Title
Intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilisation (c-IVF) for oocyte insemination during in vitro fertilisation (IVF) in couples with males presenting with normal total sperm count and motility.
Review question
Cochrane authors reviewed the evidence about the effect of ICSI versus c-IVF in couples with males presenting with normal total sperm count and motility.
Background
Since starting over 40 years ago, IVF has become the cornerstone for fertility treatment. The process of IVF involves overstimulation of the ovaries to produce multiple eggs for collection. For c-IVF, the eggs are incubated with sperm in the laboratory for the hope of fertilisation. Originally discovered in 1992, intracytoplasmic injection (ICSI) was introduced as a fertilisation technique to overcome low sperm counts. ICSI now is used also as an add-on to IVF and is also utilised in cases with a history of low or total failure fertilisation with c-IVF, and with mild male infertility or even unexplained infertility. We compare whether ICSI provides more favourable outcomes compared to c-IVF.
Study characteristics
This review includes three randomised controlled trials (RCTs) comparing ICSI with c-IVF in a total of 1539 couples undergoing fertility treatment. The evidence is current to February 2023.
Key results
The three well-designed studies comparing ICSI and c-IVF were included in the analysis. Two studies reported live birth, and we are uncertain of the effect of ICSI compared to c-IVF for live birth rates. The evidence suggests that if the chance of live birth following c-IVF is assumed to be 32%, the chance of live birth with ICSI would be between 30% and 41%. Adverse events including multiple pregnancy, ectopic pregnancy, pre-eclampsia and prematurity showed probably little or no difference between the two techniques. No study reported on the primary outcome stillbirth.
Two studies report viable intrauterine pregnancy for ICSI and c-IVF, suggesting that if the chance of viable intrauterine pregnancy following c-IVF is assumed to be 33%, the chance of viable intrauterine pregnancy with ICSI would be between 28% and 38%. The results show that there is probably little or no difference for viable intrauterine pregnancy for ICSI compared to c-IVF.
Clinical pregnancy and miscarriage rates also show probably little or no difference between the techniques.
Certainty of the evidence
There remains uncertainty about whether ICSI compared to c-IVF increases live birth rate due to the lack of studies available. The certainty of evidence was assessed as low to moderate. The reason for this is that some the studies included in this review were not clear on the methodology including randomisation process. This means the results must be treated cautiously, and further studies are need to confirm the findings.
The current available studies that compare ICSI and c-IVF in couples with males presenting with normal total sperm count and motility, show neither method was superior to the other, in achieving live birth, adverse events (multiple pregnancy, ectopic pregnancy, pre-eclampsia and prematurity), also alongside secondary outcomes, clinical pregnancy, viable intrauterine pregnancy or miscarriage.
Starting over 40 years ago, in vitro fertilisation (IVF) has become the cornerstone for fertility treatment. Since then, in 1992, Palermo and colleagues successfully applied the technique intracytoplasmic sperm injection (ICSI) to benefit couples where conventional in vitro fertilisation (c-IVF) and sub-zonal insemination (SUZI) proved unsuccessful. After this case report, ICSI has become the treatment of choice for couples with severe male factor subfertility. Over time, ICSI has been used in the treatment of couples with mild male and even unexplained infertility. This review is an update of the review, first published in 1999, comparing ICSI with c-IVF for couples with males presenting with normal total sperm count and motility.
To evaluate the effectiveness and safety of ICSI relative to c-IVF in couples with males presenting with normal total sperm count and motility.
We searched the following databases and trial registers: Cochrane Central Register of Controlled Trials (CENTRAL), Embase (excerpta Medica Database), MEDLINE (Medical Literature Analysis and Retrieval System Online) and PsycINFO (Psychological literature database) for articles between January 2010 and 22 February 2023.
We included randomised controlled trials (RCTs) that compared ICSI with c-IVF in couples with males presenting with normal total sperm count and motility.
We used standard methodical procedures recommended by Cochrane. The primary review outcomes were live birth and adverse events. Secondary outcomes included clinical pregnancy, viable intrauterine pregnancy and miscarriage.
The original review published in 2003 included one RCT. In this 2023 update, we identified an additional two RCTs totalling a cohort of 1539 couples, comparing ICSI with c-IVF techniques. Two studies reported on live birth. Using the GRADE method, we assessed the certainty of evidence and reported evidence as low-certainty for live birth.
We are uncertain of the effect of ICSI versus c-IVF for live birth rates (risk ratio (RR) 1.11, 95% confidence interval (CI 0.94 to 1.30, I2 = 0%, 2 studies, n = 1124, low-certainty evidence). The evidence suggests that if the chance of live birth following c-IVF is assumed to be 32%, the chance of live birth with ICSI would be between 30% and 41%. For adverse events; multiple pregnancy, ectopic pregnancy, pre-eclampsia and prematurity, there was probably little or no difference between the two techniques. No study reported the primary outcome stillbirth.
For secondary outcomes, we are uncertain of the effect of ICSI versus c-IVF for clinical pregnancy rates (RR 1.00, 95% CI 0.88 to 1.13, I2 = 45%, 3 studies, n = 1539, low-certainty evidence). Comparison of viable intrauterine pregnancy rates showed probably little or no difference between ICSI and c-IVF (RR 1.00, 95% CI 0.86 to 1.16, I2=75%, 2 studies, n = 1479 couples, moderate-certainty evidence). The high heterogeneity may have been caused by one older study conducted when protocols were less rigorous. The evidence suggests that if the chance of viable intrauterine pregnancy following c-IVF is assumed to be 33%, the chance of viable intrauterine pregnancy with ICSI would be between 28% and 38%.
Miscarriage rates also showed probably little or no difference between the two techniques.