Article in the Irish Examiner, 25 June 2019 – Press Association

A popular strategy for raising IVF pregnancy rates by freezing embryos has been shown to have no improvement in a large trial. Success rates after freezing all embryos for later transfer were no better than fresh transfers, a randomised trial at eight clinics in Denmark, Sweden and Spain found.

Dr Sacha Stormlund, from Copenhagen University Hospital in Denmark, said: “Our findings give no support to a general freeze-all strategy in normally menstruating women.

“The results of this trial were as we expected, namely to see similar pregnancy rates between the fresh and freeze-all treatment groups. So I think it can now plausibly be said that there is no indication for a general freeze-all strategy in women with regular menstrual cycles who are not at immediate risk of overstimulation in IVF.”

She presented the findings of the trial, which involved 460 IVF patients, at the European Society of Human Reproduction and Embryology in Vienna, Austria. The study was prompted by the growing trend of freezing all embryos generated in the first cycle of pregnancy and transferring them after thawing in a later cycle.

This approach has proved a popular alternative to using fresh embryos in the initial cycle. However, the freeze-all approach is still advised as a safety measure for IVF patients responding excessively to ovarian stimulation, such as women with polycystic ovary syndrome.

https://www.irishexaminer.com/breakingnews/world/freezing-embryos-has-no-impact-on-ivf-success-rate-study-concludes-932678.html

Marriage Diaries is a column by Telegraph Family in which people share snapshots of their relationships and their dilemmas.  They are published every Wednesday. The below story is available here.

It’s 7.30 on a Thursday morning. The post-coital glow quickly dissipates as I get out of bed and give my wife a perfunctory nod. She is distracted and is adding the time and a record of our activity to an app on her phone. While we are trying very hard to make a life, somewhere along the way something has died.

I like sex and believe it to be an important component in a loving relationship. I have been blessed with a healthy, regular intimacy with my wife. But lately, everything has become rather – how do I say this? – mechanical. We rely on diaries and ovulation aids, rather than luck and seduction.

It was not always thus. Initially in our relationship there were fireworks, as in most new loves. Sometimes there were several fireworks a day in various locations. These fizzled out over time, but have remained regular. Every so often, when the touch paper is lit, they explode unexpectedly again in impromptu displays that the neighbours can sometimes hear. These are always the moments of intimacy and excitement that reconnect us when the banality of everyday life gets in the way. They are the little reminders of the passionate people we were and can still be.

Eventually, after several carefree years of courtship and marriage, talk of children surfaced and recently we went to discuss matters with a fertility specialist (we are both over 40, so there are no guarantees). I was heartened to be told that to maximise our changes we should be having regular sex. That’s sex, on prescription, as advised by a clinician. Naturally, I had a spring my step after the appointment and in the days that followed, as I reminded my better half of this medical recommendation.

Naively and hopefully, I envisaged that the fertility mission would be accomplished with the sexual equivalent of a sustained campaign of indiscriminate carpet-bombing, which I was very much looking forward to. The reality, however, was a little more meticulous and it became apparent that, rather than shock-and-awe, we were instead going to be conducting a series of carefully controlled and targeted surgical strikes. Each was concentrated within a five-day fertility window and dictated almost to the minute by an app, which alerted us each month when the time had come to launch Operation Conception.

Day one was always a relief, coming as it usually did after a period of abstinence. Days two and three weren’t bad either. But by days four and five, the intimacy had drained from the experience and both of us knew we were just going through the motions. The pressure to perform sucked the romance and excitement from the occasion. My wife marshalled and organised. I felt like a cow being milked.

I know I should be grateful and should look at these monthly opportunities as a time of bounty. And they are by no means unpleasant. We do laugh about them and share our thoughts and feelings honestly. My wife often feels the same way. We both accept that the carefree love life we enjoyed early in our relationship was of a time and that now there is a bigger purpose. Yet I still mourn the thrill of desire for desire’s sake, and there is a small, perhaps insecure and egotistical part of me that begrudges having to perform at set times, much like an actor playing to an audience that has only turned up because the tickets are free, not because they are necessarily eager to see the show.

I am an optimist, however, and I hope that after a successful mission, normal service will resume somewhere down the line. I am also a realist and recognise that with a baby in town, there may well be a lengthy ceasefire first.

From: https://www.telegraph.co.uk/family/relationships/trying-baby-taking-joy-sex-life/?wgu=272965_16644_15613681422734_018240d3fe&wgexpiry=1569144142&WT.mc_id=tmgoff_paff-4551_subsoffers_basic_planit&utm_source=tmgoff&utm_medium=tmgoff_paff-4551&utm_content=subsoffers_basic&utm_campaign=tmgoff_paff-4551_subsoffers_basic_planit

The Irish Times Health Supplement (10 April) reported that many Irish fertility clinics are offering optional “extras” in IVF treatment, recommended by clinics in order to boost chances of becoming pregnant. A survey of patients being treated at two Dublin IVF clinics found that add-ons had increased the costs for 84 per cent of these patients.

Our medical director, Dr John Waterstone, has often spoken out against these extras as they cost patients “several thousand more euro than they had anticipated spending in the course of an IVF treatment cycle”. Dr Waterstone has suggested that the Department of Health should be aware of the potential for “financial exploitation” of patients in the area of assisted reproduction, and has urged that IVF clinics be regulated. He strongly encourages patients to check what is, and is not, included in the prices quoted by clinics.  

Waterstone Clinic operates with transparency at its core. Our clinic is committed to providing treatments that are evidence-based and proven to succeed. We make no empty promises, and we perform no unnecessary tests. Our treatment costs are all-inclusive, and there are no hidden extras. 

There are many “add on” treatments patients can access when pursuing IVF treatment, Dr John Waterstone notes that “none are likely to increase the chance of taking home a baby.” The clinicians at Waterstone Clinic only suggest tests and treatments that are medically warranted. We believe our skills, experience and state-of-the-art facilities give our patients the best chance possible to achieve their goal, without these expensive extras.

READ MORE:https://www.independent.ie/irish-news/health/desperate-couples-at-risk-of-exploitation-fertility-expert-35256095.html

https://www.irishtimes.com/life-and-style/health-family/the-high-mysterious-and-added-costs-of-ivf-1.3845858

Environmental factors such as air- borne pollutants and pesticides in our foods are leading to a decline in the quality and quantity of male sperm, says Lorraine Courtney

Men’s sperm counts have fallen by almost 60% since the 1970s, according to major new research which cautions that our modern world may be prompting a male fertility crisis. Over the past few years, various studies have pointed to declining sperm quality and quantity. This latest research, and the first systematic review of trends, looked at 180 studies over four decades. It concluded that total sperm counts in Western countries have fallen by 59% since 1973, with a 52% fall in sperm concentration, or the concentration of sperm in a man’s ejaculate.

“Decreasing sperm count has been of great concern since it was first reported 25 years ago,” says Dr Shanna H Swan, a professor in the Department of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai, New York and study leader.

“This definitive study shows, for the first time, that this decline is strong and continuing. The fact that the decline is seen in Western countries strongly suggests that chemicals in commerce are playing a causal role in this trend.” The chemicals he refers to range from everyday air pollutants to pesticides or even soap. So should the average man panic?

A first glance at the statistics suggests that we are faring well. Ireland had the highest birth rate among EU countries last year. 2016 saw 63,900 live births recorded according to figures from Eurostat, the EU statistics agency. That’s a super healthy rate of 13.5 births for every 1,000 of the population. Italy was the lowest with just 7.8 births for 1,000 of the population.

However, male infertility is a factor for half of the couples who seek fertility treatment here in Ireland. Azoospermia (absence of spermatozoa in the ejaculate) is a condition present in approximately 1% of males in the general population. Between 10-15% of infertile men who attend assisted reproductive technology clinics here have had a diagnosis of azoospermia. However, approximately 30% of couples present where there is suboptimal sperm count or reduced motility, impacting on the couples’ ability to conceive a child.

Dr Tim Dineen, head of laboratory services at Cork’s Waterstone Clinic, says the study draws attention to a trend that doctors and scientists working in reproductive medicine have been aware of for many years.

“The decline in sperm counts is very gradual and is unlikely to prevent any individual man fathering children naturally in the short term,” says Dr Dineen.

“It is also important to point out that if a man’s sperm count is so low that natural conception is impossible, intracytoplasmic sperm injection (ICSI) treatment is able to compensate for the problem very successfully.”

Treatments, in the form of ICSI, have been very successful in overcoming male subfertility and male infertility. In the Waterstone Clinic, for those couples where the female partner is younger with good ovarian reserve, a live birth rate of at least 50% (first fresh cycle) is expected.

ICSI costs €4,750 including blastocyst and embryoscope incubator culture at the clinic, which offers a range of treatments.

“It is reasonable to assume that environmental factors are to blame but no one knows exactly which factors are involved,” says Dr Dineen. “Research is urgently required to identify the environmental causes; only then can public health initiatives be undertaken in order to address the problem.”

With an eye on the future, Dr Dineen maintains that if the exact cause of the drop in sperm counts is not discovered and corrected soon, the decline will continue and major problems will arise with regard to the ability of men to father children naturally.

Read more

The work on the repair of a gene in human eggs, reported in the journal Nature, is an important scientific achievement. It made use of “Crispr” (clustered regularly interspaced short palindromic repeats) technology to make a single specific change in the three billion units of the human genome. The work is indeed a stunning application of Crispr, with some elegant and surprising results – and the publicity is good for my science – but it is not likely to change the way reproductive medical genetics is practised and it raises no new ethical problems.

The claims made for the work, amplified by the media, will raise expectations in families carrying genes with severe medical effects and has already excited the critics who fear that geneticists are busy undermining our society. So let us first look at what has been achieved in the science, and then tease out some of the implications.

Medical genetic disorders cause a great deal of suffering and affect about one person in 25. Genetic engineering and DNA sequencing invented in the 1970s led to a revolution in genetics. Mutant genes causing many genetic disorders have been identified. Advances in human embryology led to in-vitro fertilisation (IVF) in 1978, leading to the birth of more than five million children and untold happiness in their families. The question arose whether IVF could be useful in dealing with medical genetic cases.

Genetic defects

By the early 1990s geneticists could detect mutant genes in single cells taken from IVF embryos without harming the embryos. This led to the gradual introduction of preimplantation genetic diagnosis (PGD). Today parents who are concerned that they may conceive a child with a significant genetic disorder can produce embryos by IVF, these may be tested for the genetic defect and one or more unaffected embryos can then be implanted.

PGD requires a specific “probe” for each genetic mutation. Some mutations are common, such as F508 in cystic fibrosis, but for many families the mutations have to be analysed and specific probes prepared and tested. As many people know, IVF is itself complex – PGD adds another level of complexity, meaning that the number of successful clinical cases dealt with worldwide to date is still only a few thousand. PGD is in its infancy.

So what will be the clinical impact of the new method on PGD? In their experiments, biologist Shoukhrat Mitalipov and his fellow researchers treated 58 embryos in which about 50 per cent carried the normal and half the mutant gene. After treatment they found that 42 (or 72 per cent) carried two normal genes. The mutant gene had been repaired in an estimated 13 out of 29 embryos. Crucially, not all embryos were repaired, nor was it possible to say that Crispr did not cause other unintended, off-target damage to other genes. The embryos were not implanted.

The authors suggest that repair by Crispr will increase the efficiency of PGD. In fact it will have almost no practical effect on PGD services, for two reasons. First, not all of the defective genes are repaired, so after Crispr the embryos still have to be screened by standard PGD to avoid implanting mutant genes. Second, repairing is much more complicated than the current method, which is already complicated. Two Swedish commentators who work in the field note dryly: “Embryo genetic testing [PGD] during IVF remains the standard way to prevent the transmission of inherited diseases in human embryos.”

In contrast to its use in reproductive medical genetics, use of Crispr in repairing genes in body tissues is a really promising approach to treating genetic disorders after birth, but that is another story.

What do we really need to do in developing PGD? The technical priority is to make IVF itself more efficient. Then we need to refine the current methods of PGD and apply them routinely to a much wider range of genetic mutations. The social priority is to provide PGD on national health services to all couples faced with a high chance of conceiving a child with a major genetic disorder.

Ethics

Now what about the ethics? Since PGD, which is a medical procedure, is well accepted in international medicine there is nothing new on that front. If in the past, like the Catholic Church, you opposed IVF (and PGD), or the wishes of parents to avoid having children with genetic disorders, this work will not change opinions, and should not increase your concerns.

It is possible that the Crispr techniques of changing genes will be used for non-medical purposes in reproduction, for example to alter genetic qualities which have nothing to do with health. In the UK, such use is regulated by the Human Fertilisation and Embroylogy Authority, and might be made illegal (as for example is the non-medical use of PGD for sex selection). But it may be more difficult to make all applications illegal – for example, parents might wish to have a child with blue instead of brown eyes, and if so is foolishness something we should make illegal?

One thing is clear. It is long past time that we put into effect the recommendations of the Irish Commission on Assisted Human Reproduction of 2005 dealing with these issues, which are not new, and are well known to the Government. IVF is not regulated in Ireland nor is PGD, making it difficult for pioneers in the field such as Dr John Waterstone of Cork Fertility to provide a service that is badly needed in Ireland.

David McConnell is fellow emeritus of the Smurfit institute of genetics at Trinity College Dublin. He is a former chairman of The Irish Times Trust.