Over the past few decades, the use of ICSI has increased dramatically in fertility clinics. Although it was originally intended for male-factor infertility, it is now used widely even when semen characteristics are normal. Is there a benefit in using ICSI rather than conventional IVF?
In this article, we will zoom in the success rates of ICSI in different age groups, infertility factors, and how the rates compare to conventional IVF.
- ICSI success rate by ages
- Success rates of ICSI vs Conventional IVF
- How to improve ICSI success rates
ICSI success rate by ages
According to the 2015 National Summary Report released by CDC, live birth rates with ICSI treatment decrease as maternal age increases, regardless of the presence of male factor infertility. This trend is expected with all fertility treatments, due to significantly declined egg quality with advancing maternal age.
|With male factor||37%||31%||22%||11%||4%||1%|
|No male factor||34%||28%||19%||10%||4%||1%|
* Fresh non-donor eggs used
Success rates of ICSI vs Conventional IVF
Since each couple is unique in the cause of infertility, the answer as to whether ICSI or conventional IVF is more beneficial could vary. A retrospective cohort study published in 2015 is the most comprehensive study so far comparing the two strategies with different infertility factors, which will be the focus here1. A few other smaller-scale studies will also be discussed.
Note that all of the studies discussed here are retrospective studies. They either excluded frozen and donor eggs, or contained predominantly fresh, non-donor eggs.
Currently, a randomized clinical trial is under way and due for completion by December, 2020. The outcome of such randomized trial is expected to offer more definitive answers as to whether ICSI is more or less beneficial compared to IVF for non-male factor infertility2.
Male factor infertility
Among couples with male factor infertility, including abnormal sperm count, motility and morphology, ICSI showed an overall similar success outcome compared to conventional IVF1.
The percentage of cycles cancelled between egg retrieval and embryo transfer is an indication of failed fertilization. This figure is halved with ICSI as compared to conventional IVF, indicating that it can indeed improve fertilization when the sperm is at fault. However, there are no differences in pregnancy, miscarriage or live birth rates between conventional IVF and ICSI, indicating overall similar success rates1.
|Total No.||No. (%) With Outcome||Total No.||No. (%) With Outcome|
|Male Factor Infertility|
|Cycle canceled before transfer0||12 648||1715 (13.6)||164 263||10 295 (6.3)|
|Implantation ratee||22 886||5863 (25.6)||321419||82 006 (25.5)|
|Clinical intrauterine pregnancy||10 933||5232 (47.9)||153968||73 850 (48.0)|
|Livebirth||10 933||4296 (39.3)||153968||61 450 (39.9)|
|Miscarriage||5232||839 (16.0)||73 850||10 946 (14.8)|
|Among live births|
|Multiple live birth||4296||1469 (34.2)||61 450||19 002 (30.9)|
|Preterm delivery||4287||1250 (29.2)||61 347||16 822 (27.4)|
|Low birth weight in any infant||4230||1242 (29.4)||60 273||16 936 (28.1)|
Boulet et al., (2015)1
Non-male factor infertility
Among couples with non-male factor infertility, the use of ICSI is not supported by evidence. The implantation rate, pregnancy rate and live births are lower with ICSI compared to conventional IVF. Miscarriage rate is also slightly higher with ICSI1.
Among live births, the risks for multiple live birth, preterm delivery and low birth weights are similar between IVF and ICSI1.
In the 2015 National Summary Report released by CDC, conventional IVF had higher success rates compared to ICSI in non-male infertility cases before the age of 43. After 43, both treatments have very low success rates due to significantly declined egg quality.
Success rates with conventional IVF vs ICSI, adjusted by age (no male factor)
When the reason of infertility is unexplained, there is mixed evidence with regards to whether ICSI offers a better chance of reproductive success.
The large-scale 2015 study found lower rates of implantation, pregnancy and live births. Notably, among live births, ICSI cycles also tend to have slightly higher risks of preterm delivery and low birth weight1.
In contrast, a study in 2016 compared outcomes of IVF and ICSI in patients with unexplained infertility and normal semen quality and showed promising results using ICSI 3. It was found that ICSI oocytes (84.5%) had a significantly higher fertilization rate compared to those inseminated by conventional IVF (67.6%). Moreover, there were no cases of complete fertilization failure (CFF) in the ICSI group, but CFF occurred in 7.9% of the IVF group.
Failed previous IVF cycles
Although many couples turn to ICSI having failed conventional IVF cycles, ICSI does not seem to provide a better outcome.
The cancelation rate between egg retrieval and embryo transfer, implantation rate, pregnancy rate, live birth rate and miscarriage rate are all worse with ICSI compared to IVF1. However, among live births, there is a slight decrease in the risks for preterm delivery and low birth weight.
Advanced maternal age
For women older than 38 years old, ICSI and conventional IVF achieve similar reproductive outcomes. The cancelation rate between egg retrieval and embryo transfer and implantation rate are similar, while pregnancy rate and live birth rates are lower using ICSI1.
Similarly, a 2017 study published on Human Reproduction found similar treatment outcomes using ICSI and IVF with non-male factor infertility and advanced maternal age (≥40) 4. The fertilization rates are 64% and 67% respectively.
However, a more recent retrospective study analyzed couples with non-male factor infertility and advanced maternal age (≥35). The study reported better fertilization rates using ICSI (71.0%) compared to conventional IVF (50.1%)5. The top-quality embryo rate was also higher in the ICSI group (62.8%) compared to conventional IVF (45.5%).
Low oocyte yield
When only less than 5 eggs are retrieved after ovarian stimulation, a conventional IVF is more beneficial than ICSI.
Although ICSI can lower the cancelation rate between egg retrieval and embryo transfer, the rates of implantation, pregnancy, live birth, miscarriage are all worse using ICSI compared to IVF1.
A recent large population-based study collected data from almost 5000 European patients. According to preliminary results presented at the 2019 European Society of Human Reproduction and Embryology, there is no benefit from ICSI in non-male factor cases. Importantly, the study reported no benefit of using ICSI regardless of how many eggs are retrieved after ovarian stimulation. Therefore, having a low oocyte yield should not be a reason for choosing ICSI over IVF.
- Male factor infertility: ICSI better or similar to conventional IVF
- Non-male factor infertility: Conventional IVF better
- Unexplained infertility: mixed results, ICSI could be better, similar or worse
- Advanced maternal age: ICSI similar to or better than conventional IVF
- Low oocyte yield: Conventional IVF better
How to improve ICSI success rates
Conventional IVF should still be the preferred choice for most cases
As we have seen from the above statistics, the use of ICSI was introduced for male-factor infertility but seems to be only mildly beneficial. In fact, ICSI is associated with reduced reproductive success in the absence of male factor infertility when compared to conventional IVF.
Why is that the case? It could be because by bypassing natural selection, ICSI generally results in poorer quality embryos and consequently, poor success rates. However, the exception is when the sperm quality is low, in which case selecting the best performing sperm is beneficial.
In the case of unexplained infertility and advanced maternal age, there is evidence showing improved success or no difference using ICSI. Thus, it may or may not be beneficial to use ICSI in these conditions, and further research is required.
Therefore, a conventional IVF is the recommended first choice unless there is severe male infertility factor or other compelling reasons for ICSI.
Choose a clinic that uses algorithm-based strategies rather than routine ICSI
Different fertility clinics offer different treatment strategies. Some use an algorithm to determine whether you need to use a conventional IVF or ICSI, whilst others perform exclusively ICSI for every patient.
A retrospective study looked at 159,005 patients from 465 different clinics and found that patients in algorithm-based clinics undergoing fresh, non-donor cycles had significantly higher success rates compared to those in routine ICSI clinics. This is in line with the finding that ICSI does not improve success rates for most patients6.
Therefore, by going to a clinic that uses an algorithm to design your treatment instead of performing ICSI regardless of your condition is recommended.
Consider a Split-ICSI to diversify your fertilization strategy
Since most IVF cycles start with collecting a number of eggs after ovarian stimulation, you should have on average 12-15 eggs to use. This means that you do not need to use all of them for ICSI or conventional IVF. A Split-ICSI strategy incorporates both – some eggs are injected with selected sperms using ICSI, where the rest are incubated with sperm in the conventional way. Trying both provide a safety net against failed fertilization with either strategy.
In the Australian PIVET Medical Centre, split insemination of eggs by both conventional IVF and ICSI is recommended to all patients, including those with normal sperm analysis. This strategy was beneficial for couples with unexplained infertility, even when there was no apparent male-factor infertility3.
Seek fertility clinics equipped with polarized light microscopes
Traditionally, embryos assessments and ICSI are performed using white light microscopy. However, using polarized light microscopes would be more ideal for ICSI for two reasons7,8.
Firstly, polarized light microscopy has higher resolution, which can help select the best quality sperm and egg used in an ICSI.
During the process of injecting a sperm into the egg using a needle, there is also the risk of disrupting the genetic material and other important structures such as the meiotic spindle inside the egg. Using a polarized light microscope may help avoiding these structures during an ICSI to preserve embryo quality.
IVF with ICSI Success Rate at Age Under 35
*The following IVF success rate reports are base on the latest CDC data published in May 2020 (Final 2018 Data) with more than 20 transfers.
|Clinic Name||Embryo with ICSI Age <35||Live Birth Age <35||Singleton Live Births Age <35||Average number transfers Age <35||Total number transfers Age <35|
|Avg = 100.0||Avg = 50.5||Avg = 38.6||Avg = 1.1||Avg = 69.9|
IVF with ICSI Success Rate at Age 35-37
|Clinic Name||Embryo with ICSI Age 35-37||Live Births Age 35-37||Singleton Live Births Age 35-37||Average number transfers Age 35-37||Total number transfers Age 35-37|
|Avg = 100.0||Avg = 43.4||Avg = 38.5||Avg = 0.9||Avg = 43.3|
IVF with ICSI Success Rate at Age 38-40
|Clinic Name||Embryo with ICSI Age 38-40||Live Births Age 38-40||Singleton Live Births Age 38-40||Average number transfers Age 38-40||Total number transfers Age 38-40|
|Avg = 100.0||Avg = 28.7||Avg = 21.2||Avg = 0.7||Avg = 38.0|
IVF with ICSI Success Rate at Age 41-42
|Clinic Name||Embryo with ICSI Age 41-42||Live Births Age 41-42||Singleton Live Births Age 41-42||Average number transfers Age 41-42||Total number transfers Age 41-42|
|Avg = 94.8||Avg = 28.8||Avg = 26.4||Avg = 0.5||Avg = 69.3|
IVF with ICSI Success Rate at Age ≥43
|Clinic Name||Embryo with ICSI Age ≥43||Live Births Age ≥43||Singleton Live Births Age ≥43||Average number transfers Age ≥43||Total number transfers Age ≥43|
|Avg = 90.5||Avg = 10.7||Avg = 10.2||Avg = 0.3||Avg = 58.9|
1 Boulet, S. L. et al. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA 313, 255-263, doi:10.1001/jama.2014.17985 (2015).
2 Dang, V. Q. et al. The effectiveness of ICSI versus conventional IVF in couples with non-male factor infertility: study protocol for a randomised controlled trial. Hum Reprod Open 2019, hoz006, doi:10.1093/hropen/hoz006 (2019).
3 Mustafa KB, Y. J., Marjanovich N, Yovich SJ, Keane KN. IVF-ICSI Split Insemination Reveals those Cases of Unexplained Infertility Benefitting from ICSI Even when the DNA Fragmentation Index is Reduced to 15% or Even 5%. Androl Gynecol: Curr Res 4, doi:10.4172/2327-4360.1000145 (2016).
4 Tannus, S. et al. The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age. Hum Reprod 32, 119-124, doi:10.1093/humrep/dew298 (2017).
5 Farhi, J. et al. Should ICSI be implemented during IVF to all advanced-age patients with non-male factor subfertility? Reprod Biol Endocrinol 17, 30, doi:10.1186/s12958-019-0474-y (2019).
6 Peterson, A. M., Libby, V, Babayev, S.N, Zhang, S, Doody, K. Strategic implementation of ICSI leads to higher success rates than routine ICSI. Fertility and Sterility 108, e91–e92, doi:https://doi.org/10.1016/j.fertnstert.2017.07.283 (2017).
7 Vermey, B. G., Chapman, M. G., Cooke, S. & Kilani, S. The relationship between sperm head retardance using polarized light microscopy and clinical outcomes. Reprod Biomed Online 30, 67-73, doi:10.1016/j.rbmo.2014.09.011 (2015).
8 Kilani, S. C., Michael. . The use of polarized light microscopy in IVF. Expert Review of Obstretrics and Gynecology 6, 241-246, doi:10.1586/eog.11.17 (2011).