4.4 Treating Infertility

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.

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. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

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.

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.

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. (attribution: Copyright Rice University, OpenStax, under CC BY 4.0 license)

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).

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.

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.

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.