Serum progesterone may guide management of pregnant women at risk of miscarriage

Serum progesterone levels appear to be a strong prognostic factor in pregnant women with threatened miscarriage, according to a recent Singapore study.

“By using a novel approach that incorporates spot serum progesterone measurement at presentation to triage women with threatened miscarriage and guide subsequent management, this study provides early evidence of an effective and safe clinical protocol,” researchers said.

Of 1,087 pregnant women with threatened miscarriage, 77.9 percent (n=847; mean age, 30.8 years) had serum progesterone levels ≥35 nmol/L. The remaining (n=240; mean age, 31.8 years) had concentrations below this value and were designated as the high-risk group. Clinically, body mass index (BMI) was significantly elevated in the latter group (p=0.006). [Sci Rep 2020;10:9153]

A total of 251 participants experienced spontaneous miscarriages before 16 weeks of gestation, resulting in an incidence rate of 23.1 percent.

This occurred significantly more frequently among the high-risk mothers (70.8 percent vs 9.6 percent; p<0.001) even despite being treated with progestogens. Conversely, the rate of ongoing pregnancy was significantly lower in the high-risk group (29.2 percent vs 90.4 percent; p<0.001).

Comparisons of serum concentrations further showed the importance of serum progesterone. In a subgroup analysis of high-risk mothers, mean levels were significantly lower among those who miscarried than in those with ongoing pregnancies (18.0 vs 27.5 nmol/L; p<0.001). The same was true for the low-risk mothers (59.4 vs 65.7 nmol/L; p=0.028).

The researchers also found that there was no need for oral progestogens in low-risk mothers. Withholding such treatment in this group led to a 78-percent drop in progestogen medication use without triggering a significant spike in the miscarriage rate.

Logistic regression analysis validated the principal findings. In the high-risk group, each unit increase in serum progesterone reduced the risk of miscarriage by approximately 20 percent (odds ratio [OR], 0.80, 95 percent confidence interval [CI], 0.75–0.85; p<0.001).

The effect of progestogen was also significant in the low-risk group, but of only minimal magnitude (OR, 0.976, 95 percent CI, 0.96–0.99; p=0.003). In these women, maternal age appeared to be the strongest predictor of miscarriage (OR, 1.124, 95 percent CI, 1.06–1.19; p<0.001).

Notably, 13 high-risk participants refused treatment with oral progestogens. While they were excluded from the quantitative analyses, researchers reported that all of them miscarried.

“In the high-risk cohort of women, higher serum progesterone was protective against miscarriage,” the researchers said. “This has far-reaching clinical implications, because it establishes a safe clinical protocol that can be readily adapted for use in other healthcare institutions with only a single serum progesterone test.”

“Patients with high serum progesterone levels can be reassured and counselled without medical treatment, while patients with low serum progesterone levels have high risk of miscarriage even with treatment,” they added.