When should progesterone levels be checked?

When to Check Progesterone Levels

Progesterone levels should be checked in women with singleton pregnancies and prior spontaneous preterm birth (SPTB) at 16-20 weeks gestation, and in women with singleton pregnancies without prior SPTB but with short cervical length (≤20 mm) at 18-24 weeks gestation. 1

Indications for Progesterone Level Testing

Preterm Birth Prevention

• For women with singleton pregnancies and history of prior spontaneous preterm birth (SPTB), progesterone levels should be checked at 16-20 weeks gestation before initiating 17-alpha-hydroxyprogesterone caproate (17P) therapy 1
• For women with singleton pregnancies without prior SPTB but with short cervical length (≤20 mm) identified on transvaginal ultrasound at 18-24 weeks, progesterone levels should be checked before starting vaginal progesterone therapy 1

First Trimester Pregnancy Viability Assessment

• Serum progesterone can be used as a diagnostic tool in symptomatic first-trimester pregnant patients with pain or bleeding to assess pregnancy viability 2, 3
• A single progesterone level <6.3 ng/mL (<20.034 nmol/L) has high specificity (99.2%) for non-viable pregnancy, while levels ≥20-25 ng/mL (63.6-79.5 nmol/L) are associated with viable pregnancies (91.3% sensitivity) 3

Threatened Miscarriage

• In women presenting with threatened miscarriage, progesterone levels should be checked as they are typically about 10 nmol/L lower than in normal pregnancies at the same gestational age 2
• Progesterone levels below 10 ng/mL prior to 10 weeks gestation indicate subnormal corpus luteum function and may warrant hormone treatment in patients with bleeding in early pregnancy 4

Timing of Progesterone Testing

For Preterm Birth Prevention

• 16-20 weeks gestation for women with prior SPTB 1
• 18-24 weeks gestation for women undergoing cervical length screening 1

For Pregnancy Viability Assessment

• As early as 14 days post-oocyte retrieval in IVF/ICSI cycles (approximately 4 weeks gestation) 5
• Between 5-13 weeks gestation for women with threatened miscarriage symptoms 2

Interpretation of Progesterone Levels

• Normal progesterone levels increase linearly from approximately 57.5 nmol/L at 5 weeks to 80.8 nmol/L at 13 weeks gestation in normal pregnancies 2
• A transient decline in progesterone levels may be observed between 6-8 weeks gestation, corresponding to the luteal-placental shift, with lowest levels typically seen at week 7 6
• In IVF/ICSI cycles, women with ongoing pregnancies at 8 weeks typically have significantly higher serum progesterone levels (median: 430 nmol/L) compared to those with abnormal pregnancies (72 nmol/L) 5

Clinical Pitfalls and Caveats

• Progesterone testing should be performed with proper technique to yield accurate results, with quality control and monitoring 1
• Maternal factors including age, BMI, and parity can influence progesterone levels and should be considered when interpreting results 6
• For women receiving exogenous progesterone supplementation, timing of blood collection relative to administration can affect measured levels 5
• In artificial cycles for frozen embryo transfer, progesterone supplementation begins on the day of endometrial transformation and should be continued for 3-4 weeks after pregnancy confirmation 1

Treatment Based on Progesterone Levels

• For women with singleton pregnancies and prior SPTB: 17P 250 mg IM weekly from 16-20 weeks until 36 weeks 1
• For women with singleton pregnancies without prior SPTB but with short cervical length (≤20 mm): vaginal progesterone 90-mg gel or 200-mg suppository daily from diagnosis until 36 weeks 1
• For threatened miscarriage with low progesterone: oral progesterone 400 mg daily may be considered, although evidence is less robust than for vaginal administration 7