Fertility treatments are quickly evolving. It is no longer just a matter of egg meets sperm and waiting for the magic to happen.
Now there is the choice of doing preimplantation genetic screening (or PGS – we’ve covered that one pretty well here), assisted hatching, using timelapse imagery, autoimmune protocols, endometrial receptivity array (ERA), endometrial scratching… the list continues…
Unfortunately, not all of these ‘add-ons’ have the research to indicate that they will increase IVF birth rates or the evidence to say that they do not impact the future health of the baby (1). That is not to say that they won’t in the future, but for now, for some of these treatments, the research just hasn’t been done. If you are keen to use the latest technologies available though, sometimes you have to take the risk of it not being an evidence based treatment yet. Most clinics are upfront in saying ‘it may or may not work’ but if they are misleading with the evidence that is available or the treatment has actually been shown not to work and is still being recommended, well, that is another story – especially when it comes with a price tag with more zeros behind it than what you would like.
As the British Human Fertilisation and Embryology Authority (HFEA) state ‘The most important thing you can do when making decisions about fertility treatment is to ensure you are well informed.’
Never a truer word said.
Read on for a review on just two of the add-on treatments that is currently available (more reviews to follow).
As summarized by HFEA, the early embryo is surrounded by a thick layer of special proteins called the zona pellucida. Before an embryo can implant in the womb it has to break out or ‘hatch’ from its zona pellucida. It is thought that by assisting this hatching – using acid, lasers or other tools to thin or make a hole in the zona pellucida – it helps the embryo to hatch and therefore implant (2).
The National Institute for Clinical Excellence (NICE) is the British national body advising doctors on treatments. It says: “Assisted hatching is not recommended because it has not been shown to improve pregnancy rates.” Although it has been used since the late 1980’s there is still insufficient evidence to determine its impact on live birth rate and relevance to use today.
A Cochrane review, which is a very comprehensive and respected scientific review, pooled the data of 31 studies on assisted hatching which included over 5700 women doing IVF (3). When examining live birth rate of IVF cycles that used assisted hatching (and after all, this is the only outcome measure that really matters) they found that there was insufficient evidence to suggest that assisted hatching increases the chances of a take home baby.
Interestingly, there may be a slight increase in the clinical pregnancy rate for those women doing assisted hatching (3). It only just reaches statistical significance though and may only be useful in a certain subset of women doing IVF – such as those with repeated failures or traditionally considered to have a ‘poor prognosis’. Additionally, it appears that this result may only be valid when the zona pellucida was completely removed (as opposed to having a small hole made in the shell or the shell being made thinner by chemical means).
What also needs to be considered when deciding with your fertility team whether or not assisted hatching is appropriate for you, is assisted hatching increases the risk of multiples as well as the chance of monozygotic twinning (where the embryo splits in two)(3). Pregnancies with more than one baby in the womb carry risks to both the babies and the mother and should be avoided where possible.
In summary, until a proven beneficial effect of assisted hatching on live birth rates is established, it should not be offered (4).
Embryo glue is another IVF add-on with the goal of assisting the embryo to implant.
The use of embryo glue is when the embryo is placed in a substance that is believed to help it attach and implant better to the uterine lining. Traditionally, clinics used a fibrin sealant to this; however, this does not appear to have been studied recently and the focus has shifted to those substances containing hyaluronan, which are considered more effective (1). Hyaluronan is a substance that is naturally found in the reproductive tract of women and is believed to form a viscous solution that helps with the embryo transfer process (1).
A Cochrane review of nearly 4000 women found that it increased live birth rates and clinical pregnancy rates by up to 10% (5). This finding has been reported in other papers (1,4), however, as the HFEA highlights there was only one study of high quality (with others being of moderate quality) that contributed to this finding and therefore more high quality studies are needed before it can be a generalized recommendation.
Although the evidence does seem to favor the use of embryo glue, The Cochrane Review did note that the incidence of a multiple pregnancy is higher. Unlike in the use of assisted hatching, the phenomenon of the embryo splitting into twins does not seem to be a contributing factor. Instead, it is simply because the success rates of using this treatment is higher and therefore when more than one embryo is transferred they are more likely to implant. This again highlights the preference to only do single embryo transfers in order to avoid a highrisk multiple pregnancy.
There is likely to always be some guilt or wondering ‘what could have been’ when choosing whether or not to use add-ons. As fertility patients you need to know that you have done your very best to make this cycle successful. If you are looking at just comparing these two treatments though, in my opinion, it does seem conclusive that embryo glue using hyaluronan has the evidence based edge over assisted hatching with some good emerging data to support it. We are all different though with unique medical histories so, if nothing else, make sure you speak to your treating team to see what the best treatment might be for you.
- Harper, J., Jackson, E., Sermon, K., Aitken, R., Harbottle, S., Mocanu, E., Hardarson, T., Mathur, R., Viville, S., Vail, A. & Lundi, K. (2017) Adjuncts in the IVF laboratory: where is the evidence for ‘add-on’ interventions? Human Reproduction, 32 (3): 485–491.
- Human Fertilisation and Embryology Authority. Accessed 27th August 2018 https://www.hfea.gov.uk/treatments/explore-all-treatments/treatment-add-ons/
- Carney, S., Das, S., Blake, D., Farquhar, C., Seif, M. & Nelson, L. (2012) Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)). Cochrane Database of Systematic Reviews Issue 12. Art.No.: CD001894. DOI: 10.1002/14651858.CD001894.pub5.
- Datta, A., Campbell, S., Deval, B., Nargund, G. (2015) Add-ons in IVF programme – Hype or Hope? Facts Views vis ObGyn, 7 (4): 241-250.
- Bontekoe, S., Johnson, N., Blake, D. (2014) Adherence compounds in embryo transfer media for assisted reproductive technologies. Cochrane Database of Systematic Reviews Issue 2. Art. No.: CD007421. DOI: 10.1002/14651858.CD007421.pub3.