About this course:
This learning module aims to help the nurse understand the risks, diagnostics, and treatments associated with infertility.
This learning module aims to help the nurse understand the risks, diagnostics, and treatments associated with infertility.
By completing this educational activity, the learner should be able to:
recall the steps of conception
discuss the prevalence of infertility
examine the causes of female and male infertility
describe lifestyle changes that can promote fertility
discuss infertility diagnostic procedures for females and males
explain the treatment options for infertility
For this learning module, the terms male or man refer to individuals born with reproductive organs such as a penis, scrotum, and testicles. The terms female or woman refer to individuals born with reproductive organs such as ovaries, fallopian tubes, and a uterus.
According to the World Health Organization (WHO, 2020), infertility is a reproductive tract disease that results in an inability to conceive or carry a child to delivery. Infertility is the most common disease affecting individuals ages 20-45, impacting 10%-15% of all US couples. According to the Centers for Disease Control and Prevention (CDC, 2021a), 12.2% of women aged 15-49 have used fertility treatment. The WHO (2020) estimates that 48 million couples and 186 million individuals are affected by infertility globally. In developing countries, 25% of couples are affected by infertility. Often, infertility does not have any associated symptoms. To be evaluated for infertility, an individual must have engaged in regular unprotected penetrative sex for at least 12 months unless a contributing factor warrants earlier intervention, such as medical history, age, or physical assessment findings. Since fertility naturally decreases as individuals age, some healthcare providers (HCPs) will evaluate patients for infertility after six months of engaging in regular unprotected penetrative sex for those over 35. Infertility can be further defined as primary or secondary. Primary infertility occurs when an individual has never conceived a child. Secondary infertility occurs after an individual has conceived at least one child (American Society for Reproductive Medicine [ASRM], 2017a; ASRM, 2017b; CDC, 2021b; Mayo Clinic, n.d.; WHO, 2020).
Conception is a complicated process that is influenced by many factors. According to Lowdermilk and colleagues (2016), conception is defined as “the union of a single egg and sperm, [which] marks the beginning of a pregnancy” (p. 265). Conception does not occur as an isolated event but is composed of 4 sequential steps: gamete production, ovulation, fertilization, and implantation. These steps must occur for the sperm and ovum to meet in the correct location and encounter a favorable environment (Lowdermilk et al., 2016).
Gametes (sperm and eggs/ova) are produced when germ cells undergo meiosis, dividing their chromosomal number in half. Once the male and female gametes combine, this number is restored to form a zygote. Each month, an ovum within the ovarian follicles matures and is released. During this time, estrogen levels rise, which increases fallopian tube motility. Since the ovum cannot move independently, it depends on the cilia located within the fallopian tubes to propel it toward the uterus. Once the ovum is released from the ovarian follicle, it is only fertile for 24 hours. When ejaculation occurs during sexual intercourse, approximately 1 tsp of semen is introduced into the vaginal cavity. This teaspoon of semen can contain up to 500 million sperm. The sperm use their flagella to propel themselves through the female reproductive tract into the fallopian tube to meet the ovum. Although some sperm can reach the fertilization site within 5 minutes, the average transit time is 4-6 hours. Sperm can live within the female reproductive tract for 2-3 days. Many sperm never pass through the cervical mucosa; of those that do, many enter the fallopian tube that does not have an ovum present (Lowdermilk et al., 2016).
Fertilization occurs in the lower third of the fallopian tube. The ovum is surrounded by two protective layers: a thick acellular inner layer and an exterior layer of elongated cells. Once a sperm penetrates both layers, the membrane becomes impenetrable to all other sperm. This process is known as the zona reaction. The combination of sperm and egg creates a zygote, which continues to travel for 3-4 days down the fallopian tube into the uterus. During transit, numerous cell divisions occur until a blastocyte forms. The blastocyte embeds in the anterior or posterior fundal region and starts to burrow into the lining. Implantation occurs 6-10 days after conception when the entire blastocyte is covered by the endometrium (Lowdermilk et al., 2016).
Risk Factors/Causes of Infertility
There are many different risk factors
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Many issues can negatively affect a female’s ability to ovulate and conceive a child. A woman’s general health significantly influences fertility. Being underweight or overweight or having a chronic disease such as diabetes, thyroid disorder (either hyperthyroidism or hypothyroidism), lupus, rheumatoid arthritis, or hypertension decreases fertility. Other problems with the female reproductive tract that can lead to infertility include multiple abnormal pap smears requiring treatment or biopsy; uterine disorders such as fibroids, endometriosis, or a septate uterus; and ovarian disorders such as polycystic ovarian syndrome (PCOS). Dysfunction of the endocrine system can lead to hormonal imbalances that affect menstrual cycle length and regularity. Environmental factors such as smoking, excessive alcohol intake, and toxin exposure can negatively affect fertility. Since fertility declines with age, older women are at a higher risk for infertility. On average, a woman is 30% less fertile in her 30s than she was in her 20s. By the time a woman turns 40, the chance of successfully becoming pregnant without medical intervention decreases to 67%, dropping to 15% by age 45. As the average age for first-time mothers increases in the US, this is a significant contributing factor to decreasing fertility rates. Sexually transmitted infections (STIs) can cause pelvic inflammatory disease (PID), scarring, adhesions, and blocked fallopian tubes, leading to difficulty conceiving. Fallopian tube disorders, such as blocked tubes, account for 20%-35% of all infertility cases requiring intervention (Kallen & Carson, 2020; Resolve: The National Infertility Association, 2022a; WHO, 2020).
Infertility is not an exclusively female problem. In fact, 30% of all infertility cases are attributed to the male alone, with another 30% involving both partners. Many researchers attribute the current decrease in male fertility to environmental factors such as exposure to toxic substances including lead, mercury, vinyl chloride, pesticides, and x-rays; drug use; excessive alcohol intake; cigarette smoking; anabolic steroid use; pollution; and repeated exposure of the genitals to high temperatures. Some medical conditions can also contribute to male infertility, including past hernia repair, undescended testicles, a history of prostatitis, a previous or current STI, or contracting mumps after puberty. An obstruction can develop within the ejaculatory ducts or seminal vesicles, causing azoospermia or inhibiting semen from being ejaculated. The testicles may fail to produce sperm due to varicoceles or damage to the sperm-producing cells following chemotherapy. Certain hormones regulate sperm production; therefore, hormonal imbalances or dysfunction can affect sperm production. Even if a person’s body produces sperm, normal morphology and motility are needed for the sperm to traverse the female reproductive tract (Resolve: The National Infertility Association, 2022a; WHO, 2020).
People of all genders can make lifestyle changes to decrease the risk of infertility and increase fertility. These changes include the following (Mayo Clinic, n.d.; Resolve: The National Infertility Association, 2022a):
Address mental health concerns. Suffering from depression and experiencing considerable stress can negatively affect the hormones involved in ovulation and sperm production; implement self-care activities and seek professional intervention if needed.
Minimize environmental exposures. Avoid hot tubs, jacuzzi tubs, and saunas as extended exposure to high heat affects sperm production. In addition, chemicals and pollutants should be avoided in both the environment and the workplace.
Use a condom when having intercourse to prevent STIs leading to infertility.
Quit smoking. Smoking can decrease sperm production in men and lead to infertility in women; there are many benefits to quitting smoking, including an increase in fertility
Decrease alcohol intake. Having as few as five alcoholic drinks per week can decrease fertility in men and women; women should be even more cautious about alcohol consumption when engaging in unprotected intercourse, as they could be pregnant before knowing.
Maintain, or obtain, a healthy body weight. Body fat levels that are 10%-15% above or below average can affect fertility. Women who are overweight can have too much estrogen in their system, which can affect their menstrual cycle; underweight women, including those diagnosed with an eating disorder such as anorexia nervosa or bulimia, may not experience a menstrual cycle at all; women who exercise intensely, such as marathon runners and dancers, may also have irregular cycles and therefore difficulty conceiving.
Consume a well-balanced diet. People may experience infertility due to deficient vitamin B12, zinc, iron, and folic acid (e.g., due to absorption issues or poorly planned vegan or vegetarian diets). Supplementation may be needed after consulting a healthcare professional for testing.
Conceive earlier in life. Although age is not a modifiable risk factor, conceiving earlier in life, when possible, can increase the chances of conceiving without the need for intervention.
Initially, tests focus on luteinizing hormone (LH) detection, ovarian reserve testing, a transvaginal ultrasound, and blood tests. Ovulation predictor kits detect the presence of LH in urine, and a rise in LH occurs 1-2 days before ovulation. Peak fertility starts the day of the LH surge and continues for the next two days. Ovarian reserve testing determines whether a woman can produce healthy eggs and how well the ovaries respond to hormonal signals. A blood sample is taken on cycle day 3 to test for follicle-stimulating hormone (FSH) to evaluate the ovarian reserve. A transvaginal ultrasound can be completed to determine an antral follicle count, reflecting the number of follicles or egg sacs present early in the menstrual cycle. Other blood tests may include estradiol, anti-Müllerian hormone (AMH), inhibin B, thyroid-stimulating hormone (TSH), prolactin, and progesterone levels (ASRM, 2017a).
Since tubal blockage is the primary cause of infertility, HCPs should assess the fallopian tubes for any abnormalities. The following tests and procedures can determine the patency of the fallopian tubes and uterus: a hysterosalpingogram, sonohysterography, a transvaginal ultrasound, hysteroscopy, or laparoscopy. A hysterosalpingogram (HSG) is an x-ray performed using iodine contrast to determine the presence of blocked fallopian tubes or an abnormal uterine cavity shape. The iodine contrast is injected through a catheter inserted into the cervix, filling the uterus and fallopian tubes. If the tubes are open, the contrast dye will spill out. After filling the uterus with saline, a sonohysterography uses a transvaginal ultrasound to detect intrauterine problems like endometrial polyps and fibroids. A transvaginal ultrasound allows HCPs to visualize the uterus and ovaries for abnormalities such as fibroids and ovarian cysts. A hysteroscopy is a surgical procedure where the HCP passes a lighted telescope (hysteroscope) through the cervix to diagnose abnormalities within the uterine cavity, such as polyps, fibroids, and adhesions. Laparoscopy is a surgical procedure in which the HCP inserts a laparoscope through the abdominal wall into the pelvic cavity to evaluate for endometriosis, pelvic adhesions, and other abnormalities such as the shape of the reproductive organs. Although laparoscopy is minimally invasive, it is only used for fertility testing if less invasive testing is inconclusive (ASRM, 2017a).
Males with infertility rarely have a cause that can be identified. Diagnosis and testing processes for male infertility consist of a thorough history and physical examination, a semen analysis, lab work including an endocrine screening, imaging focused on accessory glands and ducts, and genetic testing. The first diagnostic step should be to complete a thorough history and physical examination focusing on potential causes of infertility, such as sexual development history (e.g., any problems with testicular descent), chronic illness, a history of significant head trauma (due to changes in the brain affecting sexual function and hormone production following head trauma), infections such as mumps or STIs, past surgical procedures including inguinal hernia repairs or a vasectomy, drug use and exposure to environmental toxins, past radiation or chemotherapy, and sexual health (e.g., libido, ability to achieve or maintain an erection, frequency of intercourse, and any previous fertility assessment results). Next, the external genitalia should be assessed for incomplete development, absence of the vasa deferentia, epididymal thickening, and decreased testicular size, which can determine seminiferous tubule volume. Next, a semen sample provided after 2-7 days of ejaculatory abstinence is analyzed for volume, pH, immature germ cells, debris, leukocyte count, and sperm characteristics (i.e., concentration, motility, morphology). The sample should be obtained in the clinic; however, it can be obtained at home and brought to the clinic. If the semen sample results show severe oligozoospermia (low sperm count) or azoospermia (no sperm present), further endocrine testing should be completed. Endocrine testing for males includes total testosterone, LH, and FSH. Serum testosterone levels should be monitored between 8 a.m. and 10 a.m. for the most accurate results. If the patient’s physical assessment and lab results do not suggest a reason for the low sperm count, a scrotal and transrectal ultrasound can be performed to determine if there is a blockage of the ejaculatory duct (Anawalt & Page, 2021).
Once the cause of female infertility is identified, a specific treatment can be initiated. There are treatments designed specifically for anovulation, starting with weight management. Since overweight or underweight women are more prone to ovulatory dysfunction, attaining a healthy weight can normalize ovulation. Some women need medication management with ovulation-inducing agents to in agents to initiate ovulation. The first medication used is clomiphene citrate (Clomid or Serophene), a selective estrogen receptor modulator (SERM) containing estrogen antagonists and agonists that increase gonadotropin release. Potential side effects of clomiphene citrate (Clomid or Serophene) include hot flashes, nausea, headaches, blurred vision, depression, mood swings, and thick, dry cervical mucus. Overstimulation of the ovaries may also occur, leading to ovarian cysts and pelvic discomfort (American Pregnancy Association, n.d.; Kuohung & Hornstein, 2021).
Another option for ovulatory dysfunction is aromatase inhibitors, a class of drugs used by postmenopausal women to stop estrogen production during breast cancer treatment. Examples of aromatase inhibitors include letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin). Aromatase inhibitors are an alternative option for patients who experience adverse effects with clomiphene citrate (Clomid or Serophene). Aromatase inhibitors have some benefits over clomiphene citrate (Clomid or Serophene), such as producing fewer follicles, minimizing the chance for a multiple gestation pregnancy, and reducing antiestrogen side effects. Aromatase inhibitors and gonadotropins have become more popular as ovarian-stimulant drugs; however, the FDA has not yet approved aromatase inhibitors for use in infertility (American Pregnancy Association, n.d.; Kuohung & Hornstein, 2021).
Insulin-sensitizing agents such as metformin (Glucophage) are used for patients with infertility related to insulin resistance. Metformin (Glucophage) is commonly used in women with PCOS due to the accompanying insulin resistance associated with this disease. Using metformin (Glucophage) to correct hyperinsulinemia can increase menstrual cyclicity and promote spontaneous ovulation. Side effects of metformin (Glucophage) include pyrosis, nausea and vomiting, bloating, flatulence, constipation or diarrhea, lactic acidosis, and liver dysfunction. In addition, women with PCOS may need to undergo laparoscopic ovarian diathermy (also referred to as laparoscopic ovarian drilling [LOD]). The procedure involves destroying portions of the ovaries with electrocautery or a laser laparoscopically while the patient is under general anesthesia. This destruction of a part of the ovaries can decrease testosterone production, increasing the regularity of ovulation; due to the invasive nature of the procedure and the risks involved, LOD should only be used when other treatment options have failed. Risks include complications from general anesthesia, surgical site infection, bleeding from the incision site or internal bleeding, injury to internal organs or blood vessels, and the creation of adhesions (or scarring). If all treatment options are exhausted, and the woman is still not able to conceive, then assisted reproductive technology (ART) is considered (American Pregnancy Association, n.d.; Kuohung & Hornstein, 2021).
Gonadotropins directly stimulate the ovaries and elicit follicle growth. They are used for patients who have not ovulated or conceived following treatment with clomiphene citrate (Clomid or Serophene) or insulin-sensitizing agents; they are also used in cases of hypopituitarism or hypothalamic amenorrhea. Gonadotropins contain either FSH or LH individually or in combination. Unlike other fertility medications, gonadotropins must be administered by intramuscular (IM) injection. There is a risk of multiple gestation and premature delivery with gonadotropin use (Kuohung & Hornstein, 2021; Society for Assisted Reproductive Technology [SART], 2021).
Bromocriptine (Parlodel), a dopamine agonist, is the first-line treatment for women with hyperprolactinemic anovulation since it reduces the amount of prolactin released by the pituitary gland. Hyperprolactinemia inhibits the release of LH and FSH, leading to the disruption of ovulation. Side effects of bromocriptine (Parlodel) include nausea and vomiting, nasal congestion, dizziness, fainting, and hypotension (American Pregnancy Association, n.d.; Kuohung & Hornstein, 2021).
Urofollitropin (Fertinex) is an injectable form of FSH administered by an HCP. It is utilized with human chorionic gonadotropin (hCG) during ART treatment in women with healthy ovaries. Urofollitropin (Fertinex) is also used in women with PCOS unable to conceive following clomiphene citrate (Clomid or Serophene) treatment. Side effects of urofollitropin (Fertinex) include abdominal or pelvic pain, bloating, and headache (Mayo Clinic, 2022).
Women whose infertility is due to tubal disorders or adhesions have different treatment options. First-line treatment for women with bilateral tubal obstruction is in vitro fertilization (IVF). Surgical reconstruction may help young women with proximal or distal bilateral tube obstruction who decline to undergo IVF or do not have access to IVF conceive. To be a candidate for surgical reconstruction, the woman must have a normal uterine cavity and the ability to ovulate. Surgical reconstruction involves resecting obstructed portions of the fallopian tube or threading a catheter through the fallopian tube to remove the blockage. Surgical intervention is not recommended for women over 39, those with extensive adhesions, or those with both proximal and distal bilateral obstruction. One of the benefits of surgical intervention is that if the procedure is successful further reproductive intervention is not needed, and natural conception can occur in the future (DiPaola, 2021; Kuohung & Hornstein, 2021).
Addressing male infertility focuses on treating the underlying cause. Surgery can correct anatomic abnormalities, blockages, varicoceles, or damage to the reproductive system. Medication can be used to correct hormone imbalances or erectile dysfunction. When taken by males, clomiphene citrate (Clomid or Serophene) triggers the pituitary gland to produce more LH and FSH. An increase in these hormones improves sperm count, morphology, and motility. Clomiphene citrate (Clomid or Serophene) also increases natural testosterone levels. Side effects include irritability, acne, pectoral muscle tenderness, and the acceleration of prostate cancer growth if already present. Due to this risk, a thorough prostate cancer screening should be completed before initiating clomiphene citrate (Clomid or Serophene) for male infertility. In males that don’t respond to clomiphene citrate (Clomid or Serophene) treatment, human chorionic gonadotropin (hCG) or human menopausal gonadotropin (HMG) injections are used. Human chorionic gonadotropin (hCG) and HMG have the same side effects as clomiphene citrate (Clomid or Serophene). Still, they are considered second-line treatment options due to their availability as injectable only. Anastrozole (Arimidex) is an aromatase inhibitor commonly used in women with estrogen-sensitive breast cancer. Anastrozole (Arimidex) is used in men with a higher-than-average estradiol level and lower than normal testosterone level. In addition to correcting the hormone imbalance, anastrozole (Arimidex) can improve sperm count, morphology, and motility. Side effects include joint pain, stomach pain, nausea, diarrhea, edema, and increased risk for fractures. These side effects are less common when anastrozole (Arimidex) is used for male infertility since the treatment is short-term (Freedom Fertility Pharmacy, 2019; National Institute of Child Health and Human Development [NICHD], 2021).
Intrauterine insemination (IUI) involves the placement of sperm into an ovulating woman’s uterus. This procedure is most effective for partners with low sperm counts or motility, who cannot achieve an erection, or who have retrograde ejaculation; females with thick cervical mucus, scarring, or cervical defects; couples unable to have sexual intercourse; and LGBTQ+ couples. Ovulation-stimulating drugs such as clomiphene citrate (Clomid or Serophene), gonadotropins, or urofollitropin (Fertinex) are often used in conjunction with IUI since the insemination procedure must be performed at the time of ovulation. Urine and blood tests and ultrasounds are used to predict ovulation, which usually occurs within 24-48 hours of an LH surge or after injection of human chorionic gonadotropin (hCG). The sperm used in the procedure can be from either a third-party donor or a male in the relationship if his sperm is healthy. The sample of sperm from either source goes through a separation process where the motile sperm are selected and concentrated. This concentrated sample is then “washed” of any toxins that may cause an adverse reaction once introduced into the uterus. Once the sperm sample is ready, it is introduced directly into the uterus via a small catheter inserted into the vagina. The success rate of IUI depends on the cause of the individual’s or couple’s infertility, whether ovulation-inducing medications were used, and the age of the woman being inseminated. Success rates of 20% per cycle can be achieved when performed monthly (NICHD, 2017; Resolve: The National Infertility Association, 2022b).
Assisted Reproductive Technology (ART)
ART includes any fertility treatment that involves handling eggs and sperm outside of the body. First, mature eggs are extracted and combined with sperm in a laboratory. The fertilized eggs are then returned to the woman’s body for implantation, frozen, or donated and used to impregnate another woman (CDC, 2019). Three different types of ART are available (CDC, 2021b):
IVF is the most common type of ART. IVF involves combining an egg and sperm in a laboratory to create an embryo. After 3-5 days, the embryo is either transferred into the female’s uterus or frozen for later use. When an embryo is frozen, thawed, and then implanted, it is known as a frozen embryo transfer (FET).
Intracytoplasmic sperm injection (ICSI) is IVF used in male infertility situations. During ICSI, a single sperm is injected into a mature egg. An alternative to ICSI is conventional fertilization. A mature egg is placed into a petri dish with many sperm during conventional fertilization, and the sperm fertilizes the egg without additional intervention.
Zygote intrafallopian transfer (ZIFT) and gamete intrafallopian transfer (GIFT) are rarely used in the US. With ZIFT, fertilization occurs in the laboratory, like IVF; however, the embryo is transferred into the fallopian tube instead of the uterus. In GIFT, the sperm and a mature egg are transferred into the female’s fallopian tube, where fertilization occurs instead of the laboratory.
ART can involve the couple’s sperm and eggs or utilize donated sperm and eggs from other individuals. Donated sperm and eggs are used when patients cannot produce their own or if there is a risk of a genetic disorder being passed to their offspring. Couples can also use donated embryos for transfer. In some cases, couples with functioning sperm and eggs opt for ART if the female is not medically well enough to become pregnant and carry a child or does not have a uterus. In this case, the embryo created from the couple’s egg and sperm is transferred into a gestational carrier (CDC, 2021b).
Each year in the US, all fertility clinics that handle either eggs or embryos report how many ART cycles were performed and the outcomes of each cycle. The CDC’s 2019 Fertility Clinic Success Rates Report shows that 330,773 ART cycles were performed, resulting in 77,998 live births. Of the cycles performed, 121,086 were banking cycles where the eggs or embryos were frozen for future use. Over the last decade, the use of ART has doubled, with an estimated 2.1% of all infants born in the US each year conceived using ART (CDC, 2022).
IVF has been used by couples wanting to avoid passing a hereditary illness to their offspring, decrease the transmission of HIV/AIDs, and overcome barriers experienced by older-aged parents and those taking medications or undergoing procedures that compromise their ability to reproduce. Several medications are used in a typical IVF cycle, depending on the protocol. Gonadotropin-releasing hormone (GnRH), produced in the pituitary gland, indirectly stimulates ovarian function. Agonists of GnRH stimulate the pituitary to release stored gonadotropins. The most used GnRH agonist is leuprolide acetate (Lupron). Adverse effects of leuprolide acetate (Lupron) include hot flashes, headache, painful intercourse, mood swings, and insomnia. GnRH antagonists are then used to suppress female hormone production, making ovarian stimulation easier to regulate. Gonadotropins are then used to stimulate the production of multiple oocytes. These medications replace female LH and FSH. Human chorionic gonadotropin stimulates the oocytes’ final maturation and progesterone production from an ovary after egg retrieval (SART, 2021; WHO, 2022b).
The most common complication following ART is a multiple gestation pregnancy. This complication can be avoided or minimized by limiting the number of embryos transferred into the uterus. Conceiving through ART can increase the risk of premature delivery and low birth weight and cause ovarian hyperstimulation syndrome, which causes the ovaries to become swollen and painful. Symptoms can last up to a week and include abdominal pain, bloating, diarrhea, nausea, and vomiting. This syndrome is directly related to hCG and other injectable ovulation-inducing medications. In addition, conception always conveys the risk of miscarriage. The risk of miscarriage with ART is 15%–25%, the same rate as pregnancies conceived naturally. There is a 2%–5% risk that the embryo implants outside the uterus, resulting in an ectopic pregnancy. There are also risks and side effects from the egg-retrieval procedure, such as bleeding, infection, and damage to the bowel, bladder, or blood vessels. Many women have bloody or clear discharge following embryo transfer and experience breast tenderness, bloating, cramping, and constipation (Mayo Clinic, 2021).
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