Upon conclusion of this learning activity, the participate should be able to:
- Define infertility.
- Discuss the causes of female and male infertility.
- Discuss infertility evaluation for females and males.
- Discuss the treatment options for infertility.
The World Health Organization (WHO) defines infertility as “a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse” (WHO, 2019b, para 1). Infertility can be further defined as primary or secondary infertility. Primary infertility occurs when a “woman is unable to bear a child, either due to the inability to become pregnant or the inability to carry a pregnancy to a live birth” (WHO, 2019b, para 5). Secondary infertility is when a “woman is unable to bear a child, either due to the inability to become pregnant or the inability to carry a pregnancy to a live birth following either a previous pregnancy or previous ability to carry a pregnancy to a live birth” (WHO, 2019b, para 6).
Infertility is a global problem and has been for nearly three decades. According to responses compiled from women in demographic and health surveys from 1990 and completed in collaboration with WHO in 2004, one in every four couples in developing countries were affected by infertility (World Health Organization, 2019a). In 2012, a WHO study revealed similar findings, determining that the overall burden of infertility in women remained similar in estimated proportions and trends from 1990 to 2010 (World Health Organization, 2019a). In the United States, 6.7% of married women are infertile and 7.3 million people ages 15-44 have used infertility services (US Department of Health and Human Services [USDHHS], 2016).
Infertility is not exclusively a female problem, as males can also endure infertility issues (USDHHS, 2019). Infertility can be related to a female factor issue, a male factor issue, or a combination of issues involving both partners (American College of Obstetricians and Gynecologists [ACOG], 2017). In fact, 30% of infertility cases are related to male factor problems and 30% involve both partners (Resolve, 2019a). The most common cause of female infertility is the absence of or irregular ovulation, also known as anovulation (ACOG, 2017). The most common cause for male infertility is a problem in the testes that affects how sperm are produced or how they function (ACOG, 2017). In 35% of couples with infertility, a male factor is also identified with a female factor (USDHHS, 2019). A male factor is the only identifiable cause of infertility in about 8% of couples (USDHHS, 2019). Almost 9% of men ages 25 to 44 years in the United States reported that they or their partner saw a doctor for infertility advice, testing, or treatment during their lifetime (USDHHS, 2019).
Causes and Risk Factors for Infertility
An infertility diagnosis can be attributed to physical causes, external causes, lifestyle choices, and environmental causes (Resolve, 2019a). The Centers for Disease Control and Prevention (CDC) (USDHHS, 2019) lists physical causes of infertility in females as: disruption of ovarian function, fallopian tube obstruction, and abnormal uterine shape. The CDC defines anovulation as a lack of ovulation during a menstrual cycle, and can be caused by polycystic ovary syndrome, diminished ovarian reserve, functional hypothalamic amenorrhea, improper function of the hypothalamus or pituitary gland, and premature ovarian insufficiency. The CDC cites polycystic ovary syndrome as the most common cause of female infertility due to anovulation. Functional hypothalamic amenorrhea is most commonly caused by excessive exercise, stress, or low body weight. Furthermore, overproduction of prolactin by the pituitary gland as well as improper function of the hypothalamus or pituitary gland may also impair a woman’s ability to ovulate (USDHHS, 2019). The CDC defines premature ovarian insufficiency as a condition in which the ovaries fail before age 40. Risk factors for a blocked fallopian tube can include a history of pelvic infection, history of ruptured appendicitis, history of sexually transmitted infections, known endometriosis, or a history of abdominal surgery (USDHHS, 2019). Additional risk factors for female infertility include:
- advanced age,
- excessive or low body fat percentage,
- chronic diseases,
- abnormal pap smears,
- hormonal imbalance,
- multiple miscarriages,
- cigarette smoking,
- alcohol consumption,
- exposure to workplace hazards or toxins,
- sexually transmitted diseases,
- history of diethylstilbestrol (DES) exposure in utero (Resolve, 2019a).
The CDC lists causes of infertility in males to include disruption of testicular or ejaculatory function, hormonal disorders, and genetic disorders. They describe disruption of testicular or ejaculatory function secondary to the presence of varicoceles, a condition in which the veins of the testicles are enlarged causing them to overheat. Trauma to the testes, cancer treatment, certain medical conditions such as diabetes, cystic fibrosis, autoimmune disorders, and certain types of infections may cause testicular failure as well, according to the CDC. Improper function of the pituitary gland with overproduction of prolactin may result in low or no sperm production (USDHHS, 2019). Other conditions such as pituitary tumors, congenital adrenal hyperplasia, exposure to too much estrogen or testosterone, Cushing’s syndrome or chronic use of glucocorticoids can also affect sperm production (USDHHS, 2019). Male fertility also declines with certain environmental risk factors, such as:
- age over 40,
- exposure to environmental hazards or toxins,
- cigarette or marijuana smoking,
- being overweight or obese,
- heavy alcohol consumption,
- prescription drugs for ulcers or psoriasis,
- DES exposure in utero,
- exposure to radiation,
- exposure of genitals to elevated temperatures such as hot tubs, whirlpools, and steam rooms (USDHHS, 2019; Resolve, 2019a).
Medical risks for male infertility may also include history of hernia repair, undescended testicles, history of prostatitis or genital infection, and mumps after puberty (Resolve, 2019a).
Management of Care
Couples who seek medical attention will each undergo physical examination to determine the overall state of health and evaluate any physical cause that may be contributing infertility (American Society for Reproductive Medicine [ASRM], 2019c). If no etiology can be identified, further testing may be recommended. Infertility evaluation should be individualized based on each couple’s circumstances (ASRM, 2019a). Females will usually undergo an analysis of body temperature and ovulation, x-ray of the fallopian tubes and uterus, and possibly laparoscopy. In males, the initial tests usually focus on semen analysis (ASRM, 2019c).
Testing for females
According to the ASRM (2019a), initial testing in female patients generally focuses on luteinizing hormone (LH) detection, ovarian reserve testing, transvaginal ultrasound, and blood tests. The ASRM also recommends the use of ovulation predictor kits to detect the presence of LH in urine. A rise in LH occurs one to two days before ovulation and peak fertility time is classified as the day of the LH surge and the following two days. The ASRM states that ovarian reserve testing is done to determine whether a woman can produce an egg (or eggs) of good quality and how well her ovaries respond to hormonal signals. To evaluate the ovarian reserve, the ASRM recommends performing a follicle stimulating hormone (FSH) blood sample on menstrual cycle day 3, followed by transvaginal ultrasound to determine an antral follicle count; which is the number of follicles or egg sacs in the early part of the menstrual cycle. Other blood tests may include estradiol, antimullerian hormone, inhibin B, thyroid stimulating hormone, prolactin levels, and progesterone levels (ASRM, 2019a).
To determine the patency of the fallopian tubes and uterus, the ASRM (2019a) advises utilization of one or more of the following tests: hysterosalpingogram (HSG), sonohysterography, transvaginal ultrasound, hysteroscopy, or laparoscopy. An HSG is described by the ASRM as an x-ray using iodine contrast to determine presence of blocked fallopian tubes or abnormal uterine cavity shape. The iodine contrast is injected through a catheter inserted into the cervix to fill the uterus and fallopian tubes. An x-ray is then performed to visualize the position and structure of the uterus and fallopian tubes. A sonohysterography uses a transvaginal ultrasound after filling the uterus with saline to detect intrauterine problems such as endometrial polyps and fibroids. A transvaginal ultrasound allows the healthcare provider to view the uterus and ovaries for abnormalities such as fibroids and ovarian cysts. A hysteroscopy is a surgical procedure where a lighted telescope (hysteroscope) is passed through the cervix to evaluate for abnormalities within the uterine cavity such as polyps, fibroids, and adhesions. Laparoscopy is a surgical procedure where a laparoscope (a fiber optic instrument) is inserted through the abdominal wall into the pelvic cavity to evaluate for endometriosis, pelvic adhesions, and other shape abnormalities (ASRM, 2019a).
Testing for males
Initial infertility testing for males usually involves a semen analysis, with a semen sample obtained through masturbation or wearing a special condom during intercourse (ASRM, 2019b). The semen analysis measures the quantity and quality of both semen and the sperm according to the ASRM, including how much semen is produced (volume), total number of sperm in the semen sample (total count), number of sperm in each milliliter of semen (concentration), percentage of sperm moving (motility), and shape of the sperm (morphology). In some instances, testing for certain hormones such as FSH and testosterone in males may also be necessary as abnormal levels may cause problems with sperm production or delivery (ASRM, 2019b).
As mentioned above, treatment is individualized and dependent upon the etiology of the infertility issue (ACOG, 2017). Noninvasive, lifestyle changes such as maintaining a healthy weight, smoking cessation, avoiding alcohol and illicit drug use can improve fertility (ACOG, 2017). Infertility treatment modalities may include medications, surgery, intrauterine insemination, or assisted reproductive technology (USDHHS, 2019a). If hormonal levels are abnormal, medications may be given to correct the hormonal imbalance and induce ovulation in females (ACOG, 2017). Some medications include clominiphene citrate (Serophene), human menopausal gonadotropin (HMG), FSH, metformin (Glucophage), bromocriptine (Parlodel) and cabergolin (Dostinex) (American Pregnancy Association [APA], 2019a). Clomiphene citrate causes ovulation by acting on the pituitary gland and is also used by females with normal ovulation to increase the number of eggs produced (USDHHS, 2019). The CDC (USDHHS, 2019) recommends using HMG in females where ovulation does not occur because of pituitary gland issues, as it acts directly on the ovaries to stimulate mature egg development. FSH works similarly to HMG to stimulate mature egg development within the ovaries. Metformin can lower the high levels of male hormones in women with insulin resistance of diabetes mellitus of polycystic ovary syndrome to help the body to ovulate, and Bromocriptine and cabergoline are medications used for women with ovulation difficulties secondary to high levels of prolactin (USDHHS, 2019).
Resolve (2019b) describes intrauterine insemination (IUI) as the placement of sperm into a woman’s uterus while she is ovulating. They further state that this procedure is used with unexplained infertility, minimal male factor infertility, and females with cervical mucus problems. It is often performed in conjunction with ovulation-stimulating drugs. Insemination is performed at the time of ovulation, usually within 24-36 hours after the LH surge is detected, or after a “trigger” injection of human chorionic gonadotropin (hCG) is administered (Resolve, 2019b).
According to the CDC (USDHHS, 2017), assisted reproductive technology (ART) includes all fertility treatments in which both eggs and embryos are handled. ART procedures involve surgical removal of eggs from a woman’s ovaries, combining them with sperm in the laboratory, and returning them to the woman’s body or donating them to another woman (USDHHS, 2017). This includes in vitro fertilization-embryo transfer (IVF-ET), gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT), and frozen embryo transfer (FET) (Society for Assisted Reproductive Technology [SART], 2019). Maternal age is the most important predictor of success (SART, 2019). See Figure 1.
“Approximately 99% of ART cycles performed are IVF-ET” (SART, 2019, para 1). According to SART, there are several medications used in a typical IVF-ET cycle depending on the protocol. Gonadotropin releasing hormone (GnRH) is a hormone produced in the pituitary gland that indirectly stimulates ovarian function. Agonists of GnRH stimulate the pituitary to release stored gonadotropins and afterwards the GnRH analogs suppress the female’s own hormone production to make ovarian stimulation easier to regulate. The most commonly used GnRH is leuprolide acetate (Lupron). Antagonists of GnRH may also be used to immediately inhibit FSH and LH production. To stimulate the ovaries to produce multiple oocytes, gonadotropins are then used. These medications replace a female’s own LH and FSH. HCG stimulates the final maturation of the oocytes and also stimulates progesterone production from the ovary after egg retrieval (SART, 2019). According to the APA (2019b), eggs are retrieved from a surgical procedure that uses ultrasound and a hollow needle to remove the eggs. The next step in the procedure involves the male providing a sperm sample. During insemination, the sperm and egg are mixed together and stored in a laboratory dish to encourage fertilization, as depicted in Figure 2. Once fertilization has occurred, the embryos are either frozen for later use (in FET) or transferred to the woman’s uterus 3 to 5 days after egg retrieval and fertilization. IVF can be used in females who do not have fallopian tubes or have a blocked fallopian tube (APA, 2019b).
The APA (2019c) states that in the GIFT procedure, there is a mixture of sperm and eggs placed into the fallopian tubes where fertilization occurs instead of in the laboratory. The ZIFT is similar to IVF and FET, but a key difference is that the fertilized embryo is transferred into the fallopian tube instead of the uterus in ZIFT. Another difference is that the fertilized eggs are transferred sooner in ZIFT, usually within 24 hours instead of the 3-5 days in an IVF cycle. This procedure can be more successful than GIFT according to the APA as the embryo is already fertilized when transferred. In both GIFT and ZIFT, the female must have at least one healthy fallopian tube (APA, 2019c).
Embryo cryopreservation or FET has emerged as an alternative to fresh embryo transfer (Roque et. al., 2015). This process allows future pregnancy opportunities without undergoing ovarian stimulation and retrieval. According to the SART (2019b), there are two techniques used: slow cooling and vitrification. With the slow cooling procedure, they describe embryos that are placed in a freezing solution while the temperature of the embryos is slowly decreased to be stored in liquid nitrogen at approximately -400F using a computer. In vitrification, the embryos are placed into special solutions and then placed immediately into liquid nitrogen according to SART. When ready to be used, embryos are thawed, but there are risks the embryo may not survive the thaw (SART, 2019b). With embryo cryopreservation, the embryo transfer is performed later in a natural cycle or in a cycle with hormonal replacement for endometrial priming (Roque, et. al., 2015). Cryopreservation also allows for preimplantation genetic diagnosis and preimplantation screening of the embryos prior to transfer (SART, 2019b).
The most common complication of ART is multifetal pregnancy (U.S. National Library of Medicine, 2019). Multifetal pregnancies carry significant risk such as preterm labor or delivery, maternal hemorrhage, delivery by cesarean section, pregnancy related hypertension, and gestational hypertension (ASRM, n.d.). There are other possible risks to in vitro fertilization. Side effects can occur from the use of injectable fertility medications including mild bruising and soreness at the injection site, nausea and vomiting, skin reddening and/or itching at the injection site, breast tenderness and increased vaginal discharge, mood swings and fatigue, and ovarian hyperstimulation syndrome (OHSS) (ASRM, n.d.). OHSS is an iatrogenic and potentially life-threatening complication of infertility treatments, in which there is an increase in capillary permeability due to higher levels of vascular endothelial growth factor, thus resulting in a fluid shift from the intravascular space to the extravascular compartments (Namavar Jahromi, et. al., 2018). OHSS can cause ascites and pulmonary edema, which can then lead to very enlarged ovaries, dehydration, difficulty breathing, and severe abdominal pain. “It is estimated that severe ovarian hyperstimulation syndrome will occur in 0.4% to 2.0% of women taking HMG or FSH” (SART, 2019c, para 3). Clients who experience OHSS may not be able to transfer embryos during that cycle and would freeze the embryos for a future transfer. There are also risks during the egg retrieval and embryo transfer, such as cramping, pelvic pain, injury to organs near the ovaries, and infection (ASRM, 2019).
Implications for Evidence-based Nursing Care
According to Stevenson, Hershberger and Bergh (2016), the nurse is a key component of the health care team and can act as a liaison for the couple through the infertility process. They warn that as technology continues to advance, nurses and other healthcare providers need to advocate for, participate in, and remain current on evidence-based practices to inform and guide couples as they make decisions, as education is an integral part of the infertility process. As one of the risk factors for in vitro fertilization is OHSS, nurses have a responsibility to provide education about symptoms to allow for early identification so supportive treatment can be implemented in a timely manner (Stevenson, Hershberger, & Bergh, 2016). Another important factor in the treatment of infertility is the possibility of strained relationships and stress (Stevenson, Hershberger, & Bergh, 2016). Luk and Loke (2015) found that infertility has a negative effect on the psychological well-being and sexual relationships of couples. Nurses are able to anticipate this potentiality, identify maladaptive behaviors, and provide support (Luk & Loke, 2016).
The cost of infertility may also cause a financial burden to many couples, as very few states have mandated insurance coverage for the involved procedures and medications (Stevenson, Hershberger, & Bergh, 2016). Many couples are required to pay out-of-pocket for all testing and treatment. “Nurses engaged in social and political structures and with policy makers can work to alleviate the financial burden for couples with infertility” (Stevenson, Hershberger, & Bergh, 2016, p. 107).
While ART can alleviate the burden of infertility, it also presents challenges to public health indicated by the high rates of multiple deliveries, preterm deliveries and low birth-weight deliveries as potential consequences of ART. Monitoring the outcomes of technologies that affect reproduction has become an important public health activity (USDHHS, 2017b). The CDC’s Division of Reproductive Health has an extensive history of surveillance and research in women’s health and fertility, adolescent reproductive health, and safe motherhood (USDHHS, 2017b). “In response to congressional mandate, the CDC began work to strengthen existing data collection efforts initiated by the [ASRM] and the [SART] and to develop a national system for monitoring ART use and outcomes” (USDHHS 2017b, para 4).
Current and future research in infertility may assist in finding innovations for new methods of contraception, help resolve issues of recurrent spontaneous miscarriages, address complications associated with pre-term birth or other neonatal complications; and be exploited to ensure zero (horizontal and vertical) transmission of human immunodeficiency virus (HIV) or other sexually transmitted diseases. Implementation research is required within developing countries where the global burden of infertility is greatest to ensure heightened emphasis on innovative, safe and cost-effective solutions, improved implementation, and integration of access to subfertility/infertility diagnosis, management and treatment (WHO, 2019c).
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