Kisspeptin as a new serum biomarker to discriminate miscarriage from viable intrauterine pregnancy

Sullivan-Pyke, Chantae S.; Haisenleder, Daniel J.; Senapati, Suneeta; Nicolais, Olivia; Eisenberg, Esther; Sammel, Mary D.; Barnhart, Kurt T.

doi:10.1016/j.fertnstert.2017.09.029

Cited by 46 publications

(45 citation statements)

References 21 publications

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“…It is well known that maternal serum hCG peaks at 8–10 weeks of gestation and then declines to reach a plateau at 18–20 weeks of gestation, while the level of KP continues to rise throughout gestation into the 3rd trimester and, unlike hCG, does not plateau . No substantial correlation between KP and hCG rates in viable intrauterine pregnancy, whereas in spontaneous abortions there is a significant correlation between KP and hCG levels …”

Section: Discussionmentioning

confidence: 99%

“…There is a strict relationship between pregnancy‐induced hypertension and elevated serum β‐hCG levels, indicating that there should be an abnormal placental secretary function in patients with severe PE . Therefore, sequential serum hCG values and transvaginal ultrasound tests are used to determine the feasibility of childbirth . Thus, KP is now known as an emerging biomarker for the discrimination of viable pregnancy due to its potential regulatory role in trophoblast function and placentation …”

Section: Discussionmentioning

confidence: 99%

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Maternal plasma kisspeptin‐10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones

Al-Kaabi

Hamdan

Al-Matubsi

2020

J of Obstet and Gynaecol

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Aims To evaluate plasma kisspeptin‐10 (KP‐10) as a marker for preeclampsia and assess its relation to altered reproductive hormones in preeclamptic pregnant women. Methods First time pregnant women (n = 100) at 20 weeks of gestation participated in this study and divided into preeclamptics (n = 60) and normotensives (n = 40). KP‐10, luteinizing hormone (LH), follicle stimulating hormone (FSH), beta‐human chorionic gonadotropin (β‐hCG), estradiol (E2) and progesterone were evaluated during 2nd and 3rd trimesters of pregnancy for all women. Results Kisspeptin‐10 levels were reduced in preeclampsia (PE) women compared with normotensive pregnancies. In the 2nd trimester, area under receiver–operator characteristic (ROC) curve was 0.662, positive and negative predictive values were 32.8 and 94.6, and test sensitivity and specificity were 55% and 87.5%, respectively. In the 3rd trimester, area under ROC curve was 0.747 positive and negative predictive values were 22.2 and 97.3, and test sensitivity and specificity were 83.3% and 67.5%, respectively. In PE patients, plasma KP‐10 demonstrated an inverse correlation with E2 (during the 2nd trimester), LH and FSH (during the 3rd trimester), and positively correlated with β‐hCG (during the 3rd trimester). Conclusion This study showed significantly reduced plasma KP‐10 levels in PE women. This suggests that KP‐10 may play an important role in the pathophysiology of PE. Therefore, combined with previous studies, to diagnose the PE, testing for maternal KP‐10 plasma levels may be useful as an effective screening, but because of low positive predictive value and inadequate test sensitivity, screening cannot be recommended. Furthermore, KP‐10 in PE patients demonstrated significant positive correlation with β‐hCG.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Maternal plasma kisspeptin‐10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones

Al-Kaabi

Hamdan

Al-Matubsi

2020

J of Obstet and Gynaecol

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“…Accordingly, inappropriately low kisspeptin levels have been proposed as biomarker of gestational alterations, such as intrauterine growth restriction and preeclampsia (22,23), and putative predictor of miscarriage risk (24). In fact, a very recent study comparing a well-defined, as yet limited (N=20), population of women with viable intrauterine pregnancy vs. women with confirmed spontaneous abortion suggested that kisspeptin levels during an early gestational window (weeks 6-10) might serve as good biomarker of pregnancy viability (25). However, to our knowledge, no single study has addressed potential dynamic changes in KISS1/kisspeptin in EP, and their eventual diagnostic utility in this condition.…”

Section: Introductionmentioning

confidence: 99%

Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications

Romero-Ruíz

Avendaño

Domı́nguez

et al. 2019

American Journal of Obstetrics and Gynecology

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Background: Ectopic pregnancy (EP) is a life-threatening condition, for which novel screening tools enabling early accurate diagnosis would improve clinical outcomes. Kisspeptins, encoded by KISS1, play an essential role in human reproduction, at least partially by regulating placental function and possibly embryo implantation. Kisspeptin levels are massively elevated in normal pregnancy and reportedly altered in various gestational pathologies. Yet, the pathophysiological role of KISS1/kisspeptin in EP has not been investigated previously. Methods: Measurements of plasma kisspeptins and KISS1 expression analyses in human embryonic/placental tissue were conducted in EP and their controls (women undergoing voluntary termination of pregnancy, VTOP) during early gestational window (<12-wks). Putative miRNA regulators of KISS1 were predicted in silico, followed by expression analyses of selected miRNAs and validation of repressive interactions in vitro. Circulating levels of these miRNAs were also assayed in EP vs. VTOP. Results: Circulating kisspeptins gradually increased during the first trimester of normal pregnancy, but were massively reduced in EP. This profile correlated with expression levels of KISS1 in human embryonic/placental tissue, which increased in VTOP but remained suppressed in EP. Bioinformatic predictions and expression analyses identified miR-27b-3p and miR-324-3p as putative repressors of KISS1 in human embryonic/placental tissue at <12-wks gestation, when expression of both miRNAs was low in VTOP controls, but significantly increased in EP. Yet, a significant repressive interaction was documented only for miR-324-3p, occurring at the predicted 3'-UTR of KISS1. Interestingly, circulating levels of miR-324-3p, but not of miR-27b-3p, were dramatically suppressed in EP, despite elevated tissue expression of the pre-miRNA, suggesting defective export in EP. A decision-tree model using kisspeptin and miR-324-3p levels was successful in discriminating EP vs. VTOP, with a receiver-operating characteristic (ROC) AUC of 0.95 ± 0.02 (95% CI). Conclusions: Our results document a massive down-regulation of KISS1/kisspeptins in early stages of EP, likely via a repressive interaction with miR-324-3p. Our data identify circulating kisspeptins and miR-324-3p as novel biomarkers for accurate for screening of EP at early gestational ages.

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“…11 It should be noted that the expression of KISS1 in the placenta or plasma kisspeptin levels may be affected by the adverse uterine environment. 12,13 Plasma or serum kisspeptin levels are significantly increased in early pregnancy compared to non-pregnant controls. [13][14][15]…”

Section: Introductionmentioning

confidence: 99%

“…12,13 Plasma or serum kisspeptin levels are significantly increased in early pregnancy compared to non-pregnant controls. [13][14][15]…”

Section: Introductionmentioning

confidence: 99%

Kisspeptin: new biomarker of pregnancy

Meena

Mathur

Meena

2019

Int J Reprod Contracept Obstet Gynecol

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Background: The recently identified hormone kisspeptin has been suggested to play an important regulatory role in placentation. The aim and objective of the study is the measurement of serum kisspeptin level in asymptomatic pregnant women and to find out the association of serum kisspeptin with gestational age in women with early pregnancy.Methods: This was a longitudinal study to the evaluation of 178 asymptomatic pregnant women with a gestation of 6 to 16 weeks attending routine antenatal booking visit recruited as study participants from the Antenatal Clinical of Obstetrics and Gynaecology Department, S.M.S. Medical College and Attached Hospitals, Jaipur, Rajasthan, India.Results: After initial clinical examination of every participant, a single blood sample was taken for the measurement of serum kisspeptin. Serum kisspeptin measurement test was performed by ELISA method and results were expressed as ng/ml. Pregnancy outcome was recorded prospectively. Mean serum kisspeptin level of study participants was 2.80±1.87ng/ml and median were 2.41 (Range 0.244-14.06ng/ml). Our result showed the relationship of serum kisspeptin with gestational age (GA) (p<0.000).Conclusions: serum kisspeptin level increases in pregnancy and showed positive relationship with gestational age significantly (p<0.000).

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Kisspeptin as a new serum biomarker to discriminate miscarriage from viable intrauterine pregnancy

Abstract: Plasma levels of kisspeptin have been suggested as a biomarker for miscarriage. This study demonstrates kisspeptin assay stability in serum and its potential clinical utility as a biomarker for early pregnancy viability.

Cited by 46 publications

References 21 publications

Maternal plasma kisspeptin‐10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones

Maternal plasma kisspeptin‐10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones

Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications

Kisspeptin: new biomarker of pregnancy

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