Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 18-11: Infertility + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Pregnancy does not result after 12 months of normal sexual activity without contraceptives +++ General Considerations ++ About 20% of couples experience infertility at some point The incidence increases with age, with a decline in fertility beginning in the early 30s and accelerating in the late 30s The male partner contributes to about 40% of cases of infertility, and a combination of male and female factors is common + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Obtain history of sexually transmitted disease or prior pregnancies Discuss ill effects of cigarettes, alcohol, and other recreational or prescription drugs on male fertility Discuss factors that may lead to scrotal hyperthermia, such as tight underwear or frequent use of saunas or hot tubs The gynecologic history should include The menstrual pattern Use and types of contraceptives Libido Sexual practices Frequency and success of coitus Correlation of intercourse with time of ovulation Family history should inquire about family members with repeated abortions General physical and genital examinations for both partners +++ Differential Diagnosis ++ Male factor infertility (hypogonadism, varicocele, alcohol or drug use, immotile cilia syndrome) Polycystic ovary syndrome Premature ovarian failure Hyperprolactinemia Hypothyroidism Inadequate luteal progesterone or short luteal phase Endometriosis Uterine leiomyomas (fibroids) or polyps Prior pelvic inflammatory disease Pelvic adhesions, eg, pelvic surgery, therapeutic abortion, ectopic pregnancy, septic abortion, intrauterine device use + Diagnosis Download Section PDF Listen +++ +++ Diagnostic Procedures +++ INITIAL TESTING ++ Complete blood count, urinalysis, cervical culture for Chlamydia, rubella antibody determination, and thyroid function tests A luteal phase serum progesterone above 3 ng/mL establishes ovulation Ovulation predictor kits have largely replaced basal body temperatures for predicting ovulation While basal body temperature charting is a natural and inexpensive way to identify most fertile days, it cannot predict ovulation but rather only retrospectively confirm that ovulation occurred Coitus resulting in conception occurs during the 6-day period ending with the day of ovulation Before additional testing, an ejaculate from the male partner for semen analysis is obtained after sexual abstinence for at least 3 days Semen should be examined within 1–2 h after collection Normal semen: volume, 2 mL; concentration, 20 million sperm per milliliter; motility, > 50% forward progression, > 25% rapid progression; and 30% normal forms If the sperm count is abnormal, search for exposure to environmental and workplace toxins, alcohol or drug abuse, and hypogonadism +++ FURTHER TESTING ++ Gross deficiencies of sperm (number, motility, or appearance) require a repeat semen analysis A screening pelvic ultrasound and hysterosalpingography to identify uterine cavity or tubal anomalies should be performed Obstruction of the uterine tubes requires either microsurgery or in vitro fertilization Absent or infrequent ovulation requires additional laboratory evaluation Elevated follicle-stimulating hormone (FSH) and LH levels indicate ovarian insufficiency Elevated LH levels in the presence of normal FSH levels may indicate the presence of polycystic ovaries Elevation of blood prolactin (PRL) levels suggests pituitary microadenoma A markedly elevated FSH (> 15–20 international units/L) on day 3 of the menstrual cycle suggests inadequate ovarian reserve Measurement of FSH on day 10 after administration of clomiphene from day 5–9, should be completed to determine if diminished ovarian reserve indicates need for donor eggs Hysterosalpingography Can demonstrates uterine abnormalities (septa, polyps, submucous myomas) and tubal obstruction A repeat radiograph 24 hours later can confirm tubal patency if there is wide pelvic dispersion of the dye Evidence suggests that an oil-based rather than water-soluble contrast medium may improve pregnancy rates; however, reports of complications associated with oil-based media resulted in its decreased usage + Treatment Download Section PDF Listen +++ +++ Medications +++ INDUCTION OF OVULATION ++ Clomiphene citrate After a normal menstrual period or induction of withdrawal bleeding with progestin, give clomiphene 50 mg once daily orally for 5 days, typically on days 3–7 of the cycle If ovulation does not occur, increase dosage to 100 mg once daily for 5 days If ovulation still does not occur, the course is repeated with 150 mg once daily for 5 days, and then 200 mg once daily for 5 days Ovulation and appropriate timing of intercourse can be facilitated with the addition of chorionic gonadotropin, 10,000 units intramuscularly Monitoring of the follicles by transvaginal ultrasound usually is necessary to appropriately time the human chorionic gonadotropin injection Letrozole Dose is 5–7.5 mg daily, starting on day 3 of the menstrual cycle Appears to be at least as effective as clomiphene for ovulation induction in women with polycystic ovary syndrome Advantages include a reduced risk of multiple pregnancy, a lack of antiestrogenic effects, and a reduced need for ultrasound monitoring Preferred in women who have a history of estrogen-dependent tumors (such as breast cancer) because estrogen levels with this drug are much lower Bromocriptine or cabergoline Used only if PRL levels are elevated and there is no withdrawal bleeding following progesterone administration (otherwise, clomiphene is used) Initial cabergoline dosage is 2.5 mg once daily orally, increased to 2.5 mg two or three times daily in increments of 1.25 mg Discontinue once pregnancy has occurred Cabergoline is often used in patients who do not respond to bromocriptine or who cannot tolerate its adverse effects While cabergoline causes fewer adverse effects than bromocriptine, it is much more expensive Human menopausal gonadotropins (hMG) or recombinant FSH is indicated in cases of hypogonadotropism and most other types of anovulation resistant to clomiphene (or letrozole) treatment See Endometriosis for its treatment +++ Surgery ++ Fertility can be improved with excision of ovarian tumors or ovarian foci of endometriosis, and microsurgical relief of tubal obstruction due to salpingitis Some cornual or fimbrial block can be relieved. Peritubal adhesions or endometriotic implants often can be treated via laparoscopy Sperm characteristics are often improved following surgical treatment of varicocele in the male partner +++ Therapeutic Procedures ++ Treat hypothyroidism or hyperthyroidism Give antibiotics for cervicitis if present In women with abnormal postcoital tests and demonstrated antisperm antibodies causing sperm agglutination or immobilization, condom use for up to 6 months may result in lower antibody levels and improved pregnancy rates Women who engage in vigorous athletic training often have low sex hormone levels; fertility improves with reduced exercise and some weight gain In cases of male partner azoospermia, artificial insemination by a donor usually results in pregnancy if female evaluation is normal + Outcome Download Section PDF Listen +++ +++ Prognosis ++ The prognosis for normal pregnancy is good if minor disorders can be treated However, the prognosis for normal pregnancy is poor if the causes of infertility are severe, untreatable, or of prolonged duration (> 3 years) In the absence of identifiable causes of infertility, 60% of couples will achieve a pregnancy within 3 years Couples with unexplained infertility who do not achieve pregnancy within 3 years should be offered ovulation induction, assisted reproductive technology (ART), or information about adoption Women over the age of 35 should be offered a more aggressive approach, with consideration of ART within 3 to 6 months if pregnancy is not achieved with more conservative approaches +++ When to Refer ++ Refer to reproductive endocrinologist for ART or surgery + References Download Section PDF Listen +++ + +American College of Obstetricians and Gynecologists. Committee Opinion No. 781: Infertility workup for the women's health specialist. Obstet Gynecol. 2019 Jun;133(6):e377–84. [PubMed: 31135764] + +Chua SJ et al. Surgery for tubal infertility. Cochrane Database Syst Rev. 2017 Jan 23;1:CD006415. [PubMed: 28112384] + +Hanson B et al. Female infertility, infertility-associated diagnoses, and comorbidities: a review. J Assist Reprod Genet. 2017 Feb;34(2):167–77. [PubMed: 27817040] + +Jeelani R et al. Imaging and the infertility evaluation. Clin Obstet Gynecol. 2017 Mar;60(1):93–107. [PubMed: 28106643]