Initial Workup for Infertility
Both partners must undergo concurrent evaluation from the outset, with the male partner receiving a reproductive history, physical examination by a trained examiner, and at least two semen analyses performed one month apart, while the female partner undergoes assessment of ovarian reserve, ovulatory function, and structural evaluation of the uterus and fallopian tubes. 1
Timing to Initiate Evaluation
- Begin evaluation after 12 months of unprotected intercourse in women under 35 years 1
- Begin evaluation after 6 months in women 35 years or older 1
- Immediate evaluation is warranted for women over 40 years or those with known conditions causing infertility 1
- After 5 unsuccessful ovulation cycles, both partners require concurrent evaluation immediately, particularly if the female partner is over 35 or if either partner has identifiable risk factors 2
Male Partner Evaluation
Essential History Components
The reproductive history must include: 1
- Coital frequency and timing (to ensure adequate exposure)
- Duration of infertility and prior fertility
- Childhood illnesses and developmental history
- Systemic medical illnesses (diabetes mellitus, upper respiratory diseases)
- Previous surgeries, medications, and allergies
- Sexual history including sexually transmitted infections
- Exposures to gonadotoxins (anabolic steroids, environmental toxins, heat exposure)
- Family reproductive history
Physical Examination
A physical examination by an examiner with appropriate training and expertise is crucial and should be performed on all men, as 0.16% of men have significant medical conditions with normal semen parameters that would be missed without examination 3. The examination must assess: 1
- Penis and urethral meatus location
- Testicular size measurement and palpation (normal volume 15-25 mL)
- Presence and consistency of vasa deferentia and epididymides
- Presence of varicocele (affects sperm production and quality)
- Body habitus and secondary sex characteristics
- Digital rectal examination when indicated
Semen Analysis
Order two semen analyses at least one month apart, as this is mandatory for accurate assessment given biological variability 1, 4. Collection parameters include: 1, 4
- 2-3 days abstinence before collection (inadequate abstinence invalidates results)
- Collection by masturbation or specialized semen collection condoms
- Specimens kept at room/body temperature
- Examination within one hour of collection (delayed analysis affects motility assessment)
WHO-based lower reference limits for interpretation: 4
- Volume ≥1.4 mL
- pH >7.2
- Sperm concentration ≥16 million/mL
- Progressive motility ≥30%
Mandatory Additional Testing Based on Semen Analysis Results
If sperm concentration <10 million/mL: Order endocrine evaluation including serum testosterone and follicle-stimulating hormone (FSH) 1, 4
If severe oligospermia (<5 million/mL) or azoospermia: Mandatory karyotyping and Y-chromosome microdeletion analysis before considering intracytoplasmic sperm injection 2, 4
If ejaculate volume <1 mL: Order post-ejaculatory urinalysis to evaluate for retrograde ejaculation, except in bilateral vasal agenesis or hypogonadism 4
If physical examination is difficult or testicular mass suspected: Order scrotal/testicular ultrasonography 1
Female Partner Evaluation
Essential History Components
The history must include: 1
- Duration attempting pregnancy
- Coital frequency and timing
- Previous pregnancies and outcomes
- Menstrual history (regularity, cycle length)
- Medical conditions (thyroid dysfunction affects ovulation)
- Current medications and allergies
- Lifestyle factors (tobacco, alcohol, illicit drugs)
Physical Examination
The examination should include: 1
- Height, weight, and BMI calculation
- Thyroid examination (hypo- and hyperthyroidism affect ovulation)
- Clinical breast examination
- Assessment for signs of androgen excess (hirsutism, acne)
- Pelvic examination
Laboratory and Imaging Tests
Ovarian reserve testing is essential and should include: 1
- Follicle-stimulating hormone (FSH) and estradiol levels on day 3 of menstrual cycle
- Anti-Müllerian hormone (AMH) levels
- Antral follicle count via transvaginal ultrasound
Structural evaluation must assess: 1
- Transvaginal ultrasound to evaluate uterine anatomy
- Hysterosalpingography or saline infusion sonography to assess tubal patency
- Additional ovulation assessment as clinically indicated (mid-luteal progesterone or home urinary luteinizing hormone kits)
Critical Pitfalls to Avoid
Do not delay male evaluation – male factors contribute to 40-50% of infertility cases, and both partners must be evaluated concurrently from the outset 1
Do not order routine hormonal testing or imaging for all infertile men – use a stepwise approach reserving these tests for those with sperm concentration <10 million/mL, abnormal semen parameters, or physical examination findings suggesting endocrinopathy 1
Do not miss significant medical conditions – men with abnormal semen parameters have significantly higher rates of testicular cancer and mortality rates compared to fertile men, and over 50% of male infertility cases stem from specific medical conditions with health implications beyond fertility 2, 1
Do not rely on a single semen analysis – at least two properly performed semen analyses at least one month apart are required to account for biological variability 1, 4
Do not assume normal semen analysis equals fertility – 25% of infertility cases remain unexplained despite normal conventional parameters 4
Ensure laboratory quality – many laboratories do not adhere to WHO standardized methods, leading to high variability and unreliable results 4
Goals of the Evaluation
The evaluation aims to identify: 1
- Potentially correctable conditions that can be treated medically or surgically
- Irreversible conditions amenable to assisted reproductive technologies using partner's sperm
- Irreversible conditions requiring donor sperm or adoption
- Genetic causes that affect treatment success or offspring health if assisted reproductive technologies are utilized