Evidence map›Paper›PMID 40170012›Full record

ArticleBMC medicine2025

School-age outcomes among IVF and ICSI-conceived children: a causal inference analysis using linked population-wide data.

Amber L Kennedy, Richard J Hiscock, Beverley J Vollenhoven, Catharyn J Stern, Lyle C Gurrin, Tiki Osianlis, Aleah Kink, Susan P Walker, Jeanie L Y Cheong, Jon L Quach and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Amber L KennedyDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia. amber.kennedy@unimelb.edu.au.
Richard J HiscockDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia.
Beverley J VollenhovenDepartment of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
Catharyn J SternDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia.
Lyle C GurrinMelbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Tiki OsianlisNewlife IVF, Box Hill, VIC, Australia.
Aleah KinkDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia.
Susan P WalkerDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia.
Jeanie L Y CheongDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia.
Jon L QuachMurdoch Children's Research Institute, Parkville, VIC, Australia.
David WilkinsonCity Fertility Centre, Melbourne, VIC, Australia.
John McBainDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia.
Mark P GreenMonash IVF, Cremorne, VIC, Australia.
Jessica A AtkinsonDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia.
Franca AgrestaMelbourne IVF, East Melbourne, VIC, Australia.
Susan P BaohmMonash IVF, Cremorne, VIC, Australia.
Stephen TongDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia.
Roxanne HastieDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia.
Anthea C LindquistDepartment of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Parkville, Melbourne, 3052, Australia. anthea.lindquist@unimelb.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUse of intracytoplasmic sperm injection (ICSI) continues to increase as the most common mode of oocyte insemination during in vitro fertilisation (IVF), sometimes in the absence of clear indications (i.e. male factor infertility). Several studies suggest an increased risk of congenital abnormalities after ICSI. The association between the ICSI technique and long-term childhood development remains unclear.

methodsOur population-based study included singleton infants conceived via IVF and born between 2005 and 2013. The cohort included state-wide linked maternal and childhood administrative data from Victoria, Australia. The primary exposure was conception via ICSI (without severe male factor infertility), with those born following standard IVF as controls. Childhood development was examined using the Australian Early Development Census (AEDC), a broad assessment of childhood development across five domains of health and neurodevelopment performed in Australian schools every triennium at school entry (age 4-6 years). Our primary outcome used a validated global measure-developmental vulnerability-defined as scoring less than the 10th percentile in two or more of the five developmental domains (DV2). Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The adjustment variable set was determined a priori via a modified Delphi procedure. Given the use of observational data, there were missing data and inherent differences in the covariate profile between exposure cohorts. Multiple imputation, bootstrapping and doubly robust inverse probability weighted regression adjustment modelling was utilised to allow a causal interpretation of results.

resultsOur cohort (N = 3656) included 1489 IVF and 2167 ICSI-conceived children. We found no causal effect of ICSI on the risk of AEDC-defined developmental vulnerability at school-entry age compared with children conceived via standard IVF; adjusted risk difference - 1.11% (95% CI - 4.23 to 2.01%) and adjusted risk ratio 0.90 (95% CI 0.68 to 1.21).

conclusionsOur findings suggest that the use of ICSI in IVF cycles without severe male factor infertility does not increase the risk of early childhood developmental vulnerability among children in their first year of school. These findings provide important reassurance for current and prospective parents and clinicians alike.

Indexed as

Child DevelopmentFertilization in VitroSperm Injections, IntracytoplasmicAdultChildChild, PreschoolCohort StudiesFemaleHumansMaleVictoriaCausal analysisChildhood developmentICSIIVF

Identifiers

PMID40170012
PMCPMC11963277

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.