Initial Infertility Laboratory Evaluation
Both partners require concurrent evaluation after 12 months of unprotected intercourse (or 6 months if female partner >35 years), with the male partner undergoing at least two semen analyses one month apart and the female partner receiving ovulation assessment, while couples should be evaluated immediately if known risk factors exist. 1
When to Initiate Evaluation
- Standard timing: Begin evaluation after 12 consecutive months of regular unprotected intercourse without conception 1
- Expedited evaluation (6 months or less) is warranted when:
- Female partner is 35-40 years old 1, 2
- Female partner is >40 years (immediate evaluation recommended) 2
- Male infertility risk factors present (history of cryptorchidism, varicocele, prior chemotherapy) 1
- Known female factors exist (irregular cycles, history of pelvic inflammatory disease, endometriosis) 1, 2
- Immediate evaluation should occur after just 5 unsuccessful ovulation cycles when either partner has identifiable risk factors 3
Male Partner Initial Laboratory Workup
Essential Testing
Two semen analyses performed at least one month apart are mandatory, as semen parameters fluctuate substantially between tests 1, 3
Semen Collection Protocol:
- Abstain from sexual activity for 2-3 days before collection 1
- Collect via masturbation or specialized collection condoms 1
- If collected at home, maintain at room/body temperature and examine within 1 hour 1
- Must be performed in a specialized andrology laboratory (point-of-care/mail-in tests are insufficient for comprehensive evaluation) 1
WHO Reference Parameters to Assess:
- Volume: 1.5-5.0 mL 1
- pH: >7.2 1
- Sperm concentration: >20 million/mL (or >15 million/mL per 2021 WHO criteria) 1
- Total motility: progressive and non-progressive movement 1
- Morphology: normal forms percentage 1
Reproductive History Components
Document the following specific elements 1, 4:
- Frequency and timing of intercourse 1
- Prior fertility history and duration of current infertility 1
- Childhood illnesses (mumps orchitis, cryptorchidism) and developmental history 1
- Systemic illnesses, previous surgeries (hernia repair, testicular surgery) 1
- Sexual history including sexually transmitted infections 1
- Gonadotoxin exposures: heat (saunas, hot tubs, laptop use), anabolic steroids, chemotherapy, radiation 1, 3
- Prescription medications (testosterone, finasteride, SSRIs) and recreational drug use 1
- Family reproductive history 1
Physical Examination Findings
The genital examination must include 1, 4:
- Penile examination with urethral meatus location 1
- Testicular measurement and palpation (normal volume 15-25 mL; small testes <15 mL suggest impaired spermatogenesis) 1
- Presence and consistency of vas deferens and epididymides (bilateral absence of vas deferens can be diagnosed on exam) 1
- Varicocele assessment (present in 15-20% of infertile men) 1, 3
- Secondary sex characteristics: body habitus, hair distribution, breast development (gynecomastia suggests hormonal abnormality) 1
- Digital rectal examination 1
When to Order Additional Male Testing
Hormonal evaluation (FSH, LH, testosterone, prolactin) is indicated when 1, 3:
- Sperm concentration <10 million/mL 3
- Abnormal testicular size or consistency on exam 1
- Clinical signs of hypogonadism 1
Genetic testing (karyotype and Y-chromosome microdeletion analysis) is mandatory before ICSI when 1, 3:
- Azoospermia (no sperm in ejaculate) 1, 3
- Severe oligospermia (<5 million/mL) 3
- Recurrent pregnancy loss (≥2 losses) 1
Sperm DNA fragmentation testing should be considered in 1:
Female Partner Initial Laboratory Workup
Ovulation Assessment
Day 21 serum progesterone (or 7 days before expected menses in irregular cycles) confirms ovulation 5, 6:
- Progesterone >3 ng/mL indicates ovulation occurred 5
- If anovulation suspected, measure TSH and prolactin 2, 6
Ovarian Reserve Testing
Assess ovarian reserve, particularly in women ≥35 years 2, 6:
- Day 3 FSH and estradiol levels 2
- Anti-Müllerian hormone (AMH) 2
- Antral follicle count via transvaginal ultrasound 2
Structural Assessment
Hysterosalpingography (HSG) evaluates uterine cavity and tubal patency in women with 2, 5:
- No risk factors for tubal disease 5
- No history of pelvic inflammatory disease, endometriosis, or ectopic pregnancy 5
Laparoscopy or hysteroscopy is recommended instead of HSG when 5, 6:
Female History and Physical Examination
Medical history must document 4, 2:
- Menstrual cycle characteristics (regularity, duration, flow) 4
- Prior pregnancies and outcomes 4
- Previous pelvic surgeries or infections 4
- Current medications 4
Physical examination includes 4:
- Height, weight, BMI calculation (obesity affects fertility) 4, 6
- Thyroid examination 4
- Clinical breast examination 4
- Pelvic examination assessing uterine size/position, adnexal masses, signs of endometriosis 4
Critical Clinical Pitfalls
Do Not Skip Male Evaluation
- Male factor contributes to 40-50% of couple infertility 2, 7
- Over 50% of male infertility cases stem from medical conditions with health implications beyond fertility 3, 4
- Men with abnormal semen parameters have significantly higher rates of testicular cancer and overall mortality 3, 4
- Without adequate male workup, female partners may pursue unnecessary, costly, invasive treatments 1
Refer Appropriately
Immediate referral to male reproductive specialist when 3:
- Any abnormal semen parameters on two analyses 3
- Azoospermia or severe oligospermia 3
- Abnormal physical examination findings 1
Consider subspecialty referral for 5, 7:
- Tubal obstruction requiring surgical intervention 5
- Unexplained infertility after initial workup 5, 7
- Women >38-40 years (may proceed directly to IVF) 7
Avoid Home Testing Reliance
Point-of-care and mail-in semen tests provide limited information and cannot substitute for specialized andrology laboratory analysis 1