INTRODUCTION — Infertility is defined as the inability of a couple to become pregnant after one year of unprotected intercourse. Infertility is a common condition: in any given year, about 15 percent of the couples in the United States who are trying to conceive are not able to do so.
The ability of a couple to become pregnant depends on several factors in both the male and female partners. Among all cases of infertility, about 20 percent can be traced to male factors, 40 percent can be traced to female factors, and 30 percent can be traced to factors in both the male and female partners. In about 15 percent of couples, the etiology for infertility cannot be traced to specific factors in either partner.
Because fertility involves a complex interaction of male and female factors, healthcare providers routinely involve both partners in the evaluation.
EVALUATION OF MEN — Fertility in men requires normal functioning of the hypothalamus, pituitary gland, and testes. Therefore, a variety of different conditions can lead to infertility. The evaluation of male infertility may point to an underlying cause, which can guide treatment. A healthcare provider usually begins with a medical history, physical examination, and a semen test. Other tests may be needed in some men.
History — A man's past health and medical history are important in the process of evaluation. A healthcare provider will ask about childhood growth and development; sexual development during puberty; sexual history; illnesses and infections; surgeries; medications; exposure to certain environmental agents (alcohol, radiation, steroids, chemotherapy, and toxic chemicals); and any previous fertility testing.
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 (show figure 1).
Special attention is given to features of testosterone deficiency, which may include loss of facial and body hair and decrease in the size of the testis.
Other conditions that can affect fertility include: Varicocele, a varicose vein of the testicle Absent vas deferens or thickening of the epididymis (show figure 1)
Semen analysis — A semen analysis (sperm count) is a central part of the evaluation of male infertility. This analysis provides information about the amount of semen, and the number, motility, and shape of sperm.
A man should avoid sex and masturbation for two to seven days before providing the semen sample. Ideally, a sample should be collected in a clinician's office after masturbation; if this is not possible, the man may be allowed to collect a sample at home in a sterile laboratory container or chemical-free condom. The sample should be delivered to the lab within one hour of collection.
If the initial semen analysis is abnormal, the clinician 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 clinician suspects a hormonal problem, blood tests to measure total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (a pituitary hormone) may be ordered.
Genetic tests — If genetic or chromosomal abnormalities are suspected, specialized blood tests may be needed to check for absent or abnormal regions of the male chromosomes (Y chromosome).
Although infertility treatments may be able to overcome genetic or chromosomal abnormalities, there is a possibility of transferring the abnormality to a child. Genetic counseling is often recommended to inform a couple about the possibility of parent-to-child transmission and possible impact of the abnormality.
Other tests — If obstruction of the reproductive tract (epididymis or vas deferens) is suspected, a transrectal ultrasound test may be ordered. This test can identify areas of blockage in the male reproductive tract.
A post-ejaculation urine sample is needed if retrograde ejaculation (movement of semen into the bladder) is suspected.
A testicular biopsy (collection of a small tissue sample) can be done by surgically opening the testis or by fine-needle aspiration (inserting a small needle into the testis 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.
EVALUATION OF WOMEN — Although a variety of tests are available for evaluating female infertility, it may not be necessary to have all of these tests. Healthcare providers usually begin with a medical history, a thorough physical examination, and some preliminary tests.
Medical history — A woman's past health and medical history may provide some clues about the cause of infertility. The healthcare provider will ask about childhood development; sexual development during puberty; sexual history; illnesses and infections; surgeries; medications used; exposure to certain environmental agents (alcohol, radiation, steroids, chemotherapy, and toxic chemicals); and any previous fertility evaluations.
Physical examination — A physical examination usually includes a general examination, with special attention to any signs of hormone deficiency 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 (show figure 2).
Blood tests — Blood tests can provide information about the levels of several hormones that play a role in female fertility; in women, key hormones are produced by the hypothalamus, the pituitary gland, and the ovaries. These hormones include follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin.
Tests to evaluate ovulation — Ovulation (the release of an egg from an ovary) is essential for fertility. Abnormalities of ovulation can often be determined from a woman's menstrual history or hormone levels such as the pre-ovulatory LH surge or luteal phase progesterone (show figure 3).
Menstrual history — Amenorrhea (absent menstrual periods) usually signals an absence of ovulation, which can cause infertility. Oligomenorrhea (irregular menstrual cycles) can be a sign of irregular ovulation; although oligomenorrhea does not make pregnancy impossible, it can interfere with the ability to become pregnant.
Basal body temperature — Monitoring of basal body temperature (measured before getting out of bed in the morning) was previously recommended to determine if ovulation occurred. A woman's temperature usually rises by 0.5ºF to 1.0ºF after ovulation. However, basal body temperature patterns can be difficult to interpret and are not generally recommended in the evaluation of infertility.
Hormone levels — Levels of luteinizing hormone (LH) rise abruptly approximately 38 hours before ovulation. This hormone surge can be detected using an over-the-counter urinary test kit. However, this kit fails to detect the hormone surge about 15 percent of the time. Therefore, a clinician 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 after ovulation. Progesterone tests are usually performed 18 to 24 days after the first day of a menstrual period.
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 makes the uterine cavity small) (show figure 4); abnormalities linked to exposure to diethylstilbestrol (DES) (a hormone used in the past to prevent miscarriage), which can cause a T-shaped uterus (show figure 5); fibroids; 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.
Hysterosalpingography — 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 is injected through the catheter, which fills the uterus and fallopian tubes. An x-ray is taken after the dye is injected, which shows the outline of the uterus and tubes (show radiograph 1). An abnormally shaped uterus or blocked fallopian tube would be visible on the x-ray (show radiograph 2).
The test is done while the woman is awake and lying on an x-ray table. Most women experience moderate to severe pelvic cramps when the dye is injected, but this usually improves after five to 10 minutes. The test is usually performed five to seven days after the menstrual period (before ovulation has occurred).
Hysteroscopy — In a hysteroscopy, a small tube with a camera is inserted through the cervix and into 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 performed in women who are thought to have an abnormal uterus, based upon hysterosalpingogram or ultrasound; several structural abnormalities can be surgically treated during hysteroscopy. Hysteroscopy is performed as a day (outpatient) surgery. Sedation with regional anesthesia (local, epidural, or spinal anesthesia) or general anesthesia is used during the procedure.
Pelvic ultrasound — In a 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 that the patient is sedated or anesthetized, and has few to no risks. It is 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.
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 that the patient receive general anesthesia.
Laparoscopy can detect damage and obstruction 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 pregnancy rates in women with infertility who have endometriosis. However, laparoscopy is not routinely done during an evaluation of infertility.
Genetic tests — 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, which is sent to a laboratory for evaluation.
Although assisted reproductive techniques may be able to overcome genetic or chromosomal abnormalities, there is a possibility of transferring the abnormality to a child. Genetic counseling is often recommended to educate a couple about the possibility of parent to child transmission, possible impact of the abnormality, and treatments available to prevent parent-to-child transmission.
EMOTIONAL SUPPORT DURING INFERTILITY EVALUATION — The process of trying to become pregnant and the inability to do so can lead to a variety of emotions, including anxiety, depression, anger, shame, and guilt. In one study, 40 percent of infertility patients suffered with some type of psychiatric disorder; the most common diagnosis was an anxiety disorder (23 percent), followed by major depressive disorder (17 percent) [1].
Both men and women can suffer from these problems, which can further hinder a couple's ability to become pregnant. Psychological distress is associated with infertility treatment failure and interventions to relieve stress are associated with increased pregnancy rates.
The best approach for treatment of psychological distress related to infertility treatment has not been determined. However, some experts suggest relaxation techniques, stress-management, coping skills training, and group support. Evaluation by a psychiatrist may be needed for some persons with significant symptoms of anxiety or depression.
TREATMENT — There are a number of options for treatment of both male and female infertility. Separate topic reviews are available. (See "Patient information: Treatment of infertility in men" and see "Patient information: Infertility treatment with clomiphene (Clomid® or Serophene®)").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
American Society for Reproductive Medicine
(www.asrm.org)
RESOLVE: The National Infertility Association
(www.resolve.org)
The International Council on Infertility Information Dissemination
(www.inciid.org)
The Hormone Foundation
(www.hormone.org/public/other.cfm, available in English and Spanish)
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2. De Kretser, DM. Male infertility. Lancet 1997; 349:787.
3. De Kretser, DM, Baker, HW. Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab 1999; 84:3443.
4. Gray, RH. Epidemiology of infertility. Curr Opin Obstet Gynecol 1990; 2:154.
5. Guzick, DS, Grefenstette, I, Baffone, K, et al. Infertility evaluation in fertile women: A model for assessing the efficacy of infertility testing. Hum Reprod 1994; 9:2306.
6. Templeton, A, Fraser, C, Thompson, B. Infertility--epidemiology and referral practice. Hum Reprod 1991; 6:1391.
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