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

Chee Wai Ku,Truls Østbye,Xiaoxuan Zhang,John Carson Allen,Valencia Ru-Yan Zhang,Nguan Soon Tan,Thiam Chye Tan

doi:10.1038/s41598-021-83805-w

Abstract

Progesterone is a steroid hormone that is critical for implantation and maintenance of pregnancy, and low levels are associated with higher miscarriage risk. However, little is known about its trajectory during early pregnancy. We sought to determine the gestational age-specific normative values of serum progesterone on a week-by-week basis, and its associated maternal and fetal factors, during the first trimester of a viable low-risk pregnancy. A cross-sectional study was conducted at KK Women’s and Children’s Hospital from 2013 to 2018. 590 women with a single viable intrauterine low-risk pregnancy, between gestational weeks 5 and 12, were recruited. Serum progesterone showed an increasing trend during the first trimester, with a transient decline between gestational weeks 6–8, corresponding to the luteal–placental shift. Lowest levels were seen at week 7. Maternal age, BMI, parity, gestational age and outcome of pregnancy at 16 weeks’ gestation were found to be associated with progesterone levels. Normative values of serum progesterone for low-risk pregnancies would form the basis for future work on pathological levels of serum progesterone that may increase risk of miscarriage. Larger studies are required to validate these normative values, and personalize them to account for maternal age, BMI, parity and gestational age.

Highlights

Progesterone is a steroid hormone that is critical for implantation and maintenance of pregnancy, and low levels are associated with higher miscarriage risk
This period has been determined by earlier studies where corpus luteum removal prior to week 7 of gestation resulted in an immediate fall in serum progesterone levels and eventual miscarriage, while corpus luteum removal after week 9 of gestation resulted in pregnancy survival[9,10]
Serum progesterone level started to decline after gestation week 5, reaching a nadir at week 7 [mean serum progesterone in week 5 = 75.0 nmol/L, compared to 66.9 nmol/L in week 6 (p = 0.057), and 63.4 nmol/L in week 7 (p = 0.029)]

Summary

Introduction

Progesterone is a steroid hormone that is critical for implantation and maintenance of pregnancy, and low levels are associated with higher miscarriage risk. We sought to determine the gestational age-specific normative values of serum progesterone on a week-by-week basis, and its associated maternal and fetal factors, during the first trimester of a viable low-risk pregnancy. Luteal-placental shift, and it occurs between weeks 6 and 8 of gestation This period has been determined by earlier studies where corpus luteum removal prior to week 7 of gestation resulted in an immediate fall in serum progesterone levels and eventual miscarriage, while corpus luteum removal after week 9 of gestation resulted in pregnancy survival[9,10]. A few studies have suggested a trajectory where progesterone level starts decreasing around gestational week 5, reaching a nadir between weeks 6 and 8 corresponding to the luteal-placental shift, before increasing thereafter[11,12]. These studies are limited by small sample sizes as well as generalizability, for example by including only anovulatory women who conceived after induction of ovulation with gonadotrophins

Objectives

Results

Discussion

Conclusion