What are the most important initial tests for a fertility workup in someone with amenorrhea?

Most Important Tests for Fertility Workup in Patients with Amenorrhea

The most important initial tests for a fertility workup in someone with amenorrhea should include serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, and thyroid-stimulating hormone (TSH), along with a pelvic ultrasound to assess structural abnormalities and ovarian morphology.

Initial Laboratory Assessment

Essential Hormonal Tests

1. FSH/LH levels - Critical for determining whether amenorrhea is due to:

   • Hypogonadotropic hypogonadism (low FSH/LH)
   • Hypergonadotropic hypogonadism/primary ovarian insufficiency (high FSH/LH)
   • Normogonadotropic disorders like PCOS 1, 2

2. Estradiol - Helps assess ovarian function and estrogen status 2

3. Prolactin - Elevated levels may indicate prolactinoma or other pituitary disorders 1, 2

   • Levels >20 μg/L are considered abnormal 2
   • Hyperprolactinemia is a common treatable cause of amenorrhea

4. TSH - Thyroid dysfunction can cause menstrual irregularities and infertility 1, 2

Additional Laboratory Tests Based on Initial Results

• Testosterone and other androgens - If PCOS is suspected (testosterone >2.5 nmol/L is abnormal) 2
• Progesterone level - To assess for ovulation (<6 nmol/L indicates anovulation) 2
• Anti-Müllerian hormone (AMH) - Useful marker for ovarian reserve assessment 2

Imaging Studies

1. Transvaginal/Pelvic Ultrasound - Essential for:

   • Evaluating endometrial thickness
   • Assessing ovarian morphology (≥20 follicles per ovary and/or ovarian volume ≥10ml suggests PCOS)
   • Ruling out structural abnormalities of the reproductive tract 1, 2

2. Brain MRI with contrast - Indicated if:

   • Prolactin is elevated
   • Multiple pituitary hormone abnormalities are present
   • Hypothalamic/pituitary disorders are suspected 2

Diagnostic Procedures

1. Progesterone Challenge Test - To determine outflow tract patency and estrogen status 3

   • A negative test with competent outflow tract suggests hypoestrogenic amenorrhea

2. Endometrial Sampling - Consider in patients with:

   • Risk factors for endometrial cancer (obesity, chronic anovulation, PCOS)
   • Abnormal endometrial thickness on ultrasound 2

Diagnostic Algorithm

1. First step: Rule out pregnancy with a pregnancy test 1, 4

2. Second step: Order baseline hormonal panel (FSH, LH, estradiol, prolactin, TSH) 1, 2

3. Third step: Based on hormonal results, categorize the type of amenorrhea:

   • High FSH/LH (>35 IU/L): Primary ovarian insufficiency 2
   • Low/normal FSH/LH: Hypothalamic amenorrhea or hyperprolactinemia 1
   • Normal FSH/LH with LH:FSH ratio >2: PCOS 2
   • Elevated prolactin: Hyperprolactinemia, requires pituitary imaging 1, 2

4. Fourth step: Perform pelvic/transvaginal ultrasound to assess structural integrity and ovarian morphology 1, 2

Common Pitfalls and Caveats

• Don't forget to rule out pregnancy first, as it's the most common cause of amenorrhea 4, 3

• Consider functional hypothalamic amenorrhea in patients with history of stress, weight loss, or excessive exercise - these patients need evaluation for eating disorders and bone density assessment 4, 5

• Be aware that patients with primary ovarian insufficiency can maintain unpredictable ovarian function and should not be presumed infertile 4, 5

• Remember that PCOS patients require screening for metabolic complications including glucose intolerance and dyslipidemia 4, 5

• Avoid missing structural abnormalities by ensuring appropriate imaging is performed, especially in cases of primary amenorrhea 6

By following this systematic approach to testing, the underlying cause of amenorrhea can be identified in most cases, allowing for appropriate treatment to address fertility concerns and prevent long-term health complications.