Relationship between relaxin-2 levels in serum and mode of conception in twin gestations: a prospective cohort study

Aim: Relaxin is a peptide hormone commonly associated with pregnancy when it is thought to play a role in modulating various physiological processes to optimize maternal-fetal adaptation. In twin pregnancies these adaptive requirements are higher than in singleton pregnancies, therefore it is important to understand how circulating relaxin behaves in such conditions. This prospective cohort study aims to determine the serum relaxin-2 levels throughout gestation in twin pregnancies and to investigate its association with the mode of conception. Methods: Blood samples were collected during each trimester of gestation from 26 women with twin pregnancies obtained through spontaneous conception (SC, n=18) or assisted reproductive technologies, specifically through intracytoplasmic sperm injection (ART, n=8). Serum relaxin-2 levels were measured by a highly sensitive ELISA method. Results: The results indicated that serum relaxin-2 level peaks in the first trimester (491.05±207.41 pg/ml), then significantly decreases in the second trimester (446.27±180.4 pg/ml; p<0.023) and in the third trimester (422.19±194.30 pg/ml; p<0.048). Interestingly, the serum relaxin-2 level was higher in the spontaneous conception group with respect to the assisted reproductive technologies group (p<0.001), when measured at each trimester of gestation. In addition, the multivariate regression analysis showed that only the assisted reproductive technologies had a significant impact on serum levels of relaxin-2 (p<0.001), and no significant association was found with other women’s clinical and demographic characteristics. Conclusions: These findings extend the current knowledge about the pattern of circulating relaxin-2 throughout gestation in twin pregnancies, providing a sensitive measurement of serum relaxin-2 levels and a description of its putative physiological roles in humans.