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 status – LH, FSH, testosterone
    • Consider infectious evaluation – CBC, gonorrhea and chlamydia cultures, and urinalysis
    • Assess spermatic function – semen analysis of at least 2 specimens (after 2-3 days of abstinence)
      • Up to 40% of subfertile men have normal sperm analysis 
      • Normal semen parameters (WHO 2010)

        Normal semen parameters*

        • Volume – ≥1.5 mL (1.4-1.7)
        • pH – ≥7.2
        • Sperm concentration – ≥15x106 spermatozoa/mL (12-16)
        • Total sperm count – ≥39x106/ejaculate (33-46)
        • Motility – within 60 min. of ejaculation
          • Total motility – ≥40% (38-42)
          • Progressive motility – ≥32% (31-34)
          • High viability with a low motility suggestive of structural defects (eg, primary ciliary dyskinesia)
        • Vitality – ≥58% live (55-63)
        • Morphology – ≥4% normal forms (3.0-4.0)
        *5th centiles and 95% confidence intervals
    • Genetic testing
      • Warranted when sperm density <5x106/mL, nonobstructive azoospermia present, or clinical suspicion
      • Karyotyping – Klinefelter most common abnormality
      • Y chromosome microdeletion
        • Not detected with standard karyotyping
        • Azoospermia factor (AZF) regions
        • Microdeletion associated with successful assisted reproductive technology
      • CFTR gene analysis to exclude cystic fibrosis, if vas deferens absent

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

Clinical Presentation

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
Test Name and Number Recommended Use Limitations Follow Up
Luteinizing Hormone and Follicle Stimulating Hormone 0070193
Method: Quantitative Electrochemiluminescent Immunoassay

Aids in determining etiology of ovulatory or androgen dysfunction

   
Progesterone Quantitative by HPLC-MS/MS, Serum or Plasma 2008509
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Determine whether progesterone is associated with ovulatory dysfunction

   
Prolactin 0070115
Method: Quantitative Chemiluminescent Immunoassay

Determine if elevated prolactin is cause of infertility

   
Macroprolactin 0020765
Method: Quantitative Chemiluminescent Immunoassay

Exclude prolactinoma

   
17-Hydroxyprogesterone Quantitative by HPLC-MS/MS, Serum or Plasma 0092332
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Assist in determining etiology of infertility

   
Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

Determine thyroid function

   
Testosterone Free, Females or Children 0081059
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry/Electrochemiluminescent Immunoassay
Total Testosterone and SHBG are measured and free testosterone is estimated from these measurements.

Assess for hyperandrogenism or PCOS

Suggested for women and children due to an improved sensitivity of testosterone by LC-MS/MS

 
Anti-Mullerian Hormone 2002656
Method: Quantitative Enzyme-Linked Immunosorbent Assay
Estimate ovarian reserve    
Estradiol, Adult Premenopausal Female, Serum or Plasma 0070045
Method: Quantitative Chemiluminescent Immunoassay

Estimate ovarian reserve

   
Semen Analysis % Abnormal

Determine if etiology of infertility is male-related

Cornerstone evaluation of male infertility

Time-sensitive test

Two semen samples should be evaluated (collected 7 days apart; 3 months after any febrile illness)

Samples are collected after a period of abstinence of >48 hours, but <7 days

Specimens should be analyzed within 1 hour of collection

 
Testosterone Free, Adult Male 0070111
Method: Quantitative Electrochemiluminescent Immunoassay
Total Testosterone and SHBG are measured and free testosterone is estimated from these measurements.

Assess androgen deficiency

Not recommended for females or children

 
Y Chromosome Microdeletion 2001778
Method: Polymerase Chain Reaction/Electrophoresis

Aids in determining  the cause of azoospermia or oligospermia and helps predict effectiveness of assisted reproductive technologies in men with Y chromosome microdeletions

   
Chromosome Analysis, Peripheral Blood 2002289
Method: Giemsa Band

Diagnose Klinefelter syndrome

Detect structural abnormalities of the Y chromosome associated with male infertility

   
Cystic Fibrosis (CFTR) Sequencing 0051110
Method: Polymerase Chain Reaction/Sequencing

Screen for cystic fibrosis mutations in males with congenital bilateral absence of the vas deferens

   
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Rule out infection

   
Gonorrhea Culture 0060110
Method: Culture/Identification

Rule out STI

   
Chlamydia trachomatis Culture 0060850
Method: Cell Culture/Immunofluorescence

Rule out STI

   
Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Rule out infection

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
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