IVF News

Only one in five primary care trusts (PCTs) in England is providing the recommended number of NHS-funded IVF cycles, it was revealed at a fertility conference in Edinburgh last week. 

The results of a survey conducted by a team at St Bartholomew's Hospital in London show that four years since the National Institute of Health and Clinical Excellence (NICE) made the recommendation that women should receive three cycles of IVF on the NHS, that guidance is not being followed and in the case of one unnamed trust - no IVF is being funded at all. 

Although the NICE guidelines were devised as guidance for PCTs rather than as a legal minimum, the researchers at St Bartholomew's have called for a common national funding policy to address the disparity in IVF provision around the country. 

Facing limited resources, trusts impose restrictions on who is eligible for treatment. Criteria such as weight, age, being a non-smoker and not having any children from previous relationships all contribute to the decision. The survey, conducted between July and September 2008, revealed that half of trusts will not fund treatment for smokers, and some trusts will only fund treatment if women are over 35 years old when natural fertility is thought to decline.

NICE's guidance suggested three funded cycles of IVF for infertile women, each cycle including one fresh embryo transfer and if that failed, as many frozen embryo transfers as possible with available embryos. The research team at St Bartholomew's, led by Parimalam Ramanathan discovered that none of the 148 trusts in England provides this. Of the 29 trusts providing three fresh cycles, 15 do not fund any frozen cycles, 14 are funding only one frozen cycle and only two trusts fund two frozen cycles. Tony Rutherford of the Assisted Conception Unit in Leeds said that if the NICE guidance was implemented in full, everyone would have 'a realistic chance of a successful singleton pregnancy'.

Rutherford also pointed out that the initiative to promote single embryo transfer in an effort to cut the number of multiple births resulting from IVF is being held back by a lack of funding. 'If more cycles were funded on the NHS then one embryo could be transferred to the womb at a time', he said. Multiple births are one of the biggest risks in IVF when more than one embryo is transferred into the womb during one cycle. Clare Lewis-Jones of the National Infertility Awareness Campaign said that 'with the move to single embryo transfer, it is even more important to end this totally unacceptable situation and allow patients access to the treatment promised to them by the government.'

In response. a Department of Health spokesman insisted that the number of PCTs providing three cycles of IVF continues to increase.

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 Amsterdam, The Netherlands: Daily sex (or ejaculating daily) for seven days improves men’s sperm quality by reducing the amount of DNA damage, according to an Australian study presented today (Tuesday) to the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam.

Until now there has been no evidence-based consensus amongst fertility specialists as to whether or not men should refrain from sex for a few days before attempting to conceive with their partner, either spontaneously or via assisted reproduction.

Dr David Greening, an obstetrician and gynaecologist with sub specialist training in reproductive endocrinology and infertility at Sydney IVF, Wollongong, Australia, said: “All that we knew was that intercourse on the day of ovulation offered the highest chance of pregnancy, but we did not know what was the best advice for the period leading up to ovulation or egg retrieval for IVF.

“I thought that frequent ejaculation might be a physiological mechanism to improve sperm DNA damage, while maintaining semen levels within the normal, fertile range.”

To investigate this hypothesis, Dr Greening studied 118 men who had higher than normal sperm DNA damage as indicated by a DNA Fragmentation Index (DFI). Men who had a more than 15% of their sperm (DFI >15%) damaged were eligible for the trial. At Sydney IVF, sperm DNA damage is defined as less than 15% DFI for excellent quality sperm, 15-24% DFI for good, 25-29% DFI for fair and more than 29% DFI for poor quality; but other laboratories can have slightly different ranges.

The men were instructed to ejaculate daily for seven days, and no other treatment or lifestyle changes were suggested. Before they started, levels of DNA damage ranged between 15% and 98% DFI, with an average 34% DFI when measured after three days’ abstinence. When the men’s sperm was re-assessed on the seventh day, Dr Greening found that 96 men (81%) had an average 12% decrease in their sperm DNA damage, while 22 men (19%) and an average increase in damage of nearly 10%. The average for the whole group dropped to 26% DFI.

Dr Greening said: “Although the mean average was 26% which is in the ‘fair’ range for sperm quality, this included 18% of men whose sperm DNA damage increased as well as those whose DNA damage decreased. Amongst the men whose damage decreased, their average dropped by 12% to just under 23% DFI, which puts them in the ‘good’ range. Also, more men moved into the ‘good’ range and out of the ‘poor’ or ‘fair’ range. These changes were substantial and statistically highly significant. 

“In addition, we found that although frequent ejaculation decreased semen volume and sperm concentrations, it did not compromise sperm motility and, in fact, this rose slightly but significantly.

“Further research is required to see whether the improvement in these men’s sperm quality translates into better pregnancy rates, but other, previous studies have shown the relationship between sperm DNA damage and pregnancy rates.

“The optimal number of days of ejaculation might be more or less than seven days, but a week appears manageable and favourable. It seems safe to conclude that couples with relatively normal semen parameters should have sex daily for up to a week before the ovulation date. In the context of assisted reproduction, this simple treatment may assist in improving sperm quality and ultimately achieving a pregnancy. In addition, these results may mean that men play a greater role in infertility than previously suspected, and that ejaculatory frequency is important for improving sperm quality, especially as men age and during assisted reproduction cycles.”

Dr Greening said he thought the reason why sperm quality improved with frequent ejaculation was because the sperm had a shorter exposure in the testicular ducts and epididymis to reactive oxygen species – very small molecules, high levels of which can damage cells. “The remainder of the men who had an increase in DFI might have a different explanation for their sperm DNA damage,” he concluded.

 

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Children conceived using IVF and intracytoplasmic sperm injection (ICSI) techniques have the same intellectual and movement abilities as naturally conceived children, a new European study shows. Researchers based at University College Medical School in London tested the developmental skills of around 1000 five-year old children conceived using IVF and ICSI. No differences were found between these children and those conceived naturally, say the scientists, who published their findings in the journal Pediatrics.



ICSI involves taking a single sperm, and injecting it directly into an egg in vitro. Some doctors have expressed fears that the egg may be damaged during the injection process, or by the chemicals used for ICSI. Others are concerned that selecting a single sperm bypasses the usual competition amongst sperm to fertilise the egg. This could lead to fertilisation with a 'substandard' sperm, which would not have succeeded if it had not been injected. But these fears have so far proved unfounded.



In the latest study, the researchers looked at 511 children conceived through ICSI, 424 conceived through IVF and 488 naturally-conceived children living in Belgium, Denmark, Greece, Sweden and the UK. The study did not include any twins, triplets or other multiple births. The team found no significant differences in verbal IQ, performance IQ or motor skills between the three groups. 'The results of this study are reassuring for parents who have conceived through ICSI or IVF', say the scientists.



A previous European study, reported in 2003, found no significant differences between the birth weight and height aged five of IVF, ICSI and non-IVF children. There were also no differences in verbal ability, total IQ or behavioural problems between the three groups. And last October, a US panel reported that overall, children conceived by in vitro fertilisation (IVF) are no more likely to have major health problems than naturally conceived children. The research reviewed 169 previously published studies.



Last November, the UK's Medical Research Council (MRC) published a report highlighting the need for 'improved monitoring and evaluation of assisted reproduction technology (ART)'. It recommended a new system to follow up the long term effects of ART, and called for more research into the safety and effectiveness of new and existing ART techniques. Commenting on the launch of the report, working group chair Catherine Peckham said at the time: 'There is widespread evidence that current ART procedures are safe', adding 'however, improved evaluation of the long term effects of ART is important'.

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British couples at risk from passing on a serious genetic disorder to their children are being refused National Health Service (NHS) funding for treatment which could allow them to have a healthy child, medical experts have warned this week. The procedure, known as pre-implantation genetic diagnosis (PGD), involves creating embryos through conventional IVF, testing them for a particular condition, and only implanting those free from that condition into the woman's womb. In the absence of this procedure, many couples wishing to have children are forced to conceive naturally and face the prospect of either having an affected child, or of terminating any pregnancies which test positive for the condition.

Alison Lashwood, consultant nurse in genetics and PGD at Guy's and St Thomas' Hospital in London, told the Times newspaper: 'There are couples we have seen who have not been given funding, who have gone on to have affected children. Others have had to go down the prenatal testing route and some have had terminations.' Earlier this week, Guy's hospital celebrated the opening of its new 'Assisted Conception Unit and PGD Centre', offering standard fertility treatments, such as IVF and ICSI, as well as the largest and most successful PGD programme in the UK.

Part of the controversy around PGD relates to the possibility of couples wanting to create so called 'designer' babies, by selecting embryos for attributes such as height, intelligence or sporting ability. However, such traits, like many common illnesses, are the result of a combination of different genetic and non-genetic factors, making the prospect of selecting embryos with such traits virtually impossible. Furthermore, the treatment is highly regulated and the overseeing body - the Human Fertilisation and Embryology Authority (HFEA) - has a definitive list of genetic disorders which it considers sufficiently 'serious' for PGD to be offered, although decisions over whether or not to award the £7,000 necessary for a PGD cycle are made locally on a case-by-case basis at the discretion of the NHS Trust.

Claire Holdcroft, an outreach worker for the Jennifer Trust, which works with families affected by the life-limiting childhood condition spinal muscular atrophy (SMA), said that ending the PGD 'postcode lottery' would help them better advise at-risk couples. 'It would be really helpful if there were nationwide standards for who should be entitled to [PGD] so everyone knew where they stood and we knew that, as a national charity, we were giving out relevant advice,' she told the BBC.

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A fertility clinic in the USA has revealed that it provides sex selection to many British couples who pay large amounts of money to travel and receive the service.

Jeffrey Steinberg opened his clinic in Manhattan, New York, in January of this year and claims that over half of the embryos currently undergoing pre-implantation genetic diagnosis (PGD) for ‘family balancing', as it has become known, are British.

‘Britain were the innovators but now they've got handcuffs on. From a medical standpoint, it's a travesty' says Steinberg.

The procedure is currently banned in the UK except for use in screening for genetic diseases such as muscular dystrophy and haemophilia, which usually only affect boys. Each proposed use of PGD must be granted by the British regulatory body, the Human Fertilisation and Embryology Authority (HFEA).

Using PGD for this purpose was banned in the 2008 Human Fertilisation and Embryology Act after a public consultation in 2003 revealed 80 per cent of the British public objected to the idea.

The HFEA have warned couples thinking of travelling abroad to receive this service to take time to explore the implications. ‘In the US there is no official regulator. Those who go overseas should make themselves aware of the laws and what impact there may be on any child that is born', said a spokesperson.

The procedure involves the extraction of a single cell from embryos created by in vitro fertilisation (IVF). The sex chromosomes in the cell are then found and examined to reveal whether the embryo is male or female. The desired sex of embryo is then implanted into the womb.

Pro-life groups in the USA have condemned the destruction of the embryos found not to be the desired sex.

The cost of receiving PGD in the USA is a big boost for the medical business; it has been estimated at £20,000 after procedures, travel and hotels.

David Karabinns of ‘The Genetics and IVF Institute' in Virginia, USA, who were among the first clinics to offer PGD for family balancing, said: ‘Just as there was an overreaction about IVF, there will be a gradual acceptance as we prove it's safe'. Most US clinics will only treat parents who already have a child of the opposite sex.

Critics of family balancing fear that it will lead to a cultural bias toward one gender and earlier this year the Pope attacked what he called, ‘the obsessive search for the perfect child'.

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One of the questions facing legislators considering changes to UK legislation regulating the provision of assisted conception procedures is the extent to which formal measures may increase the likelihood of donor-conceived people being informed about their origins.

The background to these considerations includes the 2005 legislative change enabling a donor-conceived person to learn the identity of his or her donor and research evidence indicating that relatively few parents of donor-conceived children (and, in particular, heterosexual parents using donor insemination) inform their children about their conception.

Evidence from Sweden, where donor anonymity was abolished in 1985, suggests that the level of parental disclosure increases over time (1). However, key questions remaining are whether the 'natural' pace of change is quick enough, and whether those parents who left to their own devices remain unlikely to tell their children can be encouraged to do so.

Annotation of the birth certificates of donor-conceived people has been proposed as a possible means of ensuring that more donor-conceived people learn of their status (2-4). The government has indicated its preference for educational rather than legislative measures to promote disclosure (5). However, in response to peers' concerns, it has offered further discussions before the Human Fertilisation and Embryology Bill reaches the Report stage in the House of Lords.

Any measure in this direction seeking serious consideration must ensure that individual privacy is not compromised and that additional bureaucracy and public expense are proportionate. Furthermore it must recognise the involvement of two state agencies when a child is born as a result of a donor procedure: the HFEA (through its register of information) and one of the UK's three General Register Offices (GROs) (England and Wales, Northern Ireland, Scotland). Currently there are no provisions for ensuring co-ordination of information between the HFEA and GROs. Doing so seems to offer a way of achieving, to a large extent, the objective of ensuring that more donor-conceived people become aware of their conception, while recognising that no system can guarantee total compliance (since one thing we can be sure of is that wherever there are rules someone will break them).

A possible model can be suggested, and outlined as follows:

" the HFEA notifies the relevant GRO of all donor-conceived births;

" the GRO records a link between its own birth registration and the HFEA records;

" when an application for a birth record is made to a GRO and it is satisfied that the applicant is either the individual to whom the registration relates or his or her legal parent - and those persons only - the 'full' birth certificate that is provided will indicate that the HFEA Register contains information regarding the individual to whom the certificate relates. (This could be achieved by means of an appendix to the certificate which may be detached if the certificate is subsequently required for purposes such as a passport application). As now, an un-annotated birth certificate will be provided by GRO to any other applicant;

" if the individual chooses to contact the HFEA, existing measures with regard to applications to the HFEA Register of Information will come into operation;

" information and advice concerning birth registration should be provided to people undergoing a donor procedure as part of the information, counselling and other preparation provided by a licensed treatment centre to persons undergoing a donor procedure. This should be mandatory and specified as such in the HFEA Code of Practice. Ongoing information, advice and support should also be made available to the family following the birth of a child.

The registration of a child's birth is likely to precede the formal linking of HFEA and GRO data, and so remains reliant on parental veracity. However, non-compliance should be greatly minimised by the provision of information and advice as outlined above; coupled with the knowledge of the future co-ordination of HFEA and GRO records and the knowledge that if the donor-conceived person requests a birth certificate from GRO, this will indicate his or her status.

This proposal not only safeguards individuals' privacy, so that the donor-conceived person or his or her legal parents only will be able to access information disclosing the donor-conceived person's status, but also would not establish any provisions different from those currently regulating public access to birth records that would alert any other enquirer to the possibility of donor-conception. It also avoids establishing a completely separate registration system for donor-conceived births. The downside is that it would involve additional resources insofar as GROs and the HFEA will have to establish systems for the recording of this information. However, since the state legitimises donor conception, it seems perfectly reasonable that it should accept the responsibility this entails. In any event, the limited numbers of individuals involved indicate that any such resource requirements are proportionate.

A more radical version of this model, but which could ultimately reduce bureaucracy, would transfer responsibility for the HFEA Register to the GROs - a model adopted for New Zealand's Human Assisted Reproductive Technology (HART) Register (6). A persuasive case could probably be made for this also. The GROs' current responsibilities and track record for safeguarding sensitive data relating to the Adopted Children, Parental Order, Stillbirth and Gender Recognition Registers indicate that this information would be in safe hands (a not-insignificant consideration at the present time).

 

References:

 

1. Lalos, A., Gottlieb, C. and Lalos, O. (2007) Legislated right for donor-insemination children to know their genetic origin: a study of parental thinking. Human Reproduction 22(6): 1759-1768.

2. Department of Health and Social Security (1984) Report of the Committee of Inquiry into Human Fertilisation and Embryology (The Warnock Report), Cmnd. 9314 London: HMSO: 4.25

3. House of Lords and House of Commons (2007) Joint Committee on the Human Tissue and Embryos (Draft) Bill Vol 1: Report: 276 http://www.publications.parliament.uk/pa/jt200607/jtselect/jtembryos/169/169.pdf

4. House of Lords (2007) Official Debates 10 December: Cols 91-108 http://www.publications.parliament.uk/pa/ld200708/ldhansrd/text/71210-0013.htm

5. Department of Health (2007) Government Response to the Report from the Joint Committee on the Human Tissue and Embryos (Draft) Bill. CM 7209 8 October. http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/dh_079127

6. Human Assisted Reproductive Technology (HART) Register. http://www.dia.govt.nz/diawebsite.nsf/wpg_URL/Services-Births-Deaths-and-Marriages-Human-Assisted-Reproductive-Technology-(HART)-Register?OpenDocument

 

Acknowledgements: In accepting full responsibility for the ideas contained in this Commentary, I wish to thank Lucy Frith and Caroline Jones for their invaluable advice in helping me to develop and refine them.

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Italy's highest court has approved a series of referendums on whether parts of its controversial new fertility law should be overhauled. However, the constitutional court rejected calls for a referendum on completely scrapping the law, instead allowing a public vote on some of its elements. These will include rules limiting fertility treatment to heterosexual couples, and those governing embryo research. The country's anti-clerical Radical Party, which collected the 500,000 signatures needed to call for the referendum, is reportedly outraged by the decision.



Italy's laws, said to be the most restrictive in Europe, have hardly been out of the news since they were passed last December. Before they were passed, the country had a reputation for being the 'Wild West' of fertility treatments due to its lack of restrictions, and many people travelled there to take advantage of controversial services they could not get in their own countries.



Now, the law restricts the provision of fertility treatments to 'stable heterosexual couples' who live together and are of childbearing age, and who are shown to be clinically infertile. Research using human embryos is prohibited, as well as embryo freezing, gamete donation, surrogacy and the provision of any fertility treatments for single women or same-sex couples.



The law also says that no more than three eggs can be fertilised at any one time, and that any eggs fertilised must all be transferred to the uterus simultaneously, increasing the risk of multiple births. Pre-implantation genetic diagnosis and prenatal screening for genetic disorders have also been banned. According to BBC News Online, fertility clinics across Europe have seen an increase in the numbers of Italian patients seeking treatment since the legislation came into force.



Radical Party secretary Daniele Capezzone called the referendum decision 'a scandal', adding that he expected the mainstream political parties to try to pre-empt the referendum by creating new legislation to replace the old law. Supporters of the law saw the judgement as a partial victory, since it opens the law to changes but will mean it is not completely overturned. Christian Democrat Dorina Bianchi, one of the law's main proponents, called the decision 'fair and balanced'.



The government must now hold the referendum between 15 April and 15 June, and at least 50 per cent of the electorate must vote if it is to have legal weight. However, several politicians from various parties said it would now be better for parliament to amend the law, rather than put complex questions to voters.
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Introduction: Royan International Research Award was founded by late director of Royan Institute; Dr. Saeid Kazemi Ashtiyani with the aim of encouraging the researchers and appreciation of their efforts. This annual award is a prize given to five prominent Research Projects in the field of Reproductive Biomedicine, Stem Cell Biology and Technology and other related subjects. The winners will be invited to take part in the Award Ceremony on the designated day so as to be granted their awards. Each winner will be rewarded for a certificate, the symbol of Royan Award and the amount of $5000. It is necessary for winners to present their works in Royan International Twin Congress beside the Award Ceremony. Research Projects: Research projects can lead to several papers or maybe only one paper. Additional papers should be relevant to the main project and you have to be one of the authors of each paper. Unrelated articles will be ignored so please do not attach any unrelated papers. The Scope of Subjects: The research topics may fall within the following scope: 1- Reproductive Biomedicine: Male & Female infertility, Embryology, Reproductive Endocrinology, Infertility physiology and Immunology, Reproduction Biology and Reproductive Health. 2- Stem cell biology and technology: Biology, Differentiation and Preservation, Signaling, Niche, Plasticity, Transplantation and Therapy, Gene therapy and Manipulation and Cancer Stem Cells. Online Submission: All research projects should be submitted online via the award's homepage. First it is needed to register and get a username and password by which you can login to this site and submit your project(s) in the award or abstract(s) in the congress. (Papers and projects sent by email, post or fax or after submission deadline will be ignored.) Deadline for submission is April 10 th, 2009.
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Men undertaking IVF treatment with their partners may be able to store their sperm at home, rather than in a laboratory, say researchers. Scientists from the Erfan and Bagedo Hospitals in Jeddah, Saudi Arabia, have created a way of 'air-drying' sperm which allows it to be stored at room temperature rather than in frozen storage.

To be 'air-dried', washed sperm is smeared onto a sterilised glass slide and left to dry in a cabinet for two to three hours. Filtered air is passed through the cabinet to ensure no contamination of the sample. When the sperm is needed for use in fertility treatment, it is re-suspended in a biological solution similar to that which surrounds human eggs in ovarian follicles. Although this process was seen to cause some damage to the tail and bodies of the sperm, the DNA contained inside appeared to be intact, therefore intracytoplasmic sperm injection (ICSI) was used in order to fertilise an egg. This means that a single sperm was extracted from the solution and being injected directly into an egg.

Typically, sperm samples mixed with a protective chemical are frozen in large liquid nitrogen tanks. These have to be carefully programmed to ensure that the sperm is not damaged or destroyed by cooling too fast or too slowly. The protective chemical also has to be separated from the sperm before it can be used. 'These methods are time-consuming and cumbersome compared to our simple technique of air-drying' said Dr Daniel Imoedemhe, leader of the research team. He added 'the process can be further simplified by allowing patients to take responsibility for storing their air-dried sperm at home'.

Presenting their findings at the annual conference of the European Society of Human Fertilisation and Embryology in Madrid, Spain, this week, the scientists said they had successfully created human embryos using this method. Previous experiments had been carried out successfully in mice.
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British women are being denied newer fertility drugs that help prepare the woman's body for egg stimulation, according to Bill Ledger, Professor of Obstetrics and Gynaecology at the University of Sheffield, The Times newspaper reports. IVF treatment requires a woman's ovaries to be stimulated in order to harvest eggs for external fertilisation. For this to happen the woman's natural menstrual cycle must be temporarily overcome. There are two classes of drugs that allow this to happen, which work to block a hormone called Gonadotrophin-releasing hormone (GnRH).

GnRH agonists are used in the majority of British fertility clinics. These drugs (the IVF 'long protocol') work by mimicking the hormone in the brain and binding to the receptors to block the natural hormone from attaching. These drugs are typically given for 14 to 21 days before the patient's period is due and they initially cause a sharp increase in hormone levels. As the hormone levels drop, menopause-like symptoms can occur including hot flushes, mood swings and insomnia. The alternative, newer treatment, involves using a different class of drugs - GnRH antagonists (the IVF 'short protocol'). These drugs do not bind to the hormone receptors in the brain, instead they bind to the hormone itself, allowing for a rapid decrease in hormone levels without the initial sharp increase. As antagonists reduce hormone levels much more quickly they can be given for a shorter period of time - around six days - meaning that side-effects are rare.

Developed in the 1990s, GnRH antagonists are used in 80 per cent of IVF cycles in Scandinavia. As well as reducing the instance of menopause-like side effects, the IVF short protocol also reportedly reduces the risk of ovarian hyperstimulation. British clinics have been slow to switch to the new drugs as in early trials they were shown to produce an average of 1.0 to 2.3 fewer eggs and 0.2 to 0.5 fewer good quality embryos in each cycle. Pregnancy rates were slightly lower but not statistically significant.

Professor Ledger argues that these studies took place before most doctors had experience of the new drugs and that the reason they are not used in Britain is due to the clinics' fear of falling in the success-rate league tables. The one trial that compares clinics that are experienced in the new regime found no appreciable difference in pregnancy rates between the two methods. 'The uptake of these drugs has been slower because of the conservative nature of IVF in Britain', Professor Ledger said. 'Clinics are terrified of a drop of a few points in their success rates if they switch', he added.

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