improve ivf success rates Archives - Fertility Fact Checker

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

Possible benefits of mindfulness when doing IVF (including increased DHEA and melatonin)

When I learnt at a seminar I attended this week that mindfulness can increase DHEA and melatonin levels in our blood, I was intrigued.

As you may remember from the free book, ’19 ways you can contribute to increasing your chances of IVF success’, optimized melatonin levels can be associated with higher numbers and quality of eggs come IVF egg pick up day (1).

Similarly DHEA, or dehydroepiandrosterone, is a bit of a controversial IVF supplement which is believed to increase egg quality, especially for those with diminished ovarian reserve or who have been poor responders to IVF treatment. There needs to be more larger studies supporting and evaluating its use but from the preliminary evidence there is, it seems like DHEA could be beneficial to increasing the live birth rates for some women doing IVF.

For example, in a very small study with only 33 patients (2) they found that the live birth rates for women who had DHEA supplementation were 23% where as those women who did not take the supplementation had live birth rates of around 4% (remember, it was only a very small study and although an increased birth rate of 19% for taking a tablet seems great, it is ‘only’ an extra 5 births… but it is certainly a start and a step in the right direction). You absolutely need to check with your treating fertility specialist to check that DHEA would be suitable in your situation (so no off-grid, unapproved supplementation) but maybe if we can support levels naturally through mindfulness that can only be a good thing?

What about mindfulness

At the seminar, led by mindfulness expert and international best selling author, David Michie, a study which found that when people meditate for five years or more the DHEA in their blood stream is the equivalent to someone twelve years younger was discussed. DHEA depletes as we age and if we can have the DHEA of someone twelve years younger, could that lead us to the path of having eggs twelve years younger? It seems unlikely that such a direct correlation exists, but while looking for evidence to support this theory, I found other remarkable statistics linking DHEA to mindfulness. For example, did you know people who meditate have upto 44% more DHEA than those who don’t? (3)

Whilst looking for the ‘smoking gun’ linking DHEA, mindfulness and IVF, I found that the studies linking mindfulness to increasing DHEA were sometimes just only looking at male populations, sometimes it only looked as far as it impacted cardiovascular health… unfortunately I could not find any evidence that examined directly, or even indirectly, of how mindfulness impacts DHEA in women, women with fertility problems or women doing IVF.

Mindfulness Benefits for IVF

This then lead me to think, that if you want to increase your DHEA or melatonin levels, by all means giving mindfulness a go is definitely worth it for this reason alone. But ultimately, to achieve the results that you want in the quickest time possible (forget yesterday, who doesn’t want that baby, like, 3 years ago?!) with a more evidence based approach, you are best speaking to your fertility specialist to see if supplementation might be right for you.

But mindfulness has so much more to offer than just its influence on hormone levels.

For many women doing IVF, the process can become EVERYTHING. Everything you eat, everything you touch, everything you do, the plans you make, the plans you don’t make, it all becomes linked as to how it’s going to possibly increase or decrease your chances of a take home baby this cycle. It’s mentally exhausting. Practicing mindfulness gives you the opportunity to have that weight taken off your shoulders even for the shortest time while you are doing it.

We focus so much on eating right and taking the medications at the exact time in the exact way that we forget to take care of our mental health. But as David Michie highlights, when we look at our physical health, the absence of disease does not equate to health. We can be incredibly unhealthy physically, not at all ‘fit’ and still not have an actual disease process going on. Similarly, we may not have a mental health condition, such as anxiety, depression or otherwise, but that still is not to say we are actually mentally healthy either. Mindfulness is what helps you achieve a better state of mental wellbeing as exercise helps you achieve a better state of physical wellbeing.

Other benefits of mindfulness

When we are in our one thought IVF tracked mind it is hard to open up to other things and experiences. It is, understandably, easy to get resentful with the world – especially the 25 year old you share an office with who ‘boom!’ accidentally got pregnant. Giving yourself the head space to get out of that mindset even if it is just for a short period of time at first lets you feel less stressed, develop better coping strategies, become more accepting, innovative, creative and taking one more step towards living your most vivid life.

How to practice mindfulness

I’ve written about the benefits of mindfulness to IVF success rates in previous posts and also given some practical exercises for you to get started on. Although you can get benefits from day one, overall for the best results you need to practice mindfulness on a daily basis. As David Michie points out, you don’t go to the gym just the one time and then wonder why you haven’t got abs of steel. Similarly, don’t just practice mindfulness the one time before deciding it’s not for you. Like going to the gym, it seems there is direct correlation between the hours you put in and the impact it has.

But if you want a time frame to aim for, David Michie guarantees if you practice mindfulness five times a week for six weeks you’ll definitely see these rewards.

I write a lot about mindfulness in Eat Think Grow. In fact, there are mindfulness or mindset suggestions for every day of your cycle and it is specifically tailored for women doing IVF. It focuses on helping you through every step of your IVF cycle and is written from the perspective of someone who has been there and knows how you might be feeling.

There are also other mindfulness resources around, including apps such as ‘Insight Timer’ and ‘Smiling Mind’ and books such as ‘Why Mindfulness is Better than Chocolate’.

Like so many practices that will ultimately influence your quality of eggs and overall health, the key is just to start. If you are not ready to take the plunge into a more detailed mindfulness program, such as Eat Think Grow, for now just start the day taking three deep breaths. Breathing in for about 3 seconds and out for around six, focus on nothing but these breaths. Pay attention to the temperature of the air, the sound your breath makes, the rise of you abdomen as you breathe in and lowering as you breathe out. Let your thoughts only focus on these three breaths… It will certainly be a start in clearing away some of the unwanted and often negative thoughts that may be swirling around your mind.

To sum it up

Although it seems that there is still so much that is unknown about the mind-body connection, there is still so much information that supports that the way we think and feel can have a direct relation to our physical health. Already they have linked serotonin, cortisol and other steroids (which all potentially impact our IVF health) and here we have mentioned DHEA and melatonin.

While it is likely that by practicing mindfulness you will see an improvement in these hormone levels in a natural way (which is theoretically a great thing for egg health during IVF) the other benefits of mindfulness on your ability to cope and get through what for many women may be some of the most challenging times of their life, is equally, if not more so, important.

PS If you have any worrying thoughts that turn towards harming yourself, those around you, or you feel have gone on just a bit too long, make sure you speak to a health professional that knows you. There are many treatments out there – and some of which will be suitable for women doing IVF or, hopefully, about to be, pregnant.

Reference

Fernando, S. & Rombauts, L. (2014) Melatonin: shedding light on infertility? – a review of the recent literature. Journal of Ovarian Research 7 98
Wiser, A., Gonen, O., Ghetler, Y., Shavit, T., Berkovitz, A and Shulman, A. (2010). Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: A randomized prospective study. Human Reproduction, 25 (10) 2496–2500
https://eocinstitute.org/meditation/immune-brain-chemicals-how-meditation-boosts-dhea-melatonin-gh/)

Does acupuncture increase IVF success rates? An update.

You don’t have to look far to find stories of women doing IVF reporting that acupuncture was the reason they got their take home baby. Acupuncture has many possible benefits to an IVF cycle including increasing egg quality, uterine blood flow and implantation(1) as well as reducing stress and it is certainly worth considering.

The research

Back in 2014 Nandi and colleagues summed it up perfectly when they said

basically, the evidence regarding the efficacy of acupuncture to improve clinical pregnancy rate is controversial. In spite of 40 clinical trials and nine systematic reviews, the debate still continues.’

If you are going to stop reading now, overall, that still stands.

If you are thinking about spending your hard earned cash on acupuncture, it pays to drill down a little more.

>>>If you are about to do an IVF cycle and are looking for evidence based ways to increase your success rates, make sure you check out Eat Think Grow.

Is it a sham?

In randomized control trials, when researchers are trying to ‘prove’ that a treatment, such as acupuncture, has an effect, it will often be compared to a control. The control could be receiving no treatment at all or in this case it could be the use of sham or placebo needles.

When placebo or sham needles are used the person receiving the treatment, in this case the woman doing IVF, really thinks they are having proper acupuncture. It might be that the needles just don’t penetrate the skin the same way or they are put in just slightly away from known acupoints and therefore aren’t doing what they should.

One recent systematic review looked at all the studies that examined the difference in IVF outcomes (such as clinical pregnancy or live birth) depending on whether they had placebo or actual acupuncture around the day of embryo transfer. What they found was that there was no statistical difference in clinical pregnancy rate, ongoing pregnancy rate or live birth rate between placebo or sham acupuncture and real traditional acupuncture.

When the control though was changed from being placebo to having no treatment at all there was a significant difference, in this case there was an increase in the live birth rates of those women having acupuncture when compared to those that did not. Those women that had the acupuncture were 1.15 times more likely than those that did not have the acupuncture to have a live birth (1). Interestingly it was not associated with clinical pregnancy rate or ongoing pregnancy rate.

Before rushing out to have acupuncture there are a number of things to consider.

Firstly, an odds ratio of 1.15 is still kind of small in the scheme of things. But hey, if that was a definite, I’d try it. Secondly, it’s not a definite. The research is not water tight and there remains lots of conflicting studies and also sometimes the studies they use to get to such numbers can be of low quality.

What is interesting though is that it may not be the actual acupuncture – that is the insertion of needles on the acupoints making the difference- it may be the experience. It might be the stress relieving properties of lying down for 30 minutes while the needles are in, or the placebo effect of really feeling as if you are making a difference to your next cycle or even just the chat with the practitioner.

Who knows.

Building on this theory, if you are thinking about acupuncture but aren’t so sure or can’t afford it, in the first instance I would a) find an activity that you genuinely enjoy and relaxes you and b) find an activity that you genuinely feel is going to make a difference to your cycle (you may find the mindfulness activities in Eat. Think. Grow! fits this bill ;)) It can’t hurt and just might get you some of the side benefits of acupuncture without the actual acupuncture. It would be interesting to see studies in the future that compared the IVF success rates between those that used acupuncture and those that used general relaxation strategies and determine what the difference to IVF success rates is.

It should be noted that other reviews have evaluated the impact of acupuncture in comparison to no treatment and found that it statistically increased the chances of an ongoing pregnancy but not clinical pregnancy rate or live birth rate to any statistical significance (Manheimer as cited in 3). Just to further highlight the fact that the evidence around this one really is conflicted.

Timing and dosage of acupuncture

Embryo Transfer
Many women doing acupuncture will typically go to the acupuncturist once or twice around embryo transfer and call it a day. Generally speaking this is insufficient to increase the possibility of live birth rates – though they are associated with reducing stress (3). This finding was also supported when a systematic review was completed of studies that when combined looked at the cycles of over 6300 women (4).

Egg Retrieval
This finding was similar when studies looked at women who had acupuncture around the time of egg retrieval – there was no difference in live birth rates between those that had acupuncture around the time of egg retrieval and those that didn’t (4). To be fair though, acupuncture done around the time of egg retrieval is generally more focused on pain relief being the goal of the treatment rather than increasing live birth rates, so that is reasonable.

First two weeks of cycle
The next grouping when looking at the timing of acupuncture and its impact on take home baby rates looks at women who have acupuncture during ovarian hyperstimulation – so those having acupuncture in the first half of their cycles while on gonal f, menopur or whichever follicle stimulating drug you are taking. These ladies typically had at least four sessions and it was found that overall, the pooled pregnancy rates were higher for those having acupuncture than those that were not. Specifically those that had the acupuncture throughout ovarian hyperstimulation where 2.41 times more likely to have a live birth than those that did not (4). To reach this figure there was only three studies that used the data from 435 women so it is not a large pool of women in the scheme of things and therefore, again, should be interpreted with caution. But it’s still interesting.

Entire cycle
When looking at how many treatments you would need to during a cycle, one study suggested that eleven acupuncture treatments during an IVF cycle was associated with significantly improved IVF birth outcomes and fewer miscarriages and another suggested 13–14 sessions was associated with significantly more live births compared with no treatment or embryo transfer day only acupuncture (3).

14 sessions in one cycle though is a lot! That is nearly once session of acupuncture every two days. I wonder if there are other forces at play in this group that weren’t measured in the study. For example, it would take a particular type of woman to go to acupuncture every second day during an IVF cycle. Presumably she wouldn’t work (or have a very flexible work situation), has the finances to attend all these sessions and clearly has some firm beliefs that acupuncture and/ or Chinese medicine is going to make an impact and therefore might also engage in other beneficial health practices also. Maybe these other hypothetical situations are also contributing to the increased success rates?

Like all things in fertility, it seems likely that the ultimate dosage will differ person to person (3), from what I have read though, highlighting the ineffectiveness of acupuncture on transfer day only towards live birth rates does seem more or less consistent across the research.

Types of acupuncture

The type of acupuncture can also make a difference to the likelihood of success. There is traditional acupuncture which is where needles are inserted into acupoints (usually around 4 to 10) along meridians in your body (this is the type you are probably most aware of). When these needles are stimulated by a small electrical current it then becomes electroacupuncture. There is also auricular acupuncture and laser acupuncture, which as the name suggests uses small laser beams to effect the acupoints instead of needles (4).

Essentially, out of all these types, electroacupuncture seemed to have the most affect. Those women that had electroacupuncutre in comparison to a control group were statistically more likely to have a clinical pregnancy and live birth. But noteworthy, they did not have higher ongoing pregnancy rates.

Possible harm

As stated earlier, acupuncture is generally believed to do no harm to an IVF cycle. I am only aware of one study where they found acupuncture to lower IVF success rates when done around transfer day. One theory for the reason for this result was that the acupuncturist was not ‘on site’ where the embryo transfer was being completed. It is thought that driving to this extra appointment timed just before and just after the transfer, added stress in an already stressful day and this extra stress helped explain this difference (5). It should also be noted that the group not receiving acupuncture had a freakishly high success rate – nearly double of what it would be expected to be. This in turn would make anything in comparison look bad.

Another point to take into consideration, and this assumes that you believe acupuncture does have the potential to have an impact, is that there are some acupoints that are believed to be associated with miscarriage or at the very least contra-indicated to pregnancy (3). This serves as another reminder to make sure that you are visiting an experienced practitioner.

Things to keep in mind

You can see the research is mixed. Although it may be simply that acupuncture does not work, one of the other reasons the research didn’t indicate any benefit (assuming there is one to reflect in the first place!) is that there was is so many differences in the methodology of administering acupuncture. There is simply too many variances in the methods acupuncture practitioners would use including acupuncture point selection, number of sessions, timing of when sessions are administered, type of needling control and location of treatment (1).

The Final word

As I started off saying the evidence is controversial. I believe that it is an all or nothing thing. If you are only going to go on transfer day because a friend of a friend did and she got a positive result on a pregnancy test, I’d probably give it a miss. If though you believe in Chinese medicine philosophy and are willing to integrate it into your life as well as attend as many as 14 sessions over the course of your cycle, then I think it might be worth a shot.

Also, just because the evidence that says acupuncture increases IVF success rates isn’t necessarily solid, that also doesn’t necessarily mean it doesn’t and with further study, well, who knows?

Reference

1. Cheong, Y.C., Dix, S., Hung Yu Ng, E., Ledger, W. & Farquhar, C. (2013). Acupuncture and assisted reproductive technology (Review). The Cochrane Library, Issue 7
2. Nandi, A., Shah, A., Gudi, A. & Homburg, R. (2014). Acupuncture in IVF: A review of current literature. Journal of Obstetrics & Gynaecology 34 (7) 555-561
3. Hullender Rubin, L., Anderson, B. & Craig, L. (2018). Acupuncture and in vitro fertilisation research: current and future directions. Acupuncture Medicine 36 (2) 119 – 122.
4. Qian, W, Xia, X-R., Ochin, H., Huang, C., Gao, C., Gao, L., Cui, Y-G., Liu, J-Y. & Meng, Y. (2017). Therapeutic effect of acupuncture on the outcomes of in vitro fertilization: a systematic review and meta-analysis. Archives of Gynecology and Obstetrics 295, 543–558.
5. Stener-Victorin, E. & Manheimer, E. 2011. Commentary on the Cochrane Review of acupuncture and assisted conception. Explore (NY). 2011 ; 7(2): 120–123. doi:10.1016/j.explore.2010.12.01

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.

Stress and anxiety: does it really matter to IVF?

For some of us, anxiety feels like your brain can’t stop calculating. Calculating outcomes, calculating consequences, calculating alternatives. All bad obviously. And all meaningless. After all when does an anxious person ever think an unknown outcome is going to be positive? Never, that’s when.

There are times when I have been so, so far into my wave of anxiety, I just couldn’t see out. The triggers for my anxiety are so inconsequential that a ‘normal’ person wouldn’t understand. But if you have ever had anxiety, fertility related or not, you will get what I mean.

When your friends short text message has you obsessing all day that you have somehow offended her (when the logical part of your brain, which is taking a back seat at the moment, knows you couldn’t have), when an exchange with a colleague has you literally sick to the stomach and the thought of a team meeting has your chest tightening.

I know some people won’t know what I mean by that, but I know a lot of you will.

A barrier to IVF

Stress, anxiety, fear of uncertainty, the feeling of your life constantly being on hold, the emotional cost, having ‘had enough’ and thinking that you have a poor IVF prognosis (without doctors actually stating this) are all major reasons why women don’t continue with IVF when the issue of money has been taken out of the equation¹.

A recent small study showed that for women in the US who chose not to continue with IVF despite being insured for more cycles, 39% stated that stress was the reason why they couldn’t continue treatment. Specifically, these women stated that the toll fertility treatments took on their relationship was too much as well as simply being too anxious and depressed to continue¹.

In fact, stress and anxiety being the reason women do not continue with IVF when money isn’t the issue (because their cycles are funded by researchers or government programs) is likely to be higher than 39% with the authors citing a Swedish study where the number is thought to be around 65% and an Australian study where the number was thought to be around 54%.

Women don’t start IVF and fertility treatments lightly. That take home baby is very much wanted and much sacrifice and consideration has already gone into making it happen. Therefore if it is the stress and anxiety associated with fertility treatments that is making women stop it must be HUGE, unbearable. And if so, why isn’t it talked about more and more done to help women before they get to that point?

Impact of stress on IVF success rates

The impact of stress and anxiety on IVF success rates is mixed, to say the least. One meta analysis reports that emotional stress is unlikely to have an impact on IVF pregnancy rates² and that feelings of tension, worry or depression experienced as a result of a woman’s fertility problems, its treatment, or other co-occurring life events are unlikely to further reduce chances of pregnancy. *phew*

On the other hand, there is a study that suggests that women who experience emotional distress and receive psychological intervention are twice as likely to become pregnant than those that do not³. Whilst there is a number of reasons to NOT take this statistic as a fact it highlights the potential untreated anxiety can possibly have. Although the authors report that the effect size of psychological treatments may not be as big as doubling success rates, they do nonetheless believe that larger reductions in anxiety are associated with improved pregnancy outcomes.

Whether or not stress and anxiety does hinder IVF success rates is yet to be determined. Personally, I think it is not as straight forward as just being anxious or not and there are other factors to consider such as how your body handles physical and emotional stress and what other medical conditions you may have.

Regardless of whether or not anxiety does impact success rates, I think we are all agreed that when stress and anxiety are better managed, quality of life improves along with the quality of our relationships and just the general ability to feel a little bit ‘normal’.

To sum it up, although its impact on IVF success rates is conflicted, overall, better managing our stress and anxiety can only be a good thing.

What is the best way to manage stress and anxiety when doing IVF?

Mind body interventions, such as yoga, web based interventions, cognitive behavioral therapy, acupuncture, online support groups, education sessions, guided relaxation and mindfulness classes are just some of the ways that have been studied in an effort to try and determine what best helps women doing IVF to reduce their stress and anxiety⁴. On top of this there is the more traditional methods such as exercising and eating a healthy diet.

Just as we all have different triggers and symptoms of stress and anxiety the ‘best’ way to manage it is likely to be unique to everyone.

For me, and many women, mindfulness does the trick to providing that small gap to disrupt the never ending thoughts that run around and around your mind. There has been some early studies that show that women who participated in a particular mindfulness course had improved quality of life measures and also increased pregnancy rates (44% of women in the mindfulness group had a pregnancy versus 26% of women from the control group who did not do mindfulness activities)⁵.

DIY Mindfulness

Although we cannot always be lucky enough to be asked to participate in a mindfulness based study for women doing IVF (!) we can embrace the mindful way of thinking and incorporate it into our everyday lives. We can get the benefits of unwinding and slowing our mind without the need to spend hours lying down to relax or taking time to attend particular courses and classes.

Next time you are in your anxiety wave, try this. When you have a shower (or are doing the tidying or waiting for your train or any number of mundane tasks where you notice your thoughts running away from you), list five things.

Five things that you can see (such as the soap sitting on the soap dish or the tap being twisted slightly off center). Five things that you can hear (such as the water going down the drain or the exhaust fan going around) and five things that you can feel (the tiles under your feet or the water on your back). As you get more practiced at doing this you will start to notice the details in what you are doing more, becoming more absorbed in the task that is at hand and more distanced from the ruminating thoughts in your head.

Mindfulness. Try it. And if you want additional mindfulness exercises have a look at this previous post. If nothing else, at least for a couple of minutes you will have the head space to feel just a little clearer, breaking that negative thought cycle and have the weight lifted from your chest. It does for me. And who knows, it may even improve IVF success rates.

** As always though, this article is just for general information. If your feelings of stress or anxiety is preventing you from living your life and you just don’t find enjoyment in things the way that you used to or if you have ANY feelings of self-harm or harming others, speak to your health professional immediately. They will be able to help you access treatments that you didn’t even know about so it is well worth the conversation**

References

Domar, A., Smith, K., Conboy, L., Iannone, M. & Alper, M. (2010). A prospective investigation into the reasons why insured United States patients drop out of in vitro fertilisation treatments. Fertility and Sterility. 94 (4) 1457 – 1459.
Boivin, J., Griffiths, E. & Venetis, C. (2011) Emotional distress in infertile women and failure of assisted reproductive technologies: meta-analysis of prospective psychosocial studies. British Medical Journal. 342:d223 doi:10.1136/bmj.d223
Frederkisen, Y., Farver-Vestergaard, I., Skovgård, N., Ingerslev, H. & Zachariae, R. (2010) Efficacy of psychosocial interventions for psychological and pregnancy outcomes in infertile women and men: a systematic review and meta-analysis. BMJ Open ;5:e006592. doi:10.1136/bmjopen-2014006592
LoGiudice, J. & Massaro, J. (2018). The impact of complementary therapies on psychosocial factors in women undergoing in vitro fertilization (IVF): A systematic literature review. Applied Nursing Research 39 220 -228.
Li, J., Long, L., Liu, Y., He, W. and Li, M. (2016). Effects of a mindfulness based intervention on fertility quality of life and pregnancy rates among women subjected to first in vitro fertilisation treatment. Behaviour Research and Therapy 77 96 – 104.