Abstract

Over 5 million children have been born through in vitro fertilization (IVF) across the world. IVF is only one of the many methods of assisted reproduction, which can be used to achieve pregnancy in the context of infertility or subfertility. Since the birth of the first IVF child, Louise Brown, in 1978, a number of researchers have started to study the various impacts of the conception through these methods, on both mothers and children. A growing body of evidence suggests that conception through medically assisted reproduction (MAR) is not without risk. Given that MAR is relatively new and that our look back period is short, there is limited evidence on the risks associated to these procedures, both for the mother and the child. In this chapter, we aim to explore the association between MARs and adverse perinatal outcomes specifically. We will first provide you with an overview of the prevalence and trends of use of these methods around the world, and then delve into the associations between MARs and the risk of perinatal outcomes, namely prematurity, being born with low birth weight and/or small for gestational age, and lastly the impact of MARs on cognitive functions including cerebral palsy, behavioral problems, and autism, which are identified later in the child's life.

Keywords: medically assisted reproduction, prematurity, low birth weight, small for gestational age, delay in cognitive function

### 1. Introduction

#### 1.1 Infertility and subfertility

Infertility is defined as failure to conceive within 12 months of the first pregnancy attempt [1], while subfertility describes any form or grade of reduced fertility [2, 3].

The National Survey of Family Growth interviewed over 12,000 women of childbearing age (15–44 years old) to estimate the prevalence of infertility in the United States (US) [4]. A woman was considered infertile if she reported she and her partner were continuously cohabiting during the previous 12 months or longer, were sexually active each month, had not used contraception, and had not become pregnant [4]. From 1982 to 2006–2010, the percentage of infertile women based on this definition fell from 8.5 to 6.0% [4]. These estimates are lower than the 12–18% incidence of infertility in the US [5]. The frequency of infertility in nulliparous

women (i.e., primary infertility) increased with age and was reported to be: 7.3– 9.1% in women 15–34 years old, 25% in the 35–39 year olds, and 30% in the 40– 44 year olds [4].

Infertility and subfertility may be due to conditions originating from the male and/or female reproductive systems [6]. Between 8 and 20% of couples will experience difficulty conceiving [6–9]. Between 1982–1985, the World Health Organization (WHO) performed a multicenter study where they attributed 20% of infertility cases to male factors, 38% to female factors, 27% to causal factors identified in both partners, and 15% could not be attributed to either partner [10]. In the following section, we will provide you with an overview of the main causes of infertility.

### 1.1.1 Male infertility

A cross-sectional survey of men in the United States aged between 15–44 years showed a prevalence of male infertility of 12% [11]. Male infertility accounts for 19– 57% of the identified causes of infertility in couples [9]. In about 30–40% of cases of male infertility, the cause remains unknown [11, 12]. Male infertility can be classified into four main categories which we will briefly describe in the following section.

#### 1.1.1.1 Testicular disease: endocrine and systemic disorders

Testicular diseases including primary testicular defects account for 30–40% of male infertility [13]. Primary testicular defects can be further classified into: (1) congenital disorders including Klinefelter syndrome [14] and (2) acquired disorders which can be due to infections (e.g., chlamydia) [15] and smoking [16]. Hypothalamic pituitary diseases account for 1–2% for male infertility [13]. Secondary hypogonadism can cause gonadotropin deficiencies, which in turn leads to infertility [13]. Secondary hypogonadism can be (1) congenital [17], (2) acquired (e.g., tumors of the pituitary gland [18]) or (3) systemic (e.g., obesity [19]).

#### 1.1.1.2 Genetic disorders of spermatogenesis

Genetic disorders affecting spermatogenesis can be identified in 10–20% of male infertility cases [13]. With the increasing use of genome-wide association studies, genetic disorders have been linked to male infertility [12, 20]. Specifically, microdeletions and substitutions on the Y chromosome are increasingly recognized as genetic causes of azoospermia (i.e., semen without sperm) and severe oligozoospermia (i.e., semen with a sperm concentration < 15 million sperm/mL compared to the norm of >48 million sperm/mL [20]. Additionally, mutations linked to the X chromosome in men have also been linked to azoospermia [21–23].

#### 1.1.1.3 Posttesticular defects

Posttesticular defects lead to disorders of sperm transport, which account for 10–20% of male infertility cases [13]. The epididymis is an important site for sperm maturation and essential to the sperm transport system. The vas deferens transports sperm from the epididymis to the urethra, where they are diluted by secretions from the seminal vesicles and prostate. Abnormalities at any of these sites, particularly the epididymis and vas deferens, can lead to infertility [13]. The causes of these abnormalities include congenital obstructions of the vas deferens and obstruction following an infection (e.g., chlamydia). Additionally, given that sperm must be ejaculated, any disorder of the ejaculatory ducts can also lead to infertility [13].

Medically Assisted Reproduction and the Risk of Adverse Perinatal Outcomes DOI: http://dx.doi.org/10.5772/intechopen.81337
