of the role the immune system plays on implantation failure. It is exciting work that allows many couples who have previously been given no answers to repeated implantation failure (like ourselves), another treatment option that can actually make all the difference. We now call him Dr Gavin ‘Genius’ Sacks!

The team at IVF Australia have been truly wonderful to us over the years. Both doctors and nurses are extremely professional and caring, and we felt that we were always in the best hands. Thank you to everyone involved in our whole journey to pregnancy.

It takes three to make a baby – Caroline & Drew’s Story

After yet another miscarriage Caroline awoke in the middle of the night crying, ‘If I can ‘t have children, what will I do with all this love inside me?’ The next day her husband bought her a labra-doodle pup. But it was the gift from an egg donor, which helped fill the void. 

“It’s been a huge emotional roller coaster for all of us. It’s taken three of us to make this dream come true.”  

Caroline: I had a very small but incredibly close-knit family. My parents had an excellent, marriage. As a result, I’ve always had a very clear picture of how I wanted my own marriage to be, which was why I waited so long to find the right person, because my standards were so high. I always thought having children was something you did later.  I had no idea how difficult it would be.

By the time Drew and I got married I was 38 and he was a year older.

Our romance took off quite quickly and  not long before we were married, we got pregnant and I miscarried. We dealt with that relatively well. But it was the next miscarriage six months after we married that threw us for six. I remember it was around the time of Drew’s 40th birthday and we were very excited about this pregnancy. We were booked in to have the CVS (Chorionic Villus Sampling) at 12 weeks, to check for Down’s Syndrome and other abnormalities. It never occurred to us that anything could go wrong.

Drew: The radiographer looked at the screen and said, “Hang on, something’s not right.”  She measured the length of the embryo.  “Ooh, that’s much too small and there’s no heartbeat.  I’d better call the doctor.”  She just walked out and left us. It was like being hit by a train.  No one ever told us about the possibility of losing the baby at 12 weeks. We thought once we’d had a positive eight-week scan we were okay.  We were very ignorant at that stage and it was such a shock. I remember that day so clearly walking back through the shopping centre to the car and feeling numb.

We got pregnant naturally four or five times, but none of them lasted. At the eight-week scan everything looked fine and then at the twelve-week scan they were always dead.  The last pregnancy was actually an ectopic and I had to have my fallopian tube removed. When we found out during the ultra sound the pregnancy was an ectopic, we laughed nervously, “Yeah, that’d be right. What else can you bloody hit us with?”

The bottom line was my eggs were too old. We knew nothing then about age related infertility.  When I was 39 I went to see my doctor and he showed me some startling statistics about my chances of conceiving and carrying a healthy baby to term. “There’s no question, if you’re serious about having a child, you’ve got to start IVF now, although your chances are still quite slim,” he said. I felt like I’d been shot.  I was so shocked and upset. That was a wake up call and that’s when we started down the IVF route.

Caroline: I would say to women in their twenties and thirties, “Listen.  Here are the facts about age and fertility. These are the statistics.  Do with it what you will.  But just know, if you leave it too late, you could miss out on having children altogether.”

Drew: It took a while for us to accept we’d have to do IVF. I thought, “Oh, that can’t possibly be true. This isn’t us. We’ll be right.” I was pretty surprised when we found ourselves in that position.

Caroline: I didn’t know anyone who’d done IVF, which was difficult, because I didn’t have anyone to talk to. At first, I was really embarrassed and didn’t tell anyone except my family and close friends. But as time went on, I didn’t care who knew, because it was too hard to keep a secret, on top of everything else we were going through.

Drew: We were so naïve, we were absolutely sure we’d be pregnant on the first round of IVF.

Caroline: We thought that if they transplant a live embryo inside me, of course it’s going to work!

Drew: At the first egg harvest we got a ridiculously high number of eggs, around 20, and lots of them fertilised, “Fantastic, here we go.  One go, and we’ll be right, “ we said. Little did we know!

Caroline: We did five rounds of IVF and none of them worked. One round was particularly devastating because we didn’t even get to the transfer stage. We had six eggs and three fertilised but they all died during the five-day waiting period before the transfer. It seemed so unfair. I remember howling to mum and dad on the phone, “I’ve been through all those injections, blood tests and ultra sounds and there’s nothing to even transfer.  How can this be?”

The drugs made me feel ghastly and I hated it, but I never missed a day of work. Some people succumb to the illness and depression and take to their beds. I always kept going, because I didn’t want to sit home and think about it all day. Even though, some days, it was a battle to get there, because I felt like crap.  I found the physical stuff easier to deal with than the psychological.  My head was always my greatest challenge, the whole way through. By the end of the five years, with still no success, I found it hard not to get really depressed. even though I’m usually a naturally positive person.

In some ways I wasn’t strong enough to give up. If you keep trying you delay having to face facts. It takes real strength to say,  “You know what?  I can cope with not having a family.”  I couldn’t do that.  There was no way. I was going to get a baby, come hell or high water.

I knew what it was like to have an amazing family, and I wanted that too. All our friends were having kids. When my closest friend told me she was pregnant and it wasn’t even planned, it threw me badly.

We were at the end of our own frozen egg supply and were facing a brick wall.  One morning I woke up at five o’clock sobbing and saying, “You’ve got to help me Drew!” I was beside myself.  I was frantic and wretched. I kept saying, “What am I going to do with all this love inside me?”  That weekend we went out to get Eric, our labradoodle pup to ease the pain a little. We’ve poured our love into him.

At the same time we started considering egg donation. But the IVF doctor wasn’t very hopeful, “In this country you obviously can’t pay someone for their eggs, so it’s virtually impossible to find the right egg donor unless you know someone or have a sibling who’s willing to donate,” he said.  I didn’t know anyone and I didn’t have a sibling who was suitable.

We considered advertising for a donor, but the idea of so many unknown factors, really didn’t appeal to us. So we started down the international adoption road.

We went to an information seminar about adopting from China, but it was bad timing. I was still feeling very fragile having just come out of hospital after an ectopic pregnancy, in which I lost my fallopian tube.  Dad had also just died and I was at a really low point. But we had to go to the seminar because if you don’t go you don’t get another invitation. I was still physically unwell and mentally wrecked.

Drew: I was never really sold on the adoption idea. From my point of view, I hadn’t given up on having our own children.

Caroline: Drew’s viewpoint frustrated me, because the reality was I only had one tube and my eggs were crap. I needed a backup option or else I would go nuts.  I knew I could do adoption. I thought, “I love our dog Eric! I have flipped out of my brain over a dog.  He’s not even my species. Do you think I’m going to have trouble loving a child just because it’s Chinese?  Of course not!”

Drew: I didn’t think we had any chance finding an egg donor, because if you look at all the ads in Sydney’s Child magazine, the donor section is full of heartbreaking stories about childless couples pleading for donors. I couldn’t see how we’d stand out from all the rest.

Caroline: We decided not to advertise in Sydney’s Child because we thought we’d have Buckley’s chance of attracting a donor, yet ironically because of those ads our friend Neisha decided to donate to us.  It was the weirdest thing. One day, she happened to read some of those sad ads and thought, “Oh my God, this is something I could do to help.” She has quite a few friends in the same boat as us. Thankfully she chose us!  Neisha was 36 at that stage and the IVF clinic would have preferred someone under 35 but hey, we didn’t have people queuing up to donate.

Drew: In every other way though, Neisha met all the requirements for an egg donor.

Caroline: She’d finished her family and was prepared to have contact with the babies; both being very important issues to us.  At least that’s where having been part way through the adoption process was helpful, because there are similarities between adoption and donor, in terms of children wanting to know their genetic history. I read a lot of books about children of donors and adoption and they all had questions like,  “Do you think I’m musical because my mum was musical? Do I have any predisposition to diabetes or heart disease?” All those questions become important at different stages of your life. It’s our birthright to know our genetic history; most of us take it for granted because most of us know our parents.

When Neisha decided to donate to us she rang me at work one day and I nearly died of shock.  It’s not a phone call you expect. When she told me she wanted to donate her eggs to us, I came home and said, “Drew, you’re not going to believe this…” And he said, “Quick, ring her back!  Say yes!”

Drew: My reaction was positive from the start. I thought it was a great idea. It was a gift from the gods. We were in a quandary at that stage.  We really didn’t have a clear direction and were wondering what our life was going to be about?  We were even considering doing aid work or in Africa – we wanted to do some good somewhere, to give our lives some meaning. By then, my eyes had been opened to what we could achieve as a family. While most people take for granted having a family, such a supposedly mundane aim of having kids and living in the suburbs became a holy grail for us. When we got Neisha’s offer there was really no doubt in my mind it was a good thing. There were a couple of logistical things to figure out but otherwise it was fairly plain sailing.

Caroline: Our first question to Neisha was, “Are you prepared to be really open about it?”

“Yes, sure,” she said. “If that’s what you want.”

“Okay, great!  Let’s go!”

Our girls will always know Neisha is their biological mother. Her own kids already know.  Although they’re too young to really understand, they know their Mummy gave me some eggs. It’s all very open.  There’s nothing weird about it. That’s just how it worked.

Neisha’s husband Paul was great too.  He’s a surgeon and pretty clear-cut about such things. He saw it as Neisha merely donating some cells, nothing more. He had it sorted in his mind in a minute and didn’t have a problem with it at all, thank God.  Because I know women who’ve wanted to donate but their husbands have said, “No. They’re mine.” And their ego kicks in, whereas Paul said, “It’s a cell.  It’s a scientific process.  Caroline’s the one carrying the baby and she and Drew will be getting up every night to feed it, not us.”

One of the reasons, Neisha wanted to donate was because she’s had so much joy from her own children and she knew people who would be good parents and were being denied that happiness. To her, it was never the big deal that it was to us.  Still, to this day, she has no idea what a big thing she’s done, instead she says, “I just hate it that you’re so grateful, because I don’t want it to be like that, it’s no big deal.”  And we say, “Neisha, you have no idea!” Some people donate organs to keep someone alive. Well, that’s nice.  But two new lives? Neisha’s given us a family, it’s so big, it’s almost inconceivable.

I still had to process giving up the dream of having my own biological children. Because I am so mad about my own family, I was sad their ancestry would not be continued.  But I went to a brilliant seminar run by the IVF clinic and heard an egg donor couple and an egg recipient couple tell their stories.  The light switched on for me when the egg recipient spoke about her son and said, “When Thomas was born. He wasn’t mine and he wasn’t hers. He was him. Thomas was Thomas.”   When I heard that suddenly all my concerns and fears were irrelevant. And that’s how I see Jessie and Eve. They are so strongly their own identities; it’s not even a question of who they belong to.

Drew: Since Jessie and Eve have been born, I don’t get hung up on the genetics anymore. I feel we’re the custodians of two little people.  Our job is to put them on the best possible path and then one day they’ll go off and do their own thing.