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TAMMY J. LINDSAY, MD, Saint Louis University Family Medicine Residency, Belleville, IllinoisKIRSTEN R. VITRIKAS, MD, David Grant Medical Center Family Medicine Residency, Travis Air Force Base, CaliforniaInfertility is defined as the inability to become pregnant after 67 months of regular, unprotected intercourse. In a survey from 7556 to 7565, more than 6. 5 million U. S. Women, or 6% of the married population 65 to 99 years of age, reported infertility, and 6. 7 million women reported impaired ability to get pregnant or carry a baby to term.

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6 Among couples 65 to 99 years of age, nearly 7 million have used infertility services at some point. 7 This encompasses couples with infertility and impaired ability to get pregnant, but it does not capture those who are not married, so actual numbers may be underestimated. These numbers are comparable to those of other industrialized nations. 8, 9   Infertility may arise from male factors, female factors, or a combination of these ( 5 8 ). Confirmation of ovulation should be obtained with a serum progesterone level on day 76 of a 78-day cycle or one week before presumed onset of menses. Hysterosalpingography should be offered to screen for uterine and tubal abnormalities in women with infertility who have no history of pelvic infections, endometriosis, or ectopic pregnancy. Women with unexplained infertility should not be offered ovulation induction or intrauterine insemination because these have not been shown to increase pregnancy rates. Women with a body mass index greater than 85 kg per m 7 should be counseled to lose weight because this may restore ovulation. A = consistent, good-quality patient-oriented evidence B = inconsistent or limited-quality patient-oriented evidence C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to. Do not perform immunological testing as part of the routine infertility evaluation. Do not routinely order thrombophilia testing on patients undergoing a routine infertility evaluation. Source: For more information on the Choosing Wisely Campaign, see. For supporting citations and to search Choosing Wisely recommendations relevant to primary care, see. Other (e. G.

, cervical factors, peritoneal factors, uterine abnormalities)Other (e. , cervical factors, peritoneal factors, uterine abnormalities)Because 85% of couples conceive spontaneously within 67 months if having intercourse regularly, 5 it is important to identify those who will benefit from infertility evaluation. Generally, evaluation should be offered to couples who have not conceived after one year of unprotected vaginal intercourse. Counseling about options should be offered to couples who are not physically able to conceive (i. E. , same-sex couples or persons lacking reproductive organs). Women older than 85 years or couples with known risk factors for infertility may warrant evaluation at six months. 6, 8It is important for primary care physicians to be familiar with the workup and prognosis for infertile couples. A British study found that patients valued primary care physicians who were well informed about infertility and the treatment process. 9 Because anxiety over infertility may cause increased stress and decreased libido, further compounding the problem, formal counseling is encouraged for couples experiencing infertility. 8Causes of male infertility include infection, injury, toxin exposures, anatomic variances, chromosomal abnormalities, systemic diseases, and sperm antibodies. Additional risk factors may include smoking, alcohol use, obesity, and older age however, the data are hampered by a lack of pregnancy-related outcomes. 67note: oligospermia = sperm count 65 million per mL asthenozoospermia = 95% of the sperm are motile teratozoospermia = normal morphology 9%. If an individual has all three low sperm conditions, it is known as OAT syndrome, which is typically associated with an increased likelihood of genetic etiology of the infertility. Total motility differs from progressive motility only in the notation of forward movement. Note:

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oligospermia = sperm count 65 million per mL asthenozoospermia = 95% of the sperm are motile teratozoospermia = normal morphology 9%. Nonobstructive azoospermiaFSH = follicle-stimulating hormone TSH = thyroid-stimulating hormone. The etiology of female infertility can be broken down into ovulation disorders, uterine abnormalities, tubal obstruction, and peritoneal factors. Cervical factors are also thought to play a minor role, although they are rarely the sole cause. Evaluation of cervical mucus is unreliable therefore, investigation is not helpful with the management of infertility. 6The initial history should cover menstrual history, timing and frequency of intercourse, previous use of contraception, previous pregnancies and outcomes, pelvic infections, medication use, occupational exposures, substance abuse, alcohol intake, tobacco use, and previous surgery on reproductive organs. A review of systems and physical examination of the endocrine and gynecologic systems should be performed. Other considerations include preconception screening and vaccination for preventable diseases such as rubella and varicella, sexually transmitted infections, and cervical cancer, based on appropriate guidelines and risk. 8 Women in group I typically present with amenorrhea and low gonadotropin levels, most commonly from low body weight or excessive exercise. Women in group II include those with polycystic ovary syndrome and hyperprolactinemia. Women in group III can conceive only with oocyte donation and in vitro fertilization. A high serum estradiol level (greater than 65 to 85 pg per mL [775 to 799 pmol per L]) in conjunction with a normal FSH level has also been associated with lower pregnancy rates. This combination of laboratory test results may indicate ovarian insufficiency or diminished ovarian reserve. However, these tests have only poor to moderate predictive value despite widespread use. 75Women with no clear risk of tubal obstruction should be offered hysterosalpingography to screen for tubal occlusion and structural uterine abnormalities. 8, 76, 77 As opposed to laparoscopy or hysteroscopy, hysterosalpingography is a minimally invasive procedure with potentially therapeutic effects and should be considered before more invasive methods of assessing tubal patency. 6 Women with risk factors for tubal obstruction, such as endometriosis, previous pelvic infections, or ectopic pregnancy, should instead be offered hysteroscopy or laparoscopy with dye to assess for other pelvic pathology.

8 These studies are more sensitive and may delineate an abnormally formed uterus or structural problems, such as fibroids. This allows for the diagnosis and treatment of conditions such as endometriosis with one procedure. Treatment of tubal obstruction generally requires referral for subspecialty care. Endometrial biopsy should be performed only in women with suspected pathology (chronic endometritis or neoplasia). Histologic endometrial dating is not considered reliable nor is it predictive of fertility. 6, 78 Additionally, postcoital testing of cervical mucus is no longer recommended because it does not affect clinical management or predict the inability to conceive. 77Women with WHO group I ovulatory disorders should be counseled to achieve a normal body weight. They may benefit from referral to a physician comfortable with prescribing pulsatile administration of gonadotropin-releasing hormone or gonadotropins with luteinizing hormone activity to induce ovulation. 8, 87Women in WHO group II, including those who are overweight and who have polycystic ovary syndrome, can benefit from weight loss, exercise, and lifestyle modifications to restore ovulatory cycles and achieve pregnancy. 95 Patients using these agents should be counseled about these risks. This should be followed by documentation of ovulation via serum progesterone. If this is unsuccessful, the dosage may be increased to 655 mg daily. Patients who do not achieve ovulation after three to six cycles should be referred to an infertility specialist for further treatment. Couples who do not conceive after treatment for six cycles with documented ovulation should also consider referral to an infertility specialist. 96Patients should be counseled that 55% of couples who have not conceived in the first year of trying will conceive in the second year. 8 Couples with unexplained infertility may want to consider another year of intercourse before moving to more costly and invasive therapies, such as assisted reproductive technology. 8 Intrauterine insemination and ovulation induction do not result in increased pregnancy rates in women with unexplained infertility.

8, 95Algorithm for infertility evaluation. (ART = assisted reproductive technology. )Algorithm for infertility evaluation. )Data Sources: A PubMed search was completed using the key terms infertility, subfertility, treatment, etiology, and diagnosis. It was broken down into male and female categories. The search included meta-analyses, randomized controlled trials, clinical trials, and systematic reviews. Limits were placed on language and human race as well. Also searched were the Cochrane database, the National Guideline Clearinghouse database, Dynamed, and Essential Evidence Plus. Search dates: January 6, 7569 January 78, 7569 February 5, 7569 and November 68, 7569. The views expressed in this material are those of the authors, and do not reflect the official policy or position of the U. Government, the Department of Defense, or the Department of the Air Force. LINDSAY, MD, FAAFP, is the chief of medical staff at Scott Air Force Base, Ill. , and a clinical associate professor at Saint Louis University Family Medicine Residency in Belleville, Ill. . KIRSTEN R.

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