Serum relaxin levels are reduced in pregnant women with a history of recurrent miscarriage, and correlate with maternal uterine artery Doppler indices in first trimester

Abstract

CondensationSerum relaxin levels are reduced in pregnant women with a history of recurrent miscarriage, and correlate with maternal uterine artery Doppler indices in first trimester. 3 ABSTRACTObjectives: Defective implantation is a mechanism for recurrent pregnancy loss (RPL). We sought to determine whether the serum expression of human relaxin 2 (RLX) is impaired in women with a history of RPL.Study Design: Employing a prospective case-controlled design we studied 20 pregnant women with a history of RPL and 20 age-matched women with no history of RPL (NRPL). We measured serum relaxin 2 levels by ELISA at 6-8, 10-12, 20, 34 wks gestation and in cord blood, and maternal uterine artery Doppler resistance index (RI) at ≥ 10 wks gestation.Results: Relaxin rose to a peak at 12 wks, and gradually declined towards term. At all gestations, women with a history of RPL had lower RLX levels than women without. At 10-12 wks uterine artery, uterine artery RI correlated with serum RLX for both RPL and NRPL and the presence of a notched waveform in the NRPL group was associated with higher RLX levels than the absence of a notch (mean 2.1 vs.1.3ng/ml, P < 0.05 respectively), and also at 20 wks (2.1 vs. 0.95 ng/ml, P < 0.05 respectively), but did not differ in the RPL group. Umbilical venous RLX was 4-fold higher in the RPL group than the NRPL group. Conclusion.Women with a history of RPL demonstrate attenuated levels of serum RLX across all pregnancy trimesters. How dysregulated RLX metabolism may contribute to adverse pregnancy outcome in RPL requires further investigation.

Imbalanced Angiogenesis in Peripartum Cardiomyopathy ― Diagnostic Value of Placenta Growth Factor ―

“…Interestingly, plasma concentrations of relaxin-2 have been shown to be very high during normal human pregnancy (ranging between 500 and 1,500 pg/mL), with peak values in the first trimester that decline in the second and third trimesters. 16 This observation is consistent with the markedly increased production of relaxin from gestational tissue. Outside of pregnancy, as demonstrated in the present study, plasma relaxin concentrations decline sharply and are primarily derived from non-gestational tissue, such as the myocardium.…”

Circulating levels of matrix proteases and their inhibitors in pregnant women with and without a history of recurrent pregnancy loss

“…Serum samples had been obtained and aliquoted at 6-8, 10-12, 20, and 34 weeks gestation during a previous study [9]. We excluded women who smoked cigarettes from the study.…”

“…We excluded women who smoked cigarettes from the study. Sample sizes were determined as previously described [9]. We estimated that the 20 subjects in each study arm would detect a 10% difference in MMP and TIMP levels between groups with 80% power at the 95% confidence level.…”

“…We have recently demonstrated that serum Relaxin-2 (RLX-2) levels are attenuated in women with a history of RPL [9] and correlate with uterine artery Doppler resistance parameters in first trimester, consistent with a crucial role for this peptide in implantation and placental development [10,11]. Higher rates of adverse pregnancy outcomes associated with uteroplacental insufficiency have been reported in women with a history of RPL [12].…”

Regulation of the reproductive cycle and early pregnancy by relaxin family peptides

“…Moreover, studies using monkeys have shown that supplementary relaxin in vivo is able to specifically induce a thickening of the endometrium, improved vascularization, and reduced pregnancy loss (Goldsmith et al, 2004;Hayes et al, 2004;Einspanier et al, 2009), consistent with a very positive impact on implantation and placentation. Also in women, it has been shown that there is a good association between mid-pregnancy levels of circulating relaxin, reduced spontaneous abortion, and increased blood flow (Jauniaux et al, 1994;Anumba et al, 2009).…”