What is the appropriate assessment and management plan for a 31‑year‑old woman and her partner presenting with sub‑fertility?

Assessment and Management of Sub-fertility in a 31-Year-Old Woman

Initial Assessment Timeline

For a 31-year-old woman, initiate formal fertility evaluation after 12 months of regular unprotected intercourse without conception. 1, 2 This standard timeline applies because she is under 35 years of age; earlier evaluation (after 6 months) is reserved for women over 35 years or those with specific risk factors. 1, 2

Comprehensive History—Essential Elements

Female Partner History

• Duration attempting conception (must be ≥12 months of regular unprotected intercourse without resulting live birth; miscarriages and ectopic pregnancies do not reset this clock) 3, 1
• Menstrual cycle characteristics: Regular cycles (21-35 days) suggest ovulation; irregular cycles or amenorrhea indicate ovulatory dysfunction 4, 5
• Previous pregnancies and outcomes for both partners, including any history of miscarriage, ectopic pregnancy, or live births 3, 1
• Frequency and timing of intercourse: Should be every 1-2 days beginning after menstruation ends 3, 1
• Sexually transmitted infection history, particularly pelvic inflammatory disease which causes tubal damage 3, 1
• Medical conditions associated with reproductive failure: thyroid disorders, PCOS symptoms (hirsutism, acne, irregular cycles), endometriosis symptoms (dysmenorrhea, dyspareunia, pelvic pain), hyperprolactinemia (galactorrhea) 3, 1
• Surgical history: previous pelvic/abdominal surgery, particularly procedures involving reproductive organs 3, 1
• Current medications and known teratogens 3
• Lifestyle factors: smoking status (including duration and cessation date if ex-smoker), alcohol consumption, cannabis and other substance use, caffeine intake (>5 cups/day reduces fertility), anabolic steroid use 3, 1
• Occupational exposures: shift work, chemical exposure 3
• Family history: premature ovarian insufficiency, fertility issues, congenital or chromosomal abnormalities (cystic fibrosis, Huntington's disease) 3

Male Partner History

• Erectile or ejaculatory dysfunction 3
• Testicular problems: infection, trauma, tumor, undescended testes, orchidopexy 3, 6
• Congenital anomalies 3
• Androgen use or abuse (including anabolic steroids) 3
• Childhood illnesses (mumps orchitis), systemic illnesses, gonadotoxin exposure 6
• Medications that may impair spermatogenesis 6

Physical Examination—Specific Findings to Document

Female Partner

• BMI calculation (underweight <18.5 or obese >30 both reduce fertility) 3, 1, 2
• Blood pressure measurement 1
• Thyroid examination: enlargement, nodules, tenderness 3, 1
• Signs of androgen excess: hirsutism, acne, male-pattern hair loss (suggests PCOS) 3, 1
• Clinical breast examination: galactorrhea (suggests hyperprolactinemia) 3, 1
• Pelvic examination (if clinically indicated by history): vaginal/cervical abnormalities, uterine size/shape/position/mobility, adnexal masses or tenderness, cul-de-sac nodularity (suggests endometriosis) 3, 1

Male Partner

• BMI calculation 3
• Genital examination (if significant history present): testicular size (normal >15 mL), consistency, presence of varicocele, vas deferens and epididymides assessment, secondary sex characteristics 6

Investigations—Simultaneous Evaluation of Both Partners

Both partners must be evaluated concurrently from the outset; sequential evaluation delays diagnosis and wastes time. 2, 6 Male factors contribute to approximately 50% of infertility cases. 2, 6

Female Investigations

• Ovulation confirmation: Serum progesterone >30 nmol/L measured on cycle day 21 (or 7 days before expected menses in irregular cycles) 4, 7
• Ovarian reserve testing: FSH levels (day 2-5 of cycle) 1
• Thyroid function tests if symptoms present 3
• Prolactin levels if galactorrhea or irregular cycles 3
• Transvaginal ultrasound: assess uterine anatomy, ovarian morphology, antral follicle count 1, 4
• Tubal patency assessment: Hysterosalpingography (HSG) if no risk factors for tubal disease; if history of endometriosis, pelvic infections, or ectopic pregnancy, proceed directly to laparoscopy with dye test 7, 5

Male Investigations—Mandatory for All

• Semen analysis (at least two samples, collected one month apart, after 2-3 days of abstinence): volume, pH, concentration, motility, morphology 6, 7, 5
  • If first sample abnormal, repeat in 4-6 weeks 6
  • Critical pitfall: Never rely on single semen analysis; significant day-to-day physiological variation exists 6
• Infectious disease screening: Hepatitis B surface antigen, hepatitis C antibodies, HIV status, syphilis screen 3

Management Algorithm

Step 1: Lifestyle Optimization (All Couples)

• Intercourse timing: Every 1-2 days beginning after menstruation ends 3, 1
• Smoking cessation (both partners) 3, 2
• Eliminate alcohol and recreational drugs 3, 2
• Reduce caffeine to <5 cups/day 3, 2
• BMI optimization: Weight loss if obese (BMI >30), weight gain if underweight (BMI <18.5) 2
• Avoid commercial vaginal lubricants (most reduce fertility) 3, 2
• Folic acid supplementation (female partner) 3
• Iodine supplementation (female partner) 3
• Vitamin D supplementation if risk factors present (female partner) 3

Step 2: Vaccination Status

• Measles, mumps, rubella; varicella; COVID-19 if non-immune (avoid pregnancy for 1 month after live vaccines) 3
• Influenza and pertussis best given during pregnancy for fetal immunity transfer 3

Step 3: Diagnosis-Specific Treatment

Ovulatory Dysfunction (PCOS)

• First-line: Letrozole (aromatase inhibitor) for ovulation induction 4, 5
• Second-line: Clomiphene citrate 50 mg daily for 5 days starting cycle day 5 8, 4, 7
  • Maximum 6 treatment cycles total (including 3 ovulatory cycles) 8
  • Warning: Multiple pregnancy risk; patients must be counseled 8
  • Contraindicated if ovarian cysts present (except PCOS), abnormal vaginal bleeding, or liver dysfunction 8
• Third-line: Low-dose gonadotropins (≤75 IU/day) 3
• Do not use GnRH agonists (increases multiple pregnancy without improving live birth rates) 3

Unexplained Infertility

• If prognosis >30% for spontaneous pregnancy (using Hunault score): Expectant management for 6-12 months 3
• If prognosis <30% and total motile sperm count (TMSC) >10 million: IUI with ovarian stimulation (clomiphene citrate, tamoxifen, or low-dose gonadotropins) for at least 3 cycles 3
• After 3-4 failed IUI-OS cycles or if female age >38-40 years: Proceed directly to IVF 5

Mild Male Factor Infertility (TMSC 3-10 million)

• IUI with ovarian stimulation is non-inferior to IVF 3
• At least 3 consecutive IUI cycles should be performed 3

Moderate Male Factor Infertility (TMSC <3 million)

• IUI in natural cycles may be attempted, though evidence is limited 3
• Consider early referral to fertility specialist for assisted reproductive technologies 5

Tubal Factor or Severe Male Factor

• Immediate referral for IVF 5

Step 4: Referral Criteria

Request publicly funded fertility specialist assessment if:

• Opposite-sex couples meeting eligibility criteria after 12 months of documented infertility 3
• Known permanent cause of infertility requiring assisted reproductive technology 3
• Transgender couples unable to achieve pregnancy together 3
• Single women or same-sex couples with clear biological causes OR after 12 cycles of donor insemination (6 in RTAC-accredited clinic) 3
• Patients requiring fertility preservation (oncology, transgender) 3

Private fertility assessment may be pursued if ineligible for public funding or patient preference 3

Critical Pitfalls to Avoid

• Do not delay evaluation beyond 12 months in women under 35 without risk factors 1, 2
• Do not evaluate only one partner; male factors present in 50% of cases 2, 6
• Do not rely on single semen analysis; at least two samples one month apart required 6
• Do not use clomiphene citrate beyond 6 total cycles (including 3 ovulatory cycles); prolonged use increases borderline/invasive ovarian tumor risk 8
• Do not prescribe clomiphene if ovarian cysts present (except PCOS), abnormal vaginal bleeding, or pregnancy suspected 8
• Do not perform IUI in natural cycles for unexplained infertility (does not improve live birth rates) 3
• Do not add GnRH agonists to gonadotropin protocols for IUI (increases multiple pregnancy without benefit) 3

Special Considerations for Age

At 31 years, this patient has time for stepwise approach, but age is the most important determinant of female fertility. 3 If she approaches 35 years during evaluation/treatment, accelerate timeline and consider earlier transition to IVF to avoid age-related fertility decline. 5