Urine Pregnancy Test

The urine pregnancy test detects human chorionic gonadotrophin (hCG) in urine by lateral flow immunoassay, using two antibodies against the beta subunit (or intact hCG).

Most tests detect hCG at 20 to 25 IU/L (some at 10 IU/L, and some at 50 to 100 IU/L), and are positive from about 10 to 14 days after conception (at the time of the expected period or 1 day after, in most cases), with 97 to 99% sensitivity from the first day of a missed period and specificity over 99%. A semi-quantitative or digital test can display weeks since conception from the hCG level.

Serum hCG (qualitative or quantitative) is more sensitive (detecting 1 to 5 IU/L from 8 to 11 days after ovulation) and is required for ectopic pregnancy, trophoblastic disease, and assisted conception.

hCG is produced by syncytiotrophoblast, doubles every 48 to 72 hours in the first 6 weeks in early viable pregnancy (rise of at least 49% in 48 hours for initial values under 1500 IU/L), peaks at 8 to 11 weeks (up to 100 000 IU/L), and falls to a plateau of 10 000 to 30 000 IU/L in the second half. About 3 to 4% of women of reproductive age are pregnant at any time.

Pregnancy testing precedes many investigations, drug prescriptions and radiological procedures, and is the first step in suspected ectopic pregnancy, which affects 1 to 2% of pregnancies and remains a leading cause of first trimester maternal death.

Indications. Missed period or suspected pregnancy. Abdominal pain, vaginal bleeding or collapse in a woman of reproductive age. Before imaging with ionising radiation, surgery, anaesthesia, and teratogenic or contraindicated drugs (warfarin, methotrexate, isotretinoin, valproate, mycophenolate, ACE inhibitors). Before starting contraception or insertion of an intrauterine device.

Infertility assessment and assisted reproduction. Follow up after miscarriage, termination or molar pregnancy. Unexplained amenorrhoea or abnormal bleeding. Hyperemesis. Screening in adolescents and sexual assault. Gestational trophoblastic disease monitoring uses serum hCG.

Specimen. First morning urine (the most concentrated, with highest hCG) or any random urine in a clean container, tested promptly. Dip the strip or apply drops to the cassette and read at the time stated by the manufacturer (usually 3 to 5 minutes, and not after 10 minutes). Avoid very dilute urine in early testing. Internal control line must appear for the result to be valid. Serum or plasma for laboratory tests.

Reference values. Negative in non-pregnant women (hCG under 5 IU/L in serum), and in men. Positive in pregnancy.

Interpretation.

• Positive test (two lines): pregnancy is very likely (positive predictive value over 99%). Site and viability need confirmation by ultrasound (intrauterine gestational sac at 4.5 to 5 weeks, yolk sac at 5 to 6 weeks, foetal heart activity at about 6 weeks by transvaginal scan).
• Negative test with a missed period: repeat after 3 to 7 days, or check serum hCG, since very early pregnancy, dilute urine or late ovulation can cause false negatives.
• Positive test with no intrauterine pregnancy on scan and serum hCG over the discriminatory zone (1500 to 3500 IU/L): pregnancy of unknown location, ectopic pregnancy until proven otherwise.
• Positive test with pain and bleeding: threatened or incomplete miscarriage, ectopic pregnancy, or molar pregnancy. Serial serum hCG showing a plateau or abnormal rise (under 35 to 49% in 48 hours) suggests non-viable or ectopic pregnancy, while a fall suggests resolving miscarriage.
• Persisting positive test after miscarriage, termination or delivery: hCG is cleared over 2 to 4 weeks (up to 6 weeks), and persistent or rising levels suggest retained products, gestational trophoblastic disease or a new pregnancy.
• Positive test in a man or non-pregnant woman: hCG-secreting tumours (germ cell tumours, trophoblastic tumours, some lung, gastric or ovarian cancers), pituitary hCG in perimenopause, heterophile antibodies, or false positive.
• Very high hCG (over 100 000 IU/L) with uterine size greater than dates, bleeding and hyperemesis: molar pregnancy, confirmed by ultrasound and histology.

Critical values and findings needing immediate action.

• Positive test with severe abdominal pain, shoulder tip pain, syncope, hypotension, tachycardia or peritonism: ruptured ectopic pregnancy, resuscitation, blood and surgery without delay.
• Positive test with vaginal bleeding and haemodynamic instability: miscarriage with haemorrhage, evacuation and resuscitation.
• Positive test in a woman on teratogenic drugs, with contraindicated imaging or surgery scheduled: stop or change drugs, discuss options, and review urgently.
• Positive test with severe vomiting, dehydration and electrolyte disturbance (hyperemesis): admission and fluids.
• Positive test with bleeding and a very high hCG: molar pregnancy, with referral to a trophoblastic disease centre.
• Rhesus negative woman with bleeding in pregnancy: anti-D immunoglobulin after 12 weeks, or earlier with significant bleeding or surgery.

Interferences and pitfalls.

• Testing too early (before the first day of missed period) gives false negatives, and low sensitivity tests (50 to 100 IU/L) fail in early pregnancy.
• Dilute urine, high fluid intake, and testing in the afternoon reduce sensitivity.
• High dose hook effect: very high hCG (over 500 000 IU/L, such as molar pregnancy or choriocarcinoma, or late second trimester) can overwhelm the antibodies and produce a false negative; dilute the urine 1 in 10 or test serum with dilution.
• Variant forms of hCG (hyperglycosylated, free beta, nicked) are not detected equally by all tests, and tests that miss free beta subunit give false negatives in trophoblastic disease.
• False positives: recent hCG injection (up to 10 to 14 days after 5000 to 10 000 IU), hCG-secreting tumours, heterophile antibodies (more in serum than urine), haematuria and proteinuria in some tests, and chemical (biochemical) pregnancy.
• Chemical pregnancy (very early loss): positive test followed by a normal or late period, in up to 20 to 25% of conceptions.
• Medications usually do not interfere (the contraceptive pill, antibiotics, analgesics), though some fertility drugs do.
• Evaporation lines and misreading after the stated time cause errors; a faint line is read as positive and repeated in 2 days.
• Menopausal women have low pituitary hCG that can reach 14 IU/L in serum, which rarely causes a positive urine test.
• Pregnancy cannot be dated by urine tests; ultrasound gives gestational age.

Special groups.

• Adolescents and young women: confidentiality and counselling, and routine screening before treatment.
• Women with irregular cycles, breastfeeding or on contraception: late ovulation, so negative results need repetition.
• Women with ectopic risk factors (previous ectopic pregnancy, tubal surgery, pelvic inflammatory disease, intrauterine device, assisted conception): early scan and serum hCG.
• Post-menopausal women and men: investigation of positive test for tumour.
• Regions: urine tests are often the only available test in primary care, and early pregnancy services and ultrasound are limited in many settings, so training in danger signs matters.

Follow up tests. Serum quantitative hCG (repeated at 48 hours), transvaginal ultrasound, blood group and Rhesus type, full blood count and ferritin, haemoglobin, rubella and HIV, syphilis and hepatitis B screening, urine culture, thyroid function in hyperemesis, glucose tolerance test as risk requires, progesterone in threatened miscarriage with uncertainty, histology of evacuated tissue, and serum hCG surveillance after molar pregnancy.