Firstly, I want to say thank you to all the people who commented on my previous post regarding the extra treatments my IVF clinic offers. There was some confusion between Google+ and me; unfortunately Google+ responded to my attempts to understand it by removing most of the comments from my blog. So if you need to know where your comment went, you'll have to ask Google because I'm not exactly sure. On the upside, I think I have managed to stop restricting my comments to Google+ only. Thankfully, all your lovely comments are still stored in my account but I have no idea how to link them back to my blog, sorry. I did read them all and they were very helpful; I appreciate that people made the effort to respond to my request for advice.
Okay, back to my normal blogging self:
The days following my fertility specialist announcing that I could improve my chances of achieving pregnancy by intently studying the embryos and/or by gluing them to my uterus, I was a little confused. I asked for your advice and you didn't disappoint, thank you. I was advised to find out more about the procedures before I committed, so that's exactly what I did.
Currently, there are two companies that are offering systems in the UK that analyse the earliest characteristics of developing embryos: Embryoscope and Early embryo viability assessment (Eeva); both technologies monitor early cell division events using time-lapse imaging.
Time-lapse imaging of embryos was first developed in the mid-1990s. Initially it was used as a tool to study embryo movement and development. In those early days, scientists hooked up videocassette recorders to culture incubators and captured the exact sequence of events after sperm met egg. As the research advanced, scientists investigated how early cell division characteristics, captured by time-lapse imaging, could predict the embryos destiny. After beavering away in their laboratories for many days, possibly months, the scientists made a breakthrough discovery: the timing of the first developmental events after fertilisation correlated well with blastocyst formation. Embryos whose fate it was to develop into beautiful blastocysts had a very defined schedule for each of the critical mitosis events. Building on these early observations, investigators have developed software systems, which incorporate fancy mathematical algorithms, that accurately predict which embryos will arrest and which will survive. Amazing, right?
Not only it is now possible to predict blastocyst formation but studies have shown that, using these advancements, embryos likely to yield pregnancies can be identified prior to transfer. Remarkably, transferring embryos that were rated as high, using an imaging system, led to a 66% pregnancy rate. In contrast, when embryos were transferred that were rated low only 8% of women became pregnant.
For me, the most fascinating element of these new technologies is the apparent correlation between embryos that are predicted to be poor and the presence of chromosomal abnormalities. Two studies (here and here) have demonstrated the cell cycle and fragmentation patterns, identified using time-lapse imaging, are diagnostic of faulty chromosomes.
The results from these studies sound wonderful and they are certainly extremely promising; it would be difficult to deny that this really is astonishing science time. However, no one has published any studies or clinical trials which demonstrate these imaging systems are better than an embryologist at predicting which embryos will make it to blast; my clinic is super confident that their embryologists are excellent at choosing embryos for transfer. The truth is that there have been absolutely no clinical trials published assessing whether these technologies increase pregnancy rates when compared with current methods.
A review of the use of time-lapse imaging for embryo assessment, published in March this year, concluded "before time-lapse markers are to be implemented in the clinic, additional clinical validation of their safety and efficacy and their measurement/quantification technologies is urgently required".
The FDA also seems to be under the impression that treatments should demonstrate efficacy prior to routine implementation and, not surprisingly, has decided to wait to evaluate clinical trial data before licensing the technology in the United States.
So why are these systems already in use in European clinics? I asked my fertility specialist that very question; he argued that couples should have access to all opportunities to increase their chances of success. I am unconvinced that, usually pretty desperate, couples should be expected to pay for unproven treatments. Sure, if the clinic wants to boost their success rates and offer it to their patients for free then I'm all for it. Now that I am there, I know that, even though the science is shaky, I want to do everything, even irrational things, to increase my chance of pregnancy.
I think Dr Sue Avery, from the British Fertility Society, sums it up perfectly (play the clip to find out what she says):
I guess I am struggling with the ethics of it all. I am also worried that these scenarios will become more common in the British health system as an increasing number of services are privatised. Good ethical policies in medicine and science are so important and I fear that sometimes the desire for money triumphs over reason. This weekend an argument over the patent granted for this technology has erupted in a British newspaper. The United States Patent Office has recently granted a patent whose claims include the monitoring of embryo division. How can that be? Is it ever okay to patent the measurement of naturally occurring biological processes? I am extremely keen on the idea that innovation and invention is protected by patents, and I would applaud a patent that covered the use of the mathematical algorithms or the imaging software, but the processes that underlie life itself? Should they really be able to be covered by patents?
I don't know the answer. Maybe you have some ideas and opinions about what is and isn't acceptable? If so, do share.
My doctor also suggested we try EmbryoGlue and I have done some research on that too. However, this post is getting quite long now so I am signing off and will cover EmbryoGlue in a separate post.
Side note: I did read the patent and I am not sure that the claims are as extreme as the newspaper article would have us believe.
As I was driving home from work on New Year's Eve in 2007 I smoked my last cigarette; I remember it well. The smell and taste of those last few drags can still easily be recalled from my memory. My decision to quit was fuelled by my concern that an increasing proportion of my pay check was flowing into the pockets of the tobacco giants and, of course, the fear of cancer. What never crossed my young mind, even as the last stump burned to the end, was the possibility that my favourite bad habit was damaging my fertility. I am not saying that my choice to spend my youth puffing away has left me infertile, I don't know whether anyone could tell me if that is true. However, a review of recent scientific literature performed in 2008, and another published in 2011, both concluded that cigarette smoking compromises every aspect of the reproductive system. Whilst the results are clearly not wonderful news for a smoking lady hoping to make a baby au naturel, they don't really tell you whether smoking will ruin your eye-wateringly expensive and hope-laden IVF cycle.
Yes, you guessed it, we are here again, taking another step forward in the research journey that is Operation Big Belly. And, as you may already know, we have so far investigated the possibility that food, alcohol and caffeine could reduce your chances of an IVF baby. Now that we are getting started I should remind you that the ground rules can be found here.
So, even though the clues seem to be screaming at us "Of course smoking is bloody terrible, you fools", let's ask the question anyway, we might be pleasantly surprised: will smoking screw up your chances of a successful IVF cycle? One health authority in Scotland is so sure that cigarettes are completely atrocious that it has banned couples who smoke from having IVF treatment on the NHS (see here). Now, what the Scottish choose to do might be extremely fascinating (if I were cynical I would say their decision was swayed a teeny weeny bit by the desire to spend less of their health budget on the not-so-election-busting infertile couples), but what can science tell us about smoking and IVF?
This time at least there is a respectable body of data to get yourself excited about. As far back in time as 1996, there was a healthy level of research interest in IVF and smoking. The first review of published studies that investigated the role of smoking in IVF success, found seven papers worth examining and revealed that, although there was variability between the studies, the conception rate was lower and the miscarriage rate higher in women who smoked.
A year later, a research group from Austria published the results of a meta-analysis that investigated the effects of smoking on IVF results. The data review comprised of eight studies, including the authors own, and analysed the outcomes of 2314 IVF treatments. The studies reviewed yielded conflicting results and with some indicating that smoking didn't impact the IVF success rate. However, when all the data were taken together, the meta-analysis revealed that non-smokers were significantly more likely to get pregnant during their first cycle than smokers, and that smokers require twice as many attempts to achieve pregnancy.
If you step forward just a few years more, this time to 2005, you will reach a pretty thorough review conducted by Hilary Klonoff-Cohen (we met her before here). This lovely lady has gone to the trouble of reviewing 22 articles, including the studies mentioned above, and the data, as with the previous reviews, was somewhat conflicting. She did not conduct a meta-analysis, so it is not possible to say if the studies which demonstrated no effect on IVF success rates for smokers would have remained significant when the body of evidence was examined as a whole. However, she did conclude that "despite the variations between the studies, there was compelling evidence that smoking had a negative influence on IVF outcome".
If you manage to pick yourself up from those revelations and roll forward a few years, you will find that you have landed at the feet of a second meta-analysis conducted in 2009. On this occasion, a collaboration from the UK (yay!) analysed data from 21 studies to investigate the impact of smoking on IVF outcomes. The investigators found that smokers had a lower chance of pregnancy, a higher risk of miscarriage and ectopic pregnancy, and a lower live birth rate. Non-smokers were found to be twice as likely to get pregnant and have a baby at the end of it all. Not only that but the analysis went deeper, smoking was shown to be bad for every step of the IVF process; smokers required greater stimulation, had fewer eggs, lower fertilisation rates, and a higher chance of implantation failure. The authors concluded their paper by stating "There is particularly overwhelming evidence for a decreased clinical pregnancy rate amongst smokers, in addition to the strong implication of a negative effect on live birth rate, miscarriage rate, ectopic pregnancy rate and fertilisation rate". Phew! They weren't messing about, were they?
Well, if that wasn't quite enough to put you off your cigarettes for good then maybe the final study will convince you. In 2011, a research group based in Israel discovered that, when women smoked, even if the doctor put great quality embryos back into the uterus, the pregnancy rate was lower for smokers than non-smokers. Oh dear, even an excellent embryo can't help you!
In the interest of fairness, I should point out that, since 2005, there had been one, yup just one, study that found no difference between smoking and non-smoking groups of women undergoing IVF treatment.
So there you have it. If you are planning to do IVF and you enjoy a smoke, you might want to think about enjoying it a little less often or, preferably, not indulging at all.
Writing this post has made me a little sad; I wish I could go back and plead with my younger self not to pick up that first cigarette. And, yes, there was an adolescent boy, who I was attempting to impress, connected to the decision to take my first puff. But I doubt that young lady would have listened to a word of it. Babies seemed so far away and she comes from one of the most fertile families on the planet: three brothers, three sisters and thirteen nieces and nephews. I know you shouldn't regret the past, and on many occasions smoking gave me real joy, but, as the great Cher once said, if I could turn back time.......
Do you know what helps bees to remember which plants they would like to visit again? Yes, that's right, the answer is caffeine. According to scientists, who are definitely some of my favourite people, bees like to return to flowers which produce caffeine containing nectar. If you think that's an interesting fact, you can read all about it here, I suspect you are going to enjoy this blog post. Although caffeine is a relatively simple molecule (see it's structure below), it does have some pretty impressive properties and there is considerable debate about the impact of caffeine on pregnancy. The World Health Organisation recommends that pregnant women not exceed a daily caffeine intake of 200-300 mg. However, in constrast, a recent Cochrane Review concluded that there was insufficient evidence to determine whether restricting caffeine consumption improves pregnancy outcomes (see here). But I am sure you're not so interested in bees or pregnant ladies; what you really want to know is: will caffeine make your IVF cycle less likely to succeed? Well, you're in good company because so do I.
Let's go together now and take the third step on our research journey or, as I have affectionately called it, Operation Big Belly. As you may remember, we looked at the evidence that diet can impact an IVF cycle here, whether a drink or two will reduce your chances of having an IVF baby here, and, as usual, just a reminder that the ground rules can be found here.
So then, caffeine and IVF. Well, once again, I have spent a considerable amount of time searching on-line databases to provide you with the all the latest information. And, as usual, I have found very little data on the impact of lifestyle on IVF success. This time I was looking specifically for caffeine data and, frustratingly, I haven't found a larger data set than I dug up for the effect of diet or alcohol on IVF cycles. In fact, I have managed to only scrape together two studies. Still, two studies are better that none and it does give us something to get our teeth into.
The earliest study, led by Hillary Klonoff-Cohen, was conducted between 1993 and 1998 in Southern California. During the clinical trial, 221 couples, undergoing IVF or gamete intra-fallopian transfer (GIFT), were recruited to determine if there was a link between caffeine consumption and IVF outcome. The authors reported that, for women consuming caffeine from coffee, tea, soft drinks, cocoa drinks, or chocolate, the risk of miscarriage, not becoming pregnant and not achieving a live birth was significantly increased. There was, however, much better news for the boys: male caffeine consumption did not negatively affect sperm, embryo transfer rates, the chance of getting pregnant or pregnancy outcomes. But, and this is quite a big but, men's caffeine intake did correlate well with an increase in the number of multiples. So if you don't want to have twins......
You might not like the findings from that first study, and who could blame you, neither do I. But, let's remember, it is a very small study and only a lone study. Perhaps more recent data will give us better news.
The second study we are going to take a look at was conducted in the slightly more exotic location of Saudi Arabia. This time 619 women took part and all of them went through their first IVF cycle between 2002 and 2003. Unlike the majority of the studies we have examined, this study has something special; the lifestyle results are not only based on questionnaires completed by the patients but, in addition, the actual concentration of caffeine was measured in blood and, more excitingly, in follicular fluid. The study authors concluded that they could find no association between coffee and tea consumption, or the level of caffeine in serum, and pregnancy rates (yay, some good news at last). However, they did find a negative correlation, albeit a weak one, between tea drinking and the number of good embryos - the more tea you drink the fewer the good embryos. And there was also a link between high caffeine consumption and miscarriage. Sadly, the study didn't continue to assess the women for the next nine months, so we can't tell if caffeine would have impacted the live birth rate in those women.
So, let's sum up, we have one study that shows caffeine does negatively effect IVF cycles and one that indicates it probably doesn't. Oh, if only we had more data. Hang on, what's this? Ah, I am about to break Operation Big Belly's ground rules; I have found one more relevant study that was reported at a scientific meeting but has not been formally published. However, the meeting abstract and the subsequent press release are available on-line.
The study was a large one - this time we're in Denmark - and was presented last year to the European Society of Human Reproduction and Embryology (ESHRE). The researchers followed nearly 4000 women before and after their IVF cycles to find out if drinking coffee would result in lower pregnancy or live birth rates. Once all the data were collected, the investigators found that having up to four cups of coffee per day didn't really make any difference to the IVF outcome (yay, again), but having five or more coffees reduced the pregnancy rate by a whopping 50 percent and the live birth rate by, an equally staggering, 40 percent. Oh.
It seems that, at the moment with a very limited data set, heavy coffee consumption can reduce your chances of taking home a baby after IVF. Although, of course, it is possible that future larger studies, which I hope that some smart research group is working on right now, will show that caffeine doesn't really cause less women to become pregnant or babies to be born.
So, that's caffeine dealt with. What's coming up next? Well, in case you haven't figured it out already, the first phase of Operation Big Belly is dealing with consumption: we have looked at food, alcohol and caffeine. As I am not planning to tackle illegal drugs, the only thing left to look at is cigarette smoking. Ahhh, the evil weed. Until next time....
