Updated guidelines fail to find benefit of ICSI in non-male factor treatment

ICSI in non-male factor treatment

The latest data from EIM confirmed yet again that ICSI is still favoured over conventional IVF for fertilisation in ART.

Published 23 July 2020

As registry data presented at ESHRE’s online annual meeting continue to show, ICSI remains by far the world’s favoured fertilisation method, even in non-male factor cases. Updated guidelines still cannot justify the trend.

The latest data from ESHRE’s European IVF Monitoring consortium (EIM) shows that in 2017 around two-thirds of all ART treatments were still with ICSI.(1) This has been the pattern in Europe for the past decade, with ICSI favoured over conventional IVF for all fertilisations, whether with male factor indications or not. There were 15 European countries, said EIM chair Christine Wyns in her online presentation at the 2020 annual meeting, whose proportional use of ICSI was over 75% - with Albania, Czech Republic, Moldova and Montenegro at 100%.

A similar picture was presented by David Adamson in his global report for 2016, including data from China which, from a total of 530,718 egg retrievals, recorded around two-thirds (375,770 cycles) as ICSI and one-third as conventional IVF (154,948 cycles) as IVF, a pattern now familiar throughout the world.(2) And also familiar was the slightly lower cumulative pregnancy and delivery rates (per retrieval) found with ICSI when compared to IVF. ‘The Chinese results,’ said Adamson, ‘are very equivalent to the global results.’

It was clear by the start of this decade that ICSI was the technique of choice in ART, even in non-male factor cases. So in 2016, when Human Reproduction published the late-running ICMART report for 2008-2010, recording a two-to-one preference for ICSI over IVF, the journal’s editor Hans Evers described any claimed justification for the trend as a ‘therapeutic illusion’.(3) The data, as numerous registry reports now illustrate, indicate that in non-male factor infertility ICSI offers no advantage over conventional IVF.(4) Indeed, the registries suggest that overall ICSI is even marginally less successful as a treatment than IVF. Thus, in his 2016 editorial Evers wrote: ‘Intending to improve their patients' pregnancy probability by preventing fertilization failure, well-meaning doctors actually decrease their chances. This has to stop.’ And so the Santa Claus allusion, ‘doling out nicely wrapped presents of unnecessary, ineffective and costly care’.

With similar usage and success patterns becoming evident in the SART data in the USA, the ASRM in 2012 issued its own opinion, pointing out that ICSI for unexplained infertility or for low oocyte yield or advanced maternal age ‘does not improve clinical outcomes’, adding that the risk of fertilisation failure is low and comparable between the two techniques. Now, in the face of a continuing high rate of ICSI use for non-male factor indications, the ASRM has updated this 2012 opinion.(5)

While US data indicate that 87-94% of male factor cases were appropriately treated with ICSI in 2016, ICSI use in non-male cases ranged from 68% to 72%, a rate comparable with that observed in Europe and elsewhere in the world. To emphasise its point, ASRM also cites a study of 2000-2014 data in which the increased use of ICSI did not correlate with an increase in the diagnosis of male factor in patients under 35 years, and only a modest increase in live-birth rates per cycle over the study period.(6) Against this background the ASRM opinion now examines the evidence for ICSI in a range of indications: unexplained infertility; low oocyte yield; advanced maternal age; prior failed fertilisation; for PGT; for cryopreserved oocytes; and for ‘routine use’. In all cases, the opinion adds, any justification for ICSI seems to be the risk of fertilisation failure, but no marginal benefit can be found.

Indeed, with live birth as the endpoint, none of the non-male indications are better treated with ICSI than with conventional IVF. The exception is in PGT cases, where ‘contamination of extraneous sperm could affect the accuracy of test results’. The opinion adds that ICSI has emerged as the favoured fertilisation method for cryopreserved oocytes, in which the cumulus cells are removed before freezing. However, so far, despite the huge uptake in oocyte banking, ‘limited data currently exist to support his procedure’. Similarly, ASRM can cite no studies in which ICSI might improve live birth rates in patients with poor quality oocytes.

And in cases where ICSI is applied routinely without any diagnostic guidance – as surely must happen in countries with 100% ICSI use – there is no evidence to support such blanket use, says ASRM. And as a final consideration, especially in such routine cases, ASRM warns that ‘the additional cost burden of ICSI for non–male factor indications, where data on improved live-birth outcomes over conventional insemination are limited or absent, must be considered’. It was such considerations which prompted some authorities to classify ICSI as an ‘add-on’ treatment, though such controversial suggestions were largely abandoned as a result of ICSI’s unequivocal benefit in male factor infertility.

1. See https://www.eshre.eu/ESHRE2020/Eshre/Checkvideo?videoid=1_r0ndgb45&key=0ec91c6e2c464307030b3f3f15e8c36991881303
2. See https://www.eshre.eu/ESHRE2020/Eshre/Checkvideo?videoid=1_m9zforat&key=4ed4e637d9d68688c7f7e5cad352eddff84c4703
3. Evers JLH. Santa Claus in the fertility clinic. Hum Reprod 2016; 31: 1381-1382. doi.org/10.1093/humrep/dew092
4. Bhattacharya S, Hamilton MP, Shaaban M, et al. Conventional in-vitro fertilization versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial. Lancet 2001; 357: 2075–2079.
5. Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. Intracytoplasmic sperm injection (ICSI) for non–male factor indications: a committee opinion. Fertil Steril 2020;
6. Zagadailov P, Hsu A, Stern JE, Seifer DB. Temporal differences in utilization of intracytoplasmic sperm injection among U.S. regions. Obstet Gynecol 2018; 132: 310–320.
doi: 10.1097/AOG.0000000000002730
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