4.4: Causes of Infertility

Learning Objectives

By the end of this section, you will be able to:

• Describe the different types of infertility in persons assigned female at birth
• Describe the different types of infertility in persons assigned male at birth
• Explain various treatments to improve fertility

Fertility is a delicate balance that depends on many different factors. Nutritional deficiencies, substance use, and exposure to environmental toxins can all result in poor-quality egg and sperm cells and can contribute to infertility. There are two types of infertility: primary infertility is diagnosed if a person has never been pregnant, and secondary infertility occurs when a person who has previously carried and delivered a pregnancy cannot become pregnant again. Infertility can be caused by factors in the partner assigned female at birth, the partner assigned male at birth, or both. In many cases, a specific cause can’t be found for a couple’s inability to conceive.

Infertility of Persons Assigned Female at Birth

According to a large multinational study performed by the World Health Organization, approximately 37 percent of infertile couples experience infertility of persons AFAB (Walker & Tobler, 2022). That same study identified the most common identifiable factors as follows:

• ovulatory disorders—25 percent
• endometriosis—15 percent
• pelvic adhesions—12 percent
• tubal blockage—11 percent
• other tubal/uterine abnormalities—11 percent
• hyperprolactinemia—7 percent (Walker & Tobler, 2022)

A comprehensive history and physical assessment can help to determine the possible cause(s) of a patient’s inability to conceive.

Medications can lead to infertility. Chemotherapy agents can damage the tissue of the ovary leading to infertility (Bhardwaj et al., 2023). Nonsteroidal anti-inflammatory drugs (NSAIDs) at high doses or in long-term use can cause difficulty in conceiving. Antipsychotic medications, spironolactone (Aldactone), and illegal drugs such as marijuana and cocaine can also affect fertility (NHS, 2023).

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. (CC BY 4.0; Rice University & OpenStax)

Clinical Judgment Measurement Model

Analyze Cues: Polycystic Ovary Syndrome

Irregular periods are a common symptom among patients seeking infertility treatment. Of the many potential reasons why someone may have irregular periods, polycystic ovary syndrome (PCOS) is one of the most common causes, and fertility nurses must be aware that it is present in 6 percent to 12 percent of patients of childbearing age (PCOS, 2022). However, people with PCOS have other symptoms besides irregular periods, and many people with PCOS do not have irregular cycles. The nurse must learn to recognize the other cues that make up the entire clinical presentation of PCOS, which may include:

• obesity;
• hirsutism (abnormal hair growth on the face, back, or chest);
• acne;
• male pattern hair loss;
• insulin resistance and other metabolic changes;
• polycystic ovaries noted on transvaginal ultrasound; and
• elevated serum androgen levels.

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. (CC BY 4.0; Rice University & OpenStax)

• 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. (CC BY 4.0; Rice University & OpenStax)

• 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. (CC BY 4.0; Rice University & OpenStax)

Infertility of Persons Assigned Male at Birth

Infertility in persons AMAB is responsible for around 20 percent of cases and contributes to another 30 percent to 40 percent of all infertility cases (Leslie et al., 2023). Many potential etiologies, including structural, hormonal, infectious, and genetic, exist. These factors can cause azoospermia, defined as the complete absence of sperm cells, or oligospermia, a low sperm count.

Medications can also affect infertility with persons AMAB. Chemotherapy, methotrexate (Trexall), isotretinoin (Accutane), and systemic steroids can lead to infertility. Tetracycline can affect sperm and lead to infertility (Velez & Ohlander, 2021). Antidepressants can cause premature ejaculation, erectile dysfunction, and poor libido. Opioids can cause hypogonadism. And illegal substances such as cocaine and marijuana can also lead to infertility (Velez & Ohlander, 2021).

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)

Ways to Improve Fertility

Patient teaching is an essential function for the nurse caring for patients undergoing infertility testing. Some patients may have a significant knowledge gap about how to optimize fertility or the odds for conception. Providing patient teaching and anticipatory guidance at each step can help to reduce stress and uncertainty and improve patient knowledge.

Ways to improve fertility are an appropriate teaching point for both the patient just starting out on their path to parenthood and those who are undergoing more advanced treatments. Table 4.5 presents several suggestions that can improve both male and female fertility.

Technique	Rationale
Persons Assigned Female at Birth
Maintain a healthy weight.	Being overweight or underweight can affect ovulation and the menstrual cycle. Pregnancy is riskier when the person is at a higher or lower weight.
Avoid alcohol, tobacco, and recreational drugs.	Alcohol, tobacco, and recreational drugs may affect a developing fetus if pregnancy results. Smoking and recreational drugs are known to decrease fertility and increase the risk of miscarriage.
Reduce caffeine consumption.	High levels of caffeine consumption are linked with decreased fertility.
Prevent sexually transmitted infections (STIs).	STIs can directly impact fertility by causing the formation of scar tissue or blockages in the fallopian tubes.
Avoid exposure to toxins.	Some toxins directly affect hormone levels and can disrupt estrogen and other pregnancy hormones.
Maintain a healthy diet rich in fruits, vegetables, lean protein, and whole grains.	A healthy diet promotes a healthy pregnancy and reduces the risk of some complications.
Stay hydrated.	Adequate levels of hydration can keep cervical mucus thin and easier for sperm to pass through.
Monitor ovulation.	Keeping track of ovulation helps with timing intercourse. Monitoring can identify potential problems so that medical intervention can happen sooner.
Take a prenatal vitamin.	While this doesn’t promote fertility, it is good practice for all people trying to conceive a pregnancy. Higher amounts of folate and folic acid promote spinal development in the developing fetus.
Persons Assigned Male at Birth
Maintain a healthy weight.	This can improve sperm quality.
Avoid exposure to toxins.	Avoiding toxins reduces risk of damage to sperm cells.
Eat an antioxidant-rich diet: Increase intake of fruits and vegetables. Take a multivitamin. Increase omega-3 fatty acids.	An antioxidant-rich diet may improve sperm quality and morphology (Panth et al., 2018).
Exercise regularly.	Exercise boosts testosterone levels, which can increase sperm count and quality.
Stop smoking and recreational drug use.	Smoking is associated with poor sperm quality. Steroids and cannabis can cause poor sperm function.
Avoid raising scrotal temperature: Avoid hot baths or placing laptops on the lap. Wear boxer underwear instead of tight-fitting briefs.	Raising scrotal temperature may reduce sperm count.

Table 4.5 Ways to Improve Fertility (Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology and Infertility, 2017)

Coital practices can also impact a couple’s ability to conceive. The nurse should assess for knowledge gaps related to best practices. Teaching points may include:

• How and why to track ovulation by using basal body temperature, ovulation predictor kits, or monitoring cervical mucus.
• That the fertile period begins up to a week before ovulation and continues until the day after ovulation occurs. Patients should be having intercourse at least every other day during this window.
• That no evidence suggests coital position increases or decreases the odds of conception.
• That lubricants, including saliva, olive or coconut oil, and other commercial products, should be avoided because of their effect on sperm. If necessary, get a lubricant specifically intended for couples trying to conceive (Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology and Infertility, 2017).

Legal and Ethical Issues

What Should Happen When Patients with a Questionable Ability to Parent Desire Infertility Treatment?

Imagine that you are working at a private practice fertility center and are preparing to counsel a new couple who just met with the health-care provider. The health-care provider calls you into their office to discuss the couple’s situation and plan. The provider explains that both partners are in their mid-forties, are recently married, desire conception, and have significant developmental disabilities. They currently live in supervised housing. The provider is concerned about the couple’s ability to parent a newborn and asks you to meet with them and assess the situation as well.

After meeting with the couple, you share similar concerns with the provider and especially note a limited ability to understand the complex instructions associated with in vitro fertilization, the recommended treatment. You share your assessment findings with the provider, and a discussion ensues about the ethical principles associated with withholding care. You begin researching the issue and note a committee statement put forward by the Ethics Committee of the American Society for Reproductive Medicine (ASRM). The paper states: “Offspring welfare is a valid consideration that fertility programs may take into account in accepting patients and providing services as long as they do not discriminate on the basis of disability or other impermissible factor” (Ethics Committee of the ASRM, 2013). The statement goes on to say: “While practitioners and clinics may—except in the case of impermissible discrimination—make their own moral decisions about whether to accept individuals as patients, their decisions should be based on empirical evidence, not stereotype or prejudice” (Ethics Committee of the ASRM, 2013).

You also refer to the ANA Code of Ethics, specifically to the first provisions:

1. “The nurse practices with compassion and respect for the inherent dignity, worth, and unique attributes of every person.
2. The nurse’s primary commitment is to the patient, whether an individual, family, group, community, or population.
3. The nurse promotes, advocates for, and protects the rights, health, and safety of the patient.” (American Nurses Association, 2015, p. v)

You realize that there are multiple issues at play in this situation. Not only is your priority the patient who presents at the office today but also the potential children and family that may result. How can you help this couple in a way that demonstrates compassion and respect for their dignity and self-worth? Would your opinion change if they were able to conceive naturally as opposed to undergoing infertility treatment? What impact would helping this couple have a child have not only on the couple and their family but also on the supervised housing group and community at large? Would putting this couple through an IVF cycle protect their health and safety and the safety of any child created? You take some time to reflect on these provisions and the questions they raise.

A decision is made to schedule a phone conversation between the physician, nursing staff, reproductive psychologist, and the couple’s mental health professional (with their permission). The couple’s therapist reassures the interprofessional team that the couple has a large family support system and would be adequate parents. However, it is agreed that the couple does not have the capacity to undergo an in vitro fertilization procedure but would be able to tolerate three insemination cycles. After the three attempts do not produce a pregnancy, the couple withdraws further care. Upon discussing the case with the provider, you recommend developing explicit policies and procedures to follow in case this situation arises again.