What are the evaluation and treatment options for a woman with infertility, considering her age, reproductive history, and potential underlying medical conditions?

Evaluation and Management of Female Infertility

Begin infertility evaluation after 12 months of regular unprotected intercourse in women under 35 years, but initiate evaluation after only 6 months in women 35 years or older. 1, 2, 3

When to Start Evaluation Earlier

Initiate evaluation immediately (before the standard timeframes) if any of these conditions exist: 1, 2

• History of oligo-amenorrhea (infrequent menstruation)
• Known or suspected uterine or tubal disease
• Known or suspected endometriosis
• Partner with known subfertility
• Age over 40 years (immediate evaluation warranted) 3

Essential Initial Workup

Medical and Reproductive History

Document these specific elements: 1, 4, 2

• Duration attempting pregnancy and coital frequency/timing
• Gravidity, parity, and all pregnancy outcomes with complications
• Menstrual history: age at menarche, cycle length (days), regularity, dysmenorrhea severity
• Past surgeries with indications and outcomes, previous hospitalizations
• Medical conditions affecting reproduction: thyroid disorders, hirsutism, endocrine disorders, PCOS
• Sexual history: pelvic inflammatory disease, STD history or exposure
• Current medications and allergies
• Lifestyle factors: smoking status, alcohol consumption, caffeine intake (>5 cups/day reduces fertility), recreational drug use 1
• Family history of reproductive failure

Physical Examination

Perform these specific assessments: 1, 4, 2

• Height, weight, BMI calculation (extremes of body weight reduce fertility)
• Thyroid examination: palpate for enlargement, nodules, tenderness
• Clinical breast examination
• Assessment for androgen excess: hirsutism, acne
• Pelvic examination:
  • Vaginal/cervical abnormalities, secretions, discharge
  • Uterine size, shape, position, mobility
  • Adnexal masses or tenderness
  • Cul-de-sac masses, tenderness, or nodularity suggesting endometriosis

Laboratory and Imaging Studies

Order these tests based on clinical findings: 2, 5, 6, 7

• Ovulation documentation: serum progesterone level at cycle day 21 (mid-luteal phase) 6
• Ovarian reserve testing (especially for women ≥35 years): 5, 3
  • Day 3 FSH and estradiol levels
  • Transvaginal ultrasound for antral follicle count (<5 follicles suggests diminished reserve) 1
  • Ovarian volume measurement (<3 cm³ suggests diminished reserve) 1
• Thyroid function tests if symptoms present 1
• Prolactin levels if galactorrhea present 1
• Uterine and tubal assessment:
  • Hysterosalpingography (HSG) for women with no risk factors for tubal obstruction 6, 3
  • Transvaginal ultrasound to evaluate uterine anatomy 2
  • Hysteroscopy or laparoscopy if history of endometriosis, pelvic infections, or ectopic pregnancy 6

Male Partner Evaluation (Mandatory)

Evaluate both partners simultaneously from the outset—this is non-negotiable. 1, 8, 3 Male factor contributes to infertility in 40-50% of couples. 3, 9

Order semen analysis immediately as the first diagnostic step: 1, 8

• Collect at least two samples one month apart after 2-3 days of abstinence 1, 8
• Assess volume, pH, concentration, motility, and morphology 8
• Do not rely on single analysis—semen parameters are highly variable 1

Common Causes and Their Prevalence

Understanding the distribution helps prioritize evaluation: 1, 9

• Male factor: 26-50% of cases
• Ovulatory dysfunction: 21-25% (PCOS is the leading cause, affecting at least 7% of adult women) 1, 9
• Tubal damage: 14%
• Endometriosis: affects at least one-third of infertile women 1
• Unexplained infertility: 15-30% 3, 9

Treatment Approaches

For Ovulatory Dysfunction

Clomiphene citrate is indicated for treatment of ovulatory dysfunction in women desiring pregnancy. 10 Use this algorithm:

1. Confirm adequate estrogen levels before starting clomiphene (via vaginal smears, endometrial biopsy, or bleeding response to progesterone) 10
2. Exclude pregnancy, ovarian cysts, and abnormal vaginal bleeding 10
3. Start clomiphene on cycle day 5 once ovulation is established 10
4. Limit to 6 total cycles (including 3 ovulatory cycles)—long-term cyclic therapy beyond this is not recommended 10
5. Time intercourse appropriately: every 1-2 days beginning soon after menstruation ends 2

Alternative agents include letrozole (aromatase inhibitor) and gonadotropins for ovarian stimulation. 9

For Tubal Disease

• Surgical repair for certain tubal abnormalities 5
• In vitro fertilization (IVF) for severe bilateral tubal obstruction 9

For Endometriosis

Treatment options in order of invasiveness: 5

• Surgery to remove endometrial implants
• Ovulation induction with intrauterine insemination (IUI)
• IVF

For Unexplained Infertility

Follow this stepwise approach: 6, 9

1. Another year of unprotected intercourse (reasonable first step)
2. Ovarian stimulation with IUI for 3-4 cycles
3. IVF if above approaches fail

Age-Based Treatment Modifications

For women 38-40 years or older, consider immediate IVF as first-line treatment rather than sequential approaches, given declining fecundity with age. 9

Critical Pitfalls to Avoid

• Never evaluate only one partner—simultaneous evaluation is mandatory 1, 8
• Do not delay evaluation in women >35 years—start after 6 months, not 12 1, 2
• Do not rely on single semen analysis—obtain at least two samples 1, 8
• Do not use clomiphene beyond 6 cycles—this is not recommended 10
• Do not use clomiphene if ovarian cysts present (except in PCOS) 10
• Do not overlook lifestyle modifications: counsel on smoking cessation, alcohol avoidance, weight optimization (BMI 19.8-26.0 kg/m²), and limiting caffeine to <5 cups daily 1, 2, 7

Lifestyle Modifications That Improve Fertility

Implement these evidence-based interventions: 1, 2, 7

• Smoking cessation (reduces fertility)
• Alcohol avoidance (reduces fertility)
• Discontinue recreational drugs (reduce fertility)
• Optimize body weight (very thin or obese women have lower conception rates)
• Limit caffeine to less than 5 cups per day
• Avoid commercial vaginal lubricants (most reduce fertility)
• Folic acid supplementation for all women of reproductive age 4

Success Rates

With appropriate treatment, the overall likelihood of successful pregnancy approaches 50%. 5 Success rates vary by age, diagnosis, and treatment modality, with IVF success declining significantly after age 38-40 years. 9