Comprehensive Infertility Workup for Males and Females
Initial Approach
Both partners must undergo concurrent evaluation from the outset—this is non-negotiable, as male factors directly contribute to 40-50% of infertility cases. 1, 2
Begin evaluation after 12 months of unprotected intercourse in women under 35 years, after 6 months in women 35 years or older, and immediately in women over 40 years or those with known fertility-impairing conditions. 2, 3
Male Partner Workup
Essential History Components 1, 2
- Reproductive history: Coital frequency/timing, prior fertility, duration of current infertility
- Childhood illnesses: Cryptorchidism, mumps orchitis, delayed puberty
- Systemic medical conditions: Diabetes, chronic kidney disease, cancer history
- Surgical history: Hernia repairs, orchiopexy, vasectomy
- Sexual function: Erectile or ejaculatory dysfunction
- Gonadotoxin exposures: Anabolic steroids, chemotherapy, radiation, heat exposure (saunas, hot tubs), occupational chemicals
- Medications: Testosterone replacement, finasteride, calcium channel blockers, SSRIs
- Family history: Genetic conditions, consanguinity
Physical Examination 1, 2
- Penis: Hypospadias, urethral meatus location
- Testicular assessment: Measure volume (normal >15 mL), palpate for masses or atrophy 4
- Vas deferens and epididymides: Presence, consistency, nodularity
- Varicocele: Palpate with Valsalva maneuver (present in standing position)
- Secondary sex characteristics: Body habitus, gynecomastia, hair distribution
- Digital rectal examination: Prostate size and consistency
Laboratory Testing
Semen Analysis (First-Line Test) 1, 2
- Order at least two analyses performed at least one month apart 5, 2
- Collect after 2-3 days of abstinence 4, 2
- Examine within one hour at room/body temperature 2
- Assess: volume, pH, concentration, motility, morphology 4
Hormonal Evaluation (Selective Indications) 2
- Order only when:
- Include: Total testosterone, FSH, LH 6
Genetic Testing (Mandatory in Specific Cases) 5, 2
- Karyotype and Y-chromosome microdeletion analysis required before ICSI for:
Imaging Studies
Scrotal Ultrasonography (Selective Indications) 2
- Physical examination difficult or inadequate
- Suspected testicular mass
- Confirmed azoospermia
Female Partner Workup
Essential History Components 2, 3
- Reproductive history: Duration attempting pregnancy, previous pregnancies/outcomes, pregnancy complications
- Menstrual history: Cycle length, regularity, dysmenorrhea, intermenstrual bleeding
- Medical conditions: Thyroid dysfunction, PCOS, endometriosis, diabetes, autoimmune disorders 5
- Surgical history: Pelvic surgeries, appendectomy, ovarian cystectomy
- Medications and allergies: Current medications affecting fertility
- Lifestyle factors: Tobacco, alcohol, illicit drugs, exercise patterns, diet
- Sexual history: Dyspareunia, postcoital bleeding
Physical Examination 4, 2
- General: Height, weight, BMI calculation (obesity affects ovulation) 7
- Thyroid examination: Palpate for enlargement or nodules 5
- Breast examination: Galactorrhea (suggests hyperprolactinemia)
- Signs of androgen excess: Hirsutism, acne, male-pattern baldness
- Pelvic examination:
- Vaginal/cervical abnormalities
- Uterine size, shape, position, mobility
- Adnexal masses or tenderness
- Evidence of endometriosis (nodularity, fixed uterus)
Laboratory and Imaging Tests 2, 3
Ovarian Reserve Testing
- Anti-Müllerian hormone (AMH) or
- Day 3 FSH and estradiol
Ovulation Assessment
- Mid-luteal progesterone (day 21 of 28-day cycle)
- Consider thyroid function tests (TSH) 5
Structural Evaluation
- Transvaginal ultrasound: Uterine anatomy, endometrial thickness, ovarian morphology, antral follicle count 2
- Hysterosalpingography or saline infusion sonography: Tubal patency and uterine cavity assessment 7, 3
- Laparoscopy: Reserved for suspected endometriosis or pelvic adhesions when other tests inconclusive 7
Critical Pitfalls to Avoid
- Never evaluate only one partner—simultaneous evaluation is mandatory 4, 2
- Never rely on a single semen analysis—at least two samples one month apart are required 5, 2
- Do not delay male evaluation—this wastes time and resources 2
- Do not order routine hormonal testing or imaging for all infertile men—use stepwise approach based on semen analysis and physical examination findings 2
- Do not miss significant medical conditions—men with abnormal semen parameters have higher rates of testicular cancer and overall mortality 1, 5
- Do not overlook genetic implications—genetic causes affect treatment success and offspring health if ART is utilized 2
Referral Criteria
Male Reproductive Specialist 1, 5
- Any abnormal semen parameters
- Azoospermia or severe oligospermia
- Failed ART cycles or recurrent pregnancy losses (≥2 losses) 1
Reproductive Endocrinologist
- Anovulation or ovulatory dysfunction
- Diminished ovarian reserve
- Tubal factor infertility
- Unexplained infertility after complete workup 3
Health Implications Beyond Fertility
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. 5, 4 Men with abnormal semen parameters have significantly higher rates of testicular cancer, and azoospermic men have elevated cancer risk in general. 1, 5 This makes the infertility evaluation an important health screening opportunity that should not be missed.