For some ICSI is just that next step down the fertility path when traditional IVF fails. For others their clinic ONLY fertilises eggs by using ICSI and there is no way around it. One thing is apparent though and that is that ICSI is gaining ground on IVF and becoming more and more common. Here are some answers to those common questions regarding ICSI.
What is ICSI?
ICSI, pronounced ‘ick-see’ stands for intra-cytoplasmic sperm injection. It is when the embryologist selects one sperm from the semen sample that has been provided and this single sperm is then injected directly into the egg. There are different methods and techniques that the embryologist can use to select the best sperm such as using an extra high magnification microscope or putting the sperm into substances that mature sperm then bind to and then picking one of these. For the purposes of this article we will just lump all these different methods together (as is mostly done in the literature).
There are strict rules set by various overseeing bodies that dictate which sperm is suitable for ICSI. For example sperm must be mature and of a particular size and shape. This is reassuring as it again attempts to ensure that only healthy, mature sperm are injected – though if they weren’t healthy, mature sperm the egg probably wouldn’t fertilise rather than having adverse outcomes for your baby.
Although it is a different procedure ICSI comes under the umbrella of IVF and sometimes your lab might interchange the term ICSI with IVF.
ICSI is different to IVF, which as you are likely to know is where the egg and the sperm are placed together in a dish and the sperm are left to their own devices to penetrate the shell of the egg and fertilise the egg that way. As a new patient in the fertility world IVF can seem a little bit more natural then ICSI because at least some sort of natural selection is taking place, right? That is in traditional IVF the best sperm still has to win at the end of the day, albeit in a manufactured environment. On top of injections and ‘harvesting’ your eggs ICSI can seem like yet another intervention.
Why is ICSI used?
ICSI has been traditionally used when there is significant male factor infertility and we can’t really go further without first briefly touching on sperm count. You might remember that the normal sperm count in a healthy man is around 40 million per ‘go’ (or ejaculate in case I wasn’t clear). Don’t forget though that sheer numbers is not enough and the sperm themselves need to be healthy with good motility, that is the need to have the ability to move around and get to where they need to and good morphology, meaning that they look the part with one tail and one head, for example. When a semen sample is provided, the embryologist will prepare the sperm, taking out all these stragglers leaving behind only the best of the best. Or as I have heard one consultant say SAS sperm.
Low Sperm Count
It has previously been mentioned that in instances of male factor infertility if the SAS sperm count is greater than 10 million it might be worth attempting IUI, if the count is between 5 – 10 million try IVF and anything less than this just use ICSI as the likihood of fertilisation without it would be relatively low. It is in these very low sperm counts that ICSI was first intended.
Previous Zero Fertilisation Rate
In addition to the reason of having low sperm count, another reason that ICSI might be used is if you have previously completed a cycle where there was zero fertilisation. This can happen in 10 – 20% of couples (Chen et al as cited in 1). Instead of having to live that one again, your embryologists may recommend that you skip plain old IVF and head straight to ICSI in order to give the egg and sperm the best chance to meeting and the egg fertilising. Remember though, that just because the sperm has been injected right into the egg, a little something special still has to happen and it doesn’t automatically guarantee fertilisation. It can in some instances improve it though which is why some clinics opt for ICSI as standard, though other clinics believe that with normal, healthy sperm ICSI is just not required and with mother nature not actually intending for a needle to necessarily be shoved in her eggs side they are quite possibly correct.
ICSI may also be performed in ‘rescue’ situations. That is when traditional IVF has been attempted but no fertilisation has occurred after a certain amount of time. In this case the embryologist will inject the egg with sperm in an attempt to make it easier for fertilisation to occur. When rescue IVF is needed research shows that the sooner it is done the better. One small study shows that fertilisation rates for rescue ICSI performed after 6 hours has a fertilisation rate of 70%, compared with only 48% when rescue ICSI was performed after 22 hours (1). This 70% fertilisation rate is in line with the general fertilisation rates of standard IVF (Nagy et al as cited in 1) so this is a very good outcome. The 6 hour rescue ICSI, as opposed to 22 hour rescue ICSI also has better implantation, pregnancy and live birth rates. It should be noted that in some instances clinics do not always like to practice rescue ICSI due to the risk of more than one sperm being inserted into the egg and the complications this can cause (though there are ways technician can try and see if an egg has fertilised to reduce this from happening, for example by looking at the polar body of an egg, so this doesn’t happen very often).
Extra Testing or Surgical Collection
ICSI can also be recommended if you are planning on doing embryo testing or if sperm has needed to be collected surgically through means such as Percutaneous Epididymal Sperm Aspiration (PESA), Micro-Epididymal Sperm Aspiration (MESA) or Testicular Sperm Extraction (TESE).
Does ICSI cause higher rates of birth defects?
Generally speaking, the news is good. It seems that if you are comparing IVF to ICSI there is no correlation between the use of ICSI over IVF and birth defects.
This was recently covered in a metaanalysis completed by some researchers in Europe (2). They reassuringly found that there was no difference between ICSI conceived babies and IVF conceived babies and this has also been reported elsewhere (3).
Although this study is getting a little old now (Bonduelle et al 2003, as cited in 3) research was also done assessing children’s development at two years of age which is a welcome study to have given that a lot of research stops following the babies at birth. By completing standardised testing it was found that at two years the psychomotor and cognitive development of children were the same irrespective of whether the child was conceived using IVF or ICSI.
The Centre for Disease Control reports nearly 70,000 ICSI cycles were completed in America in the year 2012. This is a number that has been steadily increasing since the introduction of ICSI and we can be forgiven for thinking that there may be some safety in numbers. With all the checks and scrutiny that IVF clinics are rightfully held to, if ICSI was causing an increase in children with birth defects it would have come to light by now. And with the first ICSI babies being conceived in the early 90’s, this provides around 25 years of longitudinal data to have had scrutinised.
There was one study however, that again studied babies born following ICSI conception or IVF conception (4). They found that ICSI babies generally were at higher risk of preterm birth and lower gestational weight and age (even accounting for the fact they were born earlier). It seems though that ICSI babies were more likely to be part of multiples which could very well account for this outcome as when they assessed just singletons the ICSI babies were no longer at a disadvantage. This was only one very small study however with flaws in its own methodology, but in the interests of presenting both sides of the story, I mention it briefly.
Interestingly some researchers hypothesise that it sometimes can be the reverse, that is children of IVF conceived births can fare worse off than ICSI (2). One theory of why this is is because IVF is used predominantly when the sperm is of sufficient quality and quantity, but there are still difficulties with fertility. This infers that it is due to maternal factors that infertility is experienced. That is IVF is traditionally used when there is female factor infertility and ICSI when there is male factor infertility. If this is the case and if there are slightly poorer outcomes for IVF babies, it would seem that it is more important to have a healthy mother producing good quality eggs which may be able to compensate in some way for poorer sperm quality. I should also stress that when comparing birth outcomes the researchers are generally looking at things like birth weight and gestational age and not major disabling defects, therefore if not totally ideal is most likely to be so insignificant to not change your decision to complete one procedure over another. Though like everything, your doctor will be the best person to walk you through the pros and cons.
Whilst we have established that there is no differerence between IVF conceived and ICSI conceived babies, in the course of researching I did find that it has been mentioned that ART babies in general have higher risk of birth defects. There are a number of possible reasons for this and one is that it may be that the reason couples have difficulty conceiving is the risk factor for the defect rather than the technology itself. Alternatively, it may be one or more then one of the steps involved in the IVF/ICSI process that causes this. For example it may be the medication used to stimulate cycles, growing embryos in a culture or transferring embryos into the uterus that possibly increases the risk of birth defects (though IUI is also included under the ART umbrella and in IUI the embryo is not created in the lab so this doesn’t necessarily explain it all).
These same researchers also suggests that babies that are the result of a frozen embryo transfer are generally at less risk of preterm birth and lower birth weight. This is good news for women who are already less then thrilled to be completing a frozen transfer due to the slightly lower success rates. It is suggested that this occurs because in frozen embryo cycles there is not the same amounts of medication being used and in the luteal phase (that is the phase after ovulation/ transfer) the hormones in your body more accurately reflect those in nature. But don’t worry fresh cycle ladies, there is some evidence that suggests that there is actually no relationship between the total dose of medication taken, number of eggs harvested and the health of your baby (this is low grade evidence though and further research is needed).
Remember, take all this with a pinch of salt and there is no point in getting concerned over this without discussing your individual situation with your doctor. Although when you are in the moment it may seem like the be all and end all, for example ART children are possibly more likely to have certain defects, the overall number of children experiencing these remain a very, very small number. It is up to you to determine what you are comfortable with but for most women the risk of not having a child far outweighs the relatively very small risk of a child with an abnormality. But again the exact numbers and percentage will vary according to your particular situation so it is best to discuss this with your clinic.
How much does ICSI cost?
Depending where in the world you live the cost of ICSI over IVF can be significant. Resolve, which is a leading information and support network for all things fertility related report that ICSI can cost up to an extra $1500 to the cycle for those women living in the United States of America. If you are in Australia, where there are already excellent Medicare rebates for IVF, the extra out of pocket expense for doing ICSI over IVF can be around $300 depending on your clinic.
1. Chen, C. & Kattera, S. 2003. Rescue ICSI of oocytes that failed to extrude the second polar body 6 h post-insemination in conventional IVF. Human Reproduction Vol.18, No.10 pp. 2118-2121
2. Pinborg A, Wennerholm UB, Romundstad LB, Loft A, Aittomaki K, Söderström-Anttila V, Nygren KG, Hazekamp J, Bergh C: Why do singletons conveived after assisted reproductive technology have adverse perinatal outcome? Systematic review and meta-analysis. Human Reproduction Update 2013, 19:87–104
3. Devroey, P. and Van Steirteghem. A. 2004. A review of ten years experience of ICSI. Human Reproduction Update, Vol.10, No.1 pp. 19±28, 2004
4. Nouri, K., Ott, J., Stoegbauer, L., Pietrowski, D., Frantal, S. and Walch, K. 2013 Obstetric and perinatal outcomes in IVF versus ICSI-conceived pregnancies at a tertiary care center – a pilot study. Reproductive Biology and Endocrinology 2013, 11:84