Increased Risk of Cerebral Palsy in IVF/ICSI Babies: Meta analysis of Current Literature

Author:

Bulut Halil1,Bastopcu Merve1,Altin Omer1,Ali 2

Affiliation:

1. Istanbul University Cerrahpasa

2. Seker

Abstract

Abstract Background: The correlation between assisted reproductive therapies (ARTs) and congenital or developmental anomalies has been acknowledged by prominent obstetric and reproductive science authorities. However, the orthopedic perspective on this aspect of ARTs remains largely unexplored. This meta-analysis aims to examine a plausible association between cerebral palsy and in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) therapies within the realm of assisted reproductive technologies (ARTs). Methods: The literature spanning from 1980 to February 2024 was systematically reviewed within the MEDLINE, Scopus, and Embase databases, adhering to the PRISMA guidelines. Data synthesis was conducted using the Jamovi program. Results: The literature review involved an initial search that yielded 192 articles, which were subsequently refined to 21 articles following the removal of duplicates and screening for relevance. These articles, selected according to the PRISMA model, collectively included data from 8,657,973 patients. Upon analyzing the dataset, it was found that among 8,400,080 control patients, there were 14,518 cases of cerebral palsy, while among 237,873 patients who underwent IVF or ICSI, 736 cases of cerebral palsy were documented. This analysis revealed that the incidence of cerebral palsy was approximately 1.9 times higher in IVF and ICSI cases compared to control groups (p < 0.001, adjusted odds ratio = 1.9, 95% confidence interval: 1.570–2.323). Conclusion As a result, the risk of developing cerebral palsy, as in many other congenital anomalies and pediatric diseases, in babies born with assisted reproductive techniques is statistically significantly higher than in normal babies. This, together with the sensitive monitoring of the neonatal period and perinatal period in women conceived with ART. It is recommended that teams collaborate with pediatric orthopedic surgeons.

Publisher

Research Square Platform LLC

Reference11 articles.

1. A thorough search utilizing pertinent keywords yielded a total of 192 articles from the designated database systems. Following the removal of duplicates and screening for relevance based on titles, the analysis narrowed down to 76 abstracts, resulting in the exclusion of 50 articles. The final filtration process, conducted in accordance with the PRISMA model, ultimately included 21 articles for detailed analysis(8–28). These selected articles collectively encompassed data from 8,657,973 patients. For a comprehensive overview of the study selection process, please refer to Fig. 1 and Table 1. 3.2 Comparison between ARTs and Control

2. After conducting a comprehensive analysis of the dataset, it was observed that among 8,400,080 control patients, 14,518 cases of cerebral palsy were identified. In contrast, among 237,873 patients who underwent either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), 736 cases of cerebral palsy were documented. Upon meticulous data synthesis, it became evident that the incidence of cerebral palsy was approximately 1.9 times higher in IVF and ICSI cases compared to other control groups. (p < 0.001,95% confidence interval: 1.570–2.323) (Fig. 2 and Fig. 3). 3.3 Heterogeneity of the literature

3. Following heterogeneity analysis, the I2 statistic was calculated to be 73.5%, which indicates a moderate to high level of heterogeneity among the studies included in the analysis. This suggests that there is a considerable amount of variability in the study results beyond what would be expected by chance alone. The p-value associated with this finding is less than 0.001, indicating that the observed heterogeneity is statistically significant. Additionally, the tau2 value, a measure of between-study variance, was calculated to be 0.1125. This further supports the presence of heterogeneity among the studies, as a tau2 value greater than zero suggests that the true effect size may vary across studies

4. Discussion

5. As infertility rates and maternal ages continue to rise, the utilization of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) is steadily increasing (2). These assisted reproductive technologies (ART) have a well-established track record of success in helping couples conceive. (1–2) However, the topic of concern regarding the prevalence of congenital anomalies in pregnancies resulting from IVF and ICSI has been a topic of ongoing debate within the medical community (1–5). Potential hypotheses behind this phenomenon include factors such as maternal age at the time of IVF/ICSI, multiparity, and innate susceptibility to natural congenital pathologies (29–30). Some causes of female infertility can predispose embryos to malformations and increase the risk of prematurity (30–31). Moreover, the risk of prematurity is heightened by multiparity, which is more prevalent in IVF/ICSI cases (28–31). There are also more speculative theories, such as the potential for DNA damage during in vitro fertilization or intracytoplasmic injection (32). While meta-analyses have investigated the association between IVF/ICSI and pediatric problems such as chromosomal anomalies and congenital heart diseases, a comprehensive perspective on congenital orthopedic problems and musculoskeletal diseases has not yet been presented(3,5). Our study represents the most thorough examination of this topic to date

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