Fertility Fact Checker

Improve your chances of IVF success using evidence based research

Is IUI the best choice for women with unexplained infertility?

Unexplained infertility IUIUp to 25% of women with fertility difficulties are ‘unexplained’.  So there are certainly a few ladies who will be interested to know that a comprehensive literature review evaluating the success of intra-uterine insemination (IUI) for women with unexplained fertility has confirmed its findings (1).

In an attempt to determine if IUI (both with and without medication) is more successful at achieving higher birth rates than timed intercourse or ‘expectant management’, the findings from 14 studies including 1867 women were combined and analysed.   ‘Expectant management’ by the way is letting nature run its course with no intervention. I find the term quite ironic in the fertility setting because that is the whole point – fertility patients are not ‘expectant!’

Remember, this review was completed to examine the impact of IUI for women with unexplained infertility. Not women with PCOS, not women who has a partner with low sperm count, just unexplained.

Interestingly, the authors included studies that examined women with mild endometriosis. Mild endometriosis was presumably not considered troublesome enough of a diagnosis to be the cause of preventing a woman getting pregnant. Women who had a diagnosis of moderate endometriosis however, were not included in the study.  It seems that having moderate endometriosis was a reason for being unable to conceive and hence these women were not categorised as ‘unexplained’.  You with me? Whilst we can appreciate why this distinction was made, I wonder if in years to come, as more research is completed if this distinction will change. From what I understand, how the reproductive system works – both in isolation and when interacting with our other systems such as the endocrine and immune system – it is in such a delicate balance. Perhaps one day even mild endometriosis will be found to have, for example, a very subtle immunological response that means it is widely recognised as a cause for fertility problems. Ultimately this may change the diagnosis and label of ‘unexplained’.  But for now and the purposes of this review, I digress.

Using IUI

In some instances of unexplained infertility IUI is considered the first port of call. It is financially less expensive and places less physical stress on the woman trying to conceive than IVF. Though if you ask me, and anyone else who has had a two week wait after an IUI, psychologically it is just as hard. IUI can be completed either with ovarian hyperstimulation or without.  Ovarian hyperstimulation is when medications are administered to stimulate the ovaries to produce and release an egg.  When there is no ovarian hyperstimulation, this is also referred to as a ‘natural cycle’.

Benefits of IUI with ovarian hyperstimulation

IUI with ovarian hyperstimulation is thought to have a few added benefits when compared to IUI without ovarian hyperstimulation. One of these is that with the hCG trigger shot (such as pregnyl or ovidrel) doctors theoretically can more accurately pin point the time of ovulation (1). This means that you can be more sure that when the sperm is inseminated, it is at the right time to fertilise the egg and hopefully get that BFP.

Another reported benefit is that IUI with ovarian hyperstimulation enables some subtle abnormalities with follicle and endometrial lining growth to be ironed out (1). I kind of see this as your reproductive system getting ‘hijacked’ and being coerced into do the ‘right thing’ through the administration of medications.

Costs of doing IUI with ovarian hyperstimulation (and not the financial kind)

From what I read, the main negative is that there is a risk of ovarian hyperstimulation syndrome (OHSS). Presumably though this would be much less of a risk than women undergoing IVF as the quantities of medication being taken and the amount of follicles and eggs that are being grown are in much smaller quantities.

Another negative is the risk of a woman falling pregnant with multiple children. If during ovarian hyperstimulation a woman has three follicles growing there is a chance that all three follicles contain eggs and could fertilise (If you have more then two follicles growing in an IUI cycle sometimes your clinic will cancel your cycle for this reason). This risk would have been a little better controlled in IVF as most often only one or two embryos are actually transferred. It is also because of the risk of multiples that NICE fertility guidelines states that ‘ovarian hyperstimulation should not be offered to women with unexplained infertility.’

Regardless of the NICE guidelines though and the very real risk of complications to yourself and your future children, I am willing to bet that most women experiencing infertility would certainly take take their chances if it meant that an IUI with ovarian hyperstimulation would mean higher success rates…am I right?

Finding your way through IUI statistics

Well, does IUI in unexplained infertility have good success rates?

Remember this is only the results from this literature review (1). There may be very real reasons why your odds are better (or worse) for a particular treatment and only a conversation with your doctor about all the alternatives can clarify that.

What this literature review did was compare a number of the different protocols of IUI against each other. These were:

  1. IUI versus timed intercourse where both were done in a natural cycle – that is without ovarian hyperstimulation
  2. IUI versus timed intercourse, both using ovarian stimulation
  3. IUI in a natural cycle versus IUI in a stimulated cycle
  4. IUI in a stimulated cycle versus timed intercourse in a natural cycle (similar to expectant management)
  5. IUI in a natural cycle versus timed intercourse in a stimulated cycle.

The findings were:

1. IUI without stimulation when compared with timed intercourse, also without stimulation was found to have no evidence of a difference in cumulative live births between the two groups. The evidence suggested that if the chance of a live birth with timed intercourse was assumed to be 16%, that of IUI would be between 15% and 34% (remember the results are reporting cumulative birth rates, not birth rates per cycle).

2. IUI versus timed intercourse, both in a stimulated cycle – again the study reported that there was no evidence of a difference between the two treatment groups with the evidence suggesting that if the chance of achieving a live birth in timed intercourse was assumed to be 26%, the chance of a live birth with IUI would be between 23% and 50% (though I can see what you are thinking, it looks like the IUI was still better, though remember that this is cumulative birth rates and the difference may not have been statistically significant)

3. IUI in a natural cycle versus IUI in a stimulated cycle – there WAS an increase in live birth rates for women who were treated with IUI in a stimulated cycle compared with those who underwent IUI in natural cycle (without stimulation). The evidence suggested that if the chance of a live birth in IUI in a stimulated cycle was assumed to be 25%, the chance of a live birth in IUI in a natural cycle would be between 9% and 21%.

4. IUI in a stimulated cycle versus timed intercourse in a natural cycle– there was no evidence of a difference in live birth rate between the two groups The evidence suggested that if the chance of a live birth in timed intercourse or expectant management in a natural cycle was assumed to be 24%, the chance of a live birth in IUI in a stimulated cycle would be between 12% and 32%.

I find this one particularly interesting as surely an IUI in a stimulated cycle would be better than just letting nature do run it’s course? What it does say though, is that in the context of this particular study, for women who are experiencing unexplained infertility, there is still just as much of a chance that a pregnancy may still occur by trying through the ‘old fashioned way’ than by having a full blown IUI!

5. IUI in a natural cycle versus timed intercourse in a stimulated cycle – There was evidence of an increase in live births for IUI.  The evidence suggested that if the chance of a live birth in timed intercourse in a stimulated cycle was assumed to be 13%, the chance of a live birth in IUI in a natural cycle would be between 14% and 34%

In Summary

Personally, I find it is difficult to see any rhyme or reason as to the above results. In some cases it is the IUI itself that seems to improve success rates but sometimes it doesn’t.  Other times medication might be key to success but then this is not continued. And then in another scenario a stimulated IUI had no statistically significant improvement over ‘expectant management’!  It did appear though that if you had decided that you needed to take action and see if an IUI was going to work for you, IUI with medication was the way to go.

The author of the study came to the conclusion that:

There was no conclusive evidence of a difference between most treatment groups in cumulative live birth rates (i.e. rates at conclusion of a course of treatment)… for couples with unexplained subfertility undergoing IUI when compared with timed intercourse, both with and without ovarian hyperstimulation

Before you ask your fertility specialist why you are doing one set of protocol over another, remember the following:

  1. As always in fertility research more evidence is required. In this instance more studies examining each of the different situations would have led to stronger quality of evidence.
  2. Your past medical history or individual set of circumstances may have led your fertility specialist to recommend one intervention of another which may seemingly contradict these findings.
  3. The above findings are for cumulative birth rates – which in this instance means that when this treatment has stopped for one reason or another, then that is the outcome. It should not be confused with the success rates for each cycle ie each monthly treatment.
  4. There is obviously a wide discrepancy in success rates across the studies which again reflects individual circumstance as well as highlighting a need for larger more precise studies.
  5. The mean or median age (depending on the study reporting) was 30 – 33 and the findings shouldn’t necessarily be extrapolated out of this age range
  6. Donor insemination was excluded from the study and it only included men with an average sperm sample.

Finally

As said previously, although this was a comprehensive review of the literature done to date these results are not necessarily the be all and end all and there is definitely room for the results to change in the future with more research.

At the moment it may appear that IUI for couples with unexplained infertility IUI isn’t necessarily the best evidence based approach to take, but does that necessarily mean that IVF is? IUI is cheaper and often physically easier for many women. For those reasons it still may be a very worth while first port of call when entering the world of fertility treatments.

Reference

Veltman-Verhulst SM, Hughes E, Ayeleke RO, Cohlen BJ. Intra-uterine insemination for unexplained subfertility. Cochrane Database of Systematic Reviews 2016, Issue 2. Art. No.: CD001838. DOI: 10.1002/14651858.CD001838.pub5.

 

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:percent- IVF success

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

Celmatix LogoYou’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

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