Researchers in a 2022 study combined the results of 26 studies that compared ICSI vs IVF in couples without male-factor infertility and found minor differences in the risk of total fertilization failure, live birth rates in women >35 and implantation rates.
Many clinics use intracytoplasmic sperm injection (ICSI) as a way to overcome male factor issues, however it’s not clear if this is beneficial to patients without male factor infertility.
Huang et al. (2022) performed a systematic review and meta-analysis to combine the results of 26 studies that compared ICSI and conventional IVF as methods of insemination among couples without male-factor infertility. Twenty of the studies were retrospective in design and 6 were randomized controlled trials. This meta-analysis included studies up to May 2022.
🔗 Original studies are referenced in this post or within the linked Remembryo posts.
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Table of Contents
No differences in fertilization rates for ICSI vs IVF with non-male factor
Based on 10 studies and 29,506 participants, there was no statistically significant difference in fertilization rates among couples with non-male factor infertility who used ICSI compared to IVF (46.8% vs 61.7%, risk ratio [95% CI]: 0.99 [0.90-1.09], high heterogeneity I2 = 95%).
They also grouped women based on age and found no differences in fertilization rates for those ≤35 or >35.
Increase in the risk of total fertilization failure for ICSI vs IVF with non-male factor
Occasionally, there may be errors in the egg or sperm that prevent binding of the sperm to the egg. In these cases total fertilization failure may occur, where there is no fertilization of any of the inseminated eggs. ICSI can bypass this step since the sperm is injected directly into the egg and it doesn’t need to bind to it.
Besides the sperm binding to the egg, there are other reasons total fertilization failure can occur, so it can happen even with ICSI.
Based on 6 studies and 52,541 participants, there was a statistically significant increase in total fertilization failure among couples with non-male factor infertility who used ICSI compared to IVF (4.6% vs 3.8%, risk ratio [95% CI]: 1.30 [1.17-1.45], moderate heterogeneity I2=42%).
So ICSI actually increased total fertilization failure compared to IVF! However, this result is based almost entirely from a single large study (Schwarze et al. 2017, which contributed 87.4% of the weight of this result), and when this study was removed from their analysis the researchers found no difference in total fertilization failure.
So in this case, it’s probably best to refer to the Schwarze et al. 2017 study to see what their results are:
- Large study that compared ICSI (n=39,564) and IVF (n=10,249) from the Latin American Registry comprised of 155 IVF centers in 15 Latin American countries.
- Increase in fertilization failure in ICSI vs IVF (4.49% vs 3.37%, difference [95% CI]: 0.71%-1.52%, p<0.0001).
- The authors note that this difference is “of little clinical significance.”
- ICSI was associated with total fertilization failure in women with ≤4 eggs compared to IVF (9.70% vs 8.43%).
- ICSI was associated with total fertilization failure in women ≥40 compared to IVF (7.06% vs 5.96%).
No differences in the rate of good quality embryos for ICSI vs IVF with non-male factor
Based on 12 studies and 10,386 participants, there was no statistically significant difference in the rate of good quality embryos among couples with non-male factor infertility who used ICSI compared to IVF (51.0% vs 49.1%, risk ratio [95% CI]: 0.94 [0.86-1.02], high heterogeneity I2 = 78%).
They grouped women based on the number of eggs retrieved as ≤5 or >5. There were no differences in good quality embryo rates when using ICSI vs IVF among these groups.
Decrease in implantation rates for ICSI vs IVF with non-male factor
Based on 10 studies and 7,151 participants, there was a statistically significant decrease in implantation rates after fresh transfer among couples with non-male factor infertility who used ICSI compared to IVF (22.6% vs 23.7%, risk ratio [95% CI]: 0.77 [0.64-0.93], high heterogeneity I2 = 67%).
Although there was a decrease in implantation rate, the ~1% difference probably isn’t clinically significant (my interpretation).
No differences in clinical pregnancy rates for ICSI vs IVF with non-male factor
Based on 11 studies and 5,064 participants, there was no statistically significant difference in clinical pregnancy rates after fresh transfer among couples with non-male factor infertility who used ICSI compared to IVF (27.7% vs 28.6%, risk ratio [95% CI]: 0.84 [0.70-1.01], high heterogeneity I2 = 65%).
Another analysis where Chinese studies and non-Chinese studies were grouped showed no difference in clinical pregnancy rates.
No differences in miscarriage rates for ICSI vs IVF with non-male factor
Based on 8 studies and 2,116 participants, there was no statistically significant difference in miscarriage rates after fresh transfer among couples with non-male factor infertility who used ICSI compared to IVF (6.5% vs 8.0%, risk ratio [95% CI]: 1.06 [0.78-1.43] no heterogeneity I2 = 0%).
Another analysis where Chinese studies and non-Chinese studies were grouped also showed no difference in miscarriage rates.
No differences in live birth rates for ICSI vs IVF with non-male factor
Based on 8 studies and 57,865 participants, there was no statistically significant difference in live birth rates after fresh transfer among couples with non-male factor infertility who used ICSI compared to IVF (23.4% vs 28.0%, risk ratio [95% CI]: 0.89 [0.77-1.03], high heterogeneity I2=72%).
Women were grouped by age as either ≤35 or >35. In the ≤35 age group there were no statistically significant differences for ICSI vs IVF (moderate heterogeneity, I2=41%). However, for women >35 there was a decrease for ICSI vs IVF (5 studies, 54,398 participants, 22.9% vs 27.5%, risk ratio [95% CI]: 0.80 [0.78-0.83], moderate heterogeneity I2=39%).
Note that this last result is mainly driven by the large Schwarze et al. 2017 study as before (it contributed 87.3% of the weight). Therefore it makes sense to look more closely at this study:
- Large study that compared ICSI (n=39,564) and IVF (n=10,249) from the Latin American Registry comprised of 155 IVF centers in 15 Latin American countries.
- In one analysis, they grouped women ≥40 and found a decrease in live birth rates for ICSI vs IVF (11.42% vs 15.05%, difference [95% CI]: -3.63% [-5.00 to -2.25], p<0.0001).
No differences in preterm delivery rate and low neonatal weights for ICSI vs IVF with non-male factor
Based on 4 studies and 1,944 participants, there was no statistically significant difference in preterm delivery rate among couples with non-male factor infertility who used ICSI compared to IVF (7.2% vs 8.0%, risk ratio [95% CI]: 0.92 [0.67-1.26], no heterogeneity I2=0%).
Based on 4 studies and 1,921 participants, there was no statistically significant difference in low neonatal weights in newborns from couples with non-male factor infertility who used ICSI compared to IVF (7.2% vs 6.3%, risk ratio [95% CI]: 1.13 [0.80-1.61], moderate heterogeneity I2=30%).
Conclusions
This study found no differences in fertilization rates, good quality embryo rates, clinical pregnancy rates, miscarriage rates, overall live birth rates, preterm delivery rates and low neonatal weights.
They found that ICSI increased the risk of total fertilization failure and decreased the live birth rate in women >35. This result was mainly driven by a single large retrospective study that found minor and possibly clinically insignificant decreases.
They also found that ICSI decreased implantation rates, however the result was probably not clinically significant.
Overall, there were either no differences between ICSI and IVF or minor differences that may not be clinically significant. Heterogeneity was high for many of the analyses, so drawing strong conclusions from the existing data isn’t possible. More high quality studies are needed to address the impact of ICSI vs IVF.
Reference
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About Embryoman
Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.
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