IVF success rates Archives - Fertility Fact Checker

Is the keto diet good for IVF?

I’ve been doing the ketogenic diet for a couple of weeks now and despite being seemingly the only person to do the ketogenic diet and not lose half their body weight in the first week*, I am loving it. Clear, defined guidelines around what is and is not ‘allowed’ is what I’m all about. My relationship with chocolate (and any source of refined sugar for that matter) was never about ‘moderation’. All or none is how we roll, and at the moment with the keto diet, it’s ‘none’. Plus, I love using the urine test analysis strips which tell you if you are in ketosis or not (is that TMI?). Clearly, it allows me to relive my days of being POAS obsessed and deriving my feelings of validation and success from the drying of urine on a test strip.

What I mean by a keto diet

I’m talking super low carbohydrates; less than 50gms per day (pretty much just incidental carbs you get from eating the non-starchy vegetables that generally grow above the ground like cabbage, broccoli, cauliflower, maybe a few berries and the like), a little bit of a protein and a whole lotta fat. The good fats though, not the nasty transfats that you get in fast and processed foods. I’m also crossing out calorie counting. It’s partly why I love keto (again, she says 2 weeks in).

By the way, did you know that the ‘keto diet’ has been around since the 1920’s and was initially developed as a way to reduce the symptoms of epilepsy in children? … Could Pete Evans actually be right and food is medicine?! (For the record, although I do believe that modification of nutrition and food intake can help improve our lifestyle risk factors that cause us to need medication in the first place I don’t believe food is actually medicine. Or that bone broth can replace baby formula. Or that anti-vaxxing should be a thing).

But what about for women doing IVF?

I know that quite a few women who are trying to conceive at least consider the keto diet. There are reported outcomes of weight loss, reducing insulin resistance and all round improvements including decreased bloating and increased energy levels after all.

I’ve done my PubMed search and like many of the big questions regarding IVF and lifestyle factors, there are very few peer reviewed articles looking directly at the ketogenic diet and its impact on the only outcome measure that really matters in an IVF cycle – the live birth rate. And even less indirect information around if you are not only looking at women labelled as obese or overweight.

There are though a few articles on the impact of ketosis and low carbohydrate diets on PCOS (a major reason why women ultimately need to use IVF) as well as on low carbohydrate diets and its impact on some IVF outcomes such as hormone levels².

Before getting started

If you see a fertility specialist, thinking about or are about to do an IVF cycle, 1000% speak to your fertility specialist first before starting keto. I’m sure that there are women who have done IVF and started keto the day before their meds started and got 50 Grade A Day 5 Blasts, but seriously, except under medical advice, the day before (or the weeks and longer before) starting an IVF cycle is NOT the time to make such radical changes to your diet. This is especially if you have thyroid issues, participate in regular hard exercise or a few other medical conditions. Again, run it by your doctor.

If you are in the lead up to an IVF cycle and want to make some dietary changes based in scientific research that will optimize your IVF cycle, make sure you have a look at Eat Think Grow. But again, still run it by your doctor and don’t make any huge changes in the short term lead up to IVF.

PCOS

According to the 2016 US Center for Disease Control’s National Summary Report which evaluates the success rates of IVF cycles, 16% of women doing IVF were diagnosed with ovulatory dysfunction – which is a ultimately why women with PCOS need to do IVF; for various reasons, normal ovulation fails to happen. So, by that thinking, if a ketogenic diet positively impacts PCOS symptoms and supports normal ovulation, than perhaps some women may not need to IVF at all?

The impact of the keto diet on PCOS was investigated back in 2005 by a small study (very small, only 11 participants, only 5 of whom actually stayed the six months to the end)¹. At the end of the study, what they found was significant (p<.05) decreases in body weight, percentage of free testosterone, insulin and LH/FSH ratios (testosterone and the LH/FSH ratio can often be higher in women with PCOS which throws the hormone cycle out and contributes to the lack of ovulation that women with PCOS experience). A reduction in all of these markers, as observed, are associated with an improvement in the ovulatory function of women with PCOS.

Although in this respect it seems tick, tick, tick for the keto diet in women with PCOS the authors themselves stated that they were unable to determine if these improvements were a result of weight loss in general (all the women started with BMI’s over 27, which is considered to be at least ‘overweight’) or the direct influence of the specific features related to the keto diet.

Low carbohydrate diet and general IVF outcomes

Melanie McGrice and her colleague, in 2011 examined how low carbohydrate diets can influence the outcomes of obese and overweight women doing fertility treatments, including IVF. A finding of their literature research appears to be that the consumption of low carbohydrate diets can reduce insulin and improve hormonal balance and ovulation function. These are factors which can also improve the quality of an IVF cycle.

There have previously been studies done investigating very low calorie diets (less than 2000kj/day) which have found that women doing IVF and on these diets had high attrition rates and low fertilization rates. Clearly, this is not what any woman doing IVF wants. As McGrice explains, the authors hypothesized that it may be the impact of ketogenesis causing this result. When the authors³ went and did another study, this time ensuring higher protein and less severe calorie restriction (around 5000kJ/day in the 2 months prior to IVF) this same negative impact was not reported. But the subjects were also consuming around 130gms of carbs a day and 23gms of fibre, so is generally not a low carbohydrate diet and ketosis was unlikely. So maybe there is something in that ketosis may have a negative impact on the egg quality?

Conversely and although not directly IVF related, there is early evidence that suggests the ketogenic diet may increase mitochondrial function. Mitochondria is often considered to be the ‘power house’ of a cell and its dysfunction is associated with cell death. Improved mitochondrial function, which is also associated with weight loss, also may result in improved ‘egg quality’⁴.

Low energy diet and IVF birth rates

Another study looked at the impact of very low energy diet on IVF success rates⁵. Sim and colleagues conducted a study where over a 12 week period, women classified as ‘obese’ were divided into two groups – the experimental group who were subjected to (or benefited from) the full changes to diet and lifestyle that researchers wanted to test and the control group, those that did not experience all these changes. Being overseen by a dietitian, for six weeks the experimental group consumed a very low energy diet. This was then increased to a ‘normal’ intake over the next six weeks in the lead up to their IVF cycles. Additionally, the experimental group had the added experience of attending a weekly support group where they were provided with dietary, psychological and exercise advice. Plus they had the added benefit of being in a group and having the opportunity to connect with other women experiencing infertility and IVF, a process which cannot be underestimated. Those in the control group were simply advised to go see their GP for weight loss advice and provided the same printed literature as the experimental group.

It was found that those women in the experimental group not only lost more weight but also had higher pregnancy rates (48% versus 14%) and higher live birth rates (44% versus 14%) plus the added benefit of only needing to do two cycles to get there take home baby, as opposed to four cycles in the control group.

In this case, participating in a fully guided meal plan and getting the right emotional support certainly appeared to contribute significantly higher pregnancy and birth rates.

Transfats

There is the concern, that in order to continue eating foods that are ‘keto’ some women may be inadvertently eating higher amounts of trans-fats – the bad one, for pretty much everything, including fertility. Transfats are found in a lot of prepared and prepackaged foods as well as some animal fats and in small amounts red meat. Speaking of the impact of eating red meat on IVF success rates, this was discussed in Eat Think Grow were it was reported that the consumption of red meat was associated with poorer embryo development and pregnancy rates⁶. Again in the quest to eat ‘keto’ it becomes a temptation to start eating more and more meat for the ease of it. I’m not saying eat more meat is necessary a bad thing for your keto diet (though some would) , but you need to be mindful of your other goals and what the evidence says there impact is on IVF success rates, not just being in ketosis.

Saying that, I would like to think by and large though, most people doing keto have enough ‘food literacy’ to know that you don’t eat prepackaged foods (cause a lot of the time they aren’t actually keto anyway) and to try and consume fats in healthier and alternative way than just having steaks 3 times a day.

To sum it up

As it stands, there is insufficient data to recommend the ketogenic diet to women doing IVF. The studies done primarily are only looking at women with PCOS and those that are labelled ‘obese’. Also, these studies are not all necessary looking only at the ‘keto diet’ as we know it. If you fall into the one of the categories of ‘obese’ or having PCOS and you have, say, six months to go before you do your IVF cycle and some significant weight loss to achieve than it would certainly be worth a go.

But the benefits you experience might be from weight loss as opposed to specifically the keto diet.

If you are three months or less before your IVF cycle, I would certainly be seeking professional advice before making such radical changes – although the data is far from water tight, in my opinion there is just enough doubt to think twice, or at least have a good discussion with your treating team and make sure that whatever changes you are making are optimized for your individual medical condition and cycle.

1. Mavropoulos, J., Yancy, W., Hepburn, J. & Westman, E. (2005). The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: A pilot study. Nutritional Metabolism 2: 35 doi: 10.1186/1743-7075-2-35

2. McGrice, M. & Porter, J. (2017). The Effect of Low Carbohydrate Diets on Fertility Hormones and Outcomes in Overweight and Obese Women: A Systematic Review. Nutrients 9(3), 204; https://doi.org/10.3390/nu9030204

3. Moran, L., Tsagareli, V., Norman, R. & Noakes, M. (2011). Diet and IVF Pilot Study: Short term weight loss improves pregnancy rates in overweight/ obese women undertaking IVF. Australian and New Zealand Journal of Obstetrics and Gynecology 51 455 – 459

4. Kulak, D. & Polotsky, A. (2013). Should the ketogenic diet be considered for enhancing fertility? Maturitas 74 p10 – 13

5. Sim, K., Dezarnaulds, G., Denyer, G., Skilton, M. and Caterson, I. (2014). Weight loss improves reproductive outcomes in obese women undergoing fertility treatment: a randomized controlled trial. Clinical Obesity 4 61 – 68

6. Braga, D., Halpern, G., Setti, A., Figueira, R., Iaconelli Jr, A. and Borges Jr, E. (2015). The impact of food intake and social habits on embryo quality and the likelihood of blastocyst formation. Reproductive BioMedicine Online 31 30–38.

*That’s a joke by the way… obviously I wouldn’t want to lose half my body weight in the first week, or at all!

7 must knows for an IVF first timer

You’ve chosen your fertility clinic, got a grasp on the type of cycle you’re doing and you’ve got an action plan for administering those needles.

There is just a few more things you need to know…

1. It all takes so much longer than what you anticipate.

I don’t mean to start all negative here, but it really does and you are either going to develop your patience skills to equal that of Mr Miyagi in the Karate Kid, or go a little cray-cray. I’m sure it will be the first of those two options, but if it’s the second, take a breath and remember you’ve got this. And if you haven’t got this, seek counseling or see a doctor that knows you well. You definitely won’t be the first.

But back to the waiting. Whether its waiting to get into a specialist for an initial appointment, waiting for day 1, waiting to get the money together to buy your medications, waiting to get bloods done in the morning, waiting for the afternoon results to come in, waiting for your what-went-wrong appointment (otherwise knows as the WTF appointment) after an unsuccessful cycle or even waiting during the dreaded two week wait for that pregnancy result there is waiting behind every twist and turn.

And while I hope you are one of the lucky ones that get pregnant and get that take home baby on the first go, unfortunately, statistics indicate that most women will need to have more than one cycle.

Hoping for the best but preparing for the worst has never been more appropriate than when starting out the IVF journey.

2. You need to be kind to yourself.

And protect yourself. There may be days when you just can’t go to another baby shower. When the thought of going to your best friends babies first birthday is just that step too far. That’s ok. A good friend will understand and one that doesn’t perhaps wasn’t really a good friend to begin with.

Sometimes you know when you need to have a break and hold onto those emotional reserves for when you really need it.

3. Most of it – out of your control.

There are very few things that you can control in this whole crazy process. People who do everything absolutely ‘right’ may fail a cycle and those that do everything ‘wrong’ have success first go. Kind of put that in the ‘ignore bucket’ like hearing about unwanted teenage pregnancies… it really doesn’t help to try and find the fairness in the situation and it doesn’t make sense.

Similarly, ‘bad’ blood tests one day may quickly turn into ‘good’ news the next day at the ultrasound. It really is a rollercoaster and you can be thinking you are ‘kicking fertility goals’ one goals one day and ready to throw in the towel the next.

The quicker you learn that so much of it is out of your control, the easier it is.

4. Get fertility fit.

Not forgetting that you really can’t control a lot of what happens during an IVF cycle, there are just a few things you can control. This includes what you eat, drink and to an extent other toxins that your body comes into contact with.

I know now, before your first cycle your thinking all you really need is a few drugs to get you ovulating or a bit of ICSI to get the sperm to meet the egg and bam! The magic is all going to happen. And hopefully it will! But if it doesn’t, chances are in a cycle or two you are going to look for alternative ways to try and improve the success of your cycle and you’ll quickly read that there are some real changes YOU can make to try and improve the egg quality, lining and implantation rates BUT ideally you’ll be starting these changes three months before your cycle for them to have full impact.

I know many women have read the well-known book about increasing egg quality . This is a great book chock full of research and ideas. But for some women, this can also be a bit intense. An alternative read is ‘Eat Think Grow’ it also has research but in a lighter format as well as practical strategies (including 4 week eating plan and mindfulness strategies) on how to implement it and get going .

5. Be your best advocate.

I’ve said it before, but no one really cares as much as you if you get this take home baby or not. Except maybe your partner that is. Doctor’s are people too and you are paying them a lot of money to help you bring this little baby into existence. If you have a question about a medication, or aren’t sure why you are doing the same protocol for the 5^th cycle in a row, ask! This is happening to your body, so make sure you understand (more or less!) why you are injecting those drugs!

Similarly, if you have done several cycles and don’t feel you are getting anywhere, or that your concerns aren’t being heard or if it is just your gut instinct, it can’t hurt to get a second opinion. Well, it might hurt the back pocket, but nowhere as near as much as extra IVF cycles does. Sometimes just putting a fresh set of eyes on your situation can come up with a new (and more successful!) plan.

6. Quality over quantity.

Like every day of the week. Try not to get down when your fertility friend has 18 eggs harvested come collection day and you are feeling like a dried up hen with your two. Although, your friends eggs might be all the highest quality, chances are they may not be. Personally, I’d take a low number of eggs with a higher quality than a large number of maybe immature and lower quality eggs any day of the week.

7. Think about what you will do with any left over embryos – if you should be so lucky.

Ok, so not really a ‘must know’ but definitely something to think about…You don’t need to set the decision in stone and situations and feelings on the issue can change in a heartbeat (literally!). But being mindful of what you might want to happen with ‘left over’ embryos now might make it a little easier in the future if you are one of the lucky ones who manage to complete their family with embryos to spare.

Good luck as you go about your first IVF cycle. Hopefully doing everything you can now to prepare your body for it and setting your mindset to roll with the punches (and the victories!) will make the rollercoaster just that little bit smoother

Have you considered PGS?

Chances are you probably have. Then when you realised that testing can cost between $3000 – $9000 on top of your IVF cycle costs¹ put this idea on the back burner as quickly as you thought to Google it.

Finances aside, logically, it makes sense that preimplantation genetic screening (PGS) should increase live birth rates significantly –you are testing your embryos so that only those which are chromosomally normal are chosen for transfer and after all, how many times have you heard that chromosomal abnormalities are one of the major reasons that a lot of IVF transfers fail? A lot.

In reality, although some evidence does exist to support this logic, overall it is scarce and IVF live birth rates following PGS, can drastically differ depending on the stage of growth your embryo is at when tested, what laboratory technique is used and not to mention the issue of ‘mosaicism’ which just ads next level confusion to the situation.

Is it PGS or PGD?

Although the two terms are often used interchangeably and to be fair the actual procedure of PGS and PGD are very similar, there are some subtle differences between the two terms. PGS, or preimplantation genetic screening is, as the name suggests, a screen of embryos for couples who have known fertility problems to try and improve their IVF success rates. This is done by routinely checking the 23 chromosomal pairs in an attempt to ensure there are no abnormalities. PGD, or preimplantation genetic diagnosis is used typically for fertile couples who carry a chromosomal mutation for a particular disease or gene, such as muscular dystrophy or cystic fibrosis and want to ensure that these conditions are not passed on to their children. It is generally used to diagnose a particular condition that the parents are known to be carriers for.

Different approaches to PGS

PGS has been around for over 20 years now² and over this time there have been several approaches¹.

The first approach was to test cells obtained from the polar bodies of fertilised eggs. Unfortunately it was found that this method was not very accurate and often resulted in lower implantation rates and therefore was believed to not be a reliable predictor of pregnancy and birth rates³. Additionally, because it was less accurate, more samples ended up needing to be tested which again increased the cost.

The next approach was to remove one or two cells from the embryo when it was at cleavage stage (and therefore only had around eight cells to begin with). Embryos tested in this fashion showed no increase in live birth rates and at times reduced birth rates³. This was thought to occur due to the damage being down to such a young embryo⁴.

The third, and current approach that is most likely what your IVF clinic supports, is to take five to ten cells from the outer layer (or trophectoderm) of a day 5 or 6 blastocyst. By this stage the embryo has up to a couple of hundred cells and it is believed that taking these cells is unlikely to cause any damage.

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Once the cells are taken they are then analysed in a laboratory. There are several different techniques to do this which can differ from laboratory to laboratory. One of the newer ways by which testing is done is using Next Generation Sequencing which has shown promising clinical results³.

Evidence supporting the use of PGS

One recent meta-analysis³ examined the results from three random control trials looking at the cycles of 659 women and showed that PGS testing on blastocysts reported a higher implantation rate (implantation rate greater than 50%) and a higher ongoing pregnancy rate (over 45%). This means that for women testing their embryos at day 5 or 6 there is a 15 to 45% chance of increasing implantation rates and 21 to 60% chances of a higher ongoing pregnancy rate than by just choosing an embryo based on morphological information (or what it looks like when examining under the microscope).

This led the authors to recommend two things. Firstly, when transferring embryos chosen after PGS single transfers should be the standard of care (no more transferring multiple embryos) given the higher success rates.

The other conclusion authors came to was that for women with normal ovarian reserve it seems possible to achieve higher pregnancy rates by using PGS than just using standard IVF practices. It has been noted, however, that unfortunately it is generally not women of ‘normal ovarian reserve’ that most need this technology and more studies are required before it can be relied on to be a standard treatment for women of advanced age, those with low ovarian reserves, recurrent pregnancy losses or where the male partner as very low sperm count.

Per transfer versus cycle start success rates

Additionally, these results, although very promising, are only looking at success rates when there are day 5 and 6 embryos to transfer and test. Although the success rates are higher for women who PGS test and can do a day 5 or 6 transfer it does not take into account the women who may have started a cycle though did not have any embryos survive to day 5 or 6 to test and transfer. In this way the results are kind of skewed.

A 2016 article⁵ did address the potential confusion between ‘per transfer’ success rates and ‘per cycle starts’ success rates. Examining the 2011-2012 US data it was found that particularly for women under 37 years of age PGS was found to reduce the chances of a live birth in both transfer only reports (39% live birth rate for PGS tested embryos vs. 46% for non PGS tested) and per cycle start (25% for PGS vs. 29% without PGS). With miscarriage rates hovering around 14% for both PGS and non PGS embryos it was suggested by the authors that not only does PGS not improve IVF outcomes but actually negatively affects them in the clinical reality of the national US data. Interestingly, for women over 37 years of age PGS was found to have a significantly lower miscarriage rate (17% of PGS embryos miscarried vs 26% of non PGS tested embryos) and higher live birth rate per cycle start and embryo transfer. So this research suggests that PGS is a of benefit for those women aged 37 years and older.

Mosaicism

Regardless of this review of the data (after all, it is not a randomised control trial, there is plenty of room for misinterpretation of data with even an article that published contradictory opinions when examining the same available data (Chang et al as cited in 5)) and all the potential conflicts in the current literature, if you had the money and thought it would mean an implantation rate of over 50% you’d still be keen though, right?

The concern is though as to the accuracy of PGS testing. It would be logical to assume that if you are told that your embryo was ‘normal’ or ‘abnormal’ than that is a pretty black and white issue. Either it has the accurate number of chromosomes and chromosomal arrangements or it doesn’t.

It seems it doesn’t necessarily work this way and that is due to ‘mosaicism’. Mosaicism occurs when the embryo can contain both normal and abnormal chromosomal arrangements in the cells that are tested. There is a very small but thought provoking pool of research that suggests that just because an embryo contains these abnormal cells it does not necessarily mean that the embryo itself will be ‘abnormal’ or wont correct itself.

The extent of the issue of mosaicism is documented in a 2016 article⁶. Medical staff working in an IVF clinic noticed that some women were having statistically improbable high numbers of abnormal embryos being reported after testing. This was especially in younger women, who you would expect to have a higher number of normal embryos. To cut a long-ish story short, after joining forces with other IVF Clinics who also noticed this trend, it led to the establishment of the ‘International PGS Consortium’ which was dedicated to investigating the effectiveness of PGS in IVF.

The consortium completed the following research⁶. Five women whose embryos underwent PGS and all their embryos were found to be ‘abnormal’ were allowed to transfer these abnormal embryos back into their uterus. That is, in the absence of any ‘normal’ embryos these women were allowed to have ‘abnormal’ embryos transferred to see if they would implant and result in a live birth. These are embryos that traditionally would have been discarded; however, from these five transfers three normal births were recorded. This trend was supported when in Italy 18 mosaic embryos (that is embryos with both normal and abnormal cells which would have been considered ‘abnormal’) were transferred which resulted in 6 chromosomally normal live births (that’s a 33% success rate for embryos that were deemed ‘abnormal’). As of the 2016 article, only 26 women with fertility problems worldwide received allegedly PGS tested abnormal embryos. This resulted in 11 chromosomally normal live births/ ongoing pregnancies and no miscarriages.

Although this is obviously only a very, very small sample size and is not the gold standard of a randomised control trial (which, to be fair, would be very difficult if not impossible to do) it does highlight doubts as to the accuracy and relevance of PGS testing. Especially for women who otherwise would have no ‘normal’ embryos to transfer. Should these women be allowed to take a chance on questionable embryos? And does taking a few cells from the outside layer of the embryo provide enough of an accurate measure to reveal what is happening inside the embryo?⁶

This concern was supported when the same researchers completed another study on 11 donated embryos that were deemed ‘abnormal’ and would have been discarded. Sending the embryos to another laboratory to be retested, researchers found that only 2 out of 11 embryos had the same reports across the two laboratories⁶. 4 out of 11 embryos that were previously reported as abnormal were now, normal and 2 out of 11 were now reported as being mosaic, having at least one normal fragment and hence a chance of a successful outcome. What is even more concerning is that even the gender identified varied between the two laboratories. Again, these results are only a very, very small sample size and is NOT statistically significant but does suggest a false positive rate for PGS as high as 55%⁶.

55% does seem extraordinarily high and some laboratories claim an accuracy rate of 99%. Quite a discrepancy. This 99% accuracy rate however, is thought to reflect accuracy in a clinical validation study and not necessarily the accuracy in true clinical matters that actually happen on a day to day basis in women doing IVF. Some estimates of the actual misdiagnosis rate sit around 5%⁴.

Time to Change?

To take into account the phenomenon of mosaicism, instead of reporting embryos as being euploid or aneuploid, or normal or abnormal, it has been suggested that embryos with less than 20% mosaicism are reported ‘normal’ and those over 80% mosaicism are reported as ‘abnormal’. This leaves those in the 20 – 80% as mosaic and depending on the advice and recommendations of the IVF Clinic, in the absence of any normal embryos potentially a consideration for transfer. Obviously though, this suggests radical change as previously any abnormality was discarded².

Putting it together

For some women, typically those who have a good IVF prognosis anyway, with normal ovarian reserve and the funds to do so, PGS testing could very well be a reliable and valid way forward. Particularly for those who have been on the IVF ‘journey’ for a considerable time and want to give themselves the very best chance of a live birth per transfer.

For others though, there is the need to stop and think. This is particularly for those who get a high number of ‘abnormal’ results and for those who are of advanced maternal age or who are unable to grow embryos to day 5.

The cost per birth for an IVF PGS cycle is estimated at being $45,300⁷. So whilst some of the evidence is promising it isn’t without its critics and until further evidence can be produced that supports a significant increase in live birth rates, you might be better off redirecting some that money into another IVF cycle. Or not. There is no clear cut answer and only through careful conversation and discussion with your fertility specialist regarding your individual situation can a decision be made as to if PGS is for you.

Reference

Twisk, M., Mastenbroek, S., van Wely, M., Heineman, M.J., Van der Veen, F. and Repping, S. (2006) Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic sperm injection. Cochrane Database of Systematic Reviews 2006, 1. Art. No.: CD005291.DOI: 10.1002/14651858.CD005291.pub2.
Gleicher, N. and Orvieto, R. (2017). Is the hypothesis of preimplantation genetic screening (PGS) still supportable? A review. Journal of Ovarian Research 10 (21). DOI 10.1186/s13048-017-0318-3
Dahdouh, E., Balayla, J. and García-Velasco, J.A. (2015). Comprehensive chromosome screening improves embryo selection: a meta-analysis. Fertility and Sterility 104(6) 1503 – 1512.
Brezina, P., Kutteh, W., Bailey, A. and Ke, R. (2016). Preimplantation genetic screening (PGS) is an excellent tool but not perfect: a guide to counselling patients considering PGS. Fertility and Sterility Reflections 105(1) 49 – 50.
Kushnir, V., Darmon, S., Albertini, D., Barad, D. and Gleicher, N. (2016). Effectiveness of in vitro fertilization with preimplantation genetic screening: a reanalysis of United States assisted reproductive technology data 2011–2012. Fertility and Sterility 106 (1) 75–79.
Gleicher, N., Vidali, A., Braverman, J., Kushnir, V., Barad, D., Hudson, C., Wu, Y.G., Zhang, L., Alberini, D. and the International PGS Consortium Study Group (2016). Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryo. Reproductive Biology and Endocrinology 14(54). DOI 10.1186/s12958-016-0193-3
Murugappan, G., Ohno, M., Lathi, R. (2015). Cost effectiveness of preimplantation genetic screening and in vitro fertilisation versus expectant management in patients with unexplained recurrent pregnancy loss. Fertility and Sterility 103 (5) 1215 – 1220.

How environmental toxins can impact your IVF cycle

It seems we can’t avoid environmental toxins. Being aware of this and where possible reducing your exposure is one step you can take to improve the chances of creating your little family.

You’ve modified your diet, significantly cut down on alcohol and well, smoking was never your thing anyway. The next thing you might be wondering is about toxins and the potential impact that has on egg and sperm quality and the little embryo about to implant. If you believe the news environmental toxins are EVERYWHERE but do they really matter or is it yet another, hippie fad?

Call them toxins, environmental contaminants, chemical contaminants or environmental toxicants, the synthetic chemicals that we come across in our daily living seem to be linked more and more to declining fertility in ‘normal’ populations and poorer outcomes in the IVF world. These chemicals have been linked to all sorts of conditions including cancers, neurological conditions and even mental health conditions. For the purposes of your upcoming IVF cycle we are most concerned with link to a decline in fertility and poorer IVF outcomes.

Endocrine Disruptors Explained

Environmental contaminants are often referred to as being ‘endocrine disruptors’ as they can interfere with the bodies endocrine, or hormone, system and more specifically in this instance with estrogen. The chemicals do this by either mimicking how estrogen works, blocking its use or simply just interfering with the way it is made or controlled (National Institute of Environmental Health Sciences). Regardless of the exact mechanism, they are preventing the normal functioning of our endocrine system from happening and this has the potential to adversely impact on our fertility and IVF success.

Endocrine disrupting contaminants are in many different substances (both natural and man-made) with some of the main ones being certain pharmaceuticals, dioxin and dioxin-like compounds, DDT and other pesticides, and plasticizers such as bisphenol A and phthalates.

Endocrine disruptors have been given a bit of attention recently and are thought to be so important as they can travel vast distances both through air and up the food chain (1) meaning that their impact can be wide reaching. The two ‘plasticizers’ have particularly been topical recently and are further discussed here (though pesticides and other contaminants are also of importance and should be reduced where possible).

Ive heard of it… but what is BPA?

Bisphenol A, or BPA, is a substance that was primarily used in the manufacturing of plastics (which is why it is called a ‘plasticizer’. It is still often used in the lining of tin cans and in some plastic drink bottles and is even used on the coating of til receipts that is then absorbed through our skin when handling the receipt (2).

There have been small studies that have been conducted analyzing the levels of BPA in the blood of women undergoing IVF and it has been found that the higher the levels of BPA the lower the fertilization rates (3). Other studies have also shown that for women doing IVF, those with higher levels of BPA in their blood had lower numbers of eggs, less mature eggs and lower rates of fertilization (2).

Now there are two things to be mindful of when getting your morning coffee – too much caffeine AND BPA from the cash register receipt!

BPA is found in many plastic containers and coatings and although the studies are small, at times contradictory and inconclusive, where possible it does seem like it is beneficial to limit the amount of BPA that you come into contact with (despite studies from the United States Food and Drug Administration saying that the level of BPA that is absorbed in day to day activities is within safe limits). This would include looking out for BPA free plastic containers (preferably glass containers because who knows what they are replacing the BPA with in other plastics), being mindful of which brands of tinned food that you eat (as BPA is often in the coating) and avoiding drinking water from plastic bottles. Oh and if you work in retail try and reduce the amount of receipt handling you do – just to be safe.

…and phthalates?

Phthalates are a group of chemicals that are used to make plastics more flexible and harder to break (Center for Disease Control; CDC). They are also used to in anything that is fragranced which is why they are found in many personal care products including perfumes, soaps, deodorants, hair sprays and even nail polishes! This is together with the hundreds of products including flooring, adhesives, detergents, lubricating oils, automotive plastics, plastic clothes such as raincoats and sometimes children’s toys, plastic packaging and medical tubing. It seems, phthalates are everywhere!

Similarly to BPA we can ingest phthalates by, for example, eating food that has been in contact with the plastic containers it has been heated in or particularly in the case of cosmetics and personal items, absorbing them through our skin. You can even breathe in phthalates. Once the phthalates are in our body, they are metabolised into metabolites are are then excreted in urine.

Reduce your exposure to phthalates by only using phthalate free makeup and toiletries.

It is by analyzing the metabolites in our urine that researchers are able to quantify how much phthalates a person has been exposed to and make comparisons to various outcomes, such as, the success of an IVF cycle. Before we look at IVF specifically, there is a significant body of research that has been done in animals implicating phthalates with poorer reproductive outcomes and also linking phthalates to an increase in oxidative stress in our body (particularly researched in men and pregnant women).

From what I have seen though, whilst it seems increasingly undeniable that the influence of phthalates negatively impacts our IVF cycles the hard human evidence demonstrating its impact in women is still coming. However, a study in 2016 (4) reported that when analyzing the metabolites found in the urine of women undergoing IVF the higher the amounts of metabolite DEHP and DiDP found, the lower the number of eggs produced and number of mature eggs produced. Additionally, an increased presence of the metabolites DiNP and DiDP were associated with lower fertilization rates. This ultimately led the researchers to conclude that higher levels of DEHP ultimately led to lower clinical pregnancy and live birth rates.

Whilst having high amounts of phthalates in your blood (and urine) isn’t going to be the only factor to make or break your cycle, or even be the major factor, it may be at the very least a significant risk factor and is certainly worth reducing your exposure where possible.

It should be noted though that not all studies support this. For example in 2017 a paper was published (5) that indicated that male, but not female, urinary concentrations of phthalates influenced blastocyst quality and another study reported that even though metabolite MEHP and MBP where found in follicular fluid and urine of females doing IVF these were not associated with the usual IVF outcomes (which may include things like egg quality, number, fertilization rates etc).

As we have already stated though, regardless of the evidence being somewhat inconclusive, there does seem to be enough evidence to suggest that it is worthwhile reducing your exposure to endocrine disruptors as much as possible.

So, how do we do this?

Throw out the plastic storage containers in your house and investing in either glass or stainless steel. Watch out for plastic recycling codes 3, 6 and 7 as these may contain endocrine disruptors. Particularly avoid reheating your food in plastics as when the plastic is heated the integrity of the plastic is changed making it easier for the transfer of phthalates to your food.
Try not to use cling film and other products to wrap your food in. Paper bags for sandwiches may seem like a throwback to the fifties but its at least worth a try. So is aluminum foil.
Use ‘natural’ cosmetics products available such as those from Nourished Life (this is an Australian website but there are others in the US). Or if this proves to be cost prohibitive looking for products that are ‘phthalate free’ (and their derivatives). This can be tricky and they can hide so it pays to do your research as sometimes the name can be somewhat ‘hidden’. Remember products that have added fragrances nearly always contain phthalates so looking for ‘fragrance free’ is worth a try also.
Beware of the scented candle! They may also be a source of phthalates.
Reducing chemical cleaners in your home. I have recently started using ‘Enjo’ and although expensive and at times does take a little more work the benefits of not having harsh chemical cleaners make it worthwhile.
Try eating organic. Non organic vegetables can often contain residue pesticides which although not directly discussed here can also be endocrine disruptors. Additionally, non organic meat can contain remnants of hormones and antibiotics given to the animals which then passes up the food chain to us.
Limit handling til receipts!
Stick as much as possible to unprocessed foods and avoid canned foods (unless you know that the lining of tins are BPA free).
Being aware of the environment you are in. For example, trying to avoid places where you know lots of air freshener or scented candles are used or if you have laid new carpet, for example, ensure it has been aired out as much as possible before you move back in.

For more practical ways to reduce your exposure to chemicals to increase your chances of IVF success, have a look at Eat Think Grow.

The bottom line

Although the evidence to say that phthalates negatively influences IVF outcomes is not yet conclusive, there does seem to be a growing body of evidence to say that they are very likely to have at least some impact. Although it will be near impossible to ever completely eliminate your exposure to phthalates, BPA and other environmental toxins, given that your IVF cycle is potentially the most important thing to ever happen to you and you want to do all you can to support its success it wouldn’t hurt to eliminate reduce your exposure as much as possible whilst still living life. This includes eating organic, reducing use of nail polish hair spray and especially fragranced cosmetics and minimising food that has been inside plastic (especially plastic that has been heated such as in a microwave) containers. You know, while living in the 21^st century, juggling work and ultrasound appointments.

References

Younglai, E, Holloway, A, Foster, W. (2005). Environmental and occupational factors affecting fertility and IVF success. Human Reproduction Update, 11 (1) 43–57, doi:10.1093/humupd/dmh055
Ehrlich, S., Williams, P., Missmer, S., Flaws, J., Ye, X., Calafat, A., Petrozza, J., Wright, D. and Hauser, R. (2012). Urinary bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF. Human Reproduction 27 (12) 3583–3592.
Fujimoto, V., Kim, D., vom Saal, F., Lamb, J., Taylor, J. & Bloom, M. (2011) Serum unconjugated bisphenol A concentrations in women may adversely influence oocyte quality during in vitro fertilization. Fertility and Sterility 95 (5) 1816 – 1819
Hauser, R., Gaskins, A,, Souter, I., Smith, K., Dodge, L., Ehrlich, S., Meeker, J., Calafat, A. and Williams, P. for the EARTH Study Team (2016). Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study. Environmental Health Perspectives 124 (6) 831- 839.
Wu, H., Ashcraft, L., Whitcomb B., Rahil, T., Tougias, E., Sites, C. and Pilsner, J. (2017). Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment. Human Reproduction 32 (1) 65- 73.

Protein – Carbs = Increased IVF success rates

Eating an ‘IVF Diet’ is a minefield. Eat organic, don’t eat sugar, eat brasil nuts, don’t eat soy – no wait, DO eat soy, eat pineapple – but don’t eat it before transfer, drink raspberry tea, avoid peppermint tea.

It does NOT STOP!

And here is one more. But this one is really promising and has some good elementary science to back it up.

Looking at the amount of carbohydrates and protein in the diets of women doing IVF, researchers where able to provide some suggested guidelines on the ratios of how much of these foods you should be eating to best increase your chances of IVF success. As always though, make sure you check with your fertility specialist before making any major changes to your diet to ensure it is right for you and your unique situation.

Peas. Obviously. And a decent source of plant based protein too.

THE IVF CONNECTION

In 2013 in a fertility clinic in the U.S, fertility doctors were noticing that young women (aged 36 and 37) of normal weight and no obvious reason for it where getting eggs of poor quality.

Although these women were eating what some would consider a healthy diet – oatmeal for breakfast, bagel for lunch and pasta for dinner it was observed that there was no protein in their diet. It was believed that the lack of protein was contributing to the poor results.

A low protein, high carbohydrate diet potentially has negatives on two fronts. One, carbohydrates essentially convert to sugars which can fuel the insulin resistance cycle and hormonal disturbances (not only in women with PCOS, 1) but proteins are the building blocks of the body – and hence our eggs. If we are missing out on them, it makes it harder for the supercharged process our ovaries are going through to make high quality eggs.

120 of these women were split into two groups, one group who ate over 25% of their diet as protein and the other that ate under 25%. They had three outcome measures: 1. Blastocyst formation (that is the embryo could make it to day 5) 2. Clinical pregnancy rates and 3. Take home baby rates

Here are the results

Protein vs Carbohydrate success rates — Blastocyst formation, clinical pregnancy rate and live birth rate for women who ate under and over 25% protein in their diet respectively

My excel spreadsheet skills aside, you can see that those women that had over 25% protein had higher rates of blastocyst formation, higher rates of clinical pregnancy and higher rates of a take home baby. Much higher rates. And with the statistical p values ranging from .002 to .0005 there is only quite a small chance that these results were due to coincidence.

BEFORE YOU START THE ATKINS DIET

Have you heard of the Atkins diet? It’s that one that says to eat ONLY meat effectively letting your body go into ketosis to burn lots of fat.

We don’t want that. Eating before going into IVF shouldn’t be about a going on a particular fad diet and if you are just about to start a cycle the goal isn’t to lose weight. You don’t want to shock your body or do anything like that. Eating sensibly is the goal. Additionally, it takes 3 months for an egg to form so any dietary changes that you are doing to increase egg quality should be done this far out from your planned IVF cycle.

THE ISSUE OF PLANT PROTEIN

If you have read The Fertility Diet you would know that not all proteins are considered equal and they recommend eating plant protein over animal protein.

They go as far as to say if you add animal protein instead of carbohydrates this causes even more disruption to normal ovulation.

Salmon. It's a protein so the picture is kind of relevant. Did you know farmed salmon has higher content than wild? I'd still stick with wild though. — Salmon. Not only is it a good source of protein but also of omega 3, win, win.

But combining these two pieces of research and eating 25% of your diet in plant proteins is HARD. I’ve been trying to do it for awhile now and it seems to be impossible. Unless it seems you eat a ton of eggs (one serving a day of fish and eggs didn’t influence ovulatory functioning apparently) and effectively cut out grains and potatoes, but then that seems like too much of a fad diet to me. There must be a happy medium.

And for me, that is sticking as close as possible to the 25% protein intake and eating as much plant proteins as possibly but inevitably there is a bit of animal protein in there as well. Also, we have to remember that The Fertility Diet is for women who wish to conceive naturally . For women doing IVF that dream has long sailed. So in my opinion, The Fertility Diet is not always going to be relevant to women doing IVF and I think it is more important to make sure you get proteins in, while following those rules of not eating too much red meat and avoiding the transfats that meat contains as much as possible.

Dairy products also contains a healthy amount of proteins. Some women would have heard that dairy is one of those inflammatory foods that should be avoided during IVF. Personally, I have not seen enough research to validate this claim and believe that dairy foods should be one of those things consumed in moderation. Or maybe its just that I love cheese too much. If you have ovulatory dysfunction as your reason for all this mess, when I say ‘mess’, I mean infertility and everything that comes after, The Fertility Diet recommends full fat varieties citing that the process of producing the skim milk and making it look creamier adds substances that disrupts hormonal and ovulatory functioning.

High Protein. Low carbohydrate. Plant based. Tick, tick, tick!

Oh, and just lastly, if you have access to Lupin Flakes, these bad boys are a whopping 40% protein. That’s pretty high for a plant based protein that is also gluten and soy free. You can use them as a breakfast cereal, make it up to be like a cous cous, a substitute for breadcrumbs, the list goes on. Check out their facebook page for details.

THE MAIN POINTS

Try and eat 25% of your diet as protein – there are free apps around that you can download onto your phone to help you monitor this. They are way easier and quicker to use than what you think. At the moment I’m using ‘My Fitness Pal’.

When increasing protein, try and make it a plant based protein (or at least not traditional meat type protein all the time). This includes fish (but remember to eat the right type of fish to avoid mercury), eggs, lentils, beans and peas.

Cheese and dairy is also high in protein (make sure the added sugar, such as in yoghurts is kept low).

Don’t make it a faddy diet and don’t lose too much weight with it (unless of course your doctor has advised you to).

Most importantly, if you are looking to make major changes to your diet make sure you consult a qualified dietitian before doing so. We all have different medical needs and histories and what is going to benefit one woman may not benefit another.

Well, I hope that is all just a little bit clearer than mud. Good Luck!

P.S If you have liked this article don’t forget to download your free guide to find 19 different ways that are easy to action that will hopefully improve your egg quality, implantation and ultimately IVF success.

References:

Chavarro, J. & Willett, W. 2009. The Fertility Diet. McGraw Hill
Johnson, Kate (2013). Low Carb Diet Improves In Vitro Fertilisation. www.medscape.com