Diagnostic Workup for Infertility - Female
The diagnostic workup for female infertility is a systematic evaluation aimed at identifying the potential causes of a woman’s inability to conceive after 12 months of regular, unprotected intercourse (or after 6 months if the woman is over 35). It generally includes a detailed medical history, physical examination, and targeted diagnostic tests to assess ovulation, ovarian reserve, tubal patency, and uterine structure.
History and Physical Examination
A detailed medical history is a cornerstone in the investigation of infertility for both partners. It provides crucial insights that guide the diagnostic process, identify potential underlying causes, and help tailor appropriate treatment options.
Components of a female medical history should include:
- Menstrual history: age at first menstrual period, cycle length, regularity, flow, dysmenorrhea.
- Obstetric history: previous pregnancies, outcomes, complications.
- Medical/surgical history: medications, thyroid disorders, diabetes, STIs, pelvic surgeries.
- Lifestyle factors: weight & BMI, smoking, alcohol, drug use, exercise, stress.
- Sexual history: frequency, timing, dyspareunia, lubricants used.
- Family history: fertility issues, miscarriages, early menopause, reproductive disorders.
A thorough medical history doesn't just check boxes—it’s about seeing the full picture. It directs further testing (hormonal, imaging, semen analysis), avoids unnecessary procedures, and ensures a more effective and personalized approach to fertility care.
Laboratory and Hormonal Evaluation
Laboratory testing of hormone levels in the blood is a key initial step in the diagnostic process. Many hormones fluctuate during the menstrual cycle, so appropriate timing of the tests is very important.
Lab tests to evaluate ovarian reserve and hypothalamic-pituitary-ovarian function:
- Follicle-stimulating hormone (FSH) - cycle day 2 or 3
- Luteinizing hormone (LH) - cycle day 2 or 3
- Estradiol (a form of estrogen) - cycle day 2 or 3
- Anti-Müllerian hormone (AMH) - independent of cycle day
- Prolactin (a pituitary hormone): independent of cycle day, but should be drawn early morning
- Thyroid function tests (TSH): independent of cycle day
- Serum progesterone (day 21 of a 28-day cycle)
Additional tests for specific conditions:
- Androgens (e.g., testosterone, DHEAS, androstenedione)
- Insulin and glucose levels
- Lipid panel
- Thyroid function tests (T3, T4)
- Infectious disease testing
Imaging and Structural Assessment
Evaluating the uterus, fallopian tubes, and ovaries is an essential part of the diagnostic process to identify any structural or functional issues that may affect conception.
- Transvaginal ultrasound: checks for ovarian cysts, fibroids, endometrial thickness.
- HSG: Hysterosalpingogram (HSG): X-ray with contrast to assess the uterine cavity for any defects and to determine patency (openness) of the fallopian tubes.
- Sonohysterogram (saline infusion ultrasound): alternative to HSG for uterine evaluation.
Additional investigations may be recommended for specific conditions. These procedures are more invasive, involving out-patient surgery, therefore, not typically a part of an initial infertility workup.
- Hysteroscopy: direct visualization of the uterine cavity if intrauterine pathology suspected.
- Laparoscopy: indicated if endometriosis, pelvic adhesions, or unexplained infertility is suspected.
Assessment of Ovulation
Ovulation is a key part of the menstrual cycle, but it doesn’t happen in every cycle or for every individual, even with “regular” menstrual cycles. Therefore, it is important to confirm that ovulation is taking place, at the appropriate time in the cycle, and that a healthy egg is being released.
- Serum progesterone – (day 21 of a 28-day cycle): blood test to confirm ovulation
- Ovulation predictor kits (urinary LH surge): over-the-counter kits with 5-7 days of testing supplies; urine is checked daily to determine when the “LH surge” occurs (indicating pending ovulation).
- Transvaginal ultrasound : sequential scans can document probable ovulation based on the appearance of follicles pre- and post-ovulation
Additional Tests
After a general evaluation (history and physical exam, basic labs, structural assessments), specialized tests may be recommended to further assess potential causes. These tests are typically ordered based on clinical suspicion.
- Endometrial biopsy: rare, may be used to assess luteal phase defect, suspected uterine infections, or recurrent pregnancy loss.
- Genetic testing: in cases of premature ovarian insufficiency, recurrent pregnancy loss, or family history of genetic disorders.
- Antiphospholipid antibodies: if there's a history of recurrent miscarriage
Diagnostic Workup for Infertility - Male
Male infertility refers to a man’s inability to cause pregnancy in a fertile female after one year of regular, unprotected sexual intercourse. The diagnostic workup for a male patient with infertility is a structured process aimed at identifying potential causes and guiding treatment. It generally includes a detailed medical history, physical examination, and targeted diagnostic tests to assess semen and sperm parameters, hormone levels, and structural integrity of the male reproductive tract.
History and Physical Examination
A detailed medical history is a cornerstone in the investigation of infertility for both partners. It provides crucial insights that guide the diagnostic process, identify potential underlying causes, and help tailor appropriate treatment options.
Components of a male medical history should include:
- Duration of infertility: length of time trying to conceive with current partner, any previous pregnancies caused
- Sexual history: frequency, timing, erectile/ejaculatory function
- Medical history: infections (e.g., mumps orchitis), trauma, surgeries
- Medications: testosterone, steroids, chemotherapy, all current or recent prescribed medications
- Lifestyle factors: smoking, alcohol, drug use, hot baths, tight underwear
- Family history: infertility, genetic disorders, cystic fibrosis
A thorough physical exam, typically performed by a urologist who specializes in male infertility, should include:
- General habitus assessment (e.g., gynecomastia, body hair, height and weight)
- Secondary sexual characteristics
- Genital exam:
- Testicular size and consistency
- Epididymis and vas deferens (congenital absence?)
- Varicocele (palpable, especially with Valsalva)
Semen Analysis
A semen analysis is a cornerstone diagnostic tool in the evaluation of male infertility. It provides critical insights into a man's reproductive potential by assessing various parameters of the ejaculate. It should be performed after 2–7 days of abstinence. If a second analysis is recommended, usually due to an abnormal result on the initial test, it should be scheduled after a minimum two-week interval.
World Health Organization (WHO) normal ranges are given below. Lab-specific ranges for the EIS andrology laboratory are determined by our laboratory director.
WHO Reference Ranges (2021):
- Volume: ≥ 1.4 mL
- Sperm concentration: ≥ 16 million/mL
- Total motility: ≥ 42%
- Progressive motility: ≥ 30%
- Morphology (normal forms): ≥ 4%
Abnormal results may prompt further evaluation, described below under Additional Testing.
Hormonal Evaluation
Blood hormone levels are ordered when the patient exhibits: abnormal semen analysis parameters, signs of hypogonadism, or an abnormal testicular exam. Hormones to be tested include:
- FSH, LH, Testosterone
- Prolactin, Estradiol, TSH
- Sex hormone binding globulin (SHBG)
Additional Testing (as indicated)
- Scrotal Ultrasound
- Varicocele
- Testicular lesions or abnormalities
- Genetic Testing
- Karyotype: if azoospermia/severe oligospermia; recurrent pregnancy loss in the partner
- Y-chromosome microdeletion (YCMD) analysis: to detect deletions on the Y chromosome
- CFTR gene testing: if congenital bilateral absence of vas deferens (CBAVD)
- DNA Fragmentation Testing: to assess sperm DNA integrity
- Post-ejaculate Urinalysis: If retrograde ejaculation is suspected (semen enters the bladder instead of exiting through the urethra during ejaculation.
- Transrectal Ultrasound (TRUS): if obstruction is suspected in the ejaculatory ducts or seminal vesicles