Freezing the chances of success

The Nationalist government's bill to regulate in vitro fertilisation and ban embryo freezing is expected to run into a political collision course if MPs raise the flag on the restrictions being imposed upon couples who cannot choose between egg freezing and embryo freezing.

Plans to ban embryo freezing by employing the novel science of oocyte vitrification, which harvests women's ova to fertilise only a maximum of two at any one time while the rest of the eggs are frozen, may also find opposition from Labour MPs.

It is an irony that the first IVF treatment to be provided by the State on the national health system will restrict choice in such a manner that couples who elect to go for a different treatment, will have to pay for it abroad: paying for having different ethical and moral standards to the State's, as it were.

It is as yet unclear as to how both sides of the Maltese parliament will play out in seeking a solution to regulate Malta's as-yet-unregulated IVF industry, single-handedly operated out of the private hospital of St James for the past 22 years - which controversially refused to freeze embryos and instead opt for the implantation of multiple embryos inside women.

As matters come to a head with the new Embryo Protection Bill, government drafted in the services of one of the pioneers of the science, obstetrician and University of Bologna researcher Eleonora Porcu, to put up a defence of the ethical and moral considerations that egg freezing provides for childless couples.

But even Porcu has not failed to remark that Malta's bill is by far the most restrictive she has ever encountered, specifically with its strict limit on the fertilisation of no more than two fresh eggs: a factor which alone will greatly affect pregnancy chances for women lucky enough to achieve success on a fresh oocyte transfer, before having to resort to frozen oocytes, where fertilisation and pregnancy rates fall sharply.

Politics and religion

Touted by Health Minister Joe Cassar as 'ray of hope' for childless couples, the future of IVF in Malta is firstly dependent on the way the political parties will play it out inside the House of Representatives.

Labour leader Joseph Muscat, the father of IVF twins, is intimate with the science of assisted reproduction. For the past years he has pledged an IVF law as the first act of legislation by a future Labour government, but with the Nationalists proposing their own in 2012  his next move will be down to the principles and science underpinning IVF.

Will he reverse the alleged 'pro-life' bias that underpins this law? His cautious silence on a bill that is being welcomed by Catholic groups for its anti-embryo freezing stance, may have found a voice in the otherwise vocal and veteran MP Evarist Bartolo, who has dubbed the bill "unworkable and humiliating".

Bartolo, who has criticised the fact that the Maltese bishops were given time to issue a pastoral letter reiterating the Vatican's stand that condemns IVF, at least 24 hours before the official publication of the Bill, has stated that mothers' lives are going to be put at risk as the rate of success in the restrictive procedure government is proposing "is next to nothing".

His most telling observation is that the Bill effectively nullifies what the select parliamentary committee on assisted reproduction in 2010 proposed, which was embryo freezing with the possibility of putting up unwanted embryos for adoption.

"This is a very restrictive and conservative bill that goes against the work done in parliament by the committee that had reached consensus on the way forward. The bill is even more restrictive than the one that had been pushed in Italy, not to give couples the opportunity to have children and form a family but to be in line with a Church that is out of touch with reality and humanity".

That religion plays a crucial part in the government's moral acrobatics over IVF may be an understatement. Deputy Prime Minister Tonio Borg, who had championed a failed proposal by pro-lifers Gift Of Life to entrench the Criminal Code's provisions on abortion in the Constitution, has attempted to rationalise the Vatican's stand on IVF, which condemns the science for interfering with the natural conception of life as obtained in natural, sexual intercourse between married couples.

"The opposite happens in IVF," the Catholic minister wrote in PN organ Il-Mument on 12 August, as he struggled with the Vatican's Humane Vitae encyclical. "A natural process that does not function is being repristined to its rightful state to create life. The fact that this cannot happen in the conjugal act, is certainly not the couple's fault but a defect in the natural process - so why not mend this defect?"

Like their Italian counterparts, the Nationalist Christian-Democrats are making their own compromise between a conservative secularism and their Catholic roots. This political equidistance can be seen in the reaction of MP Charlò Bonnici to the Bishops' pastoral which he described as a "disastrous PR exercise" for portraying parents of IVF children as sinners, even calling on the church to apologise if necessary. "That would show a much more compassionate facet of a Church built on the teachings of Christ."

An inefficient and restrictive law

Speaking to journalists, Eleonora Porcu claimed a satisfactory rate of clinical pregnancies on some 800 cycles which she claimed credit for, but even this data deserves careful deliberation by legislators.

In IVF, infertile women administer daily injections to stimulate the creation of ova - Porcu says the average number of eggs harvested after stimulation ranged from six to eight, perhaps five in certain cases.

This in itself is a limited number. In standard IVF, there is no guarantee that all six ova that get fertilised with sperm will develop into good quality blastocysts. The rationale for embryo freezing comes into play to safeguard women's health by limiting the transfer of fresh embryos to two; and offer women a back-up plan should the fresh cycle fail.

Under the proposed Embryo Protection bill, only two of the eggs would be fertilised for implantation. Unlike standard IVF, all chances for a successful fresh embryo transfer depends on the two selected ova developing into successful blastocysts for implantation.

Failing that, a frozen egg transfer will depend on the survival of the egg after thawing, and again whether will develop into good-quality embryos fit for implantation once fertilised.

Porcu claimed a success rate of 33% pregnancies on 800 fresh oocyte transfers. When MaltaToday enquired about how many successful deliveries these pregnancies brought, Porcu estimated a 20% chance of miscarriage.

The crux - and this is where the proverbial ray of hope should be shining - lies in the success rates for the remaining frozen ova, effectively the back-up plan for women who fail their first fresh cycle. Porcu said that her success rate of pregnancies (for women within their 30s) on frozen ova were much lower, at 26% on just 200 transfers.

The lower number of frozen egg transfers might just be an indication of the lower number of good quality eggs that get frozen after harvesting, and how many of them indeed survive the thawing procedure.

Number-crunching: Italy

In 2004, the Italian parliament passed a law limiting the fertilisation of no more than three eggs for

the creation of three embryos at any one time and that all the embryos created must be transferred together even if the couple does not need all the embryos. It also banned embryo freezing and the screening of embryos for genetic defects.

Like Italy's law, Malta's IVF bill has a set of regulations that places strict and remarkable limits on the use of assisted reproduction techniques.

On May 2009, the Italian Constitutional Court outlawed some of these restrictions, specifically to ensure that embryo protection was limited by the imperative that infertile women have "a concrete possibility" to achieve a successful pregnancy. This allowed doctors to define what the optimal number of embryos would be to give individual cases the best chance of achieving a pregnancy while limiting the number of frozen embryos.

As things stand, the Maltese law could be set for some fine-tuning in this regard to give doctors some leeway in increasing the number of eggs to be fertilised and implanted.

But the most acute observation comes from the University of Genoa's Paola Anserini, which following the amendments to Law 40 found an increase in the use of eggs being fertilised, and the number of resultant embryos. "The most striking results were an increase of pregnancy rate per started cycle in the post law-change group (20.42% before versus 23.49% afterwards - a 15% difference), and a trend towards a reduction in the number of triplet pregnancies (from 2.46 to 1.68%)."

To go by a study by doctors from Italy's national health institute, led by Giulia Scaravelli, which analysed the results of Law 40 during the years 2005-2007, the results of egg freezing may not be as promising as Eleanora Porcu makes them out to be.

According to the Scarvaelli study of 193 centres on the Italian national register, the pregnancy rate using frozen eggs was 12.5% and significantly lower than that using fresh eggs (24.9%) or frozen embryos (16.4%).

During these three years, 8,682 cycles done using frozen eggs (7.1% of the total number of initiated cycles), while another 2,952 (2.4% of total cycles) were from frozen embryos.

In total there was a total of 81,786 eggs, of which 52.5% (42,917) were thawed but 'only' 26.9% (22,005) were actually inseminated with sperm. Then, of those inseminated, 68% (14,966) yielded good embryos.

As Scaravelli and the authors of the ISS paper noted, these numbers were significantly lower than those using fresh oocytes in which 77.9% (197,242) of inseminated eggs generated good embryos.

Of the frozen egg cycles, the pregnancy rate per transfer using frozen eggs was 12.5% and significantly lower than that using fresh eggs (24.9%) or frozen embryos (16.4%).

There were 505 deliveries after IVF with frozen eggs and 582 babies. When considering this was the result from over 8,000 cycles, one really has to hope the science keeps improving radically.

Critics of Law 40, such as Prof. Vittorio Fineschi from the University of Foggia, said that the rigid limits on the number of embryos to be transferred and the ban on embryo freezing would create more risks to a woman's health cause by the necessity of more cycles of ovarian hyperstimulation.

This premise is based on the fact that, with such limited ovarian production, infertile women should not be restricted to one fresh transfer based on the morphological quality (best-looking) of eggs but on the morphological quality of embryos.

"The crucial point of the process is the possibility of choosing the embryos which morphologically present the best characteristics and to freeze the others," Fineschi wrote in the Journal of Medial Ethics in 2004.

"Working in this way, the percentage of clinical pregnancy is around 27-29% for each cycle of IVF, as reported by the American and European registers. To this percentage is added a further 15% in cases where a cycle of unfrozen embryos is carried out... It is clear that preventing the possibility of freezing embryos will mean a diminution in therapeutic successes of more than two-thirds, going from about 30% of national average to less than 10%."