The Complex Relationship Between Infertility – Fertility Treatments and Autism Spectrum Disorder


Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with a multifaceted etiology involving both genetic and environmental factors. The onset of ASD symptoms as early as 18 months of age suggests a critical period during which risk factors, particularly those occurring in the perinatal period, may contribute to the development of this complex disorder.

This article delves into the intricate web of associations between infertility, fertility treatments, and the risk of ASD, considering the influence of maternal metabolic and inflammatory factors, as well as epigenetic changes in offspring.

Infertility and Its Treatments:

Infertility is a prevalent concern, affecting 1 in 6 couples, and fertility treatments have become increasingly common, resulting in approximately 10 million infants born worldwide after their use.

Fertility treatments range from less invasive methods such as ovulation induction (OI) and intrauterine insemination (IUI) to more invasive procedures like in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Maternal Factors in ASD Pathogenesis:

Maternal metabolic and inflammatory factors play a pivotal role in the pathogenesis of ASD. Conditions such as polycystic ovary syndrome (PCOS), endometriosis, and obesity have been identified as common contributors. The implications of these conditions extend beyond infertility, highlighting the intricate interplay between maternal health and neurodevelopmental outcomes in offspring.

Epigenetic Changes and Assisted Reproductive Technologies:

Epigenetic changes have been implicated in the development of ASD, with studies revealing alterations in children conceived through fertility treatments. Notably, prolonged antecedent duration of infertility and the use of ICSI, primarily employed for male infertility, have been associated with epigenetic modifications. Mechanistic factors include the culture media used during embryo development and the manipulation of oocytes and sperm during ICSI.

ASD Risk in Different Fertility Treatments:

Initial studies have shown minimal risk of ASD in children born after OI, IUI, IVF, or ICSI. However, intriguingly, a potential higher risk of ASD has been observed in children born to parents with subfertility, even without undergoing fertility treatment. This raises questions about the role of infertility itself in the etiology of ASD, independent of the mode of conception.

Mediating Effect of Adverse Pregnancy Outcomes:

While individuals with subfertility and those undergoing fertility treatments face an increased risk of adverse pregnancy outcomes, such as preeclampsia, cesarean birth, multiple pregnancies, preterm birth, and severe neonatal morbidity, the mediating effect of these factors on the association between the mode of conception and ASD remains understudied. This gap in knowledge prompted the current study to comprehensively evaluate the nuanced relationship between infertility, fertility treatments, adverse pregnancy outcomes, and the risk of ASD.

Discussion: Unraveling the Complex Interplay of Infertility, Fertility Treatments, and Autism Spectrum Disorder

The findings of this population-based cohort study shed light on the intricate relationship between parental infertility, fertility treatments, adverse pregnancy outcomes, and the risk of Autism Spectrum Disorder (ASD) in offspring. The study revealed a nuanced pattern, where a slightly elevated risk of ASD was observed in children born to individuals with subfertility or those receiving fertility treatment, with some mediation by specific adverse pregnancy factors. This discussion aims to dissect and contextualize these findings within the broader landscape of existing research.

Consistent Patterns and Prior Research:

The study’s results align with previous research indicating a marginal increase in the risk of ASD in children born to individuals with isolated infertility or those who underwent fertility treatment. These findings challenge earlier assumptions that infertility treatment itself is a direct contributor to adverse perinatal outcomes. Instead, emerging evidence suggests that the baseline infertility diagnosis may be a key factor influencing the risk of ASD.

Mediation by Adverse Pregnancy Outcomes:

One notable contribution of this study lies in its exploration of the mediating role of adverse pregnancy outcomes in the association between infertility, fertility treatments, and ASD. The analysis pinpointed individual adverse outcomes, such as cesarean birth, multiple pregnancies, preterm birth, and severe neonatal morbidity, as potential mediators, particularly following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). For instance, the study revealed a substantial mediation effect of multiple pregnancies, emphasizing the importance of efforts to minimize the occurrence of multiples in patients undergoing IVF or ICSI.

Implications for Clinical Practice:

The implications of these findings extend beyond research, offering valuable insights for clinical practice. The study advocates for early and comprehensive care plans for pregnant patients following fertility treatment, with a specific focus on strategies to mitigate adverse pregnancy outcomes associated with ASD risk. This underscores the importance of integrating fertility treatment and neurodevelopmental considerations into prenatal care to enhance outcomes for both mothers and children.

Understanding the Role of Infertility:

A noteworthy aspect of the study is its emphasis on distinguishing the impact of fertility treatments from the underlying infertility itself. Contrary to assumptions that certain fertility treatments may independently contribute to ASD risk, the results indicate that ovulation induction (OI), intrauterine insemination (IUI), IVF, and ICSI do not introduce measurable risks of ASD compared to subfertility alone. The study suggests that the driver between parental infertility and ASD in the child may lie in the underlying infertility condition rather than the specific fertility treatments employed.

Specifics of Intrauterine Insemination (IUI) and Intracytoplasmic Sperm Injection (ICSI):

When delving into specific fertility treatments, the study provides valuable insights into the comparison of ICSI with IVF. Notably, ICSI did not exhibit a higher risk of ASD when compared to IVF, challenging some previous findings. The study acknowledges variations in techniques and indications for ICSI, emphasizing the need for a nuanced understanding of the diverse factors influencing the association between ICSI and ASD.

Comparisons with Previous Studies:

Comparisons with prior studies, such as those from Sweden and California, reveal variations in effect sizes. These differences may stem from diverse techniques, indications for fertility treatments, and the inclusion of multiple pregnancies in some studies. The current study adds to this body of knowledge, highlighting the need for continued exploration and refinement of our understanding of the intricate relationship between infertility treatments and neurodevelopmental outcomes.

In conclusion, this comprehensive analysis contributes substantially to our understanding of the complex interplay between infertility, fertility treatments, adverse pregnancy outcomes, and the risk of ASD. The results underscore the need for a nuanced approach in both research and clinical practice, considering the distinct contributions of infertility, specific fertility treatments, and associated pregnancy factors to the risk of ASD in offspring. Ongoing efforts to refine and expand our knowledge in this domain will undoubtedly pave the way for more targeted interventions and improved outcomes for families facing fertility challenges.

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