What initial work‑up is indicated for a woman with a two‑year history of infertility and anovulation?

Initial Work-Up for Infertility with Anovulation

For a woman with 2-year history of infertility and anovulation, begin immediately with hormonal assessment (FSH, LH, prolactin, TSH) and transvaginal ultrasound to identify the underlying cause and guide treatment. 1, 2

Essential Laboratory Testing

The hormonal panel is the cornerstone of evaluation because endocrine dysfunction accounts for the vast majority of anovulatory infertility cases 2:

• FSH and LH levels differentiate between primary ovarian insufficiency (elevated FSH >40 mIU/mL) and hypothalamic-pituitary dysfunction 2
• Prolactin level is critical because hyperprolactinemia accounts for approximately 20% of secondary amenorrhea cases and may indicate a pituitary adenoma requiring urgent MRI 2
• TSH level excludes thyroid dysfunction, a reversible cause of anovulation that when treated can restore normal menstrual cycles 2
• LH/FSH ratio >2 suggests polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility affecting at least 7% of adult women 3, 2

Additional testing should include:

• Midluteal phase progesterone (cycle day 21) to confirm ovulation status 4, 5
• Ovarian reserve testing with FSH levels 1

Imaging Studies

Transvaginal ultrasound is the initial imaging modality of choice 3, 1:

• Assess ovarian morphology for polycystic ovarian features (>25 small follicles in at least one ovary or single ovarian volume >10 mL) 3
• Perform antral follicle counts to evaluate ovarian reserve; <5 antral follicles with ovarian volume <3 cm³ suggests diminished ovarian reserve 3
• Evaluate uterine cavity for structural abnormalities 1
• Assess endometrial thickness: thin endometrium (<5mm) suggests estrogen deficiency, while thick endometrium (>8mm) suggests chronic anovulation with unopposed estrogen, increasing endometrial cancer risk 2

Tubal patency assessment should be performed with hysterosalpingography or sonohysterography with tubal contrast agent, particularly if no history of pelvic infection 1, 4

Algorithmic Interpretation of Results

If FSH is elevated (>40 mIU/mL):

• Indicates primary ovarian insufficiency 2
• Confirm with repeat FSH 4 weeks later 2
• Immediate referral to reproductive endocrinology for fertility preservation counseling 2

If prolactin is elevated (>20 μg/L):

• Order immediate pituitary MRI to rule out prolactinoma 2
• This is the most common pathologic cause of hyperprolactinemia 2

If LH/FSH ratio >2:

• Suspect PCOS 2
• Transvaginal ultrasound will confirm polycystic ovarian morphology 2
• PCOS is the most common endocrine disorder of reproductive-aged women and the leading cause of anovulatory infertility 3

If TSH is abnormal:

• Treat thyroid dysfunction first, as menstrual cycles typically normalize within 2-5 days of achieving adequate thyroid hormone replacement 2

Male Partner Evaluation

Male factor contributes to 40-50% of infertility cases, so simultaneous evaluation is essential 6, 7:

• Obtain reproductive history, physical examination, and semen analysis 1, 6
• Order at least two semen analyses separated by one month to confirm persistent abnormalities 8
• Measure serum FSH, LH, and total testosterone if semen analysis is abnormal 8

Critical Pitfalls to Avoid

• Never delay evaluation because this patient has already exceeded the 12-month threshold for infertility workup 1, 6
• Do not evaluate partners sequentially—begin both evaluations simultaneously to avoid further delays 1
• Never assume anovulation at any age is simply "normal variation" without evaluation, as prolonged hypoestrogenism increases risks of osteoporosis and cardiovascular disease 2
• Do not delay hormonal assessment, as time is critical for fertility preservation options if primary ovarian insufficiency is confirmed 2
• Avoid prolonged empiric medical therapy; if no improvement after 3-6 months, advance to assisted reproductive technologies 8

Additional History and Physical Examination Components

Document specific details 1, 6:

• Duration attempting pregnancy, frequency and timing of intercourse
• Previous pregnancies and outcomes
• Menstrual history pattern (oligomenorrhea suggests PCOS) 6
• Medical conditions associated with reproductive failure 1
• Current medications, particularly those affecting prolactin 2
• Signs of androgen excess on examination (hirsutism, acne) suggesting PCOS 1
• BMI calculation, as obesity and extreme thinness reduce fertility rates 8, 1
• Thyroid examination, clinical breast examination 1
• Pelvic examination for masses, tenderness, or anatomic abnormalities 1

Immediate Next Steps

Once hormonal testing and imaging identify the underlying cause, management can be appropriately directed 2:

• For PCOS with anovulation: Ovulation induction with clomiphene citrate or letrozole is first-line treatment 7, 9
• For hyperprolactinemia: Treat with dopamine agonists after MRI evaluation 2
• For thyroid dysfunction: Normalize thyroid function first 2
• For primary ovarian insufficiency: Immediate referral for fertility preservation counseling and consideration of donor oocytes 2

Referral to reproductive endocrinology should occur simultaneously with the initial workup to avoid further delays, particularly given the 2-year duration of infertility 2