Can We Identify Subgroups in Which ICSI is Cost-Effective Over IVF: A Secondary Analysis of a Randomised Clinical Trial

Background: The use of intracytoplasmic sperm injection (ICSI) has increased substantially worldwide, primarily in couples with non-male factor infertility. We recently published the results of a large randomised controlled trial (RCT) comparing ICSI and IVF showing no significant improvement of ICSI over IVF in couples with normal semen concentration and motility. Here, we assess the cost-effectiveness of ICSI in these couples, with additional attention for subgroups. Aim: To assess the effectiveness and cost-effectiveness of ICSI versus IVF in relation to sperm morphology. Method: We performed a cost-effectiveness alongside a randomised clinical trial comparing ICSI and IVF. Between 16th March 2018 and 12th August 2019, we had randomized 1,064 couples (532 to ICSI vs 532 to IVF) in two centres in VietNam. After comparing the difference in life birth rate, we calculated the incremental cost-effectiveness ratio as the additional cost to establish one live birth. We also looked at (cost-)effectiveness in subgroups by the baseline characteristics treatment-indication, ovarian response, total-motile-count and sperm-morphology. Results: In the base case, there were per 100 women 3.4 more babies born for an extra cost of €65,600. This translates to €19,294 per extra life birth, which is comparable to the benchmark of €15,000 per live birth. We did not find significant interaction with any of the baseline characteristics (all P-values for interaction [Formula: see text] 0.05). However, for sperm morphology, in the 458 couples with [Formula: see text]=4% normoform cells, live birth rates were 32.1% versus 32.9% (RR 0.97 (0.75 to 1.27)), while in 201 women with [Formula: see text]4% normoform cells this was 36.2% versus 29.7% (RR 1.22 (0.97, 1.54)). While this would implicate no effectiveness of ICSI in couples with completely normal sperm, in couples with normal total sperm count and motility, those with sperm morphology [Formula: see text]4% would have 6.5 additional babies per 100 women, resulting in a cost-effectiveness of €10,076 per extra life birth. Conclusion: In couples with completely normal sperm (normal total sperm count, motility and morphology) ICSI does not add anything to the chances obtained with IVF. In couples with a normal total sperm count and motility with abnormal morphology, ICSI could be considered as it seems cost-effective.