Infertility and Risk of Autism Spectrum Disorder in Children

Introduction

Infertility is one of the biggest problems of modern times. Almost 48 million couples around the world are suffering from infertility-related complications. However, on the other hand, the advent of modern medical facilities has provided options for the treatment of such conditions. Autism spectrum disorders are common psychological complications seen in children. Every one out of 100 children suffers from this condition. Recently, researchers have found a certain link between infertility and autism or autism and children born with assisted reproductive techniques.

What Are Autism Spectrum Disorders?

Autism or autism spectrum disorders are a group of neurodevelopmental disorders commonly seen in children and young individuals. This causes poor development of brain and cognitive responses. As a result, poor emotional, physical, and social development is observed. The symptoms are repetitive behavior patterns, poor social interactions, poor intelligence, emotional impairment, and poor development of body parts can be observed. Though such conditions are influenced by familial history and genetics, risk factors such as infections, poor nutrition of the mother during pregnancy, increased age, and environmental toxins may play a pivotal role in the pathogenesis of this condition.

The disorders seen in this are Asperger syndrome (a type of developmental disorder), childhood disintegrative disorder (the onset of the developmental disorder is late), and Kanner syndrome (a mental disorder characterized by limited social interaction).

What Is Infertility?

Globally, around 10 percent of women are suffering from infertility. Infertility is being unable to get pregnant even after having unprotected sex for more than one year. In such conditions, several abnormalities related to male and female reproductive systems can be observed. Such abnormalities are low sperm count, blockage, and hormonal dysregulations are present. That is why factors associated with infertility can be grouped into two groups: male factors and female factors.

1. Male Factors: One of the main factors responsible for female infertility is low sperm count. Apart from this, factors like structural abnormalities in the male reproductive system, infectious conditions, pathology in the reproductive system, and genetic disorders are responsible for such conditions.

2. Female Factors: Several pathological conditions are responsible for female infertility. These conditions are,

• Ovulatory Dysfunction and Anovulation: These conditions are responsible for dysregulation in ovulation (release of the female egg). Polycystic ovarian syndrome (PCOS) is the most common condition associated with it.

• Endometriosis: This condition is characterized by the presence of ovary-like tissue outside the ovary. In such conditions, such tissues are present in places like the pleura (covering the lungs), the pericardium (covering the heart), the rectum, the bowl, or the central nervous system. The minimal form of endometritis (stage I and stage II) is associated with increased secretion of inflammatory mediators, increased functioning of macrophages, and natural killer cells. These factors prevent the implantation of the fertilized egg and are associated with subfertility.

• Pelvic or Tubal Adhesions: In these conditions, abnormalities prevent normal passage of the sperm, and implantation of the fertilized egg is impaired. Pelvic inflammatory diseases (PID) and sexually transmitted diseases are associated with such conditions.

• Uterine Abnormalities: Structural abnormality of the female genital structure such as leiomyomas (fibroids, growth of muscle and connective tissues) and scar tissues prevent fertilization or implantation of a fertilized egg.

For the treatment of infertility different treatment modalities like intrauterine insemination (IUI, the sperm is prepared outside, and the prepared sperm is placed inside the ovary) or in vitro fertilization (IVF, sperm is prepared outside and the fertilization is done outside the ovary in an artificial medium.)

What Is the Connection Between Infertility and Autism Spectrum Disorders?

As already discussed, autism spectrum disorders are influenced by genetic, familial, and environmental factors. The connection between infertility and autism spectrum disorders is controversial. According to some research, there is an association between infertility and autism. Other researchers have failed to establish any connections between these two. However, the prevalence of autistic children in mothers who are 35 years or older is significantly high. Also, the incidence of infertility-related complications among other individuals is significantly higher. Based on current knowledge, the following connections can be made between infertility and autism spectrum disorders;

1. One of the main factors responsible for infertility is smoking and alcoholism. The continuation of such habits during pregnancy is associated with low birth weight. Specifically, maternal smoking during pregnancy is the most prevalent risk factor. The tobacco toxins cross the placental barrier and reach the fetus's blood. Nicotine, carbon monoxide, and polycyclic aromatic hydrocarbons from smoke are responsible for intrauterine growth restriction.

2. Maternal PCOS (formation of cysts in the ovary due to hormonal dysfunction) is associated with autism. Research indicates that 35 percent of women with PCOS have reported having an autistic first child. It has been established that autism is linked to fetal exposure to elevated levels of amniotic fluid hormones such as androgens, progesterone, 17a-hydroxy-progesterone, and cortisol. In PCOS mothers increased levels of these hormones are observed. In women with PCOS, the fetus experiencing high levels of androgens, leads to molecular-level changes known as epigenetic changes in the fetus. This increased level of amniotic androgen is associated with hyperandrogenemia during the second and third trimesters of pregnancy (between the third and sixth months and from the sixth month to the end of pregnancy, respectively). Apart from this, the activity of p450 aromatase, the enzyme responsible for breaking down male hormones, is decreased during this period. Researchers have also identified the involvement of genes like CYP19A, in both PCOS and autism cases.

3. The effects of treatment protocols like ovulation induction drugs and intrauterine insemination are associated with conditions like Asperger’s syndrome in children. Exposure to high levels of follicle-stimulating hormone (FSH, a type of sex hormone) may be responsible for such conditions. ASD is also seen in children born with the help of In Vitro Fertilization (IVF). Exposure to ovarian stimuli like plasma protein-A (PAPP-A) and human menopausal gonadotropins during IVF may be associated with autistic symptoms in children. The culture media used in IVF contain various substances like protein, fat, amino acids, EDTA, and antibodies, which have toxic effects on the embryo. As a result, delayed growth, low birth weight, and poor development can be seen. This increases the chances of the development of autism in children.

4. Autistic women often suffer from PCOS. This is primarily linked to adrenal hyperplasia, which refers to the excessive activity of the adrenal gland located above the kidney. These patients display elevated androgen levels and modified estrogenic signaling. They may also experience other clinical symptoms commonly associated with PCOS, such as adiposity, increased BMI (Body mass index), and insulin resistance. Apart from this, a lack of testosterone aromatization (the conversion of Testosterone to Estradiol) can result in delayed puberty and menstrual disorders in autistic individuals. This may cause infertility in autistic persons.

Conclusion

The connection between autism and infertility is not fully established. However, autistic persons may suffer from infertility due to hormonal imbalances. On the other hand, children born with the help of assisted pregnancy procedures may suffer from autism. Factors like low birth weight, hormonal therapy, and the toxic effects of drugs are responsible for this.