Does intracytoplasmic sperm injection improve the fertilization rate and decrease the total fertilization failure rate in couples with well defined unexplained infertility A systematic review and meta analysis

This meta-analysis of couples with well defined unexplained infertility undergoing IVF favors the use of intracytoplasmic sperm injection to increase fertilization rates and decrease the risk of total fertilization failure.

Lauren N. C. Johnson, M.D., Isaac E. Sasson, M.D., Ph.D., Mary D. Sammel, Sc.D., Anuja Dokras, M.D., Ph.D.

Volume 100, Issue 3, Pages 704-711, September 2013


To determine if intracytoplasmic sperm injection (ICSI), compared with conventional insemination, improves fertilization rates and prevents total failed fertilization (TFF) in couples with unexplained infertility.

Systematic review and meta-analysis.

IVF centers.

Couples with well-defined unexplained infertility undergoing IVF.

A systematic review was performed by searching Medline and Embase for 1992–2012. Studies in which sibling oocytes were randomly split between conventional insemination and ICSI were included. A random effects model was utilized for the meta-analysis. Meta-analysis of Observational Studies in Epidemiology guidelines were applied.

Main Outcome Measure(s):
Fertilization rate and TFF rate by insemination method.

Eleven studies with a total of 901 couples (female age range 30–35 years) with 11,767 sibling oocytes were included in the meta-analysis. The pooled relative risk (RR) of a mature oocyte fertilizing was higher with ICSI than with conventional insemination (RR 1.49, 95% confidence interval [CI] 1.35–1.65.) The pooled RR of fertilization per allocated oocyte (before randomization) was higher with ICSI than with conventional insemination (RR 1.27, 95% CI 1.02–1.58; n = 5 studies.) The pooled RR of TFF was significantly higher with conventional insemination than with ICSI (RR 8.22, 95% CI 4.44–15.23). The number of subjects needed to treat with ICSI to prevent one case of TFF was five.

This meta-analysis favors the use of ICSI to increase fertilization rates and decrease the risk of TFF in couples with well-defined unexplained infertility. Further studies are needed to determine the impact on clinical pregnancy and live birth rate.

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  • Fernando Bronet, PhD

    Thanks for your data. This is an old and interesting debate, what is better? According to that data it seems that we can get more embryos by using ICSI. However the clinical outcome rates (PR, IR) are not clear. In a retrospective study with our data (data not published) that included 700 IVF/ ICSI cycles (half oocytes of the same patient with IVF and half with ICSI) we found statistical differences in pregnancy rate (55.1% vs 41.3%; p=0.0164) and ongoing pregnancy rate (48.5% vs 34.8%; p=0.0159) (IVF vs. ICSI).
    We need more date in order to know what technique is better to get pregnant

  • Lauren Johnson

    Hi Micah,
    Thank you for your comments. I agree that it would be very interesting
    to see if rates of TFF vary based on the length of infertility. We did not
    investigate that in the meta-analysis. Since we compared sibling oocytes, each
    woman served as her own control, allowing us to control for potential
    confounders, including length of infertility. Additionally, only a few studies
    provided data on length of infertility, making it difficult to draw any
    conclusions. I think that prospective studies will be needed to determine
    which factors, such as length of infertility, put couples with unexplained infertility
    at higher risk for TFF.

  • Micah Hill

    Congratulations Lauren on the very nice meta-analysis. I though the approach to only including RCTs that randomized sibling oocytes was especially helpful. This was a very timely article for me, as we were discussing this issue just this month in our group. I was curious if you were able to get a sense from the source studies if the duration of unexplained infertility had any bearing on the likelihood of fertilization failure?

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