4.5: Treating Infertility

Learning Objectives

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

• Identify fertility tests and know the nursing implications of both the testing modality and the communication of results
• Describe the options available for family planning when a couple is in infertility therapy
• Identify and discuss the complications that can occur during infertility treatment

When a couple makes the decision to seek care for infertility, it is a major investment in time, energy, and finances. It can also be an extremely vulnerable time for them, as they grapple with struggling to do what is commonly perceived as “natural” and “easy.” They may deal with many challenging and changing emotions: jealousy as they witness friends and family members effortlessly starting their families, blame and resentment directed toward their partner, guilt for their own medical issues, fear that treatment may not work, and anxiety if it does work. Well-meaning family members may offer poor advice or tell them to “relax and let it happen” or that “it will happen if it’s meant to be.” The couple may wonder if they have the financial means to pay for treatment that is expensive, likely not covered by insurance, and not guaranteed to work.

While the nurse may not perform many of the clinical procedures for the patient undergoing infertility treatment, they can provide much needed support and knowledge. Infertility nurses often approach patient care with a holistic approach by advocating for their patient’s needs, providing emotional support during the difficult wait, answering countless questions, and making sure that they don’t feel alone in their journey to parenthood.

This section will delve into the different testing options for infertility assessment, discuss different family-building options, and review the potential complications of these treatments. In addition to the fertility-specific care they provide, nurses must also review strategies for advocacy and therapeutic communication, as these are essential skills when working with this population.

Link to Learning

Resolve is an infertility organization for people undergoing testing or treatment. This organization provides support, advocacy, and education to all patients on their journey through infertility. Resolve offers several ways for people to access support and advocacy opportunities that can help to empower patients and their partners.

Fertility Testing

When a patient or couple presents with difficulty in conceiving, the first step is a comprehensive assessment. Fertility factors for both sexes should be evaluated at the initial assessment so that important data that contributes to treatment planning is not missed. Before any diagnostic testing is performed, a full medical history should be taken. Topics to ask about include:

• childhood and sexual development
• full menstrual history
• pregnancy history (include the partner AMAB; have they contributed to conception of a child?)
• sexual history or practices as appropriate
• how long they have been attempting to conceive
• surgical and medical history
• previous infections or trauma (Kuohung & Hornstein, 2023)

In addition to fertility-specific testing, other diagnostic tests may be required to get a full picture of a patient’s general and reproductive health (Table 4.6).

Test	Rationale
Persons Assigned Female at Birth
Prolactin	Elevated prolactin levels can indicate the presence of a prolactinoma, a benign tumor of the pituitary gland that can affect reproductive hormones.
Thyroid-stimulating hormone (TSH)	Thyroid abnormalities can affect reproductive hormones.
Blood type and Rh factor	It is important to know blood type and Rh factor before pregnancy to assess the risk of Rh incompatibility. Blood type may be required before a surgical procedure, such as egg retrieval, laparoscopy, or hysteroscopy.
Complete blood count (CBC)	CBC screens for anemias and thalassemia. CBC may be required before a surgical procedure, such as egg retrieval, laparoscopy, or hysteroscopy.
Infectious disease panel (human immunodeficiency virus [HIV 1/2], human T-cell lymphotropic virus [HTLV 1/2], rapid plasma reagin (RPR), hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody)	Panel screens for the presence of infectious diseases, which can affect how gametes are stored in the laboratory.
Rubella and varicella	Screen determines if the patient is at risk for rubella or varicella, which can affect a pregnancy. Patient may need to be immunized prior to initiating fertility treatment.
Pap smear Cervical cultures for chlamydia and gonorrhea	Pap smear is part of general health/well-woman preventive health screening. Cultures screen for sexually transmitted infections that can impact fertility.
Person Assigned Male at Birth
Blood type and Rh factor	It may be important to know blood type and Rh factor before partner’s pregnancy to assess for the risk of Rh incompatibility.
Infectious disease panel (HIV 1/2, HTLV 1/2, RPR, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody)	Panel screens for the presence of infectious diseases, which can affect how gametes are stored in the laboratory and/or transferred to the partner.

Table 4.6 General Testing for Partners of Both Sexes Undergoing Fertility Assessment

Fertility Assessment of Persons Assigned Female at Birth

Assessing the partner AFAB includes testing the reproductive tract and the hormones controlling the function. Ovarian reserve, ovulation, and uterine and tubal function should be evaluated. These tests can help narrow down the cause of infertility to address and treat those issues.

Ovarian Reserve

A person’s ovarian reserve is the number of immature eggs that remain in the ovary. Ovarian reserve is typically high in young patients but declines with age. It can be assessed in several ways:

• Anti-Müllerian Hormone (AMH): AMH is a hormone that is produced by the granulosa cells of the ovarian follicles and can be used to assess ovarian reserve (Moolhuijsen & Visser, 2020). The higher the number of ovarian follicles that remain in the ovary, the higher the serum level of AMH. It can be measured in a simple blood test at any point in a patient’s cycle.
• Day 3 hormone assay: Measuring follicle-stimulating hormone (FSH) and estradiol (E2) levels on day 2, 3, or 4 of the menstrual cycle can be helpful in determining ovarian function. Higher levels of FSH or E2 early in the menstrual cycle indicate declining ovarian reserve because higher levels of those hormones are needed to recruit an ovarian follicle.
• Antral follicle count: The small ovarian follicles that can be seen and counted on transvaginal ultrasound are called antral follicles. This test is also performed on day 2, 3, or 4 of the menstrual cycle. The number of antral follicles on each ovary is counted and measured. A higher number of antral follicles indicate better ovarian reserve or function.
• Inhibin B: Inhibin B is a nonsteroidal hormone that is produced by developing ovarian follicles. High levels of inhibin B suppress FSH secretion from the pituitary. However, as the number of ovarian follicles declines, so too does the amount of inhibin B and its suppressive effect on FSH, accounting for the rise of FSH in older patients (Wen et al., 2021).

It is important to recognize that the above markers measure only egg quantity, not egg quality; both decline with age.

Ovulation Testing

Ovarian function is also evaluated by measuring the regularity and reliability of ovulation. Knowing when ovulation has occurred or is expected to occur is crucial for the couple to appropriately time intercourse. This can be done very simply at home using an over-the-counter ovulation predictor kit. These kits contain a test stick evaluating the presence of luteinizing hormone in the urine, which surges right before ovulation. The patient can be advised to take the test every morning or, sometimes, twice a day, as they near ovulation. Intercourse should occur every day to every other day once the test turns positive. A negative result indicates the absence of luteinizing hormone, meaning that the LH surge isn’t happening at that time. The patient may be advised to call the office when the test turns positive for further instructions, or to simply attempt intercourse at home and call with the results approximately 2 weeks later (Fauser, 2023; Su et al., 2017).

It is also possible to measure serum hormone levels to determine where a patient is in their cycle:

• Low estrogen and progesterone levels suggest early phases of the cycle, before an ovarian follicle has been recruited.
• High estrogen levels, but low progesterone levels, suggest the follicular, or early phase of the cycle. Ovulation has not yet occurred.
• High estrogen levels and high LH levels indicate the LH surge and that ovulation will begin very soon.
• High estrogen and high progesterone levels indicate that ovulation has already occurred, and the cycle is in the luteal phase (Reed & Carr, 2018).

Tracking cycle information is important because it signals that a patient is, or is not, ovulating. For example, a patient who consistently has anovulatory progesterone levels or very low estrogen levels may require ovulation induction medication because they are not ovulating, which means that pregnancy cannot occur.

Uterine Structure

Evaluating the shape and structure of the uterus is important before the patient initiates fertility treatments, which can be costly, time-intensive, and emotionally difficult. It is important to ensure that embryos or sperm are going into a uterine cavity that is capable of implantation. A sonohysterogram, also known as hysterosonogram or saline infusion sonogram, is a simple, in-office procedure that can be performed to evaluate the uterine lining and cavity. After obtaining informed consent, performing a pregnancy test, and assessing for allergies (particularly to latex), sterile saline is injected through the cervix and into the uterus. Concurrent transvaginal ultrasonography is performed to visualize the saline in the cavity. Displacement of the fluid can indicate the presence of polyps, fibroids, or other structural abnormalities. This test should be performed only between days 6 and 10 of the menstrual cycle due to the risk of a pregnancy being disrupted by the saline (ACOG, 2023a).

In some cases, there may be indication for laparoscopy, a minimally invasive surgical procedure that allows direct observation of the uterus and other pelvic structures. It is particularly useful for diagnosing endometriosis, scarring, or adhesions, which can be missed on pelvic ultrasound or hysterosalpingography, which is discussed later (Arab, 2022).

Tubal Patency

Patent fallopian tube are essential for conception. They are the site of fertilization and facilitate transmission of sperm to egg and fertilized egg to the uterus. If the tubes are blocked from scarring, infection, or trauma, pregnancy is unlikely. The primary test used to evaluate tubal patency is hysterosalpingography, which is performed at an outpatient radiology center and involves the infusion of radioactive dye through a small catheter in the cervix and into the uterus and fallopian tubes (ACOG, 2023b). A special x-ray of the pelvis is taken to visualize the path of the dye through the reproductive tract (Figure 4.18). If the fallopian tubes are open, the dye will spill out into the abdominal cavity and be reabsorbed. There is a risk of infection, so the provider may recommend prophylactic antibiotics before or after the procedure. It is also important to assess for allergies to contrast dye.

Figure 4.18 Hysterosalpingogram The left side shows a blocked fallopian tube, in which the dye is retained within the uterus and does not spill into the pelvis. The right side shows a normal hysterosalpingogram, in which the dye flows through the fallopian tube and into the pelvis. (CC BY 4.0; Rice University & OpenStax)

This test is usually performed only when indicated, such as with previous suspicious findings on a sonohysterogram, a history of chlamydia infection(s), or a previous ectopic pregnancy.

Fertility Assessment of Persons Assigned Male at Birth

Assessment of both partners should occur at the same time so that the provider has a full picture of all the clinical issues impacting the couple. Initial testing of the partner AMAB is noninvasive and usually begins with a semen analysis, a simple test that evaluates the quantity and quality of sperm in a sample.

Semen Analysis

A semen sample can be collected at home or in a designated collection room in the office. It should be collected after 3 to 7 days of abstinence. If collected at home, it should be brought into the office/laboratory within 1 hour (Sunder & Leslie, 2022). If the patient is unable to ejaculate independently, a partner can assist, but there are a few important guidelines:

• Avoid contamination of the sample with saliva.
• Avoid the use of lubricants, except for those specially designed for people who are trying to conceive.
• Ejaculation must occur in the designated collection container or a collection condom that has been provided by the laboratory.

The lab will measure pH and volume of the semen and then prepare slides to measure and assess the remainder of the parameters. The World Health Organization (WHO) has developed a series of normal limits of reference for patients undergoing semen analysis (Table 4.7).

Parameter	Value
Semen volume (mL)	1.4 (1.3–1.5)
Total sperm number (10^6 per ejaculate)	39 (35–40)
Total motility (%)	42 (40–43)
Progressive motility (%)	30 (29–31)
Nonprogressive motility (%)	1 (1–1)
Immotile sperm (%)	20 (19–20)
Vitality (%)	54 (50–56)
Normal forms (%)	4 (3.9–4)

Table 4.7 WHO Semen Analysis Reference Values (Boitrelle et al., 2021)

If the parameters are within (or very close to) the normal range, no further testing may be indicated. However, if the morphology or count is significantly lower than normal, then further testing may be indicated. This may require a referral to a urologist who specializes in reproductive issues. Specialty tests may include testing for the presence of anti-sperm antibodies, autoimmune issues, or DNA fragmentation.

Cultural Context

Semen Analysis Testing in Orthodox Jewish Patients

While a semen analysis is a noninvasive and simple test of male factor infertility, ejaculation without the intent of conception is prohibited in the Orthodox Jewish faith. This can pose a problem when patients are unable to produce a sample for analysis. The nurse can recommend that the patient speak with his rabbi, who may or may not allow the couple to produce a specimen during intercourse using a special collection condom.

Other rabbis may suggest postcoital testing (PCT) as a first step instead. The couple will be instructed to have intercourse during ovulation and then present to the clinic. A speculum will be inserted into the vagina, and a small sample of cervical fluid removed. That fluid is placed on a glass slide and examined under the microscope for the presence and movement of sperm cells.

While this testing isn’t diagnostic of male factor infertility or confirmatory for male fertility, the PCT test is less costly and invasive than a full treatment cycle, especially if no sperm are present in the sample. In addition, the preliminary data obtained from it may persuade the rabbi to approve the semen analysis if indicated.

While this approach may not be used often, it allows the couple to feel that their religion and culture are respected and valued by the provider.

Ultrasonography

Ultrasonography of the testicles can reveal the presence of structural abnormalities, such as varicocele, or blockages in the vas deferens, ejaculatory ducts, or seminal vesicles. Blockages in the ejaculatory ducts or other structures may prevent sperm from traveling through the reproductive tract and exiting the body during ejaculation, causing a low or absent sperm count.

Other Testing

Additional male factor fertility testing may include:

• Hormone testing: Hormones, such as testosterone or follicle-stimulating hormone, when imbalanced, may alter sperm count or fertility. Other hormones tested may include luteinizing hormone, estradiol, and/or prolactin. (Urology Care Foundation, n.d.)
• Genetic testing: Some genetic disorders can also alter sperm count or production. It is possible to test for chromosome abnormalities through either a blood test or the evaluation of a sperm sample (Pelzman & Hwang, 2021).
• Testicular biopsy: In rare cases, testicular biopsy may be indicated to determine whether motile sperm cells are found in the testicles.

Options for Treatment

Once the initial assessment has been completed, the provider will create a plan of care that considers the testing results and the personal desires and reproductive goals of the patient. This may involve additional testing (such as to determine the source of an infection) or planning for a treatment cycle.

The first step includes correcting any underlying causes that are contributing to subfertility (Carson & Kallen, 2021; Puscheck, 2020). For example, this may mean surgical correction of uterine abnormalities, hormonal management of hyperprolactinemia, or laparoscopic draining of hydrosalpinges. The partner AMAB may require removal of varicoceles, medical management of hormone abnormalities, such as thyroid disease or hypogonadism, or reversal of a vasectomy.

In some cases, the partner AFAB will need additional medical testing to rule out any contraindications to pregnancy. This is especially true in patients with preexisting medical conditions, such as heart disease, chronic illness, a history of cancer, or advanced age. This will be required before a treatment cycle can be initiated.

Pharmacologic Treatment

Pharmacologic management of infertility, also known as ovulation induction or ovarian stimulation, is used in conjunction with many of the treatment options available for infertility. Medication is used to stimulate superovulation, the development and maturation of several egg follicles, the number depending on the planned treatment cycle. A couple undergoing intrauterine insemination will require roughly two egg follicles, while a couple undergoing in vitro fertilization may need a greater number of follicles to have a good outcome at egg retrieval (Evans et al., 2020; Sermondad et al., 2023). Nurses should provide education to the patient that these medications can cause mood swings and depression and increase the chance of multiple fetuses. The following medications are used in fertility treatments:

• Selective estrogen receptor modulators (SERMs): Clomiphene citrate (Clomid) is the primary drug in this class of medications. It is an oral pill that is taken for 5 days, beginning at the start of a patient’s menstrual cycle, usually on day 5. It is thought to work by blocking estrogen receptors in the pituitary, inhibiting the feedback loop, and increasing the secretion of follicle-stimulating hormone.
• Leuprolide: Leuprolide (Lupron Depot) is a gonadotropin-releasing hormone agonist (GnRH-agonist) that is used to suppress natural ovulation, allowing the provider to control the patient’s cycle and appropriately time any additional procedures.
• Follitropins (FSH): Follitropins are injectable forms of FSH that are used in ovulation induction.
• Human chorionic gonadotropin (hCGhmg): hCG is the last medication in the treatment cycle. It is used to trigger follicular maturation and ovulation before intrauterine insemination or IVF. The nurse must stress that hCG can cause a false-positive result on a home pregnancy test and should be avoided for at least day 14 after injection.
• Hormonal support: The medications used during IVF can suppress endometrial development and secretion of estrogen and progesterone, and the patient may require supplemental administration of these two hormones.

Pharmacology Connections

Clomid

Clomid is a common drug prescribed in the infertility or women’s health setting. It is often used as an initial agent to induce ovulation and may be particularly useful in patients with PCOS or other ovulatory disorders.

• Generic Name: clomiphene citrate
• Trade Name: Clomid
• Class/Action: selective estrogen receptor modulators
• Route/Dosage: Clomid is available as 50-mg pills administered orally once per day for 5 days. Patients are instructed to begin taking this medication on day 5 of their cycle. The dosage can be increased to a total of 150 mg (3 pills) taken once a day for 5 days, depending on the patient’s response.
• High Alert/Black Box Warning: Some patients may develop visual symptoms that can worsen with time and use. In most cases this is reversible, but irreversible changes have been documented. Patients should be instructed to report any visual symptoms to their provider. Some patients, particularly those with PCOS, have developed ovarian hyperstimulation syndrome (OHSS) with use of this drug. The patient should always be prescribed the lowest effective dose and instructed to report symptoms of OHSS.
• Indications: indicated for the treatment of ovulatory dysfunction in persons who desire pregnancy
• Mechanism of Action: Clomid interacts with estrogen receptors in the pituitary and hypothalamus, affecting the feedback loop between estrogen and FSH. This leads to a surge of gonadotropins, increasing the number of developing ovarian follicles.
• Contraindications: hypersensitivity to Clomid, pregnancy, history of liver disease, ovarian cysts, abnormal uterine bleeding, pituitary tumor, or abnormal adrenal or thyroid hormone function
• Adverse Reactions/Side Effects: ovarian enlargement, hot flashes, headache, bloating, nausea/vomiting, breast pain
• Nursing Implications: Provide education about the medication and instructions for its use, including when to return for follow-up care. Review the signs and symptoms of OHSS. Document all education and instructions provided.

(Clomid, 2017)

Intrauterine Insemination

The fertility procedure intrauterine insemination (IUI), performed by medical providers or specially trained nurses, involves injecting specially washed sperm cells through a catheter into the uterus (Figure 4.19). Some providers prefer to do a single insemination 36 hours after hCG injection; others prefer to do inseminations at 12 and 36 hours after hCG injection. IUI can be performed after a cycle with either clomiphene citrate or injectable gonadotropins or, in some cases, after tracking an unmedicated cycle. If injectable gonadotropins are used, the provider may recommend additional progesterone support after insemination (Casarramona et al., 2022).

Figure 4.19 Intrauterine Insemination During an IUI, a specially trained practitioner passes washed sperm directly into the uterus using a very thin catheter. This procedure usually takes place around the time of ovulation to optimize the chance of conception. (CC BY 4.0; Rice University & OpenStax)

Intrauterine insemination can also be performed using donated sperm, either from an anonymous donor or from a known donor. Extensive infectious disease testing is required any time sperm from an anonymous donor is used for insemination. IUI is the preferred method of treatment for patients with unfavorable cervical mucus, semen allergy, or endometriosis, as the sperm is introduced directly into the uterus.

In Vitro Fertilization

The fertility procedure in vitro fertilization (IVF) is an intense process that involves the stimulation of superovulation, the removal of eggs through surgical aspiration, fertilization in the lab, and transfer of resulting embryo back to the uterus. The steps are as follows:

• Ovulation Induction: Medications are used to induce ovulation. Progesterone and estrogen supplementation are needed if transferring embryos during that cycle.
• Follicular Monitoring: While the patient is using the medication, they will visit the office to monitor their response to the medication. Blood work measurement of estradiol levels and an ultrasound of the ovaries to measure follicular growth and development are common. Seeing the estradiol level rise each day is a sign that the cycle is progressing well (Society for Assisted Reproductive Technology, n.d.).
• Trigger: Once the patient has ovarian follicles that measure around 19 to 24 mm and an appropriate estradiol level, the provider will make the determination that the patient is ready to have their eggs retrieved. They will take their hCG injection, which is the final injection in the cycle (Society for Assisted Reproductive Technology, n.d.-a).
• Egg Retrieval: The egg retrieval is an outpatient procedure using mild sedation. The provider will insert the transvaginal ultrasound probe to visualize the ovaries. A needle will be gently advanced through the vaginal wall and into the ovary to drain the fluid and collect the eggs. That fluid is immediately sent to the lab for analysis, and the patient is allowed to recover briefly before being sent home to rest. A sperm sample is obtained during or before the egg retrieval (Society for Assisted Reproductive Technology, n.d.-b).
• Fertilization: In the lab, the embryologist will analyze and fertilize the most mature eggs. Fertilization can occur naturally or with the use of intracytoplasmic sperm injection (ICSI). Natural fertilization occurs when the eggs and sperm cells are placed in the same dish, and fertilization is allowed to occur. ICSI is done when the embryologist selects the best sperm cells and injects them into the mature eggs, one sperm per egg Figure 4.20). Any fertilized eggs are allowed to develop into embryos and checked each day for their progress. It is common for not all eggs to be fertilized and for not all the fertilized eggs to become healthy embryos (Ho, 2023).

  

  Figure 4.20 Intracytoplasmic Sperm Injection (ICSI) ICSI is a method of fertilization in which a single sperm is injected into a mature egg. This procedure is sometimes performed during in vitro fertilization. (credit: “Icsi” by Ekem/Wikimedia Commons, Public Domain)

• Embryo Transfer: Embryo transfer usually occurs on day 5 or day 6 after egg retrieval and fertilization, once the embryos have become blastocyst. The patient should have started progesterone and estrogen supplements after the egg retrieval and will continue taking them through week 10 of pregnancy. The provider will speak with the patient before the procedure to let them know how many of their eggs have developed into blastocysts and determine a plan for transfer. Most providers will transfer only one or two embryos at a time to reduce the risk of multiples. The selected embryos are loaded into a pipette, which is gently passed through the cervix using ultrasound guidance. The embryos are deposited into the uterus, and the patient is sent home to rest for a few days. The patient is instructed to take a pregnancy test 2 weeks after their egg retrieval (Ho, 2023).
• Cryopreservation: Any extra embryos that the patient is not transferring can undergo cryopreservation, meaning they can be frozen and saved for later use. Sometimes, the patient may prefer having only a frozen embryo transfer because of their personal schedule. At other times, the patient may have genetic testing (PGD) performed on the embryo, which can delay transfer until the results are available. In general, frozen embryos can be preserved and thawed when the patient is ready for transfer (Ho, 2023).

Legal and Ethical Issues

Embryo Cryopreservation

Gamete and embryo cryopreservation is a procedure that can potentially lead to many ethical questions or concerns. While fertility practices require the patient or couple to make those decisions before initiating treatment, circumstances can change in a way that was not anticipated, leading to people changing their minds.

For example, imagine that a couple undergoes IVF and has four embryos cryopreserved at the end of their cycle. They never become pregnant, and a few years later, they decide to get divorced. Before beginning treatment, the couple had agreed to have the embryos destroyed in the event of a divorce. However, the female patient is now 42 and going through menopause. Her chances of success at another IVF cycle are minimal, and she no longer wants to discard those embryos so that she can have a chance at parenthood. How does her advancing age impact their decision and your opinion? What about if either patient develops reproductive cancer and is no longer able to make eggs or sperm?

As nurses, it is not our job to reconcile these ethical decisions. However, we may develop strong feelings about what is right or wrong. We may also need to provide education and support to patients who are dealing with these situations. Ultimately, the patients may need to take their case to court to have the judge render a decision.

Third Party Reproduction

The fertility procedure third party reproduction is the use of a third party—usually a sperm donor, an egg donor, or a gestational carrier, commonly called a surrogate—in conjunction with a treatment cycle (Salazar et al., 2023). Sperm donors can also be used with intrauterine insemination and IVF, but egg donors and gestational carriers must undergo IVF. Donors can be anonymous or known to the couple.

Gestational surrogates carry the pregnancy; they have no genetic relationship to the fetus. The embryos are formed from the gametes of either the intended parents or the selected donor(s). Traditional surrogates donate their egg and carry the fetus. However, this type of surrogacy is rarely used nowadays. Gestational carriers can also be hired through an agency or known to the couple.

The ability to use an agency gestational carrier depends on the state where the patient is seeking care. This process is completely legal and regulated in some states, like California, and expressly prohibited in other states, like Nebraska (Surrogacy laws, n.d.). Some states have other requirements in place to access gestational surrogacy, such as being a married, heterosexual couple (Surrogacy laws, n.d.).

These cycles proceed in the exact manner as a typical IVF cycle, though additional testing is required. The donor must undergo infectious disease testing, including a test less than 30 days before the egg retrieval, as well as urine drug testing, genetic carrier screening, and in some cases a psychologic screening as well. In addition, all the parties involved (donors, gestational carriers, intended parents) will likely need to obtain legal contracts that outline everybody’s rights and responsibilities throughout the cycle. These contracts should be in place before the cycle begins.

Gamete Intrafallopian Transfer, Zygote Intrafallopian Transfer, and Tubal Embryo Transfer

There are three fertility procedures that are rarely used. The first, gamete intrafallopian transfer (GIFT), is similar to IVF: The patient will undergo ovulation induction and laparoscopic egg retrieval (performed through an incision in the abdomen instead of transvaginally). The retrieved eggs and sperm provided by the partner AMAB are mixed in a pipette and transferred immediately into the fallopian tube for fertilization to occur in the body. The second, zygote intrafallopian transfer (ZIFT) is similar to both GIFT and IVF: This procedure starts as a traditional GIFT, but fertilization is allowed to occur in the laboratory. Once the fertilized eggs have formed zygotes, they are transferred back into the fallopian tubes. The final one, tubal embryo transfer (TET), is similar to ZIFT but requires that the embryo be allowed to develop to a more advanced stage before being transferred back into the fallopian tube. GIFT, ZIFT, and TET all require that the patient have at least one patent fallopian tube, which must be verified by hysterosalpingogram. Transferring the embryo into a blocked tube increases the patient’s risk for ectopic pregnancy or cycle failure. These procedures are not performed very often because of the need for laparoscopic surgery for the transfer.

Link to Learning

The American Society for Reproductive Medicine (ASRM) is the professional organization that represents professionals of all disciplines working in the reproductive medicine specialty. It offers practice and ethics statements, as well as a wealth of patient educational materials that can improve teaching.

Risks Related to Infertility Treatment

Like any medical procedure, infertility treatments do pose some risks to the patient. Educating patients about what to expect, what is normal, and what should be reported is a crucial function of all nurses practicing in this field. In addition, it is important to recognize signs and symptoms of potentially serious complications and how to manage them.

Multiples

Getting pregnant with multiples is a major risk factor for patients undergoing infertility treatment. The medications used during ovulation induction stimulate the development of several eggs, which can lead to twins, triplets, or even higher-order multiples. A multiple pregnancy is risky for both the patient and the fetuses, increasing maternal morbidity and fetal and neonatal morbidity and mortality (Practice Committee of the Society for Reproductive Endocrinology and Infertility, Quality Assurance Committee of the Society for Assisted Reproductive Technology, and the Practice Committee of the American Society for Reproductive Medicine, 2022). As a result, the American Society for Reproductive Medicine encourages both patients and providers to consider the transfer of only a single embryo, known as elective single embryo transfer (eSET), especially in patients who are good candidates.

A patient who becomes pregnant with higher-order multiples may be asked to consider a multifetal reduction, a procedure in which the number of developing fetuses is reduced to give one or more than one fetus a greater chance at survival to term. The decision to have a reduction is often very difficult for the patient, particularly if they have been trying to get pregnant for a long time. Many patients find it to be an unacceptable option.

Pregnancy Complications

Studies suggest that people undergoing infertility treatments, specifically IVF, are at higher risk for some pregnancy complications. This is often a question asked by patients as well. The issue is complicated for several reasons. First, the cause of infertility may contribute to the increased risk for some of those complications. For example, a patient with PCOS who has an increased risk for insulin resistance may develop gestational diabetes during pregnancy after IVF. However, PCOS is the major contributing factor, not the fact that the patient had IVF. Second, many of the complications, such as preterm labor, low birth weight, pre-eclampsia, and cesarean delivery, are associated with the higher rate of multiple gestation related to IVF. A 2018 study found that multiple gestations were largely responsible for the increased risk of preterm birth (Oberg et al., 2018). The authors also found that many of the placenta-related complications (placenta previa and placental abruption) were not related to the use of infertility treatment (Oberg et al., 2018). While research is ongoing, the American College of Obstetricians and Gynecologists (ACOG) makes several recommendations to address this risk:

• counsel patients about their risk before initiating treatment;
• carefully evaluate patients for and address any medical conditions that could increase the risk for perinatal complications;
• make an effort to limit the number of gestations, including eSET when appropriate, and following ASRM guidelines regarding embryo transfer;
• screen for and address any potential risk to offspring related to genetic conditions; and
• discuss the option of multifetal reduction in higher-order multiple gestations (Perinatal risks, 2020).

Miscarriage is still a risk with infertility treatment due to several factors, primarily maternal age. The rate is comparable to the rate of pregnancy loss in the general population: “The rate of miscarriage may be as low as 15 percent for women in their 20s to more than 50 percent for women in their 40s.” (American Society for Reproductive Medicine, 2015).

Ectopic Pregnancy

An ectopic pregnancy is one in which a fertilized egg implants in the fallopian tube or other location outside the uterus. This is a life-threatening situation for the patient because of the risk that the fallopian tube can rupture and cause internal bleeding. In the past, the rate of ectopic pregnancy was much higher in people undergoing infertility treatment (Cirillo et al., 2022). However, a 2022 study looking at 27,376 infertility cycles found that the ectopic pregnancy rate was comparable to that of the general population, around 1.8 percent (Cirillo et al.). Researchers did note that people undergoing infertility treatment may have characteristics that put them at higher risk for ectopic pregnancy, such as the presence of scar tissue or adhesions, pelvic infection, or endometriosis (Cirillo et al., 2022).

Serum human chorionic gonadotropin (hCG) levels are drawn every 2 days in the beginning of a pregnancy. This type of test provides a quantitative value of the amount of hormone in the blood. This is different from a home pregnancy test, which detects the presence of only a threshold amount of hCG. The levels of hCG in a healthy pregnancy typically double every 2 to 3 days. Ectopic pregnancy must be suspected when a patient has a poorly rising hCG level or the absence of an intrauterine pregnancy on a transvaginal ultrasound. Other signs and symptoms may include vaginal bleeding, pelvic pain, referred pain to the shoulder, rectal pressure, low back pain or weakness, dizziness, or fainting. If an ectopic pregnancy is suspected based on ultrasound findings and the patient is asymptomatic, they may be able to be treated with methotrexate, a chemotherapy agent that stops cells from dividing and ends the pregnancy. However, the patient may need to be treated with emergency laparoscopic surgery if the fallopian tube ruptures or if internal bleeding occurs.

Cancer

Research into the risk of cancer after undergoing infertility treatment is ongoing. However, early studies are promising. According to the National Cancer Institute Division of Cancer Epidemiology and Genetics, the effects of ovulation induction on endometrial and ovarian cancers appear to be negligible. The institute did find one exception, though: “The only significant excess risk was that of ovarian cancer associated with clomiphene exposures among [persons] who remained nulligravid during follow-up” (National Cancer Institute, n.d.). They also found a significantly higher risk for breast cancer in persons who had participated in more than 12 clomiphene cycles, which is much higher than a patient would undergo in the clinical setting (National Cancer Institute, n.d.).

A very large study looked at 1,085,172 Danish children born as a result of various types of infertility treatment and ovulation induction medications. Researchers found that while there was a very small increased risk of childhood cancer in children born because of frozen embryo transfer, this association was not found with other types of infertility treatment or medication (Hargreave et al., 2019).

Ovarian Hyperstimulation Syndrome

Ovarian hyperstimulation syndrome (OHSS) is one of the most common complications of ovulation induction medication. It occurs most commonly during IVF but happens rarely with the use of clomiphene or gonadotropins for IUI. This condition is caused by an overresponse to the ovarian stimulating medication, causing many developing egg follicles and a high estradiol level. This causes ovarian enlargement and fluid to leak into the abdomen, causing bloating. OHSS ranges from mild to severe, depending on the amount of fluid present in the abdomen. Patients with mild OHSS present with mild bloating, nausea, and weight gain. It may progress to moderate OHSS when those same symptoms are present and increased in intensity and number. Severe OHSS is diagnosed when the patient has significant bloating, leading to vomiting, pain, shortness of breath, and even blood clots in the legs.

Nurses must be aware of these symptoms, especially when working in the acute care setting where a patient may seek help. Interventions that help with OHSS include:

• increasing fluid intake of electrolyte-rich fluids
• intravenous fluids if the patient is struggling to drink enough fluid
• measuring weight daily to track fluid gain
• bed rest or decreased activity to reduce the risk of ovarian torsion
• paracentesis of the abdomen to reduce fluid accumulation (National Library of Medicine, 2021a).

OHSS can progress and become severe, especially if not appropriately managed. In most cases, OHSS resolves within 2 weeks once the patient gets their period after the cycle. However, if the patient becomes pregnant, the symptoms of OHSS can continue to be problematic for a couple of weeks (American Society for Reproductive Medicine, 2014). For this reason, some providers recommend that a couple freeze all developing embryos instead of transferring them immediately after their IVF cycle, especially if the patient is at higher risk for OHSS.

Egg-Retrieval Procedure Complications

Like all invasive procedures, the egg-retrieval procedure does pose risks, though they are rare. Complications associated with the procedure include:

• vaginal bleeding or pain
• ovarian hemorrhage due to puncture
• damage to bladder, bowel, ureter, or large blood vessels
• infection (American Society for Reproductive Medicine, 2015).

It is important for the nurse in the postanesthesia care unit, the infertility center, and the acute care center to be aware of the signs and symptoms of these conditions and alert the provider immediately. Though rare, these complications could pose a significant risk to the patient if not promptly treated.

Stress

Stress to the individual, couple, and family can be profound and challenging when undergoing infertility treatment. By the time they seek care, they have likely struggled with trying to conceive for months. They may have dealt with pregnancy loss or miscarriage and may be grieving the loss of the family they thought they would have. This stress is compounded during infertility treatment: They may be worried about being able to cope with the number of injections needed, the financial implications of their treatment, challenges to work and personal schedules, and, of course, whether the treatment will work.

Real RN Stories

Nurse: Nicole, MSN, RN
Years in Practice: 8
Clinical Setting: Outpatient infertility center
Geographic Location: California

It is always important to listen to your patient and hear what they are telling you, especially if it doesn’t match their clinical data. Several years ago, I was working as a registered nurse in an outpatient infertility center where the nurses rotated taking call each weekend to address urgent patient concerns and questions. I received a phone call on Saturday afternoon from a pregnant patient who reported significant cramping. She denied vaginal bleeding, fever, or any other symptoms.

After performing a brief assessment over the phone, I accessed her digital chart to review her clinical information. This patient had come into the office the day before for her first pregnancy scan. Everything was normal: Her beta-hCG levels had risen appropriately from the beginning of her pregnancy and a single intrauterine pregnancy (IUP) with a heartbeat was visualized on ultrasound.

Objectively, I knew that cramping was normal in early pregnancy and that all her clinical data pointed to a normal, healthy pregnancy. However, her voice didn’t sound quite right, and she seemed like she was in a lot of pain. I reassured her that it was probably normal but instructed her to head to the emergency room to get checked out, just in case. She did and notified us later that she was diagnosed with a heterotopic pregnancy. In addition to the normal intrauterine pregnancy, she had a second ectopic pregnancy in her fallopian tube that had ruptured. She was bleeding into her abdomen and required emergency surgery. Heterotopic pregnancy is a very rare, and serious, complication of infertility treatment. In fact, the physician I worked for had never seen a case of heterotopic pregnancy in his many years of practice.

Assessing your patient is sometimes more than just looking at clinical cues. As your clinical experience grows, you will start to develop nursing intuition that will help guide you in your decision making. Nursing intuition is more than just a “gut feeling.” It is the accumulation of nursing knowledge and expertise and critical thinking skills, and should be honored. This case is an example of how objective clinical data combined with my subjective assessment that something wasn’t quite right led to the patient receiving the urgent care they needed without delay.

It is not unusual for all those stressors to impact not only the couple’s marital relationship but also their relationships with others. Making a baby is an incredibly personal act, and having a highly trained and invasive medical team telling a couple when to have intercourse or avoid it can take the fun and intimacy out of the process. The couple may face pressure from family members to try again when they aren’t quite ready or to take a break when they want to dive back in with another cycle. Well-meaning family or friends may ask invasive questions or offer unhelpful advice. When added to the stress associated with the medical treatment itself, it’s no wonder that most people undergoing infertility care report high levels of stress and anxiety (Domar, n.d.).

The nurse plays a pivotal role in helping the couple deal with infertility-related stress by assessing coping skills, stress levels, and support. The nurse may be able to offer coping strategies, an empathetic ear, or education that can help to put concerns to rest. If needed, the nurse can also recommend local support groups or provide a referral to a nearby reproductive therapist who specializes in helping couples at this stage in their life.

Link to Learning

Society for Assisted Reproductive Technology (SART) is a professional organization dedicated to professionals working in the infertility field. They also record and publish member clinic statistics so that the public can make an informed decision when selecting a clinic.