adrenomedullin and Abortion--Habitual

Poor endometrial perfusion during implantation window is reported to be one of the possible causes of idiopathic recurrent spontaneous miscarriage (IRSM). We have tested the hypothesis that certain angiogenic and vasoactive factors are associated with vascular dysfunction during implantation window in IRSM and, therefore, could play a contributory role in making the endometrium unreceptive in these women. This is a prospective case-controlled study carried out on 66 women with IRSM and age and BMI matched 50 fertile women serving as controls. Endometrial expression of pro-inflammatory (IL-1β, TNF-α, IFN-γ, TGF-β1), anti-inflammatory (IL-4, -10), angiogenesis-associated cytokines (IL-2, -6, -8), angiogenic and vasoactive factors including prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), nitric oxide (NO) and adrenomedullin (ADM) were measured during implantation window by ELISA. Subendometrial blood flow (SEBF) was assessed by color Doppler ultrasonography. Multivariate analysis was used to identify the significant factor(s) responsible for vascular dysfunction in IRSM women during window of implantation and further correlated with vascular dysfunction. Endometrial expression of pro-inflammatory cytokines and PGE2 were up-regulated and anti-inflammatory and angiogenesis-associated cytokines down-regulated in IRSM women as compared with controls. Further, the angiogenic and vasoactive factors including VEGF, eNOS, NO and ADM were found to be down-regulated and SEBF grossly affected in these women. Multivariate analysis identified IL-10, followed by VEGF and eNOS as the major factors contributing towards vascular dysfunction in IRSM women. Moreover, these factors strongly correlated with blood flow impairment. This study provides an understanding that IL-10, VEGF and eNOS are the principal key components having a contributory role in endometrial vascular dysfunction in women with IRSM. Down-regulation of these factors is also associated with impaired endometrial perfusion which possibly makes the endometrium unreceptive that may eventually cause early pregnancy loss.

Topics: Abortion, Habitual; Adrenomedullin; Adult; Case-Control Studies; Dinoprostone; Embryo Implantation; Endometrium; Female; Gene Expression; Humans; Interleukin-10; Multivariate Analysis; Nitric Oxide; Nitric Oxide Synthase Type III; Pregnancy; Prospective Studies; Ultrasonography; Vascular Endothelial Growth Factor A

To evaluate uterine artery Doppler flow resistance and plasma adrenomedullin levels in women with unexplained recurrent pregnancy loss (RPL) compared to controls.. Eighty-three women, who attend the department of Obstetrics and Gynecology, Benha University, Egypt, participated in this study (RPL group: n=40, and control group: n=43). Uterine artery Doppler and plasma adrenomedullin (AM) (pg/mL) levels were measured for all women in the mid-luteal phase of a non-pregnant cycle.. Both uterine artery pulsatility index (PI) and AM levels were significantly higher in RPL group compared to controls (2.71 ± 0.259 vs 2.06 ± 0.194 for PI and 287.5 ± 80.4 pg/mL vs 156.1 ± 39.8 pg/mL for AM, P<0.01). Uterine artery PI had a significant positive correlation with plasma AM levels both in the RPL group (r=0.645, P<0.001) and in the control group (r=0.384, P=0.011). Number of previous miscarriages in RPL group was significantly correlated with both uterine artery PI (r=0.838, P=0.015) and plasma AM levels (r=0.509, P=0.001).. Uterine artery PI may be useful in identifying women with unexplained RPL who have impaired uterine circulation. Plasma AM may serve as a biochemical marker for RPL caused by impaired uterine perfusion.

Topics: Abortion, Habitual; Adrenomedullin; Adult; Biomarkers; Female; Humans; Laser-Doppler Flowmetry; Pregnancy; Pulsatile Flow; Regional Blood Flow; Ultrasonography; Uterine Artery; Uterus

To evaluate vascular changes and uterine perfusion in women with recurrent pregnancy loss.. We measured plasma levels of adrenomedullin of 100 pregnant women in the midluteal phase of a nonpregnant cycle (control group: n = 62; recurrent pregnancy loss group: n = 38). We measured the pulsatility index (PI) in the uterine arteries by transvaginal pulsed Doppler ultrasonography at the same time.. The plasma level of adrenomedullin in women with recurrent pregnancy loss (5.6 +/- 1.9, mean +/- standard deviation) was significantly higher (P >.001) than that in control women (3.6 +/- 1.7). Uterine arterial PI of women with recurrent pregnancy loss (2.70 +/- 0.47) was significantly higher (P >.001) than that in control women (2.09 +/- 0.39). Plasma level of adrenomedullin had a significant positive correlation with uterine arterial PI both in the control group (r =.58, P <.001) and in the recurrent pregnancy loss group (r =.78, P <.001). Both plasma adrenomedullin concentration (7.2 +/- 2.3) and uterine arterial PI (3.06 +/- 0.36) were significantly high in women with antiphospholipid antibodies.. Plasma adrenomedullin may serve as a useful biochemical marker for recurrent pregnancy loss caused by impaired uterine perfusion.

Topics: Abortion, Habitual; Adrenomedullin; Adult; Antibodies, Antiphospholipid; Endometrium; Female; Humans; Luteal Phase; Peptides; Prospective Studies; Ultrasonography, Doppler, Pulsed; Uterus