Diagnosis of POI

There are several steps involved before arriving at a diagnosis of POI:

1. Initial Clinical Considerations

Before considering POI:

• Exclude pregnancy as a cause of missed or irregular menstrual cycles.

• If the patient is on hormonal contraception, be mindful that symptoms may be masked—consider discontinuation if appropriate to fully assess ovarian function.

If both ovaries have been surgically removed before age 40, POI is diagnosed immediately—no further testing is necessary.

2. Clinical Presentation and Initial Screening

Health Care Professionals should assess women under 40 presenting with:

• Amenorrhoea or oligomenorrhoea, sustained for at least 4 months.

• Symptoms of hypoestrogenism (low oestrogen), such as hot flushes, night sweats, vaginal dryness, or other oestrogen deficiency signs.

Meeting these clinical criteria should prompt biochemical evaluation for POI.

3. Biochemical Confirmation (Blood Tests)

Measure serum Follicle Stimulating Hormone (FSH):

o A single elevated FSH (> 25 IU/L, within the post-menopausal range) supports the diagnosis.

o In cases of uncertainty, repeat FSH measurement after 4–6 weeks.

Measure serum estrogen (estradiol):

o A low oestrogen level helps reinforce the diagnosis but should not be used alone to confirm POI.

4. Role of Anti-Müllerian Hormone (AMH)

AMH is not recommended as the primary diagnostic test for POI:

o Although it reflects ovarian reserve, current AMH assays lack sufficient accuracy and consistency.

o FSH remains the preferred test.

However, AMH (alongside repeat FSH testing) may be employed when diagnosis remains uncertain.

5. Confirmatory Diagnosis

A confirmed diagnosis of POI requires:

- Menstrual disturbances (no or irregular periods ≥ 4 months), PLUS

- Biochemical confirmation of:

o Elevated FSH (ideally confirmed by a repeat test),

o And ideally low oestrogen levels.

6. Further Investigations to Identify Underlying Causes

Following biochemical confirmation, identify potential causes through:

Genetic testing:

o Karyotype analysis to evaluate for Turner syndrome.

o FMR1 pre-mutation testing (Fragile X-associated POI) — important for reproductive counselling.

Autoimmune screening:

o Evaluate for associated conditions (e.g., thyroid dysfunction, adrenal autoimmunity).

Medical history review:

o Assess for prior chemotherapy, radiotherapy, or ovarian/pelvic surgery—especially bilateral oophorectomy (removal of ovaries).

• Investigate environmental, metabolic, or infectious contributors as appropriate, particularly if the cause remains unclear.

In Summary:

• The 2024 ESHRE Guideline allows diagnosing POI with just one elevated FSH test, though a second is encouraged if the result is unclear.

• AMH is not recommended as the main diagnostic tool but may be used in specific uncertain cases.

• A robust diagnostic process is crucial—not only to confirm POI but also to identify underlying causes, guide management (including fertility and hormone therapy), and provide genetic counselling.