Performance of single serum progesterone in the evaluation of symptomatic first-trimester pregnant patients: a systematic review and meta-analysis

Objectives Pain and bleeding complicate 30% of pregnancies, raising concerns for viability. The objective is to evaluate the diagnostic characteristics of a single serum progesterone level in assessing pregnancy viability among symptomatic patients. Methods We conducted a predefined literature search in MEDLINE, Embase (OVID), CINAHL and Cochrane databases for studies that enrolled patients in first trimester with miscarriage symptoms, measured progesterone and reported pregnancy viability, from inception to July 2020. We extracted data for 2 × 2 tables, progesterone threshold levels and viability. We obtained summary estimates of sensitivity, specificity, Diagnostic Odds Ratio (DOR), and predictive values at given prevalence rates. Results We identified 54 publications. There was a total of 15,878 patients enrolled, of whom 7864 patients (49.5%) were confirmed to have a viable pregnancy and 8014 patients (50.5%) were confirmed to have a non-viable pregnancy. The cut-off value of progesterone ranged from 3.2 to 25 ng/mL (20.034–79.5 nmol/L). We evaluated the performance of the following progesterone cut-off categories: < 6.3, 6.3–12.6, 12.7–19.9, and 20–25 ng/mL. To detect non-viable pregnancy, progesterone with cut-off < 6.3 ng/mL had sensitivity 73.1%, specificity 99.2% and DOR 322.0 (PPV 0.91, 0.97 and 0.99 at prevalences 0.1, 0.25, 0.5, respectively, indicating higher likelihood of non-viable pregnancy), and cut-off category 20–25 ng/mL had sensitivity 91.3%, specificity 75% and DOR 31.4 (NPV 0.99, 0.96 and 0.89 at the prevalences above indicating higher likelihood of viable pregnancy). Conclusion A single progesterone level provides a clinically useful prognostic information on pregnancy viability. More than nine out of ten patients with a level < 6.3 ng/mL (< 20.034 nmol/L) will be diagnosed with a non-viable pregnancy, and more than 90% of patients with a level ≥ 20–25 ng/mL (63.6–79.5 nmol/L) will have a viable pregnancy confirmed.