8.6 Fertility

Infertility is defined as a couple not being able to get pregnant (i.e., conceive) after one year (or longer) of unprotected sex. In the United States, among women aged 15 to 49 years with no prior births, about 1 in 5 are unable to get pregnant or carry a pregnancy to term after one year of trying.^[1] Infertility can cause feelings of emotional distress and grief. Individuals and couples who are unable to conceive a child should consider making an appointment with a reproductive endocrinologist, a doctor who specializes in managing infertility. Reproductive endocrinologists can also help women with recurrent pregnancy loss, defined as having two or more spontaneous miscarriages.^[2]

Pregnancy is the result of a process that has many steps. Infertility may result from a problem with any of these steps. To become pregnant, the following steps must occur^[3]:

• A woman’s body must release an egg from one of her ovaries.
• A man’s sperm must fertilize the egg.
• The fertilized egg must go through a Fallopian tube toward the uterus.
• The embryo must attach to the inside of the uterus (referred to as implantation).

Male Infertility

Infertility in men can be caused by different factors and is typically evaluated by a semen analysis. When a semen analysis is performed, the number of sperm (concentration), motility (movement), and morphology (shape) are assessed by a specialist. A slightly abnormal semen analysis does not mean that a man is necessarily infertile. Instead, a semen analysis helps determine if and how male factors are contributing to infertility^[4]:

• Disruption of testicular or ejaculatory function can affect sperm production and sperm count.
• Varicocele, a condition in which the veins within a man’s testicle are enlarged, can impact sperm. Although there are often no symptoms, varicoceles may affect the number or shape of the sperm.
• Trauma to the testes may affect sperm production and result in a lower number of sperm.
• Heavy alcohol use, smoking, anabolic steroid use, and illicit drug use can contribute to lower sperm counts.
• Cancer treatment involving certain types of chemotherapy, radiation, or surgery to remove one or both testicles can impact sperm counts.
• Medical conditions such as diabetes, cystic fibrosis, certain types of autoimmune disorders, and certain types of infections may cause testicular failure.
• Hormonal disorders can also affect male fertility due to improper function of the hypothalamus or pituitary glands. The hypothalamus and pituitary glands in the brain produce hormones that maintain normal testicular function. Production of too much prolactin, a hormone made by the pituitary gland (often due to the presence of a benign pituitary gland tumor), or other conditions that damage or impair the function of the hypothalamus or the pituitary gland may result in low or no sperm production. These conditions may include benign and malignant (cancerous) pituitary tumors, congenital adrenal hyperplasia, exposure to too much estrogen, exposure to too much testosterone, Cushing’s syndrome, and chronic use of medications called glucocorticoids.
• Genetic conditions such as Klinefelter’s syndrome, Y-chromosome microdeletion, myotonic dystrophy, and other, less common genetic disorders may cause no sperm or low numbers of sperm to be produced.

Female Infertility

Infertility in females can be caused by numerous factors such as anovulation, Fallopian tube dysfunction, or uterine characteristics.^[5] A woman’s menstrual cycle is 28 days long on average. Day 1 is defined as the first day of “full menstrual flow.” Regular, predictable periods that occur every 21 to 35 days reflect ovulation. However, a woman with irregular periods is probably not ovulating. Disruption in ovarian function may be caused by several conditions and warrants an evaluation by a doctor. When a woman doesn’t ovulate during a menstrual cycle, it’s called anovulation. Potential causes of anovulation include the following:

• Polycystic ovary syndrome (PCOS): PCOS is a condition that causes women to not ovulate or to ovulate irregularly. Some women with PCOS have elevated levels of testosterone, which can cause acne and excess hair growth. PCOS is the most common cause of female infertility.
• Diminished ovarian reserve (DOR): Women are born with all the eggs that they will ever have, and the number of eggs declines naturally over time. DOR is a condition in which there are fewer eggs remaining in the ovaries than expected for a given age. It may occur due to congenital (condition present at birth), medical, surgical, or unexplained causes. Women with DOR may be able to conceive naturally, but will produce fewer eggs in response to fertility treatments.
• Functional hypothalamic amenorrhea (FHA): FHA is a condition caused by excessive exercise, weight loss, stress, or often a combination of these factors. It is sometimes associated with eating disorders such as anorexia.
• Improper functioning of the hypothalamus and pituitary glands: The hypothalamus and pituitary glands in the brain produce hormones that maintain normal ovarian function. Production of too much of the hormone prolactin by the pituitary gland (often as the result of a benign pituitary gland tumor) or improper function of the hypothalamus or pituitary gland may cause a woman not to ovulate.
• Premature ovarian insufficiency (POI): POI, sometimes referred to as premature menopause, occurs when a woman’s ovaries fail before she is 40 years of age. Although exposures to chemotherapy, pelvic radiation therapy, and certain medical conditions may cause POI, the cause is often unexplained.
• Menopause: Menopause is a natural decline in ovarian function that usually occurs around age 50. By definition, a woman in menopause has not had a period for at least one year.

Ovulation can be predicted by using an ovulation predictor kit and can be confirmed by a blood test to check the woman’s progesterone level on Day 21 of her menstrual cycle. The most common diagnostic tests for ovarian function include follicle-stimulating hormone (FSH) value on Day 3 to 5 of the menstrual cycle, anti-Müllerian hormone value (AMH), and antral follicle count (AFC) using a transvaginal ultrasound.

Fallopian tube obstruction is a second potential cause of infertility and refers to blocked or swollen Fallopian tubes. Risk factors for Fallopian tube dysfunction include a history of pelvic infection, ruptured appendix, gonorrhea, chlamydia, endometriosis, or prior abdominal surgery. Fallopian tubes may be evaluated by a hysterosalpingogram. A hysterosalpingogram is an X-ray of the uterus and Fallopian tubes. A radiologist injects dye into the uterus through the cervix and simultaneously takes X-ray pictures to see if the dye moves freely through the Fallopian tubes, indicating they are open.^[6]

A third potential cause of infertility is physical characteristics of the uterus such as fibroids, intrauterine adhesions, endometrial polyps, adenomyosis (endometrial tissue grows into the muscular wall of the uterus), and congenital anomalies of the uterus. Depending on a woman’s symptoms, the uterus may be evaluated by transvaginal ultrasound. A hysteroscopy may also be performed to further evaluate the uterine environment.^[7]

Lifestyle Factors and Fertility

Fertility in men and women can be affected by their lifestyle and the environment. Nurses can teach the following information to clients who are trying to conceive a baby^[8]:

• Obesity is linked to lower sperm count in males.
• Strenuous physical activity can decrease sperm count in males and ovulation in females.
• Substance misuse such as alcohol, tobacco, and street drugs can decrease fertility in both males and females.
• High blood pressure decreases sperm count in males.
• Radiation therapy and chemotherapy decrease fertility in both males and females.
• Type of underwear does not affect fertility in males.
• Exposure to endocrine-disrupting chemicals in the environment can affect fertility for both sexes.
• Being underweight can interrupt ovulation in females.

Infertility Treatment

Infertility can be treated with medications, surgery, intrauterine insemination, or assisted-reproductive technology. Health care providers recommend specific treatments for infertility on the basis of the following^[9]:

• The factors contributing to infertility.
• The duration of infertility.
• The age of the female.
• The couple’s treatment preference after counseling about success rates, risks, and benefits of each treatment option.

Male infertility may be treated with medical, surgical, or assisted-reproductive therapies depending on the underlying cause. Medical and surgical therapies are usually managed by a urologist who specializes in infertility.^[10] Several treatments for male infertility include the following^[11]:

• Hormonal Evaluation: A thorough evaluation of the hypothalamic-pituitary-testicular hormonal axis is performed, including measuring hormone levels such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Imbalances in these hormones can be corrected through hormonal therapy.
• Replacement Hormonal Therapy: Hormone replacement therapy may be recommended to address hormonal imbalances or deficiencies. This can help restore testicular function and improve sperm production.
• Vas Deferens Patency: The patency of the vas deferens (the tubes that carry sperm from the testicles) is assessed. In cases of vas occlusion or blockage, surgical correction can sometimes restore the flow of sperm, improving fertility.
• Epididymal Sperm Aspiration: In situations where the vas deferens is blocked or absent, sperm can be directly aspirated from the epididymis. While this procedure can retrieve a limited number of sperm, it may be used in conjunction with other fertility treatments.
• Intracytoplasmic Sperm Injection (ICSI): ICSI is an assisted reproductive technique where a single sperm is injected directly into an egg to facilitate fertilization. This method is particularly beneficial when sperm quality or quantity is a concern. It can be used in combination with procedures like sperm aspiration to achieve fertilization.

Common medications used to treat infertility in women are as follows^[12]:

• Clomiphene citrate is an oral medication that causes ovulation by acting on the pituitary gland. It is often used in women who have polycystic ovary syndrome (PCOS) or other problems with ovulation. It is also used in women with normal ovulation to increase the number of mature eggs produced.
• Letrozole is an oral medication that is prescribed off-label to cause ovulation. It works by temporarily lowering a woman’s progesterone level, which causes the brain to naturally make more follicle-stimulating hormone (FSH). It is often used to induce ovulation in women with PCOS and in women with normal ovulation to increase the number of mature eggs produced in the ovaries.
• Human menopausal gonadotropin (hMG) is an injectable medication used for women who don’t ovulate because of problems with their pituitary gland. hMG acts directly on the ovaries to stimulate development of mature eggs.
• Follicle-stimulating hormone (FSH) is an injectable medication that works like hMG to stimulate development of mature eggs within the ovaries.
• Gonadotropin-releasing hormone (GnRH) analogs and GnRH antagonists are medications that act on the pituitary gland to prevent a woman from ovulating. They are used during in vitro fertilization cycles or to help prepare a woman’s uterus for an embryo transfer. These medications are usually injected or given with a nasal spray.
• Metformin is an oral medication prescribed for women who have PCOS and insulin resistance or diabetes. It reduces elevated levels of male hormones and promotes ovulation.
• Bromocriptine and cabergoline are oral medications used for women with ovulation problems because of high levels of prolactin.

Side effects of many fertility drugs include increased risk of having twins, triplets, or other multiple fetuses, which can cause problems during pregnancy. Multiple fetuses also have a higher risk of being born prematurely, and premature babies are at a higher risk of health and developmental problems.^[13]