What is the recommended evaluation and management approach for a couple with infertility (failure to conceive after 12 months of regular unprotected intercourse)?

Evaluation and Management of Infertility

Begin simultaneous evaluation of both partners immediately after 12 months of regular unprotected intercourse (or after 6 months if the woman is ≥35 years old), focusing on the three most common identifiable causes: male factor (26%), ovulatory dysfunction (21%), and tubal damage (14%). 1

When to Initiate Evaluation

Standard Timeline

• Start formal infertility workup after 12 consecutive months of regular unprotected intercourse for women under 35 years 1, 2
• This threshold represents a strong recommendation from the European Association of Urology 1

Accelerated Timeline (6 Months)

• Women ≥35 years old require earlier assessment due to age-related fertility decline 1, 2
• Women with oligo-amenorrhea (infrequent menstruation) 1, 2
• Known or suspected uterine/tubal disease or endometriosis 1, 2
• Partner with known subfertility 2

Common Pitfall: Do not wait the full 12 months in women ≥35 years—this delay compromises treatment success rates 1

Initial Evaluation Strategy

Simultaneous Partner Assessment

Both partners must be evaluated concurrently—this is a strong recommendation because male factors contribute to approximately 50% of infertility cases. 1

• Evaluating only the female partner causes diagnostic delays and unnecessary interventions 1
• Male-associated factors are present in roughly half of involuntarily childless couples, usually with abnormal semen parameters 1

Female Partner Evaluation

History (Key Elements)

• Duration of attempting pregnancy and frequency/timing of intercourse 2
• Menstrual history: cycle regularity, duration, and characteristics 2
• Previous pregnancies and outcomes (including miscarriages) 2
• Medical conditions associated with reproductive failure (thyroid disorders, PCOS, diabetes) 2
• Surgical history: pelvic surgeries, hospitalizations 3
• STI history: particularly chlamydia (causes tubal damage in 14% of cases) 3
• Lifestyle factors: smoking, alcohol (>5 cups caffeine/day reduces fertility), recreational drugs, body weight extremes 2, 3
• Current medications and allergies 2

Physical Examination

• Height, weight, BMI calculation (obesity directly reduces fertility rates) 1, 2
• Thyroid examination for enlargement or nodules 2
• Clinical breast examination 2
• Signs of androgen excess: hirsutism, acne (suggests PCOS) 2
• Pelvic examination: assess for tenderness, masses, vaginal/cervical abnormalities, uterine size/shape, adnexal masses 2

Laboratory and Imaging

• Ovarian reserve testing: follicle-stimulating hormone (FSH) levels 2
• For women >35 years: day 3 FSH and estradiol levels, or antral follicle count via ultrasound 4
• Transvaginal ultrasound: evaluate uterine anatomy and assess for PCOS (>25 small follicles in at least one ovary or ovarian volume >10 mL) 2, 3
• Ovulation documentation: serum progesterone level at cycle day 21 5
• Hysterosalpingography: screen for uterine and fallopian tube patency in women with no risk factors for obstruction 2, 4
• Hysteroscopy or laparoscopy: if history of endometriosis, pelvic infections, ectopic pregnancy, or if initial screening is normal 2, 4

Male Partner Evaluation

Essential Components

• Reproductive history: previous pregnancies with other partners, sexual function, timing of intercourse 2
• Physical examination: genital examination, signs of hypogonadism 2
• Semen analysis: obtain at least two samples, one month apart 2, 6
• Assessment for underlying medical conditions affecting fertility (diabetes, thyroid disorders, genetic abnormalities) 7, 6

Common Pitfall: Failing to obtain two separate semen analyses can lead to misdiagnosis, as sperm parameters vary 2

Distribution of Infertility Causes

Identifiable Causes (85% of cases) 4

• Male factor: 26% 1
• Ovulatory dysfunction: 21% (PCOS accounts for 70% of anovulatory cases, affecting at least 7% of adult women) 1, 3
• Tubal damage: 14% (often from STI-related pelvic inflammatory disease, particularly chlamydia) 1, 3
• Endometriosis: affects at least one-third of women with infertility 3
• Uterine cavity abnormalities: interfere with implantation 3
• Unexplained infertility: 28% despite thorough evaluation 1

Modifiable Risk Factors

• Smoking: reduces fertility in both partners 1, 3
• Alcohol consumption: negatively affects fertility 1, 3
• Caffeine >5 cups/day: reduces fertility 3
• Obesity or being underweight: directly reduces fertility rates 1, 3
• Commercial vaginal lubricants: most reduce fertility 1, 3
• Recreational drug use: impairs reproductive function 1

Management Algorithm

Step 1: Lifestyle Optimization (First-Line for Elevated BMI)

For women with elevated BMI and otherwise normal fertility investigations in both partners, lifestyle modification is the most appropriate initial management. 1

• Weight optimization through dietary changes (obesity directly reduces fertility) 1
• Complete smoking cessation 1, 3
• Eliminate alcohol consumption 1, 3
• Reduce caffeine to <5 cups/day 1, 3
• Discontinue recreational drugs 1
• Avoid commercial vaginal lubricants 1

Important: GLP-1 agonists (semaglutide) are not recommended for women actively attempting conception; bariatric surgery is not first-line unless severe obesity-related comorbidities require urgent intervention 1

Step 2: Optimize Intercourse Timing

• Intercourse every 1-2 days beginning soon after menstrual period ends 2, 6
• Educate about the 6-day fertile window ending on ovulation day, characterized by stretchy cervical mucus 1
• Consider ovulation prediction methods: over-the-counter kits, digital applications, or cycle beads 1

Step 3: Cause-Specific Treatment

Ovulatory Dysfunction

• Clomiphene citrate or letrozole (aromatase inhibitor) for ovulation induction 4, 5
• PCOS patients: 70% of anovulatory women respond to oral ovulation-inducing agents 3, 4
• Gonadotropins for ovarian stimulation (risk: multiple pregnancy up to 36%, ovarian hyperstimulation syndrome 1-5%) 4

Male Factor Infertility

• Gonadotropin therapy, intrauterine insemination (IUI), or in vitro fertilization (IVF) depending on severity 4, 8

Tubal Disease

• Surgical repair or IVF (generally requires subspecialty referral) 4, 5

Endometriosis

• Surgery, ovulation induction with IUI, or IVF 4, 8

Unexplained Infertility

• Initial approach: 3-4 cycles of ovarian stimulation with IUI 4
• If unsuccessful: proceed to IVF 4
• Alternative: another year of unprotected intercourse with lifestyle optimization 5

Step 4: Age-Based Decision Making

Female age should guide treatment intensity because fecundity declines with age. 4

• Women 38-40 years or older: consider immediate IVF as first-line treatment to avoid time loss 4
• Women >35 years: reassess after 6 months of lifestyle modification rather than 12 months 1

Step 5: Indications for Immediate IVF

• Severe male factor infertility 4
• Untreated bilateral tubal factor 4
• Women ≥38-40 years (to maximize success before further age-related decline) 4
• Poor ovarian reserve: consider oocyte donation for better success rates 8

Reassessment Timeline

• Women <35 years with lifestyle factors: reassess after addressing modifiable factors and optimizing intercourse timing for 3-4 cycles 1
• Women ≥35 years: reassess after 6 months maximum of conservative management 1, 3

Common Pitfall: Do not assume fertility based on prior successful pregnancies—secondary infertility (affecting 1 in 6 couples) requires the same comprehensive evaluation as primary infertility 1