IVF or ICSI for fertility preservation?

in Reproduction and Fertility
Authors:
Bhorika AggarwalReproductive Medicine Research Group, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK

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Amanda L EvansHuman Fertilisation and Embryology Authority (HFEA), London, UK

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Howard RyanHuman Fertilisation and Embryology Authority (HFEA), London, UK

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Sarah J Martins da SilvaReproductive Medicine Research Group, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK

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Correspondence should be addressed to S J Martins da Silva: s.martinsdasilva@dundee.ac.uk

Lay summary

In IVF, eggs and sperm are added together for fertilisation to occur whereas ICSI involves injecting a single sperm into each egg. ICSI is very effective where sperm count or swimming is poor (male infertility) but is slightly riskier than IVF in terms of health problems in children, although these risks are small. However, the risk of no eggs fertilising is higher for IVF compared to ICSI and couples undertaking fertility preservation, for example, before cancer treatment, usually only have time for one attempt. Using fertility preservation treatment cycle data reported to Human Fertilisation and Embryology Authority (HFEA), this study shows that ICSI results in higher number of fertilised eggs and embryos for storage or treatment compared to IVF. However, 19% of eggs are not used in ICSI treatment, so IVF appears to be better overall. Clinics should choose IVF or ICSI for fertility preservation depending on sperm characteristics rather than using ICSI for all.

Abstract

Lay summary

In IVF, eggs and sperm are added together for fertilisation to occur whereas ICSI involves injecting a single sperm into each egg. ICSI is very effective where sperm count or swimming is poor (male infertility) but is slightly riskier than IVF in terms of health problems in children, although these risks are small. However, the risk of no eggs fertilising is higher for IVF compared to ICSI and couples undertaking fertility preservation, for example, before cancer treatment, usually only have time for one attempt. Using fertility preservation treatment cycle data reported to Human Fertilisation and Embryology Authority (HFEA), this study shows that ICSI results in higher number of fertilised eggs and embryos for storage or treatment compared to IVF. However, 19% of eggs are not used in ICSI treatment, so IVF appears to be better overall. Clinics should choose IVF or ICSI for fertility preservation depending on sperm characteristics rather than using ICSI for all.

Intracytoplasmic sperm injection (ICSI) is highly effective for male factor infertility. However, its use for non-male factor infertility has increased dramatically worldwide in the last 2 decades despite little evidence demonstrating effectiveness in this population. The rationale for using ICSI is to reduce the risk of low or total failed fertilisation (TFF), thereby increasing the number of embryos and the potential for pregnancy and live birth (Bhattacharya et al. 2013). A meta-analysis (Johnson et al. 2013) of sibling oocyte studies reported a significantly higher pooled relative risk of TFF with IVF compared to ICSI. In contrast, more recent studies of infertile couples with non-male factor infertility show no difference in fertilisation, implantation or pregnancy rates (Li et al. 2018), even in poor responder patients (Sfontouris et al. 2015) or advanced maternal age (Tannus et al. 2017).

Arguing against an approach of ICSI for all there is accumulating information on the health of offspring including, amongst others, increased risk of congenital malformations, chromosomal abnormalities and epigenetic syndromes compared to naturally conceived children (Davies et al. 2017, Xiong et al. 2017, Esteves et al. 2018) and lower sperm concentration in male offspring (Belva et al. 2019).

Overall, TFF has been reported to complicate 1–3% ICSI and 5–8% IVF cycles (Swain & Pool 2008). This is particularly relevant for couples undertaking emergency fertility preservation who may only have one opportunity to create embryos. As such, there is a genuine debate regarding the correct approach to fertilisation for this particular group of patients: whether to apply IVF or ICSI depending on sperm characteristics or to undertake ICSI for all. In an attempt to resolve this dilemma, we analysed data provided by Human Fertilisation and Embryo Authority (HFEA). We present data for UK fertility preservation cycles 2015–2018 and 218,830 oocytes retrieved (Table 1), with known insemination method, fertilisation and downstream embryo disposal (transferred, stored, donated). Fertilisation rate (FR) was calculated from the number of oocytes normally fertilised (2PN) divided by the number of inseminated oocytes (IVF) or the number of oocytes microinjected (ICSI).

Table 1

Data for all UK fertility preservation cycles reported to HFEA 2015–2018. IVF and ICSI cycles are shown by intention to treat (ITT). Despite ITT, some IVF cycles reported oocyte injection. These were excluded from analysis as numbers were very small and fertilisation data were low (11/33; 33.3% (shown in italics)), raising the possibility of rescue ICSI. Similarly, some ICSI cycles reported conventional oocyte insemination. These were also excluded from further analysis as no further information was available, fertilisation was unexpectedly low (938/5660; 16.6% (shown in italics)). 52.3% normally fertilised eggs (2PN) resulted in embryos for storage, treatment or donation. This was identical whether derived from IVF or ICSI. Overall, 99.2% of embryos were cryostored.

IVF ICSI
2015 2016 2017 2018 Total 2015 2016 2017 2018 Total
Eggs collected 13,027 17,138 21,825 25,271 77,261 26,316 34,254 37,409 43,590 141,569
Eggs inseminated (IVF) 12,618 16,792 21,277 24,663 75,350 1368 1238 1518 1536 5660
M2 eggs injected (ICSI) 14 0 19 0 33 20,313 26,368 28,751 33,469 108,901
Eggs not used 409 346 529 608 1892 4635 6648 7140 8585 27,008
2PN (IVF) 8300 10,756 13,979 15,858 48,893
2PN (ICSI) 14,643 19,308 21,194 24,126 79,271
Fertilisation rate (%) 65.8 64.1 65.7 64.3 64.9 72.1 73.2 73.7 72.1 72.8
Embryos stored 4917 5752 7331 7437 25,437 8419 10,459 11,045 11,131 41,054
Total embryos: treatment and storage 4934 5782 7373 7501 25,590 8464 10,538 11,177 11,271 41,450
% embryos stored 99.7 99.5 99.4 99.1 99.4 99.5 99.3 98.8 98.8 99.0
% embryos generated from 2PN 59.4 53.8 52.7 47.3 52.3 57.8 54.6 52.7 46.7 52.3

In total, 75,350 eggs were inseminated (IVF) and 108,901 eggs were injected (ICSI). FR was significantly higher for ICSI compared to IVF (72.8% vs 64.9%; P  < 0.00001). A significantly higher proportion of embryos resulted from ICSI per egg injected compared to IVF per egg inseminated (38.1% vs 34.0%; P  < 0.00001). However, 19.1% (27,008) eggs allocated to ICSI were not used, presumably due to immaturity or being otherwise unsuitable for injection, compared to only 2.4% (1878) eggs not used for IVF insemination. The percentage of embryos generated for treatment or storage from normally fertilised eggs (2PN) was identical between IVF and ICSI. Over 99% of all embryos were cryostored.

These data demonstrate that although a 7.9% higher FR is seen with ICSI compared to IVF, this does not compensate for the significantly higher proportion of eggs not used for microinjection, and we ,therefore recommend a strategy of IVF or ICSI depending on sperm characteristics rather than ICSI for all fertility preservation.

Declaration of interest

Sarah J Martins da Silva is an Associate Editor of Reproduction and Fertility. Sarah J Martins da Silva was not involved in the review or editorial process for this paper on which she is listed as an author.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Author contribution statement

B A analysed the data. A L E and H R collected and collated HFEA data. S M D S conceived the study. S M D S, B A and A L E wrote the paper.

References

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  • Bhattacharya S, Maheshwari A & Mollison J 2013 Factors associated with failed treatment: an analysis of 121,744 women embarking on their first IVF cycles. PLoS ONE 8 e82249. (https://doi.org/10.1371/journal.pone.0082249)

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    • Export Citation
  • Davies MJ, Rumbold AR, Marino JL, Willson K, Giles LC, Whitrow MJ, Scheil W, Moran LJ, Thompson JG & Lane M et al.2017 Maternal factors and the risk of birth defects after IVF and ICSI: a whole of population cohort study. BJOG 124 15371544. (https://doi.org/10.1111/1471-0528.14365)

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  • Esteves SC, Roque M, Bedoschi G, Haahr T & Humaidan P 2018 Intracytoplasmic sperm injection for male infertility and consequences for offspring. Nature Reviews: Urology 15 535562. (https://doi.org/10.1038/s41585-018-0051-8)

    • PubMed
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  • Johnson LN, Sasson IE, Sammel MD & Dokras A 2013 Does intracytoplasmic sperm injection improve the fertilization rate and decrease the total fertilization failure rate in couples with well-defined unexplained infertility? A systematic review and meta-analysis. Fertility and Sterility 100 7047 11. (https://doi.org/10.1016/j.fertnstert.2013.04.038)

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    • Search Google Scholar
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  • Sfontouris IA, Kolibianakis EM, Lainas GT, Navaratnarajah R, Tarlatzis BC & Lainas TG 2015 Live birth rates using conventional in vitro fertilization compared to intracytoplasmic sperm injection in Bologna poor responders with a single oocyte retrieved. Journal of Assisted Reproduction and Genetics 32 69169 7. (https://doi.org/10.1007/s10815-015-0459-5)

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  • Swain JE & Pool TB 2008 ART failure: oocyte contributions to unsuccessful fertilization. Human Reproduction Update 14 4314 4 6. (https://doi.org/10.1093/humupd/dmn025)

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    • Search Google Scholar
    • Export Citation
  • Tannus S, Son WY, Gilman A, Younes G, Shavit T & Dahan MH 2017 The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age. Human Reproduction 32 119124. (https://doi.org/10.1093/humrep/dew298)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xiong X, Dickey RP, Buekens P, Shaffer JG & Pridjian G 2017 Use of intracytoplasmic sperm injection and birth outcomes in women conceiving through in vitro fertilization. Paediatric and Perinatal Epidemiology 31 108115. (https://doi.org/10.1111/ppe.12339)

    • PubMed
    • Search Google Scholar
    • Export Citation

 

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  • Belva F, Bonduelle M & Tournaye H 2019 Endocrine and reproductive profile of boys and young adults conceived after ICSI. Current Opinion in Obstetrics and Gynecology 31 163169. (https://doi.org/10.1097/GCO.0000000000000538)

    • Search Google Scholar
    • Export Citation
  • Bhattacharya S, Maheshwari A & Mollison J 2013 Factors associated with failed treatment: an analysis of 121,744 women embarking on their first IVF cycles. PLoS ONE 8 e82249. (https://doi.org/10.1371/journal.pone.0082249)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Davies MJ, Rumbold AR, Marino JL, Willson K, Giles LC, Whitrow MJ, Scheil W, Moran LJ, Thompson JG & Lane M et al.2017 Maternal factors and the risk of birth defects after IVF and ICSI: a whole of population cohort study. BJOG 124 15371544. (https://doi.org/10.1111/1471-0528.14365)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Esteves SC, Roque M, Bedoschi G, Haahr T & Humaidan P 2018 Intracytoplasmic sperm injection for male infertility and consequences for offspring. Nature Reviews: Urology 15 535562. (https://doi.org/10.1038/s41585-018-0051-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Johnson LN, Sasson IE, Sammel MD & Dokras A 2013 Does intracytoplasmic sperm injection improve the fertilization rate and decrease the total fertilization failure rate in couples with well-defined unexplained infertility? A systematic review and meta-analysis. Fertility and Sterility 100 7047 11. (https://doi.org/10.1016/j.fertnstert.2013.04.038)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li Z, Wang AY, Bowman M, Hammarberg K, Farquhar C, Johnson L, Safi N & Sullivan EA 2018 ICSI does not increase the cumulative live birth rate in non-male factor infertility. Human Reproduction 33 13221330. (https://doi.org/10.1093/humrep/dey118)

    • Search Google Scholar
    • Export Citation
  • Sfontouris IA, Kolibianakis EM, Lainas GT, Navaratnarajah R, Tarlatzis BC & Lainas TG 2015 Live birth rates using conventional in vitro fertilization compared to intracytoplasmic sperm injection in Bologna poor responders with a single oocyte retrieved. Journal of Assisted Reproduction and Genetics 32 69169 7. (https://doi.org/10.1007/s10815-015-0459-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Swain JE & Pool TB 2008 ART failure: oocyte contributions to unsuccessful fertilization. Human Reproduction Update 14 4314 4 6. (https://doi.org/10.1093/humupd/dmn025)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tannus S, Son WY, Gilman A, Younes G, Shavit T & Dahan MH 2017 The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age. Human Reproduction 32 119124. (https://doi.org/10.1093/humrep/dew298)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xiong X, Dickey RP, Buekens P, Shaffer JG & Pridjian G 2017 Use of intracytoplasmic sperm injection and birth outcomes in women conceiving through in vitro fertilization. Paediatric and Perinatal Epidemiology 31 108115. (https://doi.org/10.1111/ppe.12339)

    • PubMed
    • Search Google Scholar
    • Export Citation