Infertility Work-Up
Begin the infertility evaluation after 12 months of unprotected intercourse in women under 35 years, but initiate immediately after 6 months in women 35 years or older, and evaluate both partners simultaneously from the outset—this concurrent assessment is mandatory and non-negotiable. 1, 2
Timing of Evaluation
- Women under 35 years: Start evaluation after 12 months of regular unprotected intercourse 1, 2
- Women 35 years or older: Begin evaluation after 6 months 1, 2
- Women over 40 years: Immediate evaluation and treatment are warranted 2
- Earlier evaluation is indicated if either partner has known infertility risk factors (male: history of cryptorchidism, varicocele; female: irregular cycles, known endometriosis, prior pelvic surgery) 3, 4
Male Partner Evaluation (Must Be Done Concurrently)
Reproductive History
- Frequency and timing of intercourse, prior fertility history, duration of current infertility 3, 1
- Childhood illnesses (mumps orchitis, cryptorchidism), developmental history 3, 1
- Sexual history including sexually transmitted diseases, erectile or ejaculatory dysfunction 3, 1
- Gonadotoxin exposure: anabolic steroids, chemotherapy, radiation, excessive heat exposure (saunas, hot tubs, laptops), smoking 3, 5
- Medications: prescription and non-prescription drugs, supplements 3, 1
- Systemic illnesses and previous surgeries, particularly inguinal or scrotal 3, 1
Physical Examination
- Penile examination: location of urethral meatus, hypospadias 3, 1
- Testicular measurement and palpation: normal volume >15 mL, assess consistency 3, 1
- Vas deferens and epididymides: check for presence and consistency (absence indicates congenital bilateral absence of vas deferens) 3, 1
- Varicocele assessment: palpate with patient standing and performing Valsalva maneuver 3, 5
- Secondary sex characteristics: body habitus, hair distribution, gynecomastia 3, 1
- Digital rectal examination: assess prostate 3, 1
Semen Analysis (First-Line Test)
- Order immediately as the first diagnostic step—obtain at least two samples collected one month apart after 2-3 days of abstinence 3, 5, 1
- Collection instructions: masturbation or intercourse using semen collection condoms; if collected at home, keep at room or body temperature and examine within one hour 3
- Parameters to assess:
Additional Male Testing Based on Initial Results
- Endocrine evaluation (serum testosterone and FSH) if: sperm concentration <10 million/mL, sexual dysfunction present, or clinical findings suggest endocrinopathy 3, 5
- Post-ejaculatory urinalysis if ejaculate volume <1 mL (except in bilateral vasal agenesis or hypogonadism) to assess for retrograde ejaculation 3
- Karyotyping and Y-chromosome microdeletion analysis mandatory before ICSI if azoospermia or severe oligospermia <5 million/mL 5
- Transrectal ultrasonography (TRUS) if azoospermic with palpable vasa and low ejaculate volume to assess for ejaculatory duct obstruction 3
- Scrotal ultrasonography if physical examination is difficult/inadequate or testicular mass suspected 3
- Referral to male reproductive specialist for any abnormal semen parameters 5
Female Partner Evaluation (Must Be Done Concurrently)
Medical History
- Menstrual cycle characteristics: regularity, duration, flow patterns (irregular cycles suggest ovulatory dysfunction) 1, 4
- Reproductive history: prior pregnancies, outcomes, contraceptive use 1
- Sexual history: frequency of intercourse, dyspareunia, sexually transmitted infections 1
- Previous surgeries: particularly pelvic, abdominal, or procedures affecting reproductive organs 1
- Current medications and family history of reproductive issues 1
- Thyroid dysfunction: both hypo- and hyperthyroidism affect ovulation 5, 4
Physical Examination
- Height, weight, BMI calculation: obesity is a significant infertility factor 1, 4
- Thyroid examination: palpate for enlargement or nodules 1
- Clinical breast examination: assess for galactorrhea (suggests hyperprolactinemia) 1
- Pelvic examination: assess for vaginal/cervical abnormalities, uterine size/shape/position/mobility, adnexal masses or tenderness, evidence of endometriosis 1
Ovulatory Function Assessment
- Home urinary luteinizing hormone (LH) kit: documents ovulation timing 6
- Serum progesterone level: mid-luteal phase (day 21 of 28-day cycle) confirms ovulation 7
- Thyroid-stimulating hormone (TSH): screen for thyroid dysfunction 4
Ovarian Reserve Testing (Especially for Women ≥35 Years)
- Day 3 FSH and estradiol levels: elevated FSH indicates diminished ovarian reserve 6, 2
- Antral follicle count via transvaginal ultrasonography: assesses ovarian reserve 6, 2
- Anti-Müllerian hormone (AMH): alternative marker of ovarian reserve 4
Structural Assessment
- Hysterosalpingography (HSG): first-line imaging to assess tubal patency and uterine cavity abnormalities 6, 2
- Transvaginal ultrasonography: evaluate uterine structure, endometrial thickness, ovarian morphology, detect fibroids or polyps 6, 2
- Hysteroscopy: if intrauterine abnormalities suspected on HSG or ultrasound 6, 2
- Laparoscopy: if endometriosis, pelvic adhesions, or tubal disease suspected, particularly with history of pelvic pain or infection 6, 2
- MRI: reserved for complex cases requiring detailed anatomic assessment 4
Critical Pitfalls to Avoid
- Never evaluate only one partner—male factor contributes to 40-50% of infertility cases, and simultaneous evaluation is mandatory 1, 2
- Do not rely on a single semen analysis—at least two samples one month apart are required for accurate assessment 3, 5, 1
- Do not delay evaluation in women ≥35 years—ovarian reserve declines rapidly, and earlier intervention improves outcomes 2
- Recognize that over 50% of male infertility cases stem from specific medical conditions with health implications beyond fertility, including higher rates of testicular cancer and overall mortality 5, 1
- Semen analysis alone cannot distinguish fertile from infertile men—clinical context and comprehensive evaluation are essential 1