Blog - Fertility Fact Checker

What are my chances of IVF success?

Along with ‘how much does it cost?’ this surely must be one of the most commonly asked questions when attending an IVF clinic for the first time. With nearly 5 million children now being born as the result of artificial reproductive technology (ART), and more than half of them since 2007, surely the success rates are improving too?

As the media likes to constantly remind us and as we do actually already know, IVF success rates are dependent on age. The common statistic floated about is that fertility is at its best age 20 – 30, ok in the early 30’s and then freefalls after 35. If you believe the Daily Mail there is pretty much no chance of getting pregnant naturally after the age of 40.

The Centre for Diseases Control and Protection (CDC) has recently published data on the success rates of various ART cycles in the United States in 2012. This is the most reliant and uptodate statistical information currently available. Of all the IVF cycles that were completed (all 176247 of them), 68% were IVF with ICSI and it sounds about right that only 5% used preimplantation genetic diagnosis (PGD) testing. The information that CDC publishes is incredibly detailed and is even broken down to success rates of individual clinics, so is definitely worth checking out if you are going to a clinic in the U.S. This information is then collated and a National Summary is provided. As I said, there is a wealth of data that is collected and published, but essentially the percentage of women lucky enough to have a live birth (including multiples) for cycles with non donor eggs according to age were:

Age:

below 35 40%

35 – 38 31.3%

38 – 40 22.2%

40 – 42 11.7%

42 – 44 4.5%

45 and over 1.8%

Remember that a cycle is the process of where on day 1 of your menstrual cycle you ring the clinic to commence your medications, then have egg pickup, fertilisation of eggs and growth of embryos until day 3 or 5 when they are usually transferred. There can be a break in this chain at any time and cycles can at times be cancelled, no fertilisation may occur or there may be no embryos of a suitable quality to be transferred. That is why the results indicated are lower than if we were to only look at success rates per transfer, with a transfer being when the embryos are physically placed in the uterus. If we were to assume that the cycle did go to plan and there were embryo’s to transfer, the success rates per transfer suddenly increase to:

Age:

below 35 46.9%

35 – 38 37.8%

38 – 40 28.4%

40 – 42 16.1%

42- 44 6.7%

45 and over 3.1%

Although these success rates seem quite high, especially in the under 35’s it needs to be remembered that there was on average 1.9 embryos transferred at a time. This naturally presents a higher risk of twins, or more, which in itself carries the main risk of premature birth and the possible complications to your child’s health that can result.

It was also interesting to note that for women aged under 35, once pregnant 86% were able to carry to term. This more than halved to 40% for women aged 45 and over. So even once the battle to actually get pregnant is won, the older we are the more difficult it is actually to carry to term. Despite the stories you hear of 60 year old women giving birth to triplets.

For donor cycles the percentage of transfers resulting in a live birth across age groups were 56% for fresh transfers and 37% for frozen. This would indicate that by far the quickest way to parenthood would be to use donor eggs from a young woman most probably in her early to mid 20’s.

But these statistics just report overall percentages for women with a range of health issues including tubal factor, such as blocked fallopian tubes (14% of women had this diagnosis), uterine factor (6%), ovulatory dysfunction (14%), diminished ovarian reserve (31%), endometriosis (9%) and unknown factors (12%). 12% of women had multiple factors, 34% were unable to get pregnant due to male factor infertility and 17% of couples had both male and female factor infertility.

Yeah, but my case isn’t that bad, my chances are higher

You’re thinking it right? And it may be true. You might be closer to 25 then 35, healthy weight, don’t drink, don’t smoke and the only factor you have is that your partner has a low sperm count meaning that in theory, with ICSI you would make the perfect embryos (forgetting the fact that nothing ever goes smoothly in IVF!). It would be hard to extrapolise your exact chances of success given the above data because we are all more than just an age. That is why Celmatix may be of use (that’s their logo to the left in case you were wondering). Celmatix is a biotech firm that has been developing a huge database, called Polaris that provides ‘personalised medicine’. Polaris is used to collate and analyse the information of over 200, 000 real IVF cycles, taking information on a woman’s age, anthropometric data, lifestyle factors, diagnosis, results of previous cycles, hormone levels and much more other genetic information. This information is compared to data already collected on the other thousands upon thousands of cycles to more accurately calculate the probability of having children either with or without IVF and the timeframe of which it may take to achieve that success. Not only can it be useful to those who are going to give up (there was one statistic that mentioned many women give up after 2 cycles – even when insurance is funding treatment- and if they stayed around for just one more cycle 40% of those women would have had a child) but can also place realistic expectations in people who are more on the optimistic side. Instead of just picking numbers out of the sky, as it sometimes seems, a womans chances of success can be calculated far, far more accurately. This helps provide women with the information required to make a more informed decision when deciding whether or not to commence or continue with fertility treatment.

Without sounding like a Celmatix representative, which I’m not!, it seems that Polaris is likely to become more and more useful as it collects more data and more clinics can access this data. This technology is still developing however and is only available to a few American trial clinics.

And a new study indicates…

There was one study published just this month (1) that used a computer model, yes, it is just a computer simulation but they seem pretty convinced as to its accuracy, that calculated if a woman definitely wanted only one child and was prepared to use IVF, she should start trying to conceive by the age of 35. If she wanted two this would drop to 31 and if she wanted 3 would drop to 28… and who has more then 3 children these days anyway? If the couple did not want to use IVF these numbers drop 3 – 5 years.

Other factors that influence success rates in IVF

Although the largest one is surely maternal age, there are other factors that may influence IVF success rates that we have no control and hence ‘blame’ for. These primarily focus on practices at the lab such as the skill of the embryologist, the culture medium that is used to hold the embryos, the use of an embryoscope, type of transfer catheter and technique in using, the freezing process… the list can go on. As I said, we, as patients, have very little control over these factors other then to ensure that we remain part of the IVF process and understand, even if it is at the most basic level, what we are undertaking. That is also why it is useful to have the ability to compare the success rates across clinics using data like that published by the CDC.

What about IUI?

IUI is often utilised where there is unexplained infertility, anovulation (lack of ovulation) and medication will be used to rectify that or there is only moderate male factor infertility (it has been quoted as a washed sperm count of over 1million is required (3), though this number is still relatively low and some clinics may recommend a higher number of around 10million). The success rates are considerably less then IVF and so too is documentation revealing the success rates. Success rates for IUI generally are between 10 – 20% though this can vary as widely as 5 -70% (apparently). This data dates back to 1985 (2); however, the accepted success rates of around 10% are still widely used.

On a side point, it is interesting to note that in 2010 a Cochrane review was done evaluating whether or not double insemination was any better at achieving pregnancy then just the traditional single insemination (4). What they found was that across 1785 women significantly more women achieved pregnancy with a double insemination then just the single insemination. Although more research is needed before any concrete conclusions can be drawn it certainly is something to consider for women who don’t wish to undergo the more intrusive IVF.

To sum it all up, it seems that age does impact on the success rates of IVF. There are more factors to consider then purely maternal age however and it is reassuring to know, at least for those in America, that there is data available that allows for comparison of success rates between fertility clinics. Perhaps in the future this data will be collected from clinics world wide, which when paired with information from Celmatrix will allow women to make much more informed decisions when choosing to, or not to, pursue IVF and other ART procedures.

References

1. Habbema, J., Eijkemans, M., Leridon, H. & Egbert R. te Velde (2015) Realizing a desired family size: when should couples start? Human Reproduction doi: 10.1093/humrep/dev148 First published online: July 15, 2015

2. Allen, N., Herbert CM 3rd, Maxson WS, Rogers BJ, Diamond MP, Wentz AC. (1985) Intrauterine insemination: a critical review. Fertility and Sterility . 1985 44(5):569-80. Herbert CM 3rd, Maxson WS, Rogers BJ, Diamond MP, Wentz AC. PMID: 3902513 [PubMed – indexed for MEDLINE]

3. Abdelkader. A & Yeh, J. (2009). The Potential Use of Intrauterine Insemination as a Basic Option for Infertility: A Review for Technology-Limited Medical Settings Obstetrics and Gynecology International Volume 2009, Article ID 584837, 11 pages http://dx.doi.org/10.1155/2009/584837

4. Cantineau, A., Heineman, M. & Cohlen, B. (2010) Single versus double intrauterine insemination in stimulated cycles for subfertile couples. The Cochrane Library

What to expect when not expecting – the initial appointment

With approximately 15% of all couples now reportedly experiencing difficulty getting pregnant (1) its no surprise that there is generally a bit of a wait to see a fertility specialist. You may want answers straight away but if a fertility specialist can fit you in tomorrow I’d be wondering why. Before you see a fertility specialist you will need a referral from your GP. GP’s will generally advise you to be trying for 12 months if you are under 35 and have no obvious reason why you are having difficulty conceiving or six months if aged over 35.

So, you’ve got your referral, googled the success rates of different clinics in your area and waited out the couple of months before your first appointment. Although each clinic will vary, here is what to expect:

Questionnaire

You will most likely be sent out a questionnaire to complete prior to your first appointment. This will ask you all sorts of details and will be reviewed by your specialist with you and your partner as part of your initial appointment. It will include queries regarding:

past medical history (bring any blood tests or other pertinent information you have had collected in the past year)
your cycles (length of cycle and length and heaviness of bleed – it may be useful to write down the dates of your last six months of periods)
how long you have been trying to conceive including how many times a week you have sex and if you experience any pain or discomfort (no such thing as privacy from here on in!)
any past investigations
any past pregnancies, miscarriages and terminations
Your partners past medical history and any previous children
Any past sexually transmitted diseases. Everything you answer matters, for example, although it may have been treated long ago, chlamydia can cause pelvic inflammatory disease which is infection in your cervix, uterus and fallopian tubes. This can potentially block your fallopian tubes meaning that the eggs will not be fertilised by the sperm and can also cause difficulty with implantation. It is also associated with ectopic pregnancy, so obviously you want to make sure that the fertility specialist has all the information straight up.

It may seem a little invasive, and yes, it is!, but it is your first step forward to getting ‘things’ sorted.

Internal Exam

The internal exam will be done by the doctor and will generally have a nurse in the room. You will need to completely undress from the waist down and is a quick and generally painless digital examination looking for signs of any structural abnormalities or endometriosis (for example, pain when pressing in a particular spot).

If the men are even suspected of having any difficulties they will also be assessed, but again it is quick and painless and nothing to worry about.

Blood Tests

Although these probably wont be done in the actual appointment, they will most likely form part of your initial work up. They include, but definitely aren’t limited to the following:

AMH – antemullarian hormone. At its most simplest, AMH is the hormone that dictates your ovarian reserve and measures how loudly the ‘biological clock is ticking’. AMH is a hormone that is excreted by the immature, or antral and preantral, follicles that are in your ovaries waiting to become ‘lead’ follicles. The result of this test can be useful to determine the amount of eggs, or ovarian reserve, that you have left with generally a higher number indicating a higher amount of eggs that can be retrieved. It is also useful in helping to diagnose polycystic ovaries as ladies with PCOS will generally have more antral follicles and hence higher levels of AMH.

Interpretation (women under age 35)	AMH Blood Level
High (often PCOS)	Over 4.0 ng/ml
Normal	1.5 – 4.0 ng/ml
Low Normal Range	1.0 – 1.5 ng/ml
Low	0.5 – 1.0 ng/ml
Very Low	Less than 0.5 ng/ml

Source: advancedfertility.com (2)

I have included the levels above just because some of the more obsessive of us like to know our results and compare against the ‘normal’. Be very careful though, as advancedfertility.com highlights all these figures are on a sliding scale and you should NOT be disappointed if you happen to be categorised as ‘low’ as opposed to ‘low normal’. The clinical difference is very small, though has been categorised for the purposes of putting it in a nice chart. Also, normal or expected AMH levels are highly dependent on your age, so it is best to speak to your specialist about your particular levels.

2. Prolactin – for this test you will be required to sit for around 20 minutes before the blood being taken and because prolactin levels can vary throughout the day it is usually preferred to take it within a couple of hours of waking and in a fasting state (3). Prolactin is important to measure as if your prolactin level is high it can inhibit the action of the follicle stimulating hormone (FSH) and gonadotropin releasing hormone (GnRH) which are needed for a lead follicle to mature and hence ovulate. If these levels are low then ovulation may not occur or may cause a shortened luteal phase (7). The normal range for women is 85 – 500 mIU/L (7) Women who are breastfeeding tend to have higher levels of prolactin which is why some people consider breastfeeding as a form of contraception (its not!). If your levels are high (and significantly high, not just marginally high) these get be treated with medications such as bromocriptine and cabergoline (4,6), but there can be other reasons for high prolactin such as any other medications, stress or if you have PCOS (5). If your male partner has low sperm count it may also be worth checking his prolactin levels as it can be associated with low sperm count, low testosterone and erectile dysfunction (3). The normal range for men is 150 – 500 mIU/L (7)

3. Leutinizing Hormone (LH). LH is the hormone that in your regular cycle will experience a sharp rise just prior to ovulation, roughly 24- 48hours. It is this ‘surge’ of LH that ovulation predictor kits often rely on to predict ovulation and hence indicate to you to have sex. LH also helps develop the corpus leuteum which is important in manufacturing progesterone after ovulation to support a pregnancy and also to limit the follicle stimulating hormone.

Luteinizing hormone in blood
Menstruating women
Follicular phase:	1.68–15 international units per liter (IU/L)
Midcycle peak:	21.9–56.6 IU/L
Luteal phase:	0.61–16.3 IU/L

Source: http://www.webmd.com/women/luteinizing-hormone?page=3 (6)

Again, I have included the above chart, but remember to take all measurements with a pinch of salt and units can alter depending on what country you are in. Some consider a normal range to be below 7 when taken on day 2 to 3 of the menstrual cycle (7)

4. FSH. In the normal cycle FSH is responsible for recruiting and growing to maturity follicles which hopefully contain healthy, viable eggs. Many ladies who have undergone IUI’s or IVF’s will be familiar with FSH in its pharmaceutical form of Gonal-F or Purgeon, to name two, and it is what is injected on a pretty much daily basis until ‘trigger’ and ovulation. FSH should be tested on day 2- 3 of your menstrual cycle and a normal range is typically between 2 – 20 U/L with a level under 6 being excellent and the ratio with LH should be as close as possible to 1:1 (7)

5. Thyroid tests. The thyroid produces T3 and T4 which controls growth, metabolism and energy level. The thyroid itself is influenced by thyroid stimulating hormone or TSH. Thyroid problems are common in women and can be a cause of infertility and having either an over or an under active thyroid can result in infertility though the risk is greater for those with an underactive thyroid (7) The accepted levels of TSH varies but for women wishing to conceive it is optimal for levels to be between .3 and 2mIU/L, though ‘normal’ levels has been altered from 5mIU/L to 2.5mIU/L. It would also be beneficial to test for thyroid antibodies as the presence of these may indicate that your antibodies are attacking your thyroid gland and hence impacting its normal functioning (7). Women with thyroid antibodies may also have elevated levels of NK cells which are associated with infertility and recurrent miscarriage as well as other autoimmune conditions (8)

6. Oestradiol (E2) is the main oestrogen in your body and FSH stimulates the ovaries to make oestradiol. The normal range at day 2 or 3 is 100 -200 pmol/L (7).

7. Progesterone is measured after ovulation has occurred and a reading of progesterone greater then 25nmol/L often confirms ovulation (7). Progesterone is important for preparing your lining to accept an embryo for implantation and also to lower the immune system to accept and support a pregnancy.

8. Free testosterone and androgen. This is useful in assisting in the diagnosis of polycystic ovarian syndrome (PCOS) and women with PCOS typically have higher levels. Free testosterone should typically be below 4pmol/L and free androgen index between 1 and 8 percent (7).

9. Autoimmune tests. The impact of the immune system infertility is not always appreciated by all fertility specialists at the beginning of your ‘journey’. Some specialists may not even test for these before three miscarriages or failed cycles. If your doctor does not test for these and especially if autoimmune conditions such as rheumatoid arthritis or type 1 diabetes is present in your family it may be worth discussing this.

Tests within this group include anti-nuclear antibodies, anti-DNA/ histone antibodies, antiphospholipid antipodies, antisperm antibodies, natural killer assay, cardiolipin antibodies. As I said, some believe that the presence of these markers are not directly relevant to fertility. There are many women on various forums and boards however who have had success only after the investigation and treatment of various autoimmune conditions.

If you have ‘unexplained’ infertility or feel immunology might be playing a part in your medical history you may want to look at Dr Alan Beer’s book, Is Your Body Baby-Friendly, which discusses immune issues in detail. Beware though! If you are just starting your fertility journey this book can be quite detailed and may be a little overwhelming. That is why if you are concerned about your autoimmune response, as a first line of investigation discuss it with your doctor and see how it relates to your specific clinical presentation.

10. Sexually Transmitted Diseases and Infection. These tests are usually done by either blood or urine test and include:

chlamydia
gonorrhoea
syphilis
rubella

Please note that while comprehensive, it is not an exhaustive list of blood tests and your clinic or treating doctor may have other tests they wish to complete depending on your clinical presentation. Conversely, and again depending on your clinical presentation and past medical history, you doctor may not feel all of the above tests are necessary.

Tracking Cycle

The tracking cycle takes place after your initial appointment but is part of the initial work up when starting fertility treatments. A tracking cycle involves you attending your clinic throughout your cycle, starting on Day 2 or 3, Day 1 being the first day of your proper bleed. You usually need to attend the clinic early in the morning when nurses and phlebotomists take the blood. There are often many women attending at the same time as you so sometimes it may take up to an hour depending on the efficiency of your clinic and how many women are waiting. Once the blood is taken the clinics laboratory will measure your blood for hormones such as oestrodial, progesterone and luteinising hormone. This will enable your doctor to compare your cycle with a ‘typical’ cycle and aid in the diagnostic process. You will need to visit the clinic several times throughout the cycle, however, the nurses will tell you when you need to attend depending on your previous blood result.

During the tracking cycle you will also need to have an ultrasound completed to see how many follicles you are producing, the size of these follicles as well as the thickness and quality of the lining in your uterus. This is a transvaginal ultrasound where, as the name suggests, the probe is placed inside of you.

Hysterosalpingogram … or HSG for short

This will likely to be done at a radiography clinic. It involves injection of a dye into your vagina and cervix which fills up the uterine cavity and fallopian tubes. Several xrays are taken and the dye allows for any blockages, fibroids or structural abnormalities can be seen. There are certainly more pleasant experiences to be had then a HSG so some women may be advised to take pain relief prior to attending. Additionally, there may also be the risk of infection so an antibiotic may also be provided for you to use as a preventative measure. HSG’s should be done in the follicular phase of the cycle (before ovulation) and are definitely NOT indicated for women who might be pregnant (as if!). On a positive note, there is some suggestion that women are able to successfully get pregnant in the cycles immediately after a HSG, the exact cause and success rates for this is unknown, it may just be injecting the dye into your reproductive system ‘cleans it out’ so to speak allowing for the released (and hopefully fertilised egg) to make its journey into the uterus easier.

Laparoscopy

This one will involve you being admitted for day surgery at your local hospital. Depending on the doctor, approximately three small incisions are made in your abdomen area – one in your belly button which you wont see, one under your pubic line and one to the side of your abdomen. These incisions enable the doctor to insert a camera to investigate from the inside, and most frequently, to see endometriosis. If endometriosis is seen, depending on the severity of the endomentriosis your doctor may remove it then and there or otherwise, make a time for you to come back.

Below are two photos from an laparoscopy (apologies, they are a little graphic…). The one on the left, shows severe endometriosis which is the black areas you can see. You can see the ovary to the right of the picture. The one on the right is the same person six years before with only mild endometriosis as indicated by the small black dots. The ovary is seen in the bottom right segment.

MALE TESTS

Sperm Analysis Test

This information is pretty easy to find else where by asking Dr Google so I’ll keep it brief. It is the one where it involves the man producing a ‘sample’. Depending on how far you live from your local clinic though he may be able to produce this at home and drive it in to the clinic, which is obviously a bit more stress free. Also, these are best completed by laboratory technicians specialising in reproductive medicine, such as the lab attached to your fertility clinic. If your GP asks for a sample before making the referral and you are required to take it to a regular pathology laboratory they often lack the expertise to accurately complete a proper count, so therefore take any results with a pinch of salt.

When getting results from a sperm analysis test results will include numbers on

count – overall number
morphology – the shape of the sperm, for example, checking they don’t have two tails etc
motility – how they are moving? are they moving in a straight line? speed, for example
‘marine sperm’ – this might only be how my Dr described it but my clinic does really report on the above as all that all really matters is how many of the best of the best are there?

DNA Fragmentation Test

At its very most basic level this test is evaluating whether or not the DNA contained in sperm is healthy or intact. Even men with seemingly healthy sperm in the sperm analysis test may have DNA fragmentation and one study suggests in 80% of couples with ‘unexplained’ infertility with further investigation, the reason for the infertility was high amounts of DNA fragmentation (10) The clinical threshold for DNA fragmentation is 30%, that is if 30% or greater of sperm is damaged this is associated with lower fertilisation, implantation and pregnancy rates. Although high amounts of DNA fragmentation is associated with poor outcomes, if using ICSI then this may not necessarily be the case due to the ability to ‘pick out’ sperm with DNA strands intact using particular tests and techniques. Additionally, depending on the quality of the oocycte, damaged DNA may also be able to be repaired resulting in a positive result (9)

Blood Tests

1. Testosterone levels in men are generally within normal ranges even if there are significant sperm production difficulties (7). The normal range of total testosterone is 8 – 27 nmol/L with free testosterone being 170 -510.

2. Luteinising hormone stimulates testosterone production and the normal range is 2 – 10U/L.

3. Follicle Stimulating Hormone. Similar to FSH stimulating maturation of ooyctes in women, in men FSH stimulates sperm production. THe normal range in men is 1 – 5 U/L.

Ultrasound

Men may also be required to have a testicular ultrasound done to investigate structural abnormalities in the testes and scrotum.

Done!

Phew! That was a lot, but hopefully it gives you a better idea as to what kind of tests you may expect when visiting a fertility specialist for the first time. As I mentioned the above is not exhaustive and conversely your doctor may not think it necessary to complete all of the above investigations. If you have any questions or disagree with any of the above, please let me know.

References

1. https://www.nichd.nih.gov/health/topics/infertility/conditioninfo/Pages/common.aspx

2. http://www.advancedfertility.com/amh-fertility-test.htm

3. http://www.drmalpani.com/knowledge-center/articles/prolactin

4. http://www.labtestsonline.org.au/learning/test-index/prolactin#tab-index=2

5. http://www.advancedfertility.com/bromocriptine-prolactin-ovulation.ht

6.http://www.webmd.com/women/luteinizing-hormone?page=3

7. Cabot, S. & Jasinska, M. (2011) Infertility: The Hidden Causes. WHAS Pty Ltd

8. Beer, A., Kantecki, J & Reed, J. (2006) Is your body baby-friendly? Ajr Publishing.

9. Sakkas, D. & Alvarez, J. (2010) Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertility & Sterility, 93 (4) 1027 – 1036.

10. Lewis, S. (2013) The place of sperm DNA fragmentation testing in current day fertility management. Middle East Fertility Society Journal. 18 (2) 78 -82

Eating pineapple to aid in implantation? Read on…

Many women undergoing fertility treatments would have at some stage come across theory of eating pineapple to aid in implantation. But there seems to be some confusion as to why pineapple and can eating canned pineapple or drinking pineapple juice be of any benefit also?

Why Pineapple?

There are many forum posts and blogs written by ladies TTC who report that pineapple, or Ananas comosus, to use the scientific name, is said to aid in implantation as it contains bromelain. Bromelain is an enzyme is found in the core, juice and skin of pineapple but is most plentifully found in pineapple stem (2). Therefore bromelain is likely to be found in low levels in pineapple juice, however, if you are buying canned or carton pineapple juice the pasteurisation and sterilisation processes it needs to go through to preserve the pineapple juice in a can or carton most likely reduces the effectiveness of any naturally occurring bromelain. That is not to say though that firstly, there is any scientific evidence supporting the theory that bromelain is beneficial in aiding implantation and secondly, even if it was that there are sufficient levels found naturally in pineapple stem for it to be of therapeutic value.

Extracted bromelain is also available as a tablet form, though the dose varies considerably according to the reason for use and it would not be advisable to self medicate.

Uses of bromelain

Bromelain is believed to have properties that can assist the human body in many ways including the prevention of blood clots, swelling and inflammation. Due to these properties it has been indicated as being useful in preventing transient ischaemic attacks or mini-strokes and angina (1). It is also beneficial for those with osteo and rheumatoid arthritis due to its anti-inflammatory and pain relieving properties and is also suggested for people with chronic, inflammatory immune conditions and also as a method of assisting in the debridement of burns, in the relief of diarrhoea and with future research may also become an adjunct cancer therapy (1). Finally, bromelain has also been administered to people who have had sports injuries in order to control the swelling and bruising (2)- is there anything it can not do?!

Bromelain and pregnancy

As this is a fertility blog though we will assume that we want to know how bromelain can assist in supporting a pregnancy. I have been unable to find any control trial experiments or scientific research that indicates that bromelain is effective in the implantation of embryos. This does not necessarily mean that bromelain has no benefit just that it has not been researched and hence its efficacy can not be determined.

Due to its anti-inflammatory and anticoagulant properties though there might be a couple of pathways in which bromelain may be effective.

Due to its anticoagulant (stops blood clots) properties it could possibly facilitate blood flow to the uterus. With improved blood flow to the uterus the lining and health of the uterus may be improved which provides a better environment for which implantation can occur. Possibly.
Due to its anti-inflammatory properties bromelain has been found to benefit those who have autoimmune conditions such as rheumatoid arthritis. Further research may one day suggest that bromelain can assist women with autoimmune conditions and markers who’s condition is resulting in infertility. There have been studies done that indicates that bromelain was able to modulate how cells binded with T cells and natural killer cells (1), two types of cells also implicated in infertility.

Well, it can’t hurt anyway?

The mechanisms of bromelain are clearly under researched, particularly with reference to fertility. Therefore any benefits and also any costs of using bromelain are unknown and hence taking bromelain tablets should be avoided without proper medical advice. Although bromelain found naturally in pineapple is likely to be in doses that are relatively low, some people advise against eating too much pineapple too early in your cycle. This is as if it is eaten before ovulation some believe that the acidity of the pineapple may increase the acidity of cervical mucous making it a hostile environment for sperm and hence fertilisation (2).

However, due to the assumed relatively low levels of bromelain existing naturally in pineapple, as long as you eat it as recommended (no more then a couple of slices a day) and after confirmed ovulation, or embryo transfer, it is unlikely to do any harm. If you are looking at taking bromelain tablets, I would definitely recommend you speaking to a health professional before doing so, particularly due to bromelains blood thinning properties and especially if your fertility specialist has put you on low dose aspirin. It has also been found to increase the effectiveness of antibiotics so again seek medical advice before commencing bromelain but especially if you are on any other medications.

If you are thinking of, or doing, IVF don’t forget to get your free IVF guide with 18 other evidence based ways that will hopefully increase your egg quality, implantation rates and ultimately, IVF success.

References

1.Pavan, R., Jain, S. & Kumar, A. (2012) Properties and Therapeutic Application of Bromelain: A Review. Biotechnology Research International, published online 2012 Dec 10. doi: 10.1155/2012/976203

2. Meschino, J. Meschino Health Comprehensive Guide to Herbs. Available from meschinohealth.com

3. Campbell, L http://natural-fertility-info.com/bromelain-pineapple-for-implantation.html

Does bed rest help after an embryo transfer?

As if there isn’t enough to worry about after an embryo transfer, worrying that you are ruining any chance of a BFP as you have to get up and go straight after an embryo transfer is up there. This is especially so for women who need to go straight back to work after taking all that time off for blood tests and monitoring, the egg collection and the transfer itself.

Everyone has an opinion on how much bed rest you need and it ranges from none at all, to 10 minutes straight after the transfer to up to three days (who has time for that?). Saying that though, who amongst us wouldn’t lie flat on our backs for three weeks if it was proven to increase the probability of a successful embryo transfer?

When I searched ‘bed rest embryo transfer’ in a medical search engine I found less than 10 articles directly related to this topic in the last 10 years. Needless to say more research would be useful. Or would it? I only say this for I couldn’t find one piece of evidence that indicates that bed rest is beneficial – has this conclusion already been drawn?

The JURY IS IN

If it were to be summed all up in one sentence, Abou-Setta et al in their 2014 Cochrane Review (1) report

there is insufficient evidence to support any specific length of time for women to remain recumbent, if at all, following embryo transfer

So it seems as if there is no evidence to support the need to rest after a transfer. To reach this conclusion they did a thorough search for all trials that had been conducted and found two studies that they thought were appropriate, consisting of 594 patients. When we think of how many embryo transfers get done every day and the amount of money that changes hands, I think that this indicates a disproportionately small number of research articles being produced. But hey.

Abou-Setta et al (1) also highlight that the research done is of low quality and recognises that more research is definitely needed in this area which may help to change future thinking.

Well at least it doesn’t do any harm…?

Gaikwad et al (2) report that even 10 minutes of bed rest following embryo transfer can be detrimental. They report on one study where there were two groups of women – one who had been told to rest following transfer and one who didn’t rest. Ultimately this study had to be abandoned for ethical reasons because it became evident early on that the women who rested following a transfer had a lower chance of a successful outcome then those who did not. Gaikwad speculates on other investigators thoughts as to whether or not the seemingly detrimental effect of bed rest is due to the position of the uterus when lying down as well as speculating that continuing on with every day living helps manage our coping strategies and anxiety levels which has previously been researched to have an impact on success rates.

The amount of time women are recommended to rest in bed also varies. This has also been researched and regardless of whether the bed rest is for 10 minutes (2), 30 minutes (3), one hour (4) or one day (5) it seems that the less time that is spent in bed post embryo transfer the better the chances of pregnancy and ultimately a take home baby. It should be noted that there is some conflicting evidence and not all researchers say that bed rest is detrimental (though they do all seem to concur that it is at the very least not beneficial).

Why is bed rest recommended?

Whilst I am sure that they exist (surely?!) I have been unable to find any articles, proper research articles or internet articles that support the need for bed rest, despite the chat rooms and forums being full of women who report that their specialist advised them to do so. Whilst these articles are also not saying to go run a marathon (who would with ovaries the sizes of oranges) why are a lot of women undergoing embryo transfers still be advised to do so? Remember though if your specialist has recommended a period of rest for you, query it with them, there could be something in your particular medical history that makes it a worthwhile pursuit… maybe…

Other reasons why bed rest is not required

Placement of embryo

Personally, despite the fact that whilst I try and linger horizontally in the ‘transfer room’ as long as possible after a transfer, the rational side of me believes that rest is not required and the embryo isn’t going to ‘fall out’ as soon as you stand up. When you look at the thousands of years of natural conceptions that happened prior to IVF, I am pretty sure that not one of those fertile women even thought to have a lie down on day 3 or 5. Especially for those ladies who do the day 5 transfers the location in your uterus where your Specialist places the embryo during the transfer is pretty much exactly where it would be by day 5 in nature, ie typically towards the top of uterine cavity after traveling through the fallopian tube. And for those ladies who don’t do day 5 transfers, embryos can move and fertilise at any point in the fallopian tube or uterus so again, no stress required! Those ladies who really do think about things a lot, yes transferred embryos can move around, but they are pretty well supported once they are in they are in there (its not as if there is just a totally empty space) and the incidence of ectopic pregnancy in IVF gestations is around 1.3% (Australian Doctor, 27th March 2015) which when you think about the overall success rates is relatively low and putting yourself on bed rest because you think the embryo is going to move around doesn’t really outweigh the reasons for NOT going on bed rest.

Circulation and blood flow

Additionally, when we are moving around the circulation through out body is improved, this includes circulation to the uterus. The longer that we are immobile or resting in bed, our circulation system slows meaning that less blood is being pumped around the body and to the uterus. One of the reasons some of us take low dose aspirin or visit the acupuncturist is to try and increase blood flow to the uterus so why would we want to do anything that inhibits this. By increasing blood flow some believe that this can increase the quality of the lining which ultimately supports implantation. When you look at it from this point of view, we really should be making sure that we are doing light exercise and improving circulation throughout the cycle.

Over thinking time

When we are on bed rest it gives us too much time to think. Whilst for a short time we may be secretly quite happy to finish off the Orange is the New Black boxset our mind will pretty soon start turning back to the little ball of cells that has been placed inside of you. One thing that fertility patients tend to do very well is think, which inevitably leads into a dangerous cycle of self blaming, stress and anxiety. No thank you. And this theory is also supported by Küçük (7) and by Gaikwad (2) as briefly mentioned above. More on the impact of stress and anxiety in future posts.

I am sure there are many other reasons why bed rest could be detrimental to embryo transfer success, but these are just to name a few.

But please tell me if have you been instructed to rest after embryo transfer and for what reasons?

And as always, the above is just for information purposes, please discuss with your treating specialist to decide what is best for your individual situation.

References

1. Abou-Setta, AM, Peters LR, D’Angelo A, Sallam HN, Hart RJ, Al-Inany HG. Post-embryo transfer interventions for assisted reproduction technology cycles (Review). Cochrane Database of Systematic Reviews 2014. Issue 8

2. Gaikwad, S., Garrido, N., Cobo, A., Pellicer, A. & Remohi, J. (2013) Bed rest after embryo transfer negatively affects in vitro fertilization: a randomized controlled clinical trial. Fertility and Sterility Vol 100 (3) 730- 735

3. Purcell, K., Schembri, M., Telles, T., Fujimoto, V. & Cedars, M. (2007) Bed rest after embryo transfer: a randomized controlled trial. Fertility and Sterility Vol 87 (6) 1322 – 1326

4. Bar-Hava I, Kerner R, Yoeli R, Ashkenazi J, Shalev Y, Orvieto R. (2005) Immediate ambulation after embryo transfer: a prospective study. Fertility and Sterility 83 (3) 594–597.

5. Amarin, Z. & Obeidat, B. (2004) Bed rest versus free mobilisation following embryo transfer: a prospective randomised study. BJOG: An International Journal of Obstetrics and Gynaecology Vol 111(11) 1273-6.

6. Australian Doctor

7. Küçük, M. (2013) Review Bed rest after embryo transfer: is it harmful? European Journal of Obstetrics & Gynecology andReproductive Biology Vo (167) 123–126