Studies cast further doubt on indiscriminate use of ICSI

No improvement was found by using intracytoplasmic sperm injection (ICSI) for non-severe male factor infertility or when male factor fertility is not the cause of couples failing to conceive, two papers have concluded.

The first paper, published in The Lancet, reported results from a randomised control trial that compared the efficacy and safety of ICSI versus conventional IVF in over 2000 couples with non-severe male factor infertility. Live birth rates were not shown to be significantly different, bringing to question whether ICSI – an invasive procedure associated with additional costs – should be recommended for this group of patients.

'The increased use of ICSI in couples with infertility without severe male factor has boomed because of the belief that use of ICSI might increase fertilisation success, and now we have shown that this is incorrect,' Professor Ben Mol, senior researcher of the study, from Monash University in Australia, explained.

In ten reproductive medicine centres across China, couples with non-severe male factor infertility were randomly assigned to receive ICSI or conventional IVF. Couples were ineligible if they were treated with donor sperm or eggs, underwent preimplantation genetic testing (PGT), used frozen semen, or had poor fertilisation in a previous IVF cycle.

'The use of ICSI far outweighs its original purpose and has been adopted as general IVF procedures globally,' Professor Mol said. 'Because a single sperm is isolated and injected into the egg, the natural selection process where a sperm cell beats millions of competitors is bypassed, which may lead concerns re potential risks to offspring health, including congenital anomalies'.

In a second paper, published in Fertility and Sterility, a large retrospective study compared ICSI versus IVF use where PGT for aneuploidy (PGT-A) tests had been conducted on non-male factor infertility samples.

A total of 30,446 non-male factor PGT-A cycles were evaluated from US-based fertility clinics
while the exclusion criteria included use of frozen oocytes and if either parent was a carrier for a genetic disease. The researchers did not find any significant differences between embryos suitable for transfer, or live birth rates, from the ICSI or IVF treatment groups.

Although ICSI is not often used outside of male-factor infertility in the UK, it is not the case in the rest of the world. Authors of the US study state that while ICSI has helped many couples, the increased cost and controversy over adverse neonatal outcomes should be taken into consideration, highlighting concerns about its overuse outside its primary indication for male infertility.