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Evidence Library · The procedure

ICSI when there is no sperm problem

Two thirds of US cycles without male factor used it. Randomized trials find no benefit.

ICSI means injecting a single sperm directly into each egg, rather than letting sperm and eggs meet in a dish. It was developed for severe male factor infertility, where it transformed outcomes.

Then it spread. In 1,395,634 US IVF cycles, ICSI use in cycles without male factor rose from 15.4% in 1996 to 66.9% in 2012. In the 317,996 non-male-factor cycles from 2008 to 2012:

Outcome, no male factorICSIConventional IVF
Live birth36.5%39.2%
Implantation23.0%25.2%

That is observational, and ICSI is probably chosen more often for poorer-prognosis cycles, so the right reading is "no evidence of benefit" rather than "ICSI causes harm". The randomized evidence is stronger and says the same thing.

1,064 couples where the male partner had entirely normal sperm count and motility, randomized: live birth after the first transfer was 184 of 532 (35%) with ICSI and 166 of 532 (31%) with conventional IVF, an absolute difference of 3.4 percentage points with a confidence interval from −2.4 to 9.2.

2,387 couples with non-severe male factor, randomized across ten centres: live birth 390 of 1,154 (33.8%) with ICSI and 430 of 1,175 (36.6%) with conventional IVF, adjusted risk ratio 0.92 (95% CI 0.83 to 1.03). The authors' conclusion: ICSI did not improve live birth rate compared with conventional IVF. Given that ICSI is an invasive procedure associated with additional costs and potential increased risks to offspring health, routine use is not recommended in this population.

Why this matters beyond the moneyICSI is not just a neutral extra. In the birth defect data later in this stage, the increase associated with IVF disappears after adjustment for parental factors and the increase associated with ICSI does not. That is a second reason to ask what a sperm-specific procedure is doing in a cycle with no sperm problem.
Where this comes from:
53. Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015;313(3):255-263.
54. Wang Y, Li R, Yang R, Zheng D, Zeng L, Lian Y, et al. Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial. Lancet. 2024;403(10430):924-934.
55. Dang VQ, Vuong LN, Luu TM, Pham TD, Ho TM, Ha AN, et al. Intracytoplasmic sperm injection versus conventional in-vitro fertilisation in couples with infertility in whom the male partner has normal total sperm count and motility: an open-label, randomised controlled trial. Lancet. 2021;397(10284):1554-1563.

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