What is the initial workup for a couple experiencing infertility?

Initial Workup for Infertility

Begin the infertility evaluation after 12 months of unprotected intercourse in women under 35 years, but initiate evaluation after only 6 months in women 35 years or older, and evaluate both partners simultaneously from the outset—this concurrent evaluation is mandatory and non-negotiable. 1, 2

When to Start the Evaluation

• Start evaluation immediately (before 12 months) if either partner has known infertility risk factors, including history of bilateral cryptorchidism in men, irregular menstrual cycles in women, prior pelvic inflammatory disease, or known endometriosis 1, 3
• Women over 40 years warrant immediate evaluation and treatment without waiting 3
• After 5 unsuccessful ovulation cycles (approximately 5 months), both partners require concurrent evaluation immediately, particularly if the female partner is over 35 years 4

Male Partner Evaluation

Reproductive History (Essential Components)

• Frequency and timing of intercourse 1
• Prior fertility with current or previous partners and duration of current infertility 1
• Childhood illnesses including cryptorchidism, developmental history, and pubertal timing 1, 2
• Systemic illnesses (diabetes mellitus), previous surgeries, and past infections 1, 2
• Sexual history including sexually transmitted diseases and erectile/ejaculatory dysfunction 1
• Gonadotoxin exposure including heat (hot tubs, saunas, laptops), anabolic steroid use, chemotherapy, and radiation 1, 5
• Prescription medications (especially testosterone, which causes azoospermia), non-prescription drugs, and recreational drug use 1, 5
• Family reproductive history 1

Physical Examination (Specific Findings to Document)

• Penile examination including location of urethral meatus to identify hypospadias 1, 2
• Testicular size measurement (normal >15 mL volume or >4 cm length) and consistency—small firm testes suggest primary testicular failure 1, 2, 5
• Presence and consistency of both vas deferens and epididymides—bilateral absence of vas deferens can be diagnosed definitively on physical examination and indicates need for cystic fibrosis carrier testing 1, 2
• Presence of varicocele (palpable with Valsalva maneuver)—affects sperm production and quality 1, 4, 2
• Secondary sex characteristics including body habitus, hair distribution, and breast development (gynecomastia suggests hormonal abnormality) 1, 2
• Digital rectal examination 1, 2

Semen Analysis (Critical First Test)

Order two semen analyses separated by at least one month to confirm persistent abnormalities—never rely on a single sample. 1, 4, 2, 5

Collection Instructions

• Abstain from sexual activity for 2-3 days before collection 1, 5, 6
• Collect by masturbation or intercourse using semen collection condoms (avoid standard condoms and lubricants as they impair sperm function) 1, 5
• If collected at home, keep specimen at room or body temperature during transport and examine within one hour 1

Parameters to Assess

• Ejaculate volume: 1.5-5.0 mL 1
• pH: >7.2 1
• Sperm concentration: >20 million/mL 1
• Total motile sperm count (TMSC): calculate from volume × concentration × % motility 5
• Sperm morphology using strict Kruger criteria 1

Action Based on Results

• Any abnormal semen parameters require referral to a male reproductive specialist for complete evaluation 4, 5
• Sperm concentration <10 million/mL requires endocrine evaluation (FSH, LH, total testosterone) and genetic testing (karyotype and Y-chromosome microdeletion analysis) before considering ICSI 4, 5
• Azoospermia or severe oligospermia <5 million/mL mandates karyotyping and Y-chromosome microdeletion analysis 4, 5
• TMSC <5 million indicates IUI will have poor success; proceed directly to IVF/ICSI 5

Critical Health Implications Beyond Fertility

• Men with abnormal semen parameters have significantly higher rates of testicular cancer and overall mortality compared to fertile men 4, 2
• Over 50% of male infertility cases stem from specific medical conditions with health implications beyond fertility, making thorough evaluation critical for the patient's overall health 4, 2

Female Partner Evaluation

Medical and Reproductive History

• Duration of infertility and how long actively trying to conceive 1, 3
• Coital frequency and timing, level of fertility awareness 1
• Results of any previous infertility evaluation and treatment 1
• Gravidity, parity, pregnancy outcomes, and associated complications 1
• Age at menarche, menstrual cycle length and characteristics (regular 21-35 day cycles suggest ovulation), onset and severity of dysmenorrhea 1, 3
• Past surgeries including indications and outcomes, previous hospitalizations, serious illnesses or injuries 1
• Medical conditions associated with reproductive failure including thyroid disorders, hirsutism, polycystic ovary syndrome, or other endocrine disorders 1, 3
• Results of cervical cancer screening and any follow-up treatment 1
• Current medication use and allergies 1
• Sexual history including pelvic inflammatory disease, history of STDs, or exposure to STDs 1
• Family history of reproductive failure or premature ovarian insufficiency 1

Physical Examination

• Height, weight, and BMI calculation (obesity and extreme thinness reduce fertility rates) 1, 5, 3
• Thyroid examination to identify enlargement, nodules, or tenderness 1, 3
• Clinical breast examination 1, 3
• Assessment for signs of androgen excess including hirsutism and acne 1, 3

Pelvic Examination

• Pelvic or abdominal tenderness, organ enlargement, or mass 1
• Vaginal or cervical abnormality, secretions, or discharge 1
• Uterine size, shape, position, and mobility 1
• Adnexal mass or tenderness 1
• Cul-de-sac mass, tenderness, or nodularity suggesting endometriosis 1

Initial Laboratory and Imaging Tests

• Ovarian reserve testing in women ≥35 years: Day 3 FSH and estradiol levels, or antral follicle count by transvaginal ultrasound 7, 3
• Ovulation documentation: Home urinary luteinizing hormone (LH) predictor kit or mid-luteal phase (day 21-23) serum progesterone level >3 ng/mL confirms ovulation 7, 3
• Thyroid function tests: TSH to screen for thyroid dysfunction, as both hypo- and hyperthyroidism affect ovulation 1, 4, 3
• Prolactin level if galactorrhea, irregular menses, or symptoms of hyperprolactinemia 1, 3
• Transvaginal ultrasound as initial imaging to evaluate uterine cavity, assess for fibroids or polyps, and count antral follicles 5, 3
• Hysterosalpingography (HSG) to assess tubal patency and uterine cavity abnormalities—perform in follicular phase after menses but before ovulation 7, 3
• Sonohysterography with tubal contrast agent is an alternative to HSG for combined tubal and uterine assessment 5

Additional Testing When Indicated

• Laparoscopy if endometriosis suspected based on pelvic pain, dyspareunia, or abnormal examination findings 1, 7
• Hysteroscopy if intrauterine abnormalities detected on imaging 7, 3
• Endometrial biopsy in women with irregular bleeding or risk factors for endometrial pathology 1

Critical Pitfalls to Avoid

• Never evaluate only one partner—simultaneous evaluation of both partners is mandatory from the outset 2, 5
• Never prescribe testosterone to men desiring fertility—it completely suppresses spermatogenesis through negative feedback and causes azoospermia 5
• Do not rely on a single semen analysis; at least two samples one month apart are required for accurate assessment 1, 4, 2, 5
• Do not delay female partner evaluation while treating male factor, as female age critically impacts outcomes 5
• Avoid using vaginal lubricants during the fertile window, as most commercially available products reduce fertility 5
• Do not perform HSG if active pelvic infection is suspected—treat infection first 3
• Recognize that semen analysis alone cannot distinguish fertile from infertile men; clinical context is essential 2

Timing and Counseling

• Time intercourse to the 6-day fertile window ending on ovulation day, characterized by stretchy cervical mucus 5
• Recommend intercourse every 1-2 days starting soon after menses ends 5
• Counsel smoking cessation, alcohol limitation, and avoidance of recreational drugs, as these impair fertility in both partners 5, 8
• Address the emotional and educational needs of couples with infertility; consider referring for psychological support, infertility support groups, or family counseling 1