Gestational age-specific normative values and determinants of serum progesterone through the first trimester of pregnancy

Abstract BACKGROUND: Progesterone is a steroid hormone that is critical for implantation and maintenance of pregnancy, with low levels being associated with a significantly higher miscarriage risk. Despite its pivotal role, especially during early pregnancy, reference range studies of serum progesterone are predominantly trimester-specific with wide ranges that are not clinically useful. Although it is established that serum progesterone exhibits an overall increasing trend during pregnancy, little is known about its trajectory during early pregnancy. We sought to find the gestational age-specific normative values and trajectory of serum progesterone, and its associated maternal and fetal factors, during the first trimester of a viable low-risk pregnancy.METHODS: A prospective cohort study was conducted at KK Women’s and Children’s Hospital from 1 April 2012 to 31 January 2018, recruiting 590 women with a single intrauterine low-risk pregnancy, presenting at antenatal clinics between gestational weeks 5 to 12. Gestational age-specific normative values and trajectory of serum progesterone were determined via quantile regression. Maternal and fetal characteristics that influence normative values of serum progesterone were determined via univariable analyses followed by multivariable regression. RESULTS: Serum progesterone showed an increasing trend during the first trimester of a viable low-risk pregnancy, with a transient decline between gestational weeks 6 to 8 corresponding to the luteal-placental shift. Lowest levels were seen at week 7 (mean serum progesterone of 75.0 nmol/L at week 5 versus 63.4 nmol/L at week 7, p=0.029; 63.4 nmol/L at week 7 versus 78.0 nmol/L at week 9, p<0.001). In a multivariable logistic regression, gestational age, maternal age, maternal body mass index at presentation, parity and fetal gender were found to be associated with progesterone levels, explaining 18.8% of the variability. CONCLUSIONS: Our study described the gestational age-specific normative values and increasing trajectory of serum progesterone, with a physiological decline during weeks 6 to 8 of gestation. This forms the basis for future work on pathological levels of serum progesterone that may lead to miscarriage. Larger studies are also required to investigate the need for normative values to be developed, and personalized to account for maternal BMI, parity and fetal gender.