Characterisation of serum progesterone and progesterone-induced blocking factor (PIBF) levels across trimesters in healthy pregnant women

Mark Kit Lim,John Carson Allen,Yin Hao Justin Lee,Thiam Chye Tan,Chee Wai Ku,Nguan Soon Tan

doi:10.1038/s41598-020-59452-y

Abstract

Progesterone-induced blocking factor (PIBF), which plays an important role in maintaining healthy pregnancies, has shown great promise as a prognostic biomarker for threatened miscarriage. To better characterise the physiological trends of progesterone and PIBF, we analysed serum progesterone and PIBF concentrations in healthy non-pregnant and pregnant women across trimesters. We saw increasing concentrations of progesterone and PIBF in pregnant women with advancing trimesters. The serum progesterone and PIBF percentiles across gestational age in healthy pregnancies can be used as a guide for the formulation of reference ranges. We also demonstrated a significant positive correlation between progesterone and PIBF levels. This study demonstrates increasing progesterone and PIBF concentrations in later trimesters and underscores the importance of progesterone and PIBF in healthy pregnancies. Characterisation of progesterone and PIBF across gestational age in healthy pregnant women may help to prognosticate pregnancy viability and support further research into the importance of progesterone and PIBF in the maintenance of healthy pregnancies.

Highlights

Progesterone and progesterone-induced blocking factor (PIBF) are important in the maintenance of healthy pregnancies
A plethora of miscarriage biomarkers, including human chorionic gonadotropin, progesterone, cancer antigen 125 (CA-125), inhibin A, activin A, pregnancy-associated plasma protein-A (PAPP-A) and kisspeptin have been proposed as tools to assess pregnancy viability[27,28,29]
Demographic variables collected from the participants (gestational age by ultrasound scan at recruitment, maternal age, body mass index (BMI), history of previous miscarriage, current smoker, and current alcohol drinker) were compared across the 4 subgroups (Table 1)

Summary

Introduction

Progesterone and progesterone-induced blocking factor (PIBF) are important in the maintenance of healthy pregnancies. Progesterone-induced blocking factor (PIBF), a protein comprising of 757 amino acid residues with a predicted molecular mass of 89 kDa, is important in the maintenance of human pregnancy and the progesterone dependent immunomodulation by the mother[1]. A study reported that the use of anti-NK or anti-natural cytotoxic antibodies led to the reversal of the phenomenon of fetal resorption in mice with depleted PIBF, supporting the importance of PIBF in www.nature.com/scientificreports modulating NK cell activity and thereby ensuring healthy pregnancies[18]. The presence of vaginal bleeding is associated with a 2.6 times higher incidence of fetal loss[25], and causes substantial anxiety and stress for the expectant mother[24,26]. A plethora of miscarriage biomarkers, including human chorionic gonadotropin (hCG), progesterone, cancer antigen 125 (CA-125), inhibin A, activin A, pregnancy-associated plasma protein-A (PAPP-A) and kisspeptin have been proposed as tools to assess pregnancy viability[27,28,29]

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Conclusion