When is human chorionic gonadotropin (hCG) and progesterone testing necessary?

When to Obtain hCG and Progesterone Testing

hCG and progesterone testing are necessary in cases of suspected pregnancy, pregnancy complications, gestational trophoblastic disease, and unexplained persistent low-level hCG, with specific timing and indications for each scenario.

Pregnancy Confirmation and Dating

• hCG testing is appropriate when pregnancy is suspected but not yet confirmed, especially when a woman has missed her period or has symptoms of early pregnancy 1
• Qualitative urine pregnancy tests can detect hCG at concentrations of 20-25 mIU/mL, but may not detect very early pregnancies or may remain positive for several weeks after pregnancy termination 1
• For more accurate results, serum hCG testing may be necessary, particularly when the timing of conception is uncertain 1
• Most qualitative pregnancy tests require an additional 11 days past the expected menses to detect 100% of pregnancies 1

Suspected Abnormal Pregnancy

• Combined hCG and progesterone testing is indicated when an abnormal pregnancy (ectopic pregnancy or spontaneous abortion) is suspected 2, 3
• A serum progesterone level below 30 nmol/L (approximately 10 ng/mL) combined with abnormal hCG increases has a high predictive value for pathological pregnancy 2
• Progesterone levels below 15 ng/mL can help differentiate between normal intrauterine pregnancy and abnormal intrauterine or ectopic pregnancy 4
• Serial hCG measurements (48 hours apart) are recommended when ectopic pregnancy is suspected, but a single progesterone measurement may provide earlier diagnostic information 3

Monitoring After Molar Pregnancy

• After diagnosis of hydatidiform mole (HM), serum hCG should be monitored at least once every 2 weeks until normalization 1
• For partial hydatidiform mole (PHM), one additional normal hCG value is required before discharge from monitoring 1
• For complete hydatidiform mole (CHM), monthly hCG monitoring for up to 6 months is recommended 1
• Plateauing or rising hCG levels after molar pregnancy treatment suggests development of gestational trophoblastic neoplasia (GTN) 1

Unexplained Persistent Low-Level hCG

• When unexplained persistent low-level hCG is detected, a structured diagnostic workup is necessary 1
• This includes:
  • Careful history taking to exclude exogenous hCG use 1
  • Ultrasound to exclude pregnancy or retained products of conception 1
  • Testing for assay-interfering molecules if urine hCG is negative 1
  • Measurement of additional tumor markers for germ cell tumors 1
  • Assessment of hormones to identify menopause/pituitary hCG 1
  • Evaluation of kidney function to exclude renal failure 1

Prenatal Screening

• hCG is used as part of multiple marker screening (MMS) for fetal aneuploidy, particularly Down syndrome and trisomy 18 1
• In most cases of Down syndrome, hCG levels are higher than normal 1
• In most cases of trisomy 18, hCG levels are lower than normal 1
• First trimester screening includes measurement of hCG (or free beta-hCG) along with pregnancy-associated plasma protein A (PAPP-A) and nuchal translucency (NT) measurement between 11-14 weeks gestation 1

Substance Use Disorder Screening

• hCG testing may be used to verify that a urine sample belongs to a pregnant woman when screening for substance use disorders 1
• If a human chorionic gonadotropin test result is negative in a known pregnant woman, a repeat sample should be requested 1

Contraception Initiation

• hCG testing is often performed before initiating contraception, but may not be necessary in all cases 1
• A healthcare provider can be reasonably certain a woman is not pregnant if she meets any of these criteria:
  • ≤7 days after the start of normal menses
  • Has not had sexual intercourse since the start of last normal menses
  • Has been correctly and consistently using a reliable contraceptive method
  • ≤7 days after spontaneous or induced abortion
  • Within 4 weeks postpartum
  • Fully or nearly fully breastfeeding, amenorrheic, and <6 months postpartum 1

Special Considerations

• The discriminatory level of hCG (level at which a gestational sac should be visible on transvaginal ultrasound) is approximately 3,000 mIU/mL 1
• If no gestational sac is visible with hCG ≥3,000 mIU/mL, a viable intrauterine pregnancy is unlikely 1
• For women with twin pregnancies comprising a complete hydatidiform mole with a normal cotwin, close monitoring with hCG is essential 1
• Progesterone testing is particularly valuable in early pregnancy when ultrasound cannot definitively diagnose the location or viability of a pregnancy 5

Pitfalls and Caveats

• False-positive and false-negative hCG results can occur due to assay-interfering molecules, sample adulteration, or improper timing 1
• hCG can remain detectable for several weeks after pregnancy termination (spontaneous or induced) 1
• Different hCG assays may have varying sensitivities and specificities; using the same laboratory for serial measurements is recommended 1
• Progesterone levels should be interpreted in conjunction with clinical findings and hCG results for optimal diagnostic accuracy 2, 3