The impact of specific fertility treatments on cognitive development in childhood and adolescence: a systematic review
Bibliographic record
Abstract
STUDY QUESTION: Does fertility treatment influence cognitive ability in school aged children, and does the impact vary with the type of treatment? SUMMARY ANSWER: The available high-quality evidence indicates that specific treatments may give rise to different effects on cognitive development, with certain treatments, including ICSI, associated with cognitive impairment. WHAT IS KNOWN ALREADY: Previous reviews of the literature concerning cognitive outcomes among children conceived with medical assistance have concluded that study findings are generally 'reassuring', but limited attention has been paid to the quality of this research. In addition, no review has separately assessed the range of treatment modalities available, which vary in invasiveness, and thus, potentially, in their effects on developmental outcomes. STUDY DESIGN, SIZE, DURATION: A systematic review was undertaken. We searched PubMed, PsycINFO and the Educational Resources Information Centre database to identify English-language studies published up until 21 November 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two authors independently reviewed identified articles, extracted data and assessed study quality. Studies were eligible if they assessed cognitive development from age 4 years or more, among children conceived with fertility treatment compared with either children conceived naturally or children born from a different type of fertility treatment. Where available, data were extracted and reported separately according to the various components of treatment (e.g. mode of fertilization, embryo freezing, etc.). Risk of bias was assessed using the Newcastle-Ottawa Scale, with a score ≥7/9 indicative of high quality. MAIN RESULTS AND THE ROLE OF CHANCE: The search identified 861 articles, of which 35 were included. Of these, seven were rated high quality. Most studies (n = 22) were subject to selection bias, due to the exclusion of children at increased risk of cognitive impairment. Among high-quality studies, there was no difference in cognitive outcomes among children conceived with conventional IVF and those conceived naturally. Findings among high-quality studies of children conceived with ICSI were inconsistent: when compared with children conceived naturally, one study reported lower intelligence quotient (IQ; 5-7 points, on average) among ICSI children whereas the remaining two high-quality studies reported no difference between groups. Furthermore, among the three high-quality studies comparing children conceived with ICSI compared with conventional IVF, one reported a significant increase in the risk of mental retardation, one reported a small difference in IQ (3 points lower, on average) and one no difference at all. There were scant studies examining exposure to embryo freezing, or less invasive treatments such as ovulation induction without IVF/ICSI. LIMITATION, REASONS FOR CAUTION: Most existing studies had methodological limitations including selection bias and/or failure to address confounding by family background. In addition, a meta-analysis could not be performed due to heterogeneity in the assessment of cognitive outcomes. These factors impeded our ability to synthesize the evidence and draw reliable conclusions. WIDER IMPLICATIONS OF THE FINDINGS: The conflicting findings among studies of children conceived with ICSI require clarification, in light of the increasing use of this technique for reasons other than male-factor infertility. Further population-based studies are needed that utilize contemporary data to examine specific aspects of treatment and combinations of techniques (e.g. ICSI with frozen embryo cycles). Importantly, studies should include the complete group of children exposed to treatment. STUDY FUNDING/COMPETING INTEREST(S): A.R.R. is supported by a Career Development Fellowship from the National Health and Medical Research Council of Australia. L.J.M. is funded by a fellowship from the Heart Foundation of Australia. The authors declare there are no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.031 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.008 |
| Bibliometrics | 0.005 | 0.006 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".