Scientists at the University of Oxford, UK, believe they have identified the way in which embryos implant in the uterus, providing essential information which may be used in the future for infertility treatments and offering hope to thousands of infertile couples.

Implantation of an embryo to the lining of the mother's uterus is an essential process that takes place at an early stage of development. The embryo initially attaches and forms a contact with the uterus lining, which triggers a cascade of signals in both the embryo and the uterus. This allows cells from the embryo to start moving across into the uterus, finding blood vessels in the mother and eventually forming the placenta.

Problems in the implantation process can lead to loss of potential pregnancies, even in couples trying to conceive without infertility problems. Current estimates suggest that infertility affects one in seven couples in the UK, with around 32,000 couples seeking infertility treatment each year. It is thought that a significant number of these patients could be infertile as a result of implantation problems.

The team of scientists, led by Professor Helen Mardon from the Nuffield Department of Obstetrics and Gynaecology at Oxford, along with Professor Anne J Ridley at King's College, London, added embryos to a layer of cells from uterus lining in a culture dish to mimic events in the womb. They were then able to video embryos implanting themselves in the cell layer, allowing the scientists to dissect the molecular processes involved. Their findings were published in the journal Proceedings of the National Academy of Sciences.

Their investigation led them identify two proteins that are essential players in the implantation process. They are from the Rho GTPase family of proteins, and ensure that cells in a particular part of the uterus lining move out of the way of the 'invading' embryonic cells.

Professor Mardon said: 'We have shown that two proteins, called Rac1 and RhoA, control the invasion. The first stimulates cells in the womb lining to move and allow the embryo to invade and implant properly while the second inhibits this. We believe this controlled balance of the two proteins is critical for successful implantation of the embryo. If the balance of Rho GTPases is altered, the cells of the womb lining don't migrate and the embryo doesn't implant'.

The findings bring new hope to people with infertility issues. The new information will help the understanding of how this process works, and therefore aid 'the development of drugs to help embryos implant properly', said Prof Mardon.

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One of the trickiest jobs facing a clinical embryologist is the visual assessment of human embryos. Embryo selection prior to embryo transfer clearly has an enormous impact on the success of the treatment and embryo selection for cryopreservation is equally important to the future success of frozen embryo transfers. Despite the evident importance of this procedure embryo quality is largely guesswork, embryo grading is often inconsistent (even within a given clinic) and there is little or no quality assurance.

There have been some excellent attempts recently to develop non-invasive techniques to assess the quality of human embryos. These include assessment of pronuclear morphology and alignment and the measurement of nutrient uptake by embryos growing in microdrops. Many clinics now utilise the pronuclear morphology technique which is claimed to significantly increase pregnancy rate. I am yet to be convinced about this but it is certainly a step in the right direction. More promising seems to be the nutrient uptake work which at long last can begin to quantify embryo quality. The only problem with the uptake work is at present the procedure requires quite significant analytical expertise making the procedure difficult and expensive to introduce into routine clinical practice. This kind of work is nevertheless essential if we are to move forward in our understanding of embryo quality.

Embryo grading is another cause for concern. First of all there is the inconsistency of the grading scales used. Some clinics use numbers, some use letters and some even ?enhance? their grades with + or - . The result is a confused and often meaningless system with no continuity in the profession. The assessment of the extent of fragmentation is also very erratic with some embryologists over or under-estimating the extent of fragmentation. Some laboratories examine their embryos under high magnification and light intensity, others under the dissecting microscope only. In a scientific procedure, variations such as these will make the overall picture meaningless. A similar situation existed in immunology before the introduction of the CD antigen system, no one really knew which cell was which! It is clearly not practical to attempt to assess surface antigens on human embryos but we should at least attempt to design an international grading scale which means the same thing in each and every laboratory around the World. I would propose either a numerical or percentage scale with no + or ? variables. This will require a lot of hard work and training but if it can be achieved we will at last be able to compare data from different laboratories in a meaningful and scientific way. It is also interesting that many patients focus a lot of attention on the grades of their embryos. If we are going to serve our patients to the best of our abilities it is essential that we have a consistent and meaningful embryo grading system.

Finally it is of some concern that very few laboratories take part in quality assurance (Q.A.) schemes in embryology. Many clinics undertake Q.A. in andrology but very few appear to be involved in any sort of embryological QA. This means that individual embryologists or even complete large clinics may be working inconsistently. There is now an excellent on-line QA website which provides real time QA for each individual embryologist and comparisons with other clinics in the scheme. Such services could dramatically improve the quality of embryology, improve the service we offer to our patients and at last allow clinical embryologists to compare their data in a truly meaningful and scientific way.
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Emotionally and Physically Preparing for IVF

Your Emotional Preparedness:

There are many complex emotions that you will be encountering as you are anticipating your IVF cycle. If you are using donor eggs, donor sperm, or a surrogate, the emotions that you have will be even more splintered, as you also must consider the weight of genetics in this equation.

Before you proceed with IVF, you will want to speak with a psychotherapist that is trained in infertility. There are some very natural concerns that you will have and feelings that you will be confronted with. Your therapist can give you gentle guidance as you navigate through these new features, in your pursuit of pregnancy.

Some emotions that you can expect to have are:

• Loss or mourning over lost pregnancies, cycles that failed before and possibly even the loss of your ovaries. If you are having IVF, there is a strong likelihood that you have encountered a great loss to get there. It is natural that you will feel grief, as you are anticipating your cycle.

• Fear of not being a "real" parent is another very normal emotion that you may experience as you are preparing for your IVF cycle. Your child will not be any less than your child, and you will be no less their mother. You'll still be the one they turn to, when they fall off their first bike. You're just like any other pregnant woman, only you will have fought harder to get there.

• Being afraid that it won't work after all of the time, money and emotions that you've invested in the procedure is natural. The truth is, it may not work and you need to understand that prior to moving forward. Your counselor will help guide you in this matter.
• You may feel scared that you will let down your donor, if they are a friend or family member. You may feel as though you are personally disappointing someone, who went through an enormous quest to help you, if the cycle fails. It's important to know that you have no control over the outcome and they have been counseled in the possibilities of a failed cycle, prior to the retrieval.
  
  Don't be concerned if you start to question the decision to utilize IVF, donor eggs or sperm. When you are faced with a huge decision it's not unusual to falter now and then. This is a big step and it takes some getting used to.
  
  Finally, after all of these concerns and emotions, you may also feel something you haven't felt in a long time; you may feel hope. Donor eggs may not be a certainty and IVF may not be 100% successful; but you can permit yourself to enjoy a dash of hope, in your anticipation.

Your Physical Preparedness:

As your cycle approaches, there are a few things that you can do to prepare yourself. It goes without say that you should limit your caffeine intake, eliminate smoking, and drinking alcohol. Light to moderate exercise is beneficial to both your emotional and physical well-being, which ultimately is good for your reproductive health. Consult your doctor before you start a new fitness plan and it's important to remember that a rigorous routine should be omitted.

Remember that you're not just preparing for IVF, you're preparing for a pregnancy. It's recommended that women who are attempting pregnancy begin taking folic acid, prior to conception and you may want to include prenatal vitamins, in your daily routine. This will create the best environment for your fetus.

A diet that is high in leafy greens, fruits, vegetables, calcium as well as protein, is optimal for your pregnancy. You may want to talk to your doctor or nutritionist about foods that would be most beneficial to you, during your pregnancy, or even to help you build a pre-pregnancy meal plan, to prepare you for conception. Do not begin any restrictive diets, such as low-calorie or low-carbohydrate. Though it's not ideal to be overweight in pregnancy, this is not the time to start a weight loss plan.

The month prior to your transfer your doctor may ask you to participate in a mock cycle, to show that you and your donor respond properly to your respective hormone therapies. The endometrium used to be accessed via biopsy, but this technology did not prove itself reliable. Today you will most likely have an ultrasound about 10-12 days into your estrogen-enhanced cycle to measure your endometrius.

You may need to start birth control pills to regulate your cycle so that you can synchronize with your donor's. You may also be asked to use a gonadotropin releasing hormone (GnRH) antagonist, which inhibits the luteinizing hormone (LH) surge; so that your own cycle does not get canceled and the uterine lining is ready for the implanted embryo.

You may still feel unprepared when it is time to begin your cycle, but that is completely normal as well. You may never feel completely prepared. The important part is that you have made your decision and are headed toward the next step in your pursuit to have your child.

For More Information Visit: http://www.conceivableworld.com

 

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New Zealand's Advisory Committee on Assisted Reproductive Technology (ACART) has announced two proposals to legalise currently prohibited fertility practices. It has published two consultation documents proposing first, that women should be allowed to use frozen eggs that had been extracted and stored prior to chemotherapy treatment for cancer and, secondly, that existing regulations on the creation of 'saviour siblings' should be expanded, to include not just siblings but also other close members of the family and also to extend beyond purely inherited conditions to others that might be amenable to treatment using donor tissues.

ACART, an independent governmental advisory group, indicated in its first discussion document that the time had arrived to legalise the usage of frozen eggs. Although freezing of ova has been permitted in New Zealand since 2005, it is only more recently that robust evidence has existed to demonstrate the safety of the technique, prompting ACART to propose steps to legalise its usage.

Additional advantages mentioned in the document include that egg freezing avoids certain religious difficulties surrounding the freezing of embryos and that, whereas those who can source suitable sperm at the time of freezing are currently able to store frozen embryos for use, others are discriminated against by only being able to store eggs which they are, at the present time, unable to use.

On the matter of 'saviour siblings', in the second document, ACART suggested that there is insufficient justification for restricting 'saviour' tissues to siblings alone. It further argued that as the existing rationale that the donor sibling benefits from PGD by being genetic disease free is spurious, the practice need not be restricted to inherited conditions. Objections based on the commodification of the child and of the potential psychological damage consequent upon this commodification were rejected, as was the possibility of allowing the deliberate selection of an embryo which contained a genetic disorder, on the basis that there was a morally relevant difference in purpose between selecting an embryo with a genetic disorder and selecting one without.

Early resistance to the proposals has been shown by 'Family First NZ' who criticised ACART for endorsing the production of children as 'spare parts factories for relatives' and for, in theory, making it possible for a women to give consent for her frozen eggs to be used by a surrogate mother after her own death, creating 'a baby beyond the grave' which would never know its genetic mother.

The New Zealand Ministry of Health, however, backed the proposals, saying that the proposed changes could potentially help infertile cancer sufferers to have babies and also help treat very rare diseases. ACART's consultations on the proposal to legalise frozen egg usage and on the draft guidelines for extended use of PGD both remain open until 5 September.

 

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Data presented at the annual conference of the European Society of Human Reproduction and Embryology (ESHRE) has shown that more than three million babies have been born using IVF and other assisted reproductive technologies (ART) since the world's first IVF baby was born in 1978.

Data were first collected on the number of ART births worldwide in 1989 - and in that year only about 30,000 babies were born following ART. Two years ago, that figure had risen to 200,000 babies in a year. This year's data, from the International Committee for Monitoring Assisted Reproductive Technologies (ICMART), includes reports from 52 countries, and covers almost 600,000 IVF cycles and 122,000 newborn babies. 'The ICMART report covers two-thirds of the world's ART activity, so the total number of ART cycles in the world can be estimated at one million a year, and the number of babies produced at around 200,000 a year', said ICMART member Dr Jacques de Mouzon. As yet, the data does not include information on most African nations or many Asian countries.

The data also showed that huge variation exists in the availability of ART treatments - and their success rates - across the countries represented. Availability was found to be at its highest in Israel, which gave 3,260 cycles per million population, followed by Denmark, at 2,031 cycles per million. Denmark also had the greatest proportion of ART births out of all births, at 3.9 per cent. In Latin American countries there tended to be fewer than 100 cycles per million population provided, and ART births represent less than 0.1 per cent of all births.

In terms of where most ART takes place, the greatest number of cycles was recorded in Europe, where 56 per cent of all ART treatment cycles were initiated. Almost half of all the cycles reported in the world took place in just four countries - the USA, Germany, France and the UK. The world data also showed a general move toward single embryo transfer (SET), leading to a decline in multiple pregnancies and births.

ART figures for Europe were also presented to the conference. Professor Anders Nyboe Andersen, of the Rigshospitalet at Copenhagen University in Denmark and co-ordinator of the European IVF monitoring programme, spoke of data collected for 2003 on ARTs in 28 countries - four more countries than provided data for 2002. In 2003, there were 357,884 cycles provided across Europe, a 10 per cent increase on 2002. However, the statistics also showed that people in the UK are among the least likely in Europe to get the treatment they need - the UK came twelfth out of the 15 European countries that provided data for 2003, with only Macedonia, Croatia and Austria performing fewer cycles of fertility treatment per head of population.

Last year it was reported that there was a decline in the number of twin births following the use of ARTs, and a fall from 3.6 per cent to 1.3 per cent of triplet births - this is a trend that appears to be continuing, with SET being favoured in many countries. 'The Nordic countries and Belgium lead the way in this', said Andersen. By way of illustration, he added that 'in Sweden today there is 70 per cent elective SET, which has resulted in a decline in twin birth rates to five per cent, which is sensational'.

Professor Karl Nygren, chair of ESHRE's European IVF Monitoring Programme and the ICMART Committee, said that the two reports show an increased use of IVF and other ARTs around the world, despite there still being inequalities in provision. He added that 'ART is increasingly being used in India and China and we look forward to them contributing data in the future'.

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Embryo freezing is generally seen as a routine part of IVF and ICSI treatment. It offers many benefits, not least the fact that embryos left over from a fresh cycle can be stored for future use. This has implications for the patient's health and wellbeing - it avoids unnecessary gonadotrophin stimulation and repeated egg collections - and is less costly in the long run for the patient or NHS. Embryo transfer (ET) can be delayed when there is a risk of ovarian hyperstimulation syndrome or the patient is unwell. Embryo storage is also the most reliable option for a woman with a partner who wishes to have children after sterilising cancer therapy. Facilitated by a reliable freezing programme, a move towards single ET would result in fewer multiple pregnancies.

Patients often ask about the risks associated with embryo freezing and the frequency of their questions increases after media reports which suggest that freezing may be unsafe. But how well founded are such reports: is freezing hazardous or are alarming reports just hype? The question 'Is embryo freezing safe?' begs several others, including 'What are the risks for the embryos?'; 'Will they still be able to develop normally?'; 'What are the risks for the woman?' But the question probably of most concern to patients is 'Are there risks for children conceived from frozen embryos?' or, put another way, 'Will they be normal?'

Embryos may be damaged by the processes of freezing and thawing or by technical or human error. Measures actively introduced by clinics, in conjunction with the HFEA's new adverse incident reporting scheme, minimise these latter risks. There is also a remote possibility of contamination with pathogens during storage in liquid nitrogen, although to the best of my knowledge this has never occurred during routine storage.

What are the risks from freezing and thawing per se? These can be measured in terms of embryo survival, viability after transfer, and whether freezing modifies gene expression or embryo phenotype. Cells of any kind, including embryos, endure a variety of insults during freezing. They are placed in solutions of potentially toxic cryoprotectants, before cooling to -196 degrees Celsius. Even under the strictly controlled conditions required for survival, the cells must withstand potentially lethal ice formation, transmembrane water movement and extreme changes in external electrolyte concentrations, temperature and pH. Thawing reverses these processes. After enduring such unphysiological conditions it is perhaps not surprising that some embryos fail to survive freezing. Survival varies from clinic to clinic: freezing is hazardous for some embryos (20-40 per cent don't survive) and some 'survivors' have one or more blastomeres damaged, but as many as 60 per cent of embryos may be completely intact after thawing.

Are these 'surviving' embryos viable? Can they implant and develop normally? HFEA data show that frozen ET's are significantly less likely to result in live births than fresh transfers. However, such data require further scrutiny since frozen ETs are rarely strictly comparable with fresh transfers. This is because the 'best' embryos are selected for fresh cycles and because embryos that have sustained some damage during freezing or thawing are often transferred. Additionally, more recipients of frozen embryos than fresh have previously had a failed transfer.

Several recent studies suggest that undamaged frozen-thawed embryos are as viable as their unfrozen counterparts. Damaged embryos can develop normally but their potential is reduced in vitro as well as in vivo. In one study, the rates of implantation and clinical pregnancy were significantly higher when intact embryos only were transferred, compared with transfers in which at least one embryo was damaged. In cycles where all embryos transferred were damaged, there was a significantly lower live birth rate and significantly fewer babies born per embryo transferred, compared with transfers of intact embryos. Comparing matched transfers of intact fresh and frozen embryos, the implantation rates were similar. In summary, some embryos simply don't survive freezing, others suffer damage that reduces their capacity for implantation, but about 50 per cent of embryos survive with all blastomeres intact and appear to have the same implantation potential as their unfrozen counterparts.

Do we have evidence that embryos are subtly changed by freezing? Reports of modified gene expression in frozen embryos raised concern. One study assessed levels of messenger RNA (mRNA) in the tuberous sclerosis gene, mutations of which result in the growth of benign tumours in various organs that may have severe consequences. mRNA levels were significantly lower in frozen-thawed than in fresh day two embryos. In embryos frozen on day three, the level of mRNA was similar to that in fresh embryos and, in embryos frozen on day two and then thawed and cultured for 24 hours to day three, the levels of mRNA were restored to normal day three levels.

What is the significance of these observations? They tell us that gene expression may be modified by freezing but we don't know whether there is any functional significance of this change. Is there a corresponding change in the protein encoded by the gene? Any change in cellular function? Or any long term effects? Animal studies suggest embryos are able to withstand quite extreme changes in gene expression. Other studies comparing the phenotype of frozen and thawed mouse embryos, e.g. distribution of cell surface antigens, have shown that although changes may be seen after freezing, normal developmental patterns are usually restored later. Whilst we can't ignore reports of modified gene expression, we need more extensive studies to allow considered judgement of their significance.

What of the risk to mothers? Generally, the incidence of risk to mothers after frozen ET is reported as similar to that after fresh transfer. Last year patients were alarmed by an American report showing a 17-fold increase in the risk of ectopic pregnancy after frozen ET in a sample of only 19 pregnancies. Data from clinics in Manchester and Aberdeen are reassuring, showing similar incidence of ectopics occurring after fresh and frozen ET in large groups of patients.

Patients are most concerned that freezing should carry no risk to any children conceived. Encouragingly, the incidence of pre-term birth, low birth weight and perinatal mortality is similar to that seen after fresh ET. The follow-up of birth defects, development and long-term health is more problematic. Several groups have reported on the occurrence of birth defects. All suggest that the incidence in frozen embryo conceptions is no different from that in fresh IVF or ICSI, but the evidence is inconclusive. Sample size is the major problem - when an anomaly has a low incidence in the general population then very large samples are required to show any significant increase after an intervention. We have simply not had follow-up studies of a sufficient number of children to be certain that there are no increased risks after freezing.

A few small studies have followed-up the development of children conceived from frozen embryos. They show no evidence of variation in several categories including growth, psychomotor development, health, intelligence or scholastic achievement. However, the authors point out that the samples are small and there are methodological difficulties: the question of how far follow-up can intrude into the lives of children is a major issue for researchers.

There is no evidence from human studies for the long-term safety of embryo freezing because the oldest children conceived from frozen embryos are barely 20 years old. Animal studies are generally encouraging: frozen embryos are used widely in commercial cattle breeding without evidence of increased abnormalities. In mice, no increase in mutation rate was seen after frozen embryo transfer and the offspring developed and reproduced normally. One long-term study did cause some alarm: while no major anomalies were found in mice conceived from frozen embryos, some more subtle changes were observed: e.g. in adult male body weight in one of two strains, but not in females; in some aspects of early development e.g. late eruption of incisor teeth but only in the strain of mice that developed more slowly; in learning, including avoidance conditioning; and in the size and shape of some bones in the mandible. These findings are difficult to interpret and continue to engage scientists in debate, particularly as most parameters of development showed no variation with freezing. Importantly, the study has never been repeated - perhaps it should be!

In conclusion, many embryos that would otherwise be discarded soon after fertilisation, retain full viability after freezing, but some embryos don't survive and others have their developmental potential reduced. Otherwise there is no sound evidence that embryo freezing is hazardous. However, reports of modified gene expression in thawed embryos and minor phenotypic changes in animals conceived from frozen embryos cannot be ignored, and well designed experiments to pursue these possibilities are needed. Meanwhile, the benefits of embryo freezing appear to outweigh any potential risks. My fear is that if patients become alarmed by unfounded reports of the risks of freezing based on inadequate evidence, they will be deterred from accepting the transfer of just one embryo at a time which, by reducing the incidence of multiple births, is the best route to minimising the risks to mothers and children conceived by ET, and increasing the number of healthy babies born.

Maureen Wood is a research embryologist in the Department of Obstetrics and Gynaecology, Aberdeen.
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The chronically thin endometrium has remained an unresolved clinical problem since the inception of IVF. It has been known for a very long time that best pregnancy rates are achieved when the endometrium reaches a thickness of 9mm on ultrasound measurement, but that 7mm really represents the minimum thickness for reasonable pregnancy chances.

 

There are, of course, other parameters that count as well: For example, how the endometrium looks also matters. Ideally, it should present not only with appropriate thickness but also nicely layered. Innumerable studies have been reported in the literature, and almost as many suggestions have been made on what can or should be done in case the endometrium does not meet expectations.

 

Here is the scenario as it presents itself over and over again in association with IVF at the Center for Human Reproduction (CHR): With the IVF cycle coming closer and closer to the day embryos have to be transferred, the patient's endometrium still does not meet minimum criteria for transfer.

 

What to do?

 

Most IVF centers follow standard treatment algorithms that sometimes work: We usually start by giving or increasing estrogen support; if that does not work, a vasodilator is added. At CHR, a clinic for IVF in New York, we usually utilize a beta-blocker, called Atenolol or, believe it or not, Viagra, as many colleagues do. When nothing works, however, the choices become stark: either the whole cycle is simply cancelled or the patients still go to egg retrieval, embryos are created, but not transferred into the uterus. That means patients have to go through an all-freeze cycle, where all embryos are cryopreserved. This is because it would be a total waste of good embryos to transfer embryos into an inadequate endometrium.

 

This year, CHR had a Chinese patient from out of state in a similar situation. Her situation was even worse, in fact, because in addition to very thin endometrium, she also had a fluid accumulation in her endometrial cavity. Seeing the dismal pregnancy chance with the condition of her endometrium, Dr. Norbert Gleicher, CHR's Medical Director, suggested she cancel the embryo transfer and freeze all embryos. However, she opted to go through embryo transfer, due to the time constraints involved in her long-distance care. She asked Dr. Gleicher if there was anything "experimental" that could be done.

 

Dr. Gleicher offered her aspiration of the fluid, and decided to treat her off label (with appropriate informed consent) with an FDA-approved drug with well known systemic effects, which he thought, theoretically, may have a chance to beneficially affect the endometrium.

 

Two days later, the patient demonstrated a perfect endometrium! She had egg retrieval, had a routine embryo transfer (after preimplantation genetic diagnosis, PGD) and is now pregnant with twins.

 

After two more patients (and one other at a nearby center) with dramatically improved endometrium after this experimental treatment, CHR decided to develop two prospectively randomized clinical trials to prove this hypothesis. If proven, being able to go from utterly insufficient endometrium to perfect endometrium with this medication will have a tremendous impact on IVF outcomes. Dr. David Barad, Clinical Director of IVF at CHR, is hopeful: "Preliminary results so far have been remarkable. This promises to be another clinical "hit" after DHEA treatment, produced by CHR research."

 

The Center For Human Reproduction in New York, NY specializes in infertility treatment, egg donation and research related to fertility. The CHR provides a low cost of IVF and discounted IVF costs for families with need. Their website is www.centerforhumanreprod.com

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Viagra, the 'wonder-drug' promoted for its ability to relieve impotence in men, may have some unwanted side-effects. Research presented today in Cheltenham, UK, at the annual meeting of the British Fertility Society, suggests that men who are taking Viagra when trying to start a family may actually be decreasing their ability to father a child. However, Viagra manufacturers Pfizer deny that the drug causes fertility problems.

Viagra was designed to enable an increase of blood flow to the penis to overcome impotence problems. However, since its release it has increasingly been used 'recreationally', and is also used by fertility clinics in order to aid patients' semen production. Viagra is what is known as a 'phosphodiesterase inhibitor', a type of chemical known to affect sperm function, so the study looked at what effect the drug has on sperm. The researchers discovered that using Viagra speeds up chemical changes within sperm, rendering them infertile by the time they reach an egg. This chemical change, known as the acrosome reaction, normally only occurs when a sperm reaches an egg, and is when sperm release enzymes that break down the outer layer of the egg allowing the sperm head to penetrate it more easily. However, if the acrosome reaction occurs too early, the sperm become ineffective and unable to enter the egg, as they have no digestive enzymes left.

Scientists from the School of Medicine, Obstetrics and Gynaecology at Queen's University, Belfast, took 45 semen samples and split them into two groups. Half of the samples were treated with Viagra, while the other half was used as control. The research team found that while Viagra increased sperm motility, up to 79 per cent more sperm in the Viagra-treated samples had clearly undergone premature acrosome reactions. These findings lead the researchers to say they had 'significant concerns for Viagra use in assisted reproduction'. They added that the findings echo previous studies in mice that showed that the presence of Viagra meant that fewer eggs would be fertilised and fewer resulting embryos developed normally.

Dr Sheena Lewis, a member of the team, said that their 'message is that caution should be taken when using recreational drugs if you are hoping to start a family'. But a representative of the European Society for Sexual Medicine, Dr John Dean, said it was important that the study wasn't reported in an alarmist fashion, adding that sperm is highly sensitive in laboratory conditions. 'Childless couples - and the general population - should be aware that in the five years that Viagra has been around no overall detrimental effect on fertility has been observed', he said.

However, Pfizer says that there has been no evidence of Viagra affecting fertility following its use by 23 million men over six years. 'It's one study and it was in a test tube basically, not in real people', said spokesman David Watts.
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Scientists looking at pregnancy rates in women who have previously had IVF treatment say that lifestyle factors play a large part in whether a woman will go on to achieve a natural pregnancy or not. Speaking at the annual meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Barcelona, Dr Ame Lintsen, from Radboud University in Nijmegen, the Netherlands, said that maintaining a healthy lifestyle after IVF treatment maximized the chances of a subsequent natural pregnancy.

The research team found all women who had undergone IVF treatment in the Netherlands between 1983 and 1995 (in the OMEA project) and asked them to answer a questionnaire on their lifestyle and reproductive history; 8669 women responded to the survey. The scientists were looking to find out the rate of the first natural conception after cessation of IVF treatment according to a woman's maternal age, pregnancy history, duration and cause of subfertility, the number of IVF cycles previously attempted, Body Mass Index, smoking and alcohol and caffeine intake. They found distinct patterns in the rate of subsequent pregnancies and the lifestyle of the women concerned.

The researchers found that 1349 of the women (16 per cent) had conceived naturally after stopping IVF treatment (in a maximum timeframe of 13 years). Forty-five per cent of these had conceived within 6 months after their last IVF cycle. However, they also discovered that smoking more than one cigarette a day made a woman 44 per cent less likely than average to conceive naturally; drinking more than four cups of coffee (or other caffeine drinks) a day made a woman 26 per cent less likely to do so, consuming alcohol on more than three occasions per week made her 26 per cent less likely to conceive and being significantly overweight reduced the chances of a subsequent natural conception by 29 per cent.

Similarly, increasing maternal age and having had more than four previous IVF attempts also appeared to reduce the chances of a subsequent natural conception, said the researchers, as did the original cause of a woman's subfertility. If this was due to uterine, cervical or ovarian problems or subfertility in their male partners, the women had a significantly greater chance of achieving a successful natural pregnancy after stopping IVF. However, if the woman's subfertility was 'unexplained' or the problem was with tubal pathology, her chances of a natural pregnancy greatly decreased.

Commenting on the findings, Dr Lintsen said that the results showed that 'women can influence their natural fecundity with healthy lifestyle choices'. Professor Bill Ledger, Professor of Obstetrics and Gynecology at Sheffield University in the UK, said that 'lots of women drink 20 cups of coffee a day and get pregnant falling off a log'. But, he added, 'it doesn't have a massive effect, but if you are already infertile, it could just tip you over the edge. You don't have to stop, just drink less'.

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