Infertility

Diagnosis

Indications for Testing

• Inability to achieve pregnancy within 12 months

Laboratory Testing and Clinical Assessment

• Female
  • Full physical examination and complete medical history
  • Cervical cytology and screening for sexually transmitted infections
  • Document ovulation – midluteal progesterone level, urinary luteinizing hormone (LH)
  • Determine etiology if ovulatory dysfunction is suspected – follicle stimulating hormone (FSH), prolactin, thyroid stimulating hormone, 17-hydroxyprogesterone, testosterone
    • If prolactin is elevated and CT/MRI of sella is negative, consider macroprolactin testing
  • Assess ovarian reserve – FSH and estradiol measures on day 3 of menstrual cycle; anti-Müllerian hormone; inhibin B
  • Assess anatomic dysfunction – transvaginal ultrasound, hysterosalpingography, laparoscopy
• Male
  • Full physical exam and complete medical history
  • Assess androgen deficiency – LH, FSH, testosterone
  • Consider infectious evaluation – CBC, gonorrhea and chlamydia cultures, and urinalysis
  • Assess spermatic function – semen analysis of at least 2 specimens (cornerstone test for male infertility)
    • Up to 40% of subfertile men have normal sperm analysis 
    • Normal semen parameters

      Volume ≥1.2 mL pH 7.2-8.0 Sperm concentration ≥15x106 spermatozoa/mL Total sperm count ≥39x106/ejaculate Motility (within 60 min. of ejaculation) ≥25% with rapid progression ≥50% with forward progression High viability with a low motility suggestive of structural defects (eg, primary ciliary dyskinesia) Vitality ≥75% live ≤25% dead Morphology ≥40% normal forms White blood cells <1x106/ml Immunobead test and mixed antiglobulin reaction for antisperm antibodies present in 4-8% of infertile men Only considered clinically significant if >50% of spermatozoa are coated

  • Y chromosome studies
    • Chromosome analysis
    • Y chromosome microdeletion
      • Azoospermia factor (AZF)
      • Microdeletion associated with successful assisted reproductive technology
  • If vas deferens absent, CFTR gene analysis to exclude cystic fibrosis
  • Inhibin B – differentiate cryptorchidism from anorchia

Differential Diagnosis

• Refer to etiology in Clinical Background

Clinical Background

Infertility is a common problem in the U.S. affecting millions of couples who incur significant expense for fertility treatments.

Epidemiology

• Prevalence – 10-15% of couples in U.S. (~2 million couples)
• Definition – inability to conceive after 12 months of frequent, unprotected intercourse

Etiology

• Female factors – ~50% of cases
  • Ovarian dysfunction
    • Aging
    • Endocrine disorders
    • Polycystic ovarian syndrome
    • Premature ovarian failure
  • Tubal factors
    • Obstruction – history of pelvic inflammatory disease, tubal pregnancy, tubal or pelvic surgery
    • Endometriosis
  • Uterine/cervical factors – uncommon etiologies
    • Congenital anomaly
    • Fibroids
    • Polyps
    • Poor cervical mucous quality
  • Lifestyle
    • Tobacco
    • Alcohol
    • Body mass
  • Endocrine/metabolic disorders
    • Congenital adrenal hyperplasia
    • Virilizing tumors
    • Adrenal failure
    • Cushing syndrome
    • Hypo/hyperthyroidism
    • Diabetes mellitus
    • X chromosome abnormalities
  • Genetic disease
    • Cystic fibrosis
    • Turner syndrome
• Male factors – ~50% of cases
  • Primary/secondary hypogonadism
  • Orchitis – usually infectious (eg, mumps)
  • Altered sperm (eg, cystic fibrosis)
  • Y chromosome abnormalities/microdeletions
  • Trauma
  • Exposure to toxic agents (eg, chemotherapy, radiation)
  • Testicular tumor
  • Unknown

Clinical Presentation

• Female
  • Irregular menses
  • Galactorrhea
  • Signs of hyperandrogenism (eg, hirsutism)
• Male
  • Varicocele or hydrocele
  • Signs of androgen deficiency
  • Small testes
  • Signs of infection (eg, epididymitis)
  • Obstruction/absence of the ejaculatory ducts
  • Testicular tumor

Treatment

• Ovulation induction
• Intrauterine insemination
• In vitro fertilization
  • Ovarian stimulation followed by egg retrieval
  • Egg fertilization, embryo culture
  • Embryo transfer to uterus
• Intracytoplasmic sperm injection
• Egg donation/donor insemination
• Gonadotropin treatment for men with gonadotropin deficiency

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Thyroid Stimulating Hormone 0070145 Method: Quantitative Chemiluminescent Immunoassay
Testosterone, Females or Children 0081058 Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Testosterone, Free and Total (Includes Sex Hormone Binding Globulin), Females or Children 0081056 Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry/Electrochemiluminescent Immunoassay The concentration of free testosterone is derived from a mathematical expression based on the constant for the binding of testosterone to sex hormone binding globulin.
Testosterone, Bioavailable and Sex Hormone Binding Globulin (Includes Total Testosterone), Females or Children 0081057 Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry/Electrochemiluminescent Immunoassay The concentrations of free and bioavailable testosterone are derived from mathematical expressions based on constants for the binding of testosterone to albumin and/or sex hormone binding globulin.
Inhibin B 0070413 Method: Quantitative Enzyme-Linked Immunosorbent Assay
Follicle Stimulating Hormone, Serum 0070055 Method: Quantitative Electrochemiluminescent Immunoassay
Estriol, Serum 0070051 Method: Quantitative Chemiluminescent Immunoassay
Free Estradiol by ED/LC-MS/MS 2006160 Method: Quantitative Equilibrium Dialysis/High Performance Liquid Chromatography-Tandem Mass Spectrometry

Diagnostic Algorithm

  Secondary Amenorrhea Testing Algorithm