How should I evaluate and manage a woman who has been trying to conceive for 12 months (or 6 months if she is over 35 years old) with possible infertility?

Evaluation and Management of Female Infertility

When to Begin Evaluation

Begin infertility evaluation after 12 months of regular unprotected intercourse in women under 35 years, but initiate evaluation after only 6 months in women over 35 years due to age-related fertility decline. 1, 2

Expedited Evaluation Criteria

• Women aged >35 years warrant assessment after 6 months rather than 12 months 1, 2
• Women aged >40 years require immediate evaluation and treatment 3
• Earlier evaluation (before 6-12 months) is justified for: 1
  • History of oligo-amenorrhea (infrequent menstruation)
  • Known or suspected uterine or tubal disease
  • Known or suspected endometriosis
  • Partner with known subfertility or male factor risk factors

Initial Evaluation: Both Partners Simultaneously

Evaluate both partners at the same time—male factors contribute to approximately 50% of infertility cases, making concurrent assessment essential to avoid diagnostic delays. 1, 2

Female Partner Medical History

Obtain detailed information on: 1

• Reproductive history: Duration of attempting pregnancy, coital frequency and timing, gravidity, parity, pregnancy outcomes and complications
• Menstrual history: Age at menarche, cycle length and regularity, dysmenorrhea severity
• Medical conditions: Thyroid disorders, hirsutism, other endocrine disorders, past surgeries with indications and outcomes
• Sexual history: Pelvic inflammatory disease, STD history or exposure
• Lifestyle factors: Smoking status, alcohol consumption, caffeine intake (>5 cups/day reduces fertility), recreational drug use, use of vaginal lubricants 1
• Medications: Current prescriptions, over-the-counter drugs, allergies
• Family history: Reproductive failure in relatives

Female Partner Physical Examination

Perform systematic assessment including: 1

• General: Height, weight, BMI calculation (obesity and extreme thinness reduce fertility) 1
• Thyroid: Palpate for enlargement, nodules, tenderness
• Breast: Clinical breast examination, assess for galactorrhea
• Androgen excess: Evaluate for hirsutism, acne, male-pattern hair distribution
• Pelvic examination:
  • Vaginal/cervical abnormalities, secretions, discharge
  • Uterine size, shape, position, mobility
  • Adnexal masses or tenderness
  • Cul-de-sac masses, tenderness, nodularity
  • Pelvic or abdominal tenderness or organ enlargement

Male Partner Evaluation

Concurrent male assessment must include: 1, 2

• Reproductive history: Duration of infertility, prior fertility, coital frequency and timing, contraception methods used
• Medical history: Systemic illnesses (diabetes mellitus), prior surgeries, past infections, medications, gonadal toxin exposure including heat
• Sexual history: Sexual dysfunction, partner's history of pelvic inflammatory disease or STDs
• Semen analysis: At least two samples collected one month apart 4

Laboratory and Diagnostic Testing

Ovulatory Function Assessment

• Mid-luteal progesterone: Measure on day 21-23 of a 28-day cycle; values ≥25 nmol/L (≈8 ng/mL) confirm ovulation 5
• Day 3 FSH and estradiol: Assess ovarian reserve in early follicular phase (days 2-5 or days 3) 5, 4
• Anti-Müllerian Hormone (AMH): Can be measured any day of the cycle; shows strongest correlation with antral follicle count and outperforms FSH for ovarian reserve assessment 5
• TSH: Routine screening recommended as thyroid disorders directly impair fertility 5

Timing Considerations for Hormone Testing

• For regular cycles: FSH and estradiol on day 3, progesterone on day 21-23 5
• For amenorrhea: Measure LH, FSH, and estradiol randomly 5
• For oligomenorrhea: Test during early follicular phase (days 2-5) 5
• AMH is stable across the cycle and unaffected by exogenous hormones 5

Structural Assessment

• Transvaginal ultrasound: Evaluate uterine anatomy, antral follicle count, and screen for PCOS (≥25 follicles 2-9 mm or ovarian volume >10 mL) 5, 4
• Hysterosalpingography: Assess tubal patency and uterine cavity 1
• Laparoscopy or hysteroscopy: Reserved for suspected endometriosis, adhesions, or when initial screening is normal but infertility persists 1

Common Causes to Identify

The diagnostic workup should systematically evaluate: 2

• Male factor: 26% of cases (requires concurrent semen analysis)
• Ovulatory failure: 21% of cases (PCOS is most common cause, affecting ≥7% of adult women)
• Tubal damage: 14% of cases
• Unexplained: 28% of cases despite thorough evaluation

Lifestyle Modifications During Evaluation

Counsel all patients on modifiable factors that reduce fertility: 1, 2

• Eliminate: Smoking, alcohol, recreational drugs, commercial vaginal lubricants
• Reduce: Caffeine to <5 cups per day
• Optimize: Body weight (both obesity and extreme thinness impair fertility)
• Timing: Intercourse every 1-2 days beginning soon after menstruation ends 4
• Fertile window: Educate about the 6-day window ending on ovulation day, characterized by stretchy cervical mucus 2

Referral Criteria

Refer for specialist care when: 1

• Initial evaluation reveals abnormalities requiring advanced testing (endometrial biopsy, specialized imaging, laparoscopy)
• Treatment with clomiphene citrate or other ovulation induction is needed
• Assisted reproductive technology (IVF/ICSI) is indicated
• Male factor infertility requires urological expertise
• Unexplained infertility persists after basic evaluation

Critical Pitfalls to Avoid

• Do not delay evaluation in women ≥35 years: Waiting 12 months compromises treatment success due to progressive age-related fertility decline 2, 3
• Do not evaluate only the female partner: Male factors are present in ~50% of cases; simultaneous assessment prevents unnecessary female-focused interventions 2
• Do not assume fertility based on prior pregnancies: Secondary infertility requires the same comprehensive evaluation as primary infertility 2
• Do not overlook lifestyle counseling: Modifiable factors (smoking, obesity, caffeine) directly impact fertility outcomes 1, 2