Definitions
• Fecundability –
The probability of conceiving during a single monthly cycle. In “normally fertile” couples it is 20–25%, with a cumulative 85–90% chance of pregnancy within 12 months.
• Infertility –
The inability to conceive after 12 months of appropriately timed intercourse without contraception in women aged <35 years or after 6 months in women aged ≥35 years.
• Primary infertility –
This refers to couples who have never achieved a pregnancy.
• Secondary infertility –
It implies at least one previous conception.
Incidence
• 10–15% of reproductive age married couples are infertile.
• The prevalence of infertility has remained constant, but the number of office visits to physicians by “infertile” couples has tripled over the past 20 years. This “infertility epidemic” has been attributed primarily to elective postponement of childbearing and increased insurance coverage of elective fertility therapy.
Risk factors
• Fecundability begins to slowly decline after age 28 and usually declines at a more rapid rate after age 35.
• Cigarette smoking, recreational drug use, and certain occupational and environmental exposures decrease the fertility rate.
Initial assessment
The primary goals of an infertility evaluation are to provide a rational approach to diagnosis, to present an accurate assessment of ongoing progress and prognosis, and to educate the couple about reproductive physiology.
• History –
Relevant details include the female patient’s age, previous pregnancies, and duration of conception attempts, timing of intercourse, lubricant use, and erectile or ejaculatory dysfunction. A comprehensive gynecologic history should include menarche, menstrual intervals, prior history of sexually transmitted infections, prior tubal or pelvic surgery, prior pelvic infection or ectopic pregnancy, and prior abnormal Pap smears necessitating of the loop electrosurgical excision procedure (LEEP) or cryosurgery.
• Physical examination –
Features of an endocrine disorder (hirsutism, hepatomegaly, thyromegaly) or gynecologic pathology (fibroids, endometriosis) may be evident.
• Laboratory tests –
Fertility-related testing includes day 3 follicle stimulating hormone (FSH), estradiol, thyroid-stimulating hormone (TSH), prolactin, hysterosalpingogram for the female patient, and semen analysis for the male partner. Additional non-fertility tests usually include complete blood count, Papanicolaou (Pap) smear, and prenatal viral titers (eg, HIV, hepatitis B and C, rubella and varicella) and ethnic-specific genetic screening (cystic fibrosis, hemoglobin electrophoresis, Tay–Sachs disease, Canavan disease, spinal muscular atrophy, etc).
Basic work-up
The common causes of infertility are evaluated by:
1 Confirmation of predictable ovulation (menstrual intervals, urinary LH kits, basal body temperature)
2 Ovarian reserve (day 3 FSH, estradiol, clomiphene citrate challenge test, anti-müllerian hormone [emerging evidence])
3 Semen analysis
4 Evaluation of tubal patency and uterine factors (hysterosalpingogram, saline sonohysterogram (FemVue)
5 Endocrinopathies (thyroid dysfunction, hyperprolactinemia, polycystic ovarian syndrome [PCOS])
Causes of infertility
Female factor (50%)
1 Ovarian factor (anovulation, ovulatory dysfunction, premature ovarian insufficiency) (20%)
• History –
Secondary amenorrhea, irregular menses.
• Physical examination –
Obesity, hirsutism, galactorrhea, lean body habitus (hypothalamic amenorrhea).
• Screening tests –
Typical confirmation of ovulation by history (predictable menstrual intervals [21–35 days], urinary kits to detect the midcycle LH surge (indicative of ovulation), recording daily basal body temperature recordings, or mid to late luteal phase serum progesterone concentration. Ovarian reserve may be assessed with day 3 FSH, estradiol, antimüllerian hormone, and/or clomiphene challenge test.
• Treatment –
Ovulation induction
2 Tubal and peritoneal factors (20%)
• History –
Prior pelvic infection or ectopic pregnancy may suggest pelvic adhesive disease or tubal disease. Secondary dysmenorrhea or cyclic pelvic pain may prompt suspicion of endometriosis. However, there are no identifiable risk factors in >50% of patients.
• Physical examination –
Retroverted fixed uterus, rectovaginal nodularity, and uterosacral nodularity are possible clinical signs of endometriosis.
• Screening tests –
Hysterosalpingogram (HSG) involves an injection of a radio-opaque dye through the cervix into the uterus with spillage into the peritoneal cavity. It assesses tubal patency as well as the contour of the uterine cavity to exclude filling defects (eg, endometrial polyps, fibroids, synechiae). Recently, newer saline sonohysterogram methods, utilizing echogenic distending fluid (eg, FemVue) have been utilized. Laparoscopy with tubal lavage or fertiloscopy is the “gold standard” diagnostic test because it can exclude adhesions and endometriosis.
• Treatment –
Tubal surgery (tuboplasty) or in vitro fertilization.
Male factor (35%)
• History –
Testicular injury, genitourinary infection, chemotherapy or radiation exposure, genitourinary surgery, erectile or ejaculatory dysfunction, or tobacco or recreational drug use.
• Physical examination –
Hypospadias, varicocele, cryptorchidism (undescended testes), atropic testicles.
• Screening test –
Semen analysis is the primary screening test for male infertility. Semen sample should be produced after 2–3 days of abstinence. If a single sample has abnormal parameters (eg, concentration, motility, or morphology) it should be repeated 4 weeks later.
• Treatment –
Surgical correction of varicocele; intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection (ICSI) depending upon semen parameters.
3 Unexplained (idiopathic) infertility (10–15%)
• History –
Female patient is ovulatory and all ovarian reserve, endocrine, hysterosalpingogram, and semen analysis testing is normal.
• Physical examination –
Physical examination and screening tests are unremarkable.
• Treatment –
Ovulation induction and superovulation with intrauterine insemination (IUI) or in vitro fertilization.
• Prognosis –
About 60% of couples with unexplained infertility who receive no treatment will conceive within 3–5 years.
4 Cervical factor (10%)
• History –
Prior cervical surgery (cone biopsy, cautery), infection, or in utero diethylstilbestrol (DES) exposure.
• Physical examination –
Cervical abnormalities, lesions.
• Screening tests –
None is reliable. The postcoital test is a historical method to evaluate sperm–cervical mucus interaction. However, this test is no longer viewed as a standard of care given its significant diagnostic limitations.
• Treatment –
IUI.