The day to day of IVF

Later this month I will present to a group of GP’s in Melbourne and Sydney on arrayCGH technology, a form of microarray used in Preimplantation Genetic Diagnosis (PGD) at Melbourne IVF, IVFAustralia and Queensland Fertility Group.  The significance of this technology is its ability to rapidly screen all 24 chromosomes in a developing embryo created in IVF treatment, prior to transfer to the woman’s uterus, which increases her likelihood of pregnancy success.

The ability to screen all 24 chromosomes in a developing embryo means that we are able to identify extra or missing chromosomes, which allows us to accurately know - prior to selecting an embryo for implantation - which embryos will not initiate a pregnancy, which embryos may implant but are likely to miscarry, and which embryos may result in the birth of a baby affected with a condition such as Down Syndrome.

Having worked in the field of PGD and human genetics for more than 25 years, there is no doubt that microarray technology has provided one of the most significant IVF breakthroughs in recent times.  Melbourne IVF developed earlier forms of CGH testing in the mid-1990s, in fact we were the first clinic in the world to produce a baby from an embryo that had had all of its chromosomes tested prior to transfer. But at the time the test was slow and laborious and all of the embryos had to be frozen while we waited for the results, which was certainly not ideal.  Now with the type of microarray testing we have implemented, the test not only provides full chromosomal analysis of embryos, but it is rapid, highly accurate, and patients are able to have a fresh embryo transfer. Consequently, more patients are achieving pregnancy success as a result, than ever before.

I first came across 24Sure arrayCGH when biotech company Blue Gnome presented their technology at the European Society of Human Reproduction and Embryology (ESHRE) Annual Meeting in July Rome in 2010.  Within 6 months, we had introduced 24Sure arrayCGH technology to Melbourne IVF –the first Australian IVF clinic to offer this advanced technology to patients, now known as Advanced Embryo Selection.

Since this time, the research conducted at Melbourne IVF using arrayCGH has attracted significant attention, both locally and internationally.  In 2011, I received the award for Best Scientific Paper at the World Congress on Human Reproduction, and was subsequently an invited speaker at ESHRE in 2012. I was also invited to present the work at the PGD International Society meeting in Austria this year and at the prestigious International IVI Congress in Spain in 2013.

24Sure arrayCGH is not the only microarray technology available.  Some IVF units across Australia offer similar technologies, and whilst they all provide the ability to screen all 24 chromosomes in a developing embryo, the benefits and features are different. 

There is no question that from the perspective of a patient who is trying to conceive, the ability to determine chromosomally normal embryos, is the single most important feature of microarray technology.  Similar forms of microarray technologies, offered by other IVF units around Australia, offer additional features that are largely irrelevant.  Features such as the ability to determine parental origin of aneuploidies, distinguish between mitotic and meiotic errors, or confirming genetic parentage sound important, but when it comes to treating infertile couples in IVF, they do not improve the success rate of embryos implanting and going on to form a healthy pregnancy.  This is ultimately the only reason patients come to Melbourne IVF for this technology – the desire for a healthy baby.

One of the benefits of our arrayCGH is that we can get results rapidly, so we don’t have to freeze embryos and patients don’t have to wait 4 or more weeks to get their embryos transferred.

The other key difference is that our test works on just a single cell. This means we can accurately test embryos on day 3 and do not have to wait till they grow to the blastocyst stage on day 5 or 6.  Only about 50% of embryos grow to the blastocyst stage in the lab. If you have to wait till day 5 or 6 to do the testing then only a few embryos can be tested and more than half of the patients will not have any embryos at all to test. We’ve had many babies born from embryos that would not have been tested (and probably would have been discarded) if we had to wait till they were at the blastocyst stage. Some patients have asked me about a study from the USA which suggests that day 3 biopsy damages embryos. Maybe in some labs this is the case, because different scientists can have different levels of skill. However, at Melbourne IVF we have more experience than anyone in the world at cleavage stage biopsy (I won a scientific prize for developing the technique way back in 1986!) and we know that testing on day 3 means more babies are born to more patients.

My award winning research has also shown that chromosomal mosaicism (where some cells in the embryo are normal and some are abnormal) in day 3 embryos is much less than previously thought, and about the same level as mosaicism found in blastocysts. This reinforces our position that testing a single cell from day 3 embryos is in the patient’s best interests.

For these reasons, we believe 24sure arrayCGH, available as Advanced Embryo Selection at Melbourne IVF, IVFAustralia and Queensland Fertility Group, is the technology of choice for full chromosome screening.

Watch Leeanda talk more about Advanced Embryo Selection:

The obsession with the celebrity world seemed to lift to new heights recently, when Australian media reported on a UK based sperm donor service that stated it aimed to match women with anonymous celebrity dads when it launched in the New Year.  Marketing to celebrity obsessed women, the service claimed women will give their child ‘a head start in life’ by using sperm from a ‘proven winner’.

The service later turned out to be a hoax, but it attracted a lot of media interest; not only because the concept of a celebrity sperm donor service was so ridiculous, but because in countries like the UK and Australia where there is a severe shortage of donor sperm, any service that promises to have the solution to sourcing local donor sperm is going to capture the attention of those needing it. 

Australia has been suffering a sperm donor shortage for years.  Sperm donation in the UK and Australia is an altruistic act for men with a genuine desire to help individuals or couples who can’t have children for medical or social reasons.   Men who do donate in Australia are those that have experienced the joys of fatherhood themselves, and who wish for others to have the same opportunity; or those that have no prospect of becoming fathers themselves but wish to help others achieve their quest for a baby.

As societal trends have evolved over recent years, the demand from single women and same sex couples wishing to access donor sperm has increased (10% increase at IVFAustralia in the last three years), while the number of sperm donors has been steadily declining for the last decade. At IVFAustralia, we normally have around 15 to 20 donors at any one time, while demand usually requires 30 to 40 donors.

Using a sperm donor is the only opportunity for these women to have a child of their own and to experience the joys of parenthood.  We are actively searching for young Australian men to become sperm donors, to help these women achieve their goal of becoming mothers.  So, if you are a healthy male aged between 25 and 45, I urge you to continue reading.

It takes a special kind of person to consider donating, let alone to actually go through with the process.  Even for men who have a genuine desire to help others, there are some concerns which may put them off the idea.

Full anonymity is no longer possible in Australia. The potential for a child to seek out their genetic father is now a requirement. This does not mean being confronted at your front door by an 18 year old claiming that ‘you are my Dad’. A child will be able to find out if they are the result of donor conception by approaching a Government register, on which your name will have been lodged by the original treating clinic. Depending on the State, you will be contacted to notify you of the enquiry, and be given the opportunity to make contact – much in the way adopted children are linked with their original parents. This openness dissuades many potential donors.

All donors are required to discuss this issue in formal counselling sessions, and if the man has a partner, they are also required to attend the counselling sessions to ensure they understand the social, ethical and legal implications before consent forms are signed. Payment for sperm donation is also illegal, however compensation for time spent at appointments is available.

While there are occasional sensational media articles highlighting the possible implications of donation, such as legal parentage rights, rights over the child’s upbringing or any financial obligation, I encourage anybody considering becoming a sperm donor and concerned about these issues to consider these facts.

Legislation in Australia is designed to protect the rights of the donor, the recipient, but most importantly the children resulting from sperm donation. Over the years, legislation has been guided by donor conceived children - now in their late 20s and early 30s. There has, therefore, been a move away from complete anonymity, as it is deemed in the best interests of the child to have the right to know their biological origins, and to have the right to contact their biological father in the future.

Under current legislation, where the sperm donor is ‘clinic recruited’, the law protects the identity of both the donor and the recipient, until the donor conceived person turns 18 years of age. At this time, identifying details of the donor may be released to the donor conceived offspring if they request them (the donor’s information is kept on a central donor registry). Contact between a recipient and an anonymous sperm donor prior to the donor conceived child turning 18 years of age, can however be established where both parties have provided consent.

In terms of future parental obligations, laws in most States mean that sperm donors whose semen is used in assisted reproductive treatment will normally be presumed for all purposes not to be the legal father of any resulting child.  This is regardless of whether or not he is known to the woman or her partner (female or male). This means that the child has no rights to any financial or other consideration from the donor, while the donor has no parental rights over the child.
Whenever I deliver a baby conceived through donor sperm, it is such a joy to see a woman cuddling her ‘so wanted child’ .I truly admire the generosity of the donor who has felt it appropriate to help out in this situation.

In addition to the single women, we also have many infertile couples, in whom the problem is a lack of sperm production in the male. Donor sperm will be their only chance to produce the pregnancy that they so desire.

Sadly, we need more men to consider becoming sperm donors to help the hundreds of women across Australia fulfil their desire of becoming mothers.  Men should ideally be healthy, and aged between 25 and 45.  If you, or anyone you know, are interested in learning more, contact our sperm donor nurse who will talk to you confidentially about what is involved.

To find out more about becoming or using donor sperm, visit our websites:

> Sperm Donation in Sydney
> Sperm Donation in Queensland
> Sperm Donation in Melbourne
 

60 Minutes featured a story on ovarian tissue grafting, a procedure that is attracting more attention for its ability to preserve a woman’s fertility until later in life. I was interviewed by 60 Minutes in relation to our research in this area, where the procedure is used to help women preserve ovarian tissue and hopefully eggs, prior to undergoing cancer treatment that may leave them infertile. What makes this procedure so exciting is the possibility of being able to preserve a woman’s fertility until she has recovered from cancer and is ready to start her family – sometimes years down the track.

The publicity around this procedure was very much welcomed. It helped raise awareness amongst the thousands of Australian women impacted by cancer in their reproductive years, and we received many enquiries from women who have had a cancer diagnosis either recently or in the past. We can’t stress enough the importance of women having the opportunity to discuss their options prior to undergoing cancer treatment, and we continue to look for ways to raise awareness amongst the public and the medical profession.

But as reported in the 60 Minutes story, the procedure has attracted publicity for reasons beyond helping cancer patients. A clinic in the US is advocating freezing the tissue of young women so that the tissue can be grafted later to help them conceive if required in their forties, thereby promoting the procedure to woman as a way to put their fertility ‘on ice’ as a form of reproductive insurance. It’s being touted the ‘future of fertility for all women’ - not just those who have had cancer - and there are now two clinics in the world that offer ovarian tissue freezing for social reasons so that women can have babies later in life, well into their 40s and even their 50s.

In Australia, ovarian tissue freezing and grafting has been performed for some years and the grafting is still considered an experimental form of treatment by all fertility specialists across the country. This is because around the world only 19 babies have been born, despite many many attempts. Fertility specialists around the world agree that it is very difficult to grow good eggs from grafted ovarian tissue. In fact some of the reported births are now thought to be spontaneous pregnancies in women whose own ovarian tissue has started to function again, rather than pregnancies from the grafted tissue!

Here, the technique is offered routinely for medical reasons only, and we believe there are very good reasons for this.

Ovarian tissue grafting involves removing a small piece of ovarian tissue from one ovary, slicing the tissue into tiny pieces and freezing them until the woman is ready to conceive. The tissue is then grafted back into the woman’s pelvis where the grafted ovarian tissue can start to produce reproductive hormones and follicular development. The idea is that pregnancy can be achieved either with ovarian stimulation and IVF, or perhaps even naturally.

The procedure is deemed suitable for girls in their teenage years and women in their 20s, when it is believed to yield a higher chance of success due to the abundance of immature and better eggs in the wall of the ovary. These women are often impacted by cancers such as leukaemia, Hodgkin’s lymphoma, breast cancer and ovarian cancer.

But it’s not a procedure that comes without its own risks. Laparoscopy is a procedure used to remove the tissue and then graft. This operation has a 1/1000 risk of complications and a 1/50000 risk of life-threatening complications. The removal of the tissue can potentially cause damage to the ovaries and it does reduce the number of eggs available for spontaneous ovulation and reproductive function. That is why we only remove the tissue when a woman’s ovarian function has a high chance of being severely damaged by the cancer treatment.

Also, should a woman undergo the procedure, then later on when she is ready, there is no guarantee that she will be able to achieve her so longed for baby. So to offer the procedure for non-medical reasons does not make medical sense. It also raises ethical questions about women beyond their natural reproductive years having children – perhaps a topic for another blog post.

For women seeking fertility preservation techniques for social reasons there is no doubt that despite the genuine desire to meet their life partner and start their family in their 20s or 30s, for many women this choice is dictated by circumstance. Our message to these women remains – ‘don’t put off having children’, however we realise this cannot always be avoided. These women should not be denied the option to preserve their fertility, but they should know that there are other options available.

Egg freezing is a method of freezing unfertilised eggs, with a view to them being used in the future. The eggs are thawed and fertilised with sperm to form an embryo so that it can be transferred back to the woman’s uterus with a subsequent chance of pregnancy. This is a good option for women in their early 30s who are concerned that they won’t have met their life partner before their eggs start to age and thus are less likely to produce a pregnancy. Melbourne IVF has been freezing eggs since 1999, mostly as a form of fertility preservation for patients facing cancer where other fertility preservation techniques are not suitable, but more commonly in the last 2 to 5 years for social reasons. The success rates of egg survival after freezing and thawing have improved significantly over the years with many babies born through our program, but, as with any form of fertility treatment, there are still no guarantees. For every 10 eggs frozen, we can expect to only obtain 2-3 good embryos, which means only 2-3 opportunities to conceive.

Likewise, while we know from our own and international experience that ovarian tissue grafting can be successful, it is by no means a golden solution. Worldwide there have been around19 babies born in the last 8 years and in Australia whilst we have come close, we are yet to welcome our first baby following the procedure. We have however successfully removed, frozen and grafted ovarian tissue for more than 10 women facing serious cancer diagnosis. To date only a couple of these women have actively been trying to conceive. However tissue freezing has given these the opportunity to take a positive step towards preserving their fertility – which is a chance at a future family of their own that would otherwise not have existed.

As part of the Fertility Preservation Service at Melbourne IVF and the Women’s Hospital, we have been performing ovarian tissue grafting since 2006. We believe we are not far from having our first birth with several patients now starting to undergo treatment currently with promising outcomes. This will be an enormous achievement that we hope will reinforce ovarian tissue grafting as a technique that can give hope to thousands of women facing cancer in Australia each year.

Dr Kate Stern is Head of the Fertility Preservation Service at Melbourne IVF and the Women’s Hospital in Melbourne.

Dr Kate Stern was recently interviewed on 60 Minutes about the ovarian tissue grafting procedure - read the full transcript here.