21 minute read
ON FERTILE GROUND
from RCSI Alumni Magazine 2023
by RCSI
RCSI alumni have been at the forefront of the development of fertility services both in Ireland and abroad since these first became available over 40 years ago.
With IVF in Ireland to be publicly funded from this year, we speak to alumni who are experts in this field.
In a landmark development for healthcare in Ireland, last year it was announced that Budget 2023 would allocate €10 million towards publicly funded in vitro fertilisation (IVF) treatment, to commence in September of this year. However, there remains a significant lack of clarity on how the plan will be implemented, a real cause for concern for those hoping to access the service.
In recent years, six national fertility hubs have been established in Dublin, Cork, Galway and Limerick, designed to streamline referral pathways and investigative processes for public patients. Yet while these hubs provide some surgical and medical treatments, IVF and embryo creation are not part of their remit. It is the ambition of the Irish government to establish public IVF clinics, but it seems that those seeking to access IVF publicly will be accommodated, at least in the short term, by existing private clinics.
According to the Health Service Executive (HSE), the ‘national eligibility framework’ for who will be able to access these services has yet to be finalised, and as of earlier this year remains under development at the Department of Health. A further, crucial step in the rollout of services requires the realisation and enactment of the Health (Assisted Human Reproduction) Bill 2022, which is presently at Committee Stage in the Dáil, and the establishment of the proposed new Assisted Human Reproduction Regulatory Authority. So close, and yet so far.
RCSI alumni have been at the forefront of the development of fertility services both in Ireland and abroad since these first became available over 40 years ago. The hope of all those involved in the subspecialty is that the investment of public funding will allow for the implementation of equitable, timely and transparent treatment for all who wish to avail of it.
Dr Tony Walsh Medicine Class of 1980
Barrister-at-Law, Founder of SIMS IVF, Scientific Adviser, First IVF, Clane, Co Kildare
I first became interested in fertility treatment in the early 1980s when I wrote a computer programme for the fertility clinic at St James’s Hospital. In 1983, while working with Professor Robbie Harrison, I presented a scientific paper to the International Federation of Fertility Societies (IFFS) meeting in Dublin. The paper evaluated fertility investigations by weighted indices, tests and procedures and modelled this data mathematically to try to predict the best sequence of testing to achieve a pregnancy. This approach was taken up in part by the WHO as part of their recommendations for fertility treatment and investigation. At that time, women could be put through laparoscopic surgery before their male partner had even had a semen analysis carried out, so part of our work was to show that fertility investigations needed to be addressed logically and sequentially, and be evidence-based.
I spent time at Bourn Hall in Cambridge with Professor Patrick Steptoe and Professor Bob Edwards and did further work with Professor Sam Abdalla of the Lister Hospital in London. Sam taught me the GIFT (Gamete IntraFallopian Transfer) procedure, which was uncontroversial in Ireland, as it did not involve creating embryos. At the time, Sam had begun transvaginal egg retrieval, which was less surgically invasive, and he shifted to IVF.
I was given the opportunity to open an IVF unit in Clane in 1988 and I left the public system to do this. I was halfway through an MD thesis and membership examinations, and it felt a little isolating.
IVF represented real progress for patients but there was a slow build-up in the number of patients as there was still a lot of stigma and mistrust. At St James’s Hospital, I had found it deeply upsetting that the fertility clinic was held after hours, and couples would slink in and out. It’s almost incomprehensible to people today how difficult a time it was for reproductive medicine in Ireland.
In 1990 I continued my fellowship attachments at the University of Michigan, Ann Arbor, working with Dr Edwin Peterson. On my return, I worked in Wexford and then set up a campus company providing IVF procedures at Dublin City University (DCU). In the meantime, Professor Harrison had opened up an IVF unit at the Rotunda; it grew quickly and became the dominant provider of IVF in the State. This unit was eventually bought by us at Sims Clinic in 2014 and I became its Medical Director.
Developing from the campus company at DCU, I founded what became the Sims IVF Clinic with a business partner, Gerry Murphy. About a year later, Dr David Walsh (no relation), who had returned from Vanderbilt in the US, joined me and we had a wonderful medical partnership for 25 years.
Sims grew very quickly and in 2011 we moved to the present Sims IVF building in Clonskeagh where we developed a dedicated small fertility hospital with operating suites, laboratories, and ten single-bed day wards. When I saw how far we had brought reproductive medicine in Ireland it was one of the proudest moments of my life. Sims was bought by an Australian company, Virtus Health Care Ltd, in 2014.
In terms of the science, the big milestones were ovarian stimulation with gonadotrophic hormones, GIFT, IVF, ICSI (Intracytoplasm Sperm Injection; the insertion of sperm into the egg, 1992) and then the grow-out of embryos to the blastocyst stage of development, which we pioneered in Ireland. That was a big step and improved pregnancy rates.
SIMS GREW VERY QUICKLY. WHEN I SAW HOW FAR WE HAD BROUGHT REPRODUCTIVE MEDICINE IN IRELAND IT WAS ONE OF THE PROUDEST MOMENTS OF MY LIFE.
The next phase was looking at the embryo to identify it as being ‘normal’. Later, more invasive procedures involving pre-genetic screening and pregenetic diagnosis were developed.
Helping people to get pregnant is one thing, but selecting out what is considered an abnormal embryo is another. At that stage I distanced myself from where I felt the science was heading, stopped being clinically active and concentrated on research.
I’m disappointed for patients that the price of the IVF procedure has not reduced despite the big increase in numbers, as it has in other areas.
I have done a lot of work in the area of quality management and I believe regulation and standards are good for everyone. I hope that when public funding is introduced that patients will have choice, and that all the reputable units operating in Ireland will have structured participation.
I also hope the allocation of patient funding will be sufficient to allow the absolute best treatments to be available, providing the best chance to achieve a pregnancy, and that the selection criteria are more inclusive than they have been in some NHS regions in the UK, while accepting that a realistic chance of success has to be a factor. The payment of donors and for surrogacy is a sensitive issue which poses difficult ethical questions. IVF is a challenging topic and ethically complicated. The government needs to get everything right from the start, ensure that the patients are the priority, and make sure parish pump politics don’t get involved.”
Dr Denis Vaughan Medicine Class of 2009 Reproductive Endocrinologist, Director of Clinical Research, Co-Director of Oncofertility, Beth Israel Deaconess Medical Center and Boston IVF, Clinical Instructor, Harvard Medical School
I completed my intern year at Beaumont Hospital and my SHO years at the Coombe Women & Infants University Hospital. I was a junior registrar at the Rotunda Hospital when Professor Edgar Mocanu was Medical Director of the Human Assisted Reproduction Ireland (HARI) unit. I got a flavour of the subspecialty then and decided I wanted to pursue a career in reproductive medicine and surgery. Both Professor Mocanu and my mentor, Professor Fergal Malone, advised me to go abroad given the lack of a formal training programme in Ireland.
The US has the most organised and internationally recognised fellowships in reproductive endocrinology and infertility (REI). Because it is such a competitive field, you have to do residency in the US to get into a fellowship programme, so I went back to the beginning and in 2013 was fortunate to match into a four-year residency training programme at Tufts Medical Centre in Boston, and then into a three-year REI fellowship at Beth Israel Deaconess Medical Center (BIDMC) and Boston IVF. I completed this in 2020.
The quality of research innovation and training were the primary drivers in terms of me moving to the US. Boston IVF is the third-largest infertility group in the US. It is a private practice affiliated with Harvard Medical School and functions as the REI division of BIDMC. Most of the clinical work is done at a separate facility in Waltham, ten miles west of Boston.
As well as being a clinician, I hold roles as the Director of Clinical Research and Co-Director of Oncofertility. Boston IVF is unique as it has the clinical volume to run studies and access to the biotech innovation of Harvard and MIT. That was what drew me to this programme in the first place, because we don’t have to deal with the bureaucracy of some academic institutions. We can decide which studies we want to run, and are approached by different startups and pharma groups to run trials and studies. Boston is a world leader for medicine and biotechnology.
In the US, a number of states have mandated insurance benefits for infertility; Massachusetts’ are the most generous. Insurance companies provide either dollar amounts or specify the number of IVF cycles that will be covered. Essentially, our patients have to have private health insurance, but BIDMC also has a fellows’ clinic which provides care to those without insurance up to a certain point, much like the fertility hubs in Ireland. They can provide ovulation induction and consultations with the fellows supervised by one of the consultants free of charge, and there are discounts on intrauterine insemination, but they don’t have access to IVF unless they self-pay or meet criteria and agree to participate in a clinical IVF study. Most of these studies involve drugs already in use in Europe, so they are not experimental. It’s a good way of getting access to IVF for uninsured patients.
Fertility medicine is much more regulated in the US than in Ireland. The training programmes here are rigorous and accredited by the American Board of Obstetrics and Gynecology. In Ireland, there are people practising reproductive medicine who aren’t subspecialty trained – they are general obstetricians/gynaecologists. Friends and colleagues working in reproductive medicine in Ireland say it’s difficult to recruit talent because it’s relatively poorly reimbursed compared to private obstetrics.
In the US, the level of quality control and detailed outcomes reporting is very good. It’s not mandatory, but it’s highly encouraged. Our clinics report to the Centre for Disease Control and Prevention (CDC) and the Society of Assisted Reproductive Technology (SART) which publish those success rates each year. This protects patients from being sold add-on treatments, which are used a lot more in Ireland than in the US, and ultimately leads to better patient care. Nobody has any idea which is the best clinic in Ireland, because the results are not published anywhere.
In the US, the live birth rate per cycle is about 10 to 15 per cent higher than in Ireland. Europe and the UK tend to lag behind the US, Canada and Australia. That’s explained by IVF becoming mainstream later in Europe than it did here, differences in lab quality and a lack of subspecialty-trained physicians. That’s not to say there aren’t great clinics in Ireland or Europe, there certainly are, but there is more variability from clinic to clinic. I see many second and third opinions, including 15-20 patients a year from Ireland, who have gone through multiple failed treatments. I often notice the use of add-on treatments, for which data is lacking.
I think formalised specialist training and tighter regulation would make a big difference in terms of the reproductive care provided in Ireland, and increase access to essential services such as the use of donor sperm, donor eggs, surrogacy and gestational carriers.
While most of the technologies in run-of-the-mill IVF are available in Ireland, others are still in the experimental phase. For instance, preimplantation genetic testing (PGT) of embryos, such as screening for Down syndrome or other chromosomal abnormalities, is done routinely in most US clinics, but much less frequently in Ireland. Although it isn’t perfect, we know that the use of PGT increases the live birth rate per embryo transfer cycle.
At Harvard, we are working on using AI and predictive modelling to evaluate the optimisation of protocol or dosing of medication in IVF. Image recognition software – watching an embryo develop in the lab and predictive modelling based on morpho-kinetics to determine which embryo is most likely to result in a live birth – is something else we are working on. I think these technologies will become part of routine practice very soon. That’s why I’m here, at Harvard, because we’re at the cutting edge. We see it first, before it gets into clinical practice, and we work with companies to optimise it.
When the public funding is released, I hope patients in Ireland will be able to choose where they want to get treated and there will be greater transparency at clinic level in terms of what treatment is provided, the evidence behind it, and the clinics’ relative success rates.
The other thing I think needs to improve in Ireland is access to oncofertility. Many patients who have been newly diagnosed with cancer will have to get chemotherapy, which we know is toxic to the ovaries. Those patients are at risk of premature menopause, so they should have rapid access to fertility preservation care before receiving chemotherapy. At Boston IVF, oncofertility patients are seen within 72 hours of their diagnosis, and we initiate treatment within one week. We perform either egg freezing or embryo creation, or – if a patient is very sick – we remove part of the ovary and freeze the ovarian tissue for later use so it can be transplanted back in once their cancer is in remission. It’s relatively new, there have been only 250-300 live births globally; it’s not available in Ireland. I know from friends and family in Ireland that fertility preservation is often not even mentioned to cancer patients, and later they find out they’ve lost the opportunity to have a biologically related child. There’s more awareness in the US regarding infertility but, thankfully, awareness is increasing in Ireland and stigma is diminishing.”
Dr Sorca O’Brien GSM Class of 2021
Post-CCST ASPIRE Fellow in Infertility at NMH and Merrion Fertility Clinic
The post-CCST fellowships were brought in in areas where there are gaps in training, and my specific fellowship and MD are involved in looking at the integration of fertility services into the Irish public hospital system.
Infertility is a pathology. It is classified as a medical disease and as such fertility treatment and preservation should be funded as a medical disease and covered through the public hospital system.
My personal career goal is to contribute to a well-funded, formally established, freely available, equitable public fertility service, with every treatment option available to all individuals and couples. We are a long way off that.
It has taken 22 years, since Micheál Martin as Minister for Health commissioned experts to determine a position on IVF as a public service, to get to the current situation where the legislation is now waiting to be debated in the Dáil. From a clinical perspective, it should never have taken this long because there are people who have aged out of any potential to benefit, people who had no option other than to pay or to borrow, or who had to forego things such as buying a house or having a wedding or holidays because they were funnelling all their money into IVF treatment.
IVF generally costs in the region of €6,000 per cycle. A standard, stereotypical couple might be a heterosexual couple who have been trying to conceive for one to two years, and haven’t been successful. They can self-refer, or they can be referred by a GP, or, if they’ve come to the public clinic, we might advise that they need to have IVF because of their clinical characteristics. They go through a standard set of investigations.
With some couples, it’s clear straight away that they’re going to need a lot of interventional support to try to conceive a baby. In some couples, the female partner might have premature ovarian insufficiency, or very early menopause, or the male partner might have very little or no sperm. That’s a different conversation, and we might be talking about third-party treatments with donor eggs or donor sperm.
We also have same-sex female couples coming to us who require donor sperm treatment, single women coming to us for egg freezing or for donor sperm solo parenting, and our demographic is changing quite significantly. We do also look after small numbers of surrogacy cases, where the female partner shouldn’t or can’t carry a pregnancy for some reason.
The government announcement was unexpected but welcome. And everyone who works in the area is wondering how publicly funded IVF will be delivered. I believe the government wants to establish national fertility centres and create a new infrastructure in public buildings staffed by publicly employed staff and to take it out of the private clinic sphere. That will be a challenge because the existing private clinics already find staffing a challenge and the lab techniques and embryology are very subspecialised. We don’t have a dedicated embryology course at university level in Ireland. I think it’s more important for people to get the treatment when they need it than when it’s available in a dedicated public building.”
Ms Katie Mulrooney
Postgraduate Pharmacy Class of 2019
Support Pharmacist at O’Sheas Pharmacy, Kilkenny
As a pharmacist, there is a range of different services, products and advice I can offer to patients at every stage of their fertility journey.
This usually starts with simple supplementation prior to conception. Currently the only two recommended by the HSE are folic acid and vitamin D, which should be taken by all women from their early 20s through their childbearing years. When it comes to supplements to aid conception, it’s a question of identifying the right products at the start of the pregnancy journey.
In terms of devices, we can advise on cycle trackers, ovulation tests and pregnancy tests.
We also provide advice as to whether particular medications are suitable or unsuitable for use during pregnancy. One of the great things about pharmacists is that they are very accessible. Women don’t need to make an appointment to discuss things with a qualified healthcare professional and we can advise on alternatives to traditional medicines for minor ailments.
Women trying to conceive may be undergoing fertility treatments, some of which involve medicines. Every pharmacist is trained to deal with the dispensing of fertility-related products and prescriptions. Usually prescriptions come to us via email and we can discuss with the patient what’s needed, taking into account their background and level of knowledge. If it is their first time, we help minimise their stress and anxiety. In advance of the start date of the cycle, we go through the various tablets, pessaries, liquids and injections involved. It’s important for the pharmacist to inform the patient about the correct timing and storage of the various products and make sure the patient knows how to take them to get the best out of the cycle and make it a positive experience. It’s a lovely journey to be on with the patient when successful.
Most fertility drugs are now covered on the Drugs Payment Scheme (DPS), which makes fertility treatment much more a ordable. As pharmacists, part of our job is to figure out the most cost-effective way of managing the cycle for the patient.
Conceiving is one thing, but getting through the pregnancy is another. There are lots of pregnancy risks such as pre-eclampsia that present opportunities for the pharmacist to be involved. Thankfully, Cariban is now covered on the DPS for expectant mothers experiencing hyperemesis. Doors are opening all the time to facilitate the pregnancy journey.”
MOST FERTILITY DRUGS ARE NOW COVERED ON THE DPS, WHICH MAKES FERTILITY TREATMENT MUCH MORE AFFORDABLE.
Professor Cathy Allen Medicine Class of 1995 Consultant Obstetrician & Gynaecologist, Specialist in Reproductive Medicine & Surgery, National Maternity Hospital, St Michael’s Hospital, and Merrion Fertility Clinic
Infertility is still not universally recognised as a disease in Ireland, and recognition is what gives rise to change.
During my undergraduate degree at RCSI, I undertook a summer project with Professor Robbie Harrison, the pioneer of assisted conception and IVF in Ireland. He was a very colourful character and the area caught my imagination, even though my research involved being in an abattoir to collect the ovaries of freshly slaughtered heifers – not very glamorous. But it exposed me to the fascinating field of Assisted Reproductive Technology (ART) and to clinicians, researchers and embryologists in the international arena.
My obstetrics and gynaecology training in Ireland was via the old apprenticeship model followed by the new structured training (SpR) schemes, and I returned to work under Professor Harrison at the HARI unit of the Rotunda Hospital. After completing specialist training, I had further training at Oxford Fertility Unit, John Radcliffe Hospital, UK, a centre of excellence for assisted conception and laparoscopic reproductive surgery.
I took up a consultant post at the National Maternity Hospital (NMH) in 2009. Half of my time is in obstetrics and gynaecology in the public system, the rest is in fertility services at Merrion Fertility Clinic, the associated not-for-profit assisted conception unit.
The decline of religious influence on women’s healthcare has allowed growth in fertility and other areas of reproductive health. Case complexity is increasing. Some of our current fertility patients, including those with cystic brosis, congenital heart defects or childhood cancers, would not have been expected to survive when I was a junior doctor, let alone start their own families. This improvement is wonderful. The need for more subspecialists in reproductive medicine becomes ever more apparent, so encouraging trainees to specialise in the area is a high priority.
Recurring miscarriage (RM) is one of the services for which I have responsibility in the NMH. There is often overlap between causes of RM and those of subfertility, so we combine the expertise available in the public hospital and the assisted conception unit. RM patients are not necessarily infertile, but they may need fertility treatment. Patients appreciate when their history of miscarriage/fertility challenges can be managed by the same team before a successful pregnancy is achieved, which may itself require extra surveillance. We have a special ‘TLC’ clinic dedicated to the early pregnancy care of women who’ve suffered RM, as their physical and psychological needs may be complex.
The socio-demographic trend towards delaying childbearing results in challenges for some; advanced female age is a risk factor for infertility or RM. The incidence of chromosomal aneuploidy in eggs and embryos increases with age and these conceptions are prone to natural selection mechanisms. Advances in genomics have had a huge influence on foetal medicine and perinatal care in general, but also on assisted conception. Preimplantation Genetic Testing for Aneuploidy (PGTA) offers the possibility of screening embryos (created in vitro) for chromosomal normality before they are transferred to the uterus. For some individuals this can be helpful, but it’s expensive. Preimplantation genetic testing (PGT) can also be used to screen embryos for single gene disorders, such as cystic fibrosis, or in cases where one parent carries a chromosomal balanced translocation.
Currently, only those who can afford IVF can access it. The promised government funding could vastly improve the quality of care being offered to fertility patients in this country. Whenever a necessary service is not provided publicly, the private sector fills the void. In Ireland we have seen major investments by private companies into the assisted conception ‘market’. Many are excellent institutions providing high-quality services, but there may be pressure to consider profit margins in the clinical care of patients, rather than evidence-based medicine. Public sector resourcing is likely to have more transparent structures for governance, oversight, and accountability. The subfertility road is extremely stressful, and contrasting messages between healthcare providers can add to patients’ stress. Public funding would enhance the chance of proper standards and therapies being appraised without a commercial bias. It would also make life a lot easier for doctors, who could recommend the best therapy for individuals based on medical rather than financial considerations.” ■
