4.3 Causes of Infertility

Hormonal and Ovulatory Dysfunction

Ovulatory dysfunction makes up the largest percentage of cases of female factor infertility. If an egg is not released by the ovary on a regular basis, there is no opportunity for fertilization or conception. The two main types of ovulatory dysfunction are oligoovulation, a pattern of irregular ovulation, and anovulation, the complete absence of ovulation. The World Health Organization has subdivided ovulatory disorders into four classifications (Walker & Tobler, 2022).

1. Hypogonadotropic hypogonadal anovulation: This disorder is characterized by decreased secretion of gonadotropin-releasing hormone (GnRH). When GnRH secretion is decreased, the secretion of FSH and LH from the anterior pituitary gland is also suppressed. This leads to low estrogen, poor follicular growth, and anovulation. Also known as hypothalamic amenorrhea, this condition is most common in people with eating disorders, excessive exercise, decreased caloric intake, or significant weight loss.
2. Normogonadotropic normoestrogenic anovulation: Polycystic ovary syndrome (PCOS) is the most common type of normogonadotropic normoestrogenic anovulation, affecting 8 percent of all persons AFAB of childbearing age (Walker & Tobler, 2022). It is responsible for between 80 percent and 85 percent of all cases of anovulation (Walker & Tobler, 2022). People can be diagnosed with PCOS if they have at least two of the three criteria: oligo/anovulation, clinical signs of high androgens (acne, hirsutism, male pattern hair loss), or polycystic ovaries on ultrasound (Figure 4.12) (Tay et al., 2020). People with PCOS often do not ovulate regularly; it is believed that there is an abnormal pulsing of GnRH, which leads to dysfunction in developing a mature follicle (Walker & Tobler, 2022).
3. Hypergonadotropic hypoestrogenic anovulation: This type of anovulation is associated with the natural aging process, as well as primary ovarian insufficiency (POI), defined as ovarian failure before the age of 40. The number and quality of eggs that a person has decreases with age. It is believed that the decrease in quality is due to the increased occurrence of meiotic nondisjunction (errors in cell division), which can lead to chromosomal abnormalities. POI is most notably associated with Turner syndrome, a genetic syndrome that causes a person AFAB to have a 45X karyotype, instead of the typical 46XX. In addition, cigarette smoking is associated with premature menopause and decreased numbers of ovarian follicles (Walker & Tobler, 2022).
4. Hyperprolactinemic anovulation: Hyperprolactinemia, or elevated serum prolactin levels, can lead to several effects:
   • suppression of GnRH from the hypothalamus
   • low LH, which causes anovulation and amenorrhea
   • poor progesterone secretion from the corpus luteum
   Normal prolactin levels are typically under 20 ng/mL. Serum levels above 100 ng/mL are typically associated with pituitary microadenomas, a benign tumor of the pituitary gland.

Figure 4.12 Polycystic Ovary An ovary with PCOS contains many small follicles. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

Endometrial or Uterine Problems

Structural problems in the uterus can also prevent pregnancy from happening, as implantation may not be possible. These may include the following:

• Uterine fibroids: Uterine fibroids are noncancerous growths that occur in the muscle tissue of the uterus. They can be subserosal (in the outer wall of the uterus), intramural (in the muscular layer), or submucosal (in the inner layer; Figure 4.13). Not all fibroids will affect fertility, and, in fact, most will not. However, very large fibroids, or those that protrude into the endometrial cavity are more likely to make conception more difficult (Fibroids and fertility, n.d.).

  Figure 4.13 Uterine Fibroids Fibroids are benign tumors that are found in the uterus. They can occur in the inner lining of the cavity, in the muscular lining, or in the outer serosal layer of the uterus. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)
• Uterine polyps: Uterine polyps are also noncancerous growths, but these are found in the endometrial lining. Polyps are often an incidental finding during testing, but their effect on fertility is not clear (Chami & Saridogan, 2017). While many people with uterine polyp can successfully carry a pregnancy to term, research does suggest that removing them may be beneficial before proceeding with fertility treatment, particularly in vitro fertilization (IVF).
• Abnormal shape: Congenital abnormalities of the uterus can present in many ways (Figure 4.14). Depending on the extent of the abnormality, sperm may not be able to reach the egg, or implantation of a fertilized egg may not be possible.

  Figure 4.14 Congenital Abnormalities of the Uterus Congenital abnormalities of the uterus can cause the uterus to present in many different shapes and conformations. Depending on the shape, it may be difficult for someone to become and stay pregnant. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)
• Scarring: Scarring from previous trauma, surgeries, or infections can block the passage of sperm through the uterus or the movement of a fertilized egg into the uterus. It can also prevent implantation from occurring in the uterus and may increase the risk for ectopic pregnancy elsewhere in the reproductive tract.
• Endometriosis: Endometriosis is the development of endometrial tissue outside the uterus. This tissue responds to the hormones of the menstrual cycle, which cause it to grow and proliferate and then break down and bleed, just like a menstrual period. However, blood from endometriosis has nowhere to go and becomes trapped in the body, causing scar tissue or adhesions. This tissue can block sperm or the egg from reaching the fallopian tube for fertilization to take place (Hill et al., 2020).
• Endometritis: Endometritis is an inflammation or infection of the endometrial lining of the uterus. If present, it can prevent implantation and contribute to infertility. Endometritis can be acute, such as a postpartum infection after a cesarean delivery, or it can be chronic.

Tubal Issues

Blockages in the fallopian tube(s), also known as tubal occlusion, can prevent sperm cells from reaching the egg. These blockages can result from several factors, including:

• infection
• inflammation
• scar tissue from endometriosis or previous pelvic or abdominal surgery
• adhesions
• structural issues (Roberts, 2023)

A hydrosalpinx is a type of blockage in the fallopian tube caused by the buildup of fluid. Like a blockage from scar tissue, it causes difficulty for the movement of both sperm and egg and results in infertility (Figure 4.15). Hydrosalpinx also increases the risk for ectopic pregnancy, where a fertilized egg implants outside the uterus, most commonly in the fallopian tube. The risk factors for developing a hydrosalpinx are the same as for a tubal blockage, including infection, pelvic inflammatory disease (PID), and scar tissue or adhesions from prior abdominal surgery (Yao et al., 2023).

Figure 4.15 Hydrosalpinx in the Fallopian Tube A hydrosalpinx is an accumulation of fluid in the fallopian tube, which prevents the passage of sperm or egg. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

Issues with Sperm Transport

Blockages in the vas deferens or ejaculatory ducts can prevent the release of sperm cells during ejaculation or the transport of sperm through the reproductive tract. These blockages can result from:

• scar tissue after surgery, trauma, or injury
• infection
• the presence of a tumor that presses on the reproductive structures
• a vasectomy
• congenital absence of the vas deferens (World Health Organization, 2023a).

Hormonal Causes

Abnormalities in hormones produced by the pituitary gland, hypothalamus, or testes can lead to the poor production of sperm. These hormones include testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin. Hormonal abnormalities can be caused by pituitary or hypothalamic disease or tumors, some drugs or medications, and even hyperthyroidism. Testosterone supplementation can also significantly reduce sperm production (Patel et al., 2019).

Alterations in Spermatogenesis

Spermatogenesis is the production of mature sperm cells. Exposure to some toxins can affect gonadal production. These are known as gonadotoxins and can reduce the ability of the testes to make healthy, motile sperm cells. Potential gonadotoxins include drugs and medications, infection, chronic illness, exposure to chemicals, previous radiation or chemotherapy, or exposure of the testicles to heat (Durairajanayagam, 2018; Schlegel et al., 2021).

Varicoceles may also impact spermatogenesis. A varicocele is an enlargement of the veins in the spermatic cord of the scrotum, sometimes to the point where they are visible (Figure 4.16). They are a typical anatomic finding in around 15 percent of persons assigned male at birth (Leslie et al., 2023). While most varicoceles do not cause any problems, they can cause infertility or depressed sperm counts in a small percentage of patients (Leslie et al., 2023). The exact mechanism of action is unknown, but it is hypothesized that the pooling of blood in the enlarged veins may raise scrotal temperature (Leslie et al., 2023).

Figure 4.16 Varicocele A varicocele is a tortuous enlargement of the scrotal veins in the testicle. It is a normal finding in some people but can cause discomfort and, in some cases, infertility. (credit: modification of work from Anatomy and Physiology 2e. attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

Presence of Sperm Antibodies

Sperm antibodies are produced when the immune system does not recognize sperm cells as part of the body and initiates an immunologic reaction. This reaction damages sperm cells and may make them immotile, or unable to move. While not common, this condition does occur in some patients after testicular trauma, infections, or vasectomy reversal (Silva et al., 2021).

Difficulties with Sexual Intercourse

Finally, disorders of sexual intercourse can also affect conception. Erectile or ejaculatory disorders can prevent the transmission of sperm into the female reproductive tract. This is frequently caused by age, chronic illness like diabetes, and psychosocial issues. In addition to more commonly known conditions such as premature ejaculation, erectile dysfunction, and insufficient sexual practices, a condition called retrograde ejaculation can contribute to a low sperm count. Retrograde ejaculation is the backward movement of ejaculate into the bladder instead of being expelled from the urethra (National Institute of Diabetes and Digestive and Kidney Disease, n.d.). Impotence can also be caused by alcohol abuse or antihypertensive medications.

Stress

Many people who struggle with infertility report high levels of stress, but whether high levels of stress cause infertility is unknown (Rooney & Domar, 2018). Further study is needed to explore this relationship, but the nature of self-reported symptoms can make it difficult to get a true understanding of what is happening. Patients may be underestimating or minimizing their symptoms or experiences to appear that they are doing better than they are, or patients may experience falsely elevated (or depressed) optimism depending on where they are in their treatment cycle (Rooney & Domar, 2018). Stress has been shown to increase cortisol, which can lead to infertility.

High stress levels are very common in patients undergoing infertility treatment, and can contribute to depression, anxiety, and reduced quality of life (Figure 4.17). Implementation of a mind-body or mindfulness program may help to reduce symptoms of stress and improve coping. Such programs have been successful in helping patients to reduce stress and even improve pregnancy rates through many different modalities, including “cognitive behavior therapy, relaxation training, lifestyle changes, journaling, self-awareness, and social support components” (Rooney & Domar, 2018). Offering these types of programs or collaborating with professionals who do is an effective way to help patients deal with the psychosocial complications associated with infertility treatment.

Figure 4.17 Stress and Infertility While the relationship between stress and infertility is complicated, many couples undergoing fertility treatment report high levels of stress. The nurse can help by providing community resources and ideas for stress management. (credit: “Anxious black woman covering face with hand on bed” by Alex Green/Pexels, CC0)