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OVERVIEW OF INFERTILITY — Infertility is defined as a couple's inability to become pregnant after one year of unprotected intercourse if the female partner is under 35 years of age, or six months if the female partner is 35 or older. Infertility is a common condition: in any given year, approximately 15 percent of the couples in the United States who are trying to conceive are not able to do so. When a couple experiences infertility, it can be due to medical problems with one or both partners. In some cases, a specific cause cannot be identified.
When a couple is having difficulty getting pregnant, health care providers routinely involve both partners in the evaluation in order to try to diagnose and treat the cause(s). In some cases, there are things a couple can do to increase their chances of getting pregnant. These include keeping track of the female partner's menstrual cycle and timing intercourse for when ovulation is most likely (figure 1). It may also help to make lifestyle changes like maintaining a healthy weight, avoiding smoking, and limiting alcohol, caffeine, and other drugs. A health care provider can give advice on when a formal evaluation is indicated and what tests are most appropriate.
This article discusses the evaluation of infertility in couples (in which one partner is male and the other is female). More information about treatment options for infertility is available separately. (See "Patient education: Treatment of male infertility (Beyond the Basics)" and "Patient education: Ovulation induction with clomiphene or letrozole (Beyond the Basics)" and "Patient education: Infertility treatment with gonadotropins (Beyond the Basics)" and "Patient education: In vitro fertilization (IVF) (Beyond the Basics)".)
EVALUATION OF MALE INFERTILITY — In order to achieve pregnancy through intercourse, the male partner's sperm must fertilize the female partner's egg (figure 1). If the male does not make any sperm (or does not make enough sperm), or if the sperm are unhealthy (for example, if they move too slowly or are abnormally shaped), getting a partner pregnant without intervention will be difficult or impossible. Different medical conditions can cause problems with sperm count or function.
The evaluation of male infertility aims to identify the underlying cause, which can guide treatment. A health care provider usually begins with a medical history, physical examination, and a test called a semen analysis. Other tests may be needed as well.
History — The evaluation will involve reviewing past health and medical history. A health care provider will ask about childhood growth and development; sexual development during puberty; sexual history; illnesses and infections, including sexually transmitted infections; surgeries; medications; exposure to certain environmental agents (such as alcohol, radiation, steroids, chemotherapy, or toxic chemicals); and whether a fertility evaluation has been done before.
Physical examination — A physical examination usually includes measurement of height and weight, assessment of body fat and muscle distribution, inspection of the skin and hair pattern, and visual examination of the genitals and breasts.
The health care provider will also look for any signs that might suggest testosterone deficiency, such as loss of facial and body hair or a decrease in the size of the testicles. Other conditions that might affect fertility include varicocele (a group of swollen veins in the scrotum), being born without a vas deferens (the tube sperm travel through to reach the penis), or a thickening of the epididymis (a small organ that sits on top of the testicle) (figure 2).
Semen analysis — A semen analysis is a central part of the evaluation of male infertility. This analysis provides information about the amount of semen and the number, motility (movement), and shape of sperm.
The male partner should avoid ejaculation (whether through sex or masturbation) for two to seven days before providing the semen sample. Ideally, a sample should be collected in a health care provider's office after masturbation; if this is not possible, the alternative is to collect a sample at home in a sterile laboratory container or chemical-free condom. The sample should be delivered to the laboratory within one hour of collection.
If the initial semen analysis is abnormal, the provider will often request an additional sample; this is best done one to two weeks later.
Blood tests — Blood tests provide information about hormones that play a role in male fertility. If sperm concentration is low or the provider suspects a hormonal problem, blood tests may be ordered to measure total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (a pituitary hormone).
Genetic tests — If genetic or chromosomal abnormalities are suspected, specialized blood tests may be recommended to check for the number and structure of the chromosomes as well as absent or abnormal regions of the male (Y) chromosomes. For example, some males inherit genes associated with cystic fibrosis that can result in infertility due to a low sperm count. However, these men do not have the other usual signs of cystic fibrosis, such as lung or gastrointestinal disease.
Depending on the results of genetic tests, genetic counseling may be recommended to ensure that a couple understands their situation and the likelihood (and potential implication) of passing an abnormal gene on to a child. (See 'Genetic counseling' below.)
Other tests — Other tests may also be ordered, depending on the situation:
●Transrectal ultrasound – If a blockage (for example, in the vas deferens) is suspected, a transrectal ultrasound test may be ordered. This involves inserting a small probe into the rectum to capture images of the internal structures.
●Post-ejaculation urine test – If something called retrograde ejaculation (when semen enters the bladder) is suspected, a urine sample will be taken after ejaculation and tested for the presence of sperm.
●Testicular biopsy – A biopsy is a collection of a small tissue sample. This may be recommended if a semen analysis shows that no sperm are present. A biopsy can be done by surgically opening the testicle or by fine-needle aspiration (inserting a small needle into the testicle and withdrawing a sample of tissue). An open biopsy is usually done in an operating room with general anesthesia, while a fine-needle aspiration may be done with local anesthesia in an office setting. The biopsy allows the physician to examine the microscopic structure of the testes and determine if sperm are present. The presence of sperm production in the testes when there are none in the ejaculated fluid suggests a blockage in the reproductive tract.
EVALUATION OF FEMALE INFERTILITY — Although a variety of tests are available for evaluating female infertility (the inability to get pregnant), it may not be necessary to have all of these tests. Health care providers usually begin with a medical history, a thorough physical examination, and some preliminary tests.
Medical history — The evaluation will involve reviewing past health and medical history. The health care provider will ask about childhood development; sexual development during puberty; sexual history; illnesses and infections, including sexually transmitted infections; surgeries; medications used; exposure to certain environmental agents (such as alcohol, radiation, steroids, chemotherapy, or toxic chemicals); and whether a fertility evaluation has been done before.
Menstrual history — Ovulation is the time during the menstrual cycle when the ovary releases an egg into the fallopian tube; if the egg is fertilized by a partner's sperm, this results in pregnancy (figure 1). In order to get pregnant, a couple needs to have intercourse near the time of ovulation.
Amenorrhea (the medical term for absent menstrual periods) usually signals that ovulation is not happening, which can cause infertility. Oligomenorrhea (irregular menstrual cycles) can be a sign of irregular or absent ovulation; although oligomenorrhea does not make pregnancy impossible, it can make it harder since the timing of ovulation may be unpredictable. (See "Patient education: Absent or irregular periods (Beyond the Basics)".)
Physical examination — A physical examination usually includes a general examination, with special attention to any signs that might suggest an imbalance in hormone levels (for example, excess facial hair) or signs of other conditions that might impair fertility. The provider will also perform a pelvic examination, which can identify abnormalities of the reproductive tract and signs of low hormone levels (figure 3). The physical examination may be performed by a primary care provider, gynecologist, or infertility specialist.
Blood tests — Blood tests can provide information about the levels of several hormones that play a role in female fertility; key hormones are produced by the hypothalamus, the pituitary gland, and the ovaries. These hormones can include follicle-stimulating hormone (FSH), estradiol, and anti-müllerian hormone (AMH) level to assess how well the ovaries are functioning, thyroid stimulating hormone (TSH) to test thyroid function, and prolactin to check for a benign pituitary tumor.
Levels of luteinizing hormone (LH) rise abruptly beginning approximately 38 hours before ovulation (figure 4). This hormone surge can be detected using an over-the-counter home urine test. However, this kit fails to detect the hormone surge approximately 15 percent of the time. For this reason, a health care provider may recommend a blood test to confirm ovulation.
Blood levels of the hormone progesterone are a more accurate indicator of ovulation. Normally, levels of progesterone rise approximately one week after ovulation. A test to measure the progesterone level is usually performed 20 to 24 days after the first day of a menstrual period if the person has regular periods.
Tests to evaluate the uterus and fallopian tubes — Uterine abnormalities that can contribute to infertility include congenital structural abnormalities, such as a uterine septum (a band of tissue that divides the uterine cavity) (figure 5); fibroids (benign growths); polyps; and structural abnormalities that can result from gynecologic procedures.
Scarring and obstruction of the fallopian tubes can occur as a result of pelvic inflammatory disease, endometriosis, or pelvic adhesions (scar tissue) from abdominal infection or surgery.
Hysterosalpingogram — Hysterosalpingogram (HSG) is used to help identify structural abnormalities of the uterus and fallopian tubes. It involves inserting a small catheter through the cervix and into the uterus. A liquid dye that can be seen on X-ray is injected through the catheter and fills the uterus and fallopian tubes. An X-ray is taken after the liquid is injected and shows the outline of the uterus and tubes. An abnormally shaped uterus or blocked fallopian tube would be visible on the X-ray.
The test is done while the person is awake and lying on an X-ray table. Most people experience moderate to severe pelvic cramps when the liquid is injected, but this usually improves after 5 to 10 minutes; mild pain can last for a few hours and is usually relieved by taking non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. The test is usually performed 6 to 12 days after the start of the menstrual period (before ovulation has occurred). After an HSG, the person may experience leaking of the dye from the vagina, as well as a small amount of vaginal bleeding, for a day or two.
Sonohysterogram — A sonohysterogram is a type of pelvic ultrasound that involves inserting sterile fluid through a catheter into the uterus and then looking at the uterus with ultrasound. The fluid makes it easier to see the inside of the uterus in more detail. By injecting air bubbles, it is also possible to see if the fallopian tubes are open or blocked.
Hysteroscopy — In a hysteroscopy, a small tube containing a light source is inserted through the cervix and into the uterus to directly visualize the lining of the uterus and the openings where the fallopian tubes enter the uterus. Air or fluid is injected to expand the uterus and to allow the physician to see inside the uterus.
A hysteroscopy is usually done if a person's history or the results of an HSG or ultrasound suggest issues with the uterus such as fibroids or a septum. Diagnostic hysteroscopy can be performed in the physician's office without anesthesia or sedation. If hysteroscopic surgery is necessary, this is usually performed in an outpatient operating room with a regional anesthesia (local, epidural, or spinal) or general anesthesia.
Pelvic ultrasound — In a pelvic (transvaginal) ultrasound, a small ultrasound probe is inserted into the vagina; this provides a clearer image of the uterus and ovaries than ultrasound that is performed through the abdomen. It does not require sedation or anesthesia and has few to no risks. It can be used to measure the size and shape of the uterus and ovaries and to determine if there are structural abnormalities such as fibroids or ovarian cysts. If abnormalities are seen, further testing may be needed to see the inside of the uterus in more detail.
Laparoscopy — During laparoscopy, a thin, lighted tube is inserted through a small incision in the abdomen, allowing the physician to view the uterus, ovaries, and fallopian tubes. Laparoscopy is performed as a day surgery procedure and requires general anesthesia. It may be recommended in some cases (eg, if certain conditions are suspected), but is not a routine part of an initial infertility evaluation.
Laparoscopy can detect damage and blockage of the fallopian tubes, endometriosis, and other abnormalities of the pelvic structures. It is the best test for diagnosis of endometriosis or pelvic adhesions (scarring). Furthermore, endometriosis can be treated during laparoscopy, which can help to improve the chances of pregnancy for people who have endometriosis.
Genetic testing — Genetic testing may be recommended if there is a suspicion that genetic or chromosomal abnormalities are contributing to infertility. These tests usually require a small blood sample from both partners, which is sent to a laboratory for evaluation.
GENETIC COUNSELING — Genetic counseling is often recommended to educate a couple about the possibility of passing an abnormal gene to a child, the possible impact of the abnormality, and whether treatments are available to prevent this. In some cases, it may be possible to undergo in vitro fertilization (IVF) with genetic testing of the embryo before implantation. (See "Patient education: In vitro fertilization (IVF) (Beyond the Basics)", section on 'Preimplantation genetic testing (PGT) of embryos'.)
EMOTIONAL SUPPORT DURING INFERTILITY EVALUATION — Dealing with infertility can be very stressful for a couple. Either of both partners may struggle with feelings of sadness, anxiety, anger, or guilt. Some people find it helpful to talk with a counselor or attend a support group with other people who are also dealing with infertility.
If you or your partner is struggling with anxiety or depression, talk to a health care provider. There are treatments that can help.
INFERTILITY TREATMENT — There are a number of options for treatment of both male and female infertility. These are discussed in more detail separately. (See "Patient education: Treatment of male infertility (Beyond the Basics)" and "Patient education: Ovulation induction with clomiphene or letrozole (Beyond the Basics)" and "Patient education: Infertility treatment with gonadotropins (Beyond the Basics)" and "Patient education: In vitro fertilization (IVF) (Beyond the Basics)".)
In many cases, treatment is successful and a couple is able to get pregnant with one or more interventions. In other cases, treatment does not work. In this case, couples may choose to look into other options, such as treatments with eggs donated from another female, adoption, or having another person (called a "gestational carrier" or "surrogate") carry a pregnancy for them.
WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient education: Infertility in couples (The Basics)
Patient education: Female infertility (The Basics)
Patient education: Male infertility (The Basics)
Patient education: Testicular cancer (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Treatment of male infertility (Beyond the Basics)
Patient education: Absent or irregular periods (Beyond the Basics)
Patient education: Ovulation induction with clomiphene or letrozole (Beyond the Basics)
Patient education: Infertility treatment with gonadotropins (Beyond the Basics)
Patient education: In vitro fertilization (IVF) (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Functional hypothalamic amenorrhea: Pathophysiology and clinical manifestations
Female infertility: Causes
Causes of male infertility
Effects of advanced maternal age on pregnancy
Effects of cytotoxic agents on gonadal function in adult men
Female infertility: Evaluation
Approach to the male with infertility
Female infertility: Reproductive surgery
Natural fertility and impact of lifestyle factors
Overview of ovulation induction
Female infertility: Treatments
Ovulation induction with clomiphene citrate
Endometriosis: Treatment of infertility in females
Treatments for male infertility
Use of assisted reproduction in HIV- and hepatitis-infected couples
The following organizations also provide reliable health information:
●National Library of Medicine
●American Society for Reproductive Medicine
●The Centers for Disease Control and Prevention
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