What is the recommended initial evaluation and management for a reproductive‑age couple who have had one year of regular, unprotected intercourse without achieving pregnancy?

Initial Evaluation and Management of Basic Infertility

For a reproductive-age couple with one year of regular unprotected intercourse without pregnancy, initiate simultaneous evaluation of both partners immediately, focusing on the three essential diagnostic pillars: ovulation assessment, semen analysis, and tubal/uterine evaluation. 1, 2

Definition and Timing Thresholds

• Infertility is defined as failure to achieve pregnancy after 12 consecutive months of regular unprotected intercourse in women under 35 years. 1, 2
• Accelerate evaluation to 6 months for women aged 35 years or older, as age-related fertility decline justifies earlier intervention. 1, 2
• Begin evaluation immediately (without waiting 12 months) if the woman has oligo-amenorrhea, known/suspected tubal disease, endometriosis, or a partner with known subfertility. 2, 3

Critical First Principle: Evaluate Both Partners Simultaneously

Both partners must be investigated concurrently from the outset—this is a strong recommendation because male factors contribute to approximately 50% of infertility cases. 1, 2 Delaying male evaluation wastes time and leads to unnecessary female-focused interventions. 1

Initial History: Female Partner

Document the following specific elements:

• Duration of infertility: Confirm 12 months of regular intercourse (every 1–2 days throughout the cycle). 2, 4
• Menstrual pattern: Cycle length, regularity, and presence of oligo-amenorrhea (suggests ovulatory dysfunction). 2
• Prior pregnancies: Include miscarriages and ectopic pregnancies—these do not reset the 12-month clock. 2
• Pelvic inflammatory disease or STI history: Key risk factor for tubal damage. 2
• Medical conditions: Thyroid disorders, PCOS symptoms (hirsutism, acne, irregular cycles), endometriosis symptoms (dysmenorrhea, dyspareunia), hyperprolactinemia (galactorrhea). 2
• Prior pelvic/abdominal surgery: Especially involving reproductive organs. 2
• Lifestyle factors: Current smoking, alcohol use, recreational drugs (including cannabis), caffeine intake >5 cups/day, occupational exposures (shift work, chemicals). 2
• Family history: Premature ovarian insufficiency, fertility problems, heritable disorders (e.g., cystic fibrosis). 2

Initial History: Male Partner

• Erectile or ejaculatory dysfunction. 2
• Testicular pathology: Infection, trauma, tumor, undescended testes, prior orchidopexy. 2
• Congenital genital anomalies. 2
• Anabolic steroid or exogenous androgen use. 2

Physical Examination: Female Partner

• BMI calculation: Values <18.5 kg/m² or >30 kg/m² reduce fertility in both partners. 2
• Thyroid examination: Palpate for enlargement, nodules, or tenderness. 2
• Signs of androgen excess: Hirsutism, acne, male-pattern alopecia (suggest PCOS). 2
• Breast examination: Check for galactorrhea (indicates hyperprolactinemia). 2
• Pelvic examination: Assess for uterine abnormalities, adnexal masses, cul-de-sac nodularity (endometriosis). 2

Essential Laboratory and Imaging Tests

Female Partner

• Ovulation documentation: Use home urinary LH predictor kits to detect the LH surge, or measure mid-luteal progesterone (cycle day 21 in 28-day cycles). 2, 5
• Ovarian reserve testing (especially if age ≥35 years): Day 3 FSH and estradiol levels, or transvaginal ultrasound for antral follicle count. 2, 5
• Thyroid function tests: Only if clinical features suggest thyroid disease. 2
• Serum prolactin: Only if galactorrhea or irregular cycles are present. 2
• Tubal patency and uterine anatomy: Hysterosalpingography (HSG) or transvaginal ultrasound; reserve laparoscopy for cases where HSG is abnormal or endometriosis is suspected. 2, 5

Male Partner

• Semen analysis: Obtain at least two samples, one month apart, to assess sperm concentration, motility, and morphology. 2, 6
• Infectious disease screening (before assisted reproduction): Hepatitis B surface antigen, hepatitis C antibodies, HIV, syphilis. 2

First-Line Management: Lifestyle Optimization

Before any medical intervention, implement these evidence-based modifications:

• Intercourse timing: Every 1–2 days beginning soon after menstruation ends, continuing throughout the cycle to cover the 6-day fertile window (ending on ovulation day, characterized by slippery, stretchy cervical mucus). 2, 4
• Smoking cessation for both partners. 2
• Eliminate alcohol and recreational drug use. 2
• Limit caffeine to <5 cups/day. 2
• Avoid commercial vaginal lubricants, which impair sperm motility. 2, 4
• Weight optimization: Target BMI 18.5–30 kg/m². For women with elevated BMI and otherwise normal investigations, lifestyle modification and dietary changes are the most appropriate initial management. 1
• Folic acid supplementation for the female partner. 2
• Iodine and vitamin D supplementation (vitamin D when risk factors for deficiency exist). 2

Common Diagnostic Pitfalls to Avoid

• Do not limit evaluation to the female partner alone—male factors account for ~50% of cases. 1, 2
• Do not wait the full 12 months in women ≥35 years; evaluate after 6 months. 1, 2
• Do not assume fertility based on prior pregnancies; secondary infertility requires the same comprehensive workup. 1
• Do not perform endometrial biopsy, varicocele screening, or routine Chlamydia testing in asymptomatic patients—these tests do not correlate with pregnancy outcomes. 7
• Do not order post-coital tests or sperm-penetration assays—results are not consistently related to pregnancy. 7

When to Refer to a Fertility Specialist

• After completing the basic evaluation outlined above, refer if:
  • Permanent causes requiring assisted reproductive technology are identified (e.g., bilateral tubal occlusion, severe male factor with total motile sperm count <3 million). 2
  • 12 months of documented infertility have elapsed in opposite-sex couples under 35 years, or 6 months in women ≥35 years. 2
  • Unexplained infertility is diagnosed after normal ovulation, tubal patency, and semen analysis. 3
  • The couple requires fertility preservation (e.g., oncology, gender-affirming care). 2

Treatment Algorithms Based on Diagnosis

Ovulatory Dysfunction (e.g., PCOS)

• First-line: Clomiphene citrate or letrozole (aromatase inhibitor) for ovulation induction with timed intercourse. 8
• Third-line: Low-dose gonadotropins ≤75 IU/day if oral agents fail. 2
• Avoid GnRH agonists in intrauterine insemination (IUI) protocols—they increase multiple-pregnancy rates without improving live births. 2

Unexplained Infertility

• If Hunault prognostic score >30%, pursue expectant management for 6–12 months with optimized intercourse timing. 2
• If prognosis <30%** and **total motile sperm count >10 million, proceed with IUI combined with ovarian stimulation (clomiphene, tamoxifen, or low-dose gonadotropins) for ≥3 cycles. 2
• Do not perform IUI in natural cycles—it does not improve live-birth rates. 2

Male Factor Infertility

• Mild factor (TMSC 3–10 million): IUI with ovarian stimulation is non-inferior to IVF. 2
• Moderate factor (TMSC <3 million): Consider IUI in natural cycles or proceed directly to IVF with intracytoplasmic sperm injection (ICSI). 2
• Perform at least three consecutive IUI cycles before escalating to IVF. 2

Tubal Disease or Endometriosis

• Mild endometriosis: Ovarian stimulation with IUI for 3–4 cycles, then IVF if unsuccessful. 8
• Bilateral tubal occlusion or severe tubal damage: Proceed directly to IVF. 8

Age-Related Considerations

• Female age is the strongest predictor of fertility success. 2
• For women aged 38–40 years or older, consider immediate IVF as first-line treatment to avoid delays. 8