Sildenafil stimulates human trophoblast invasion through nitric oxide and guanosine 3′,5′-cyclic monophosphate signaling

Bolnick, Jay M.; Kilburn, Brian A.; Bolnick, Alan; Diamond, Michael P.; Singh, Manvinder; Hertz, Michael; Dai, Jing; Armant, D. Randall

doi:10.1016/j.fertnstert.2015.02.025

Cited by 21 publications

(14 citation statements)

References 60 publications

(72 reference statements)

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“…Bolnick et al have also reported that trophoblast invasion, a process that is defective in preeclampsia, may be promoted by sildenafil in culture studies (41). Our findings confirm the beneficial effects of sildenafil in an independent mouse model of preeclampsia and provide evidence that improvement in maternal hypertension by sildenafil is associated with better placental perfusion and improved fetal weights.…”

Section: Discussionsupporting

confidence: 85%

Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia

Burke¹,

Zsengellér²,

Khankin³

et al. 2016

Journal of Clinical Investigation

122

101

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Section: Discussionsupporting

confidence: 85%

Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia

Burke¹,

Zsengellér²,

Khankin³

et al. 2016

Journal of Clinical Investigation

122

101

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“…This is the case for Resveratrol [ 32 ], which normalized the activity of SOD in the HTR8-SVneo H/R stressed cells, as well as the concentration of Malondialdehyde (a marker of oxidative stress targeting unsaturated fatty acids), and decreased apoptosis. Similarly, Sildenafil citrate (Viagra) applied to H/R HTR-8/SVneo cells can promote cell survival, if in the presence of NO and cGMP [ 33 ]. Oxidative stress-induced apoptosis can also be attenuated by HBEGF treatment in first trimester placental explants, as well as on the HTR-8/SVneo cells [ 34 ].…”

Section: Cellular Sources Of Oxidative Stress In the Human Placentmentioning

confidence: 99%

Oxidative Stress in Preeclampsia and Placental Diseases

Aouache

Biquard

Vaiman

et al. 2018

IJMS

408

259

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Preeclampsia is a persistent hypertensive gestational disease characterized by high blood pressure and proteinuria, which presents from the second trimester of pregnancy. At the cellular level, preeclampsia has largely been associated with the release of free radicals by the placenta. Placenta-borne oxidative and nitrosative stresses are even sometimes considered as the major molecular determinants of the maternal disease. In this review, we present the recent literature evaluating free radical production in both normal and pathological placentas (including preeclampsia and other major pregnancy diseases), in humans and animal models. We then assess the putative effects of these free radicals on the placenta and maternal endothelium. This analysis was conducted with regard to recent papers and possible therapeutic avenues.

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“…[13][14][15] Furthermore, studies also showed that SC could promote endometrial proliferation and even enhance human trophoblast invasion. 16,17 A vaginal route of administration was chosen since the use of intravaginal sildenafil suppositories decreased the incidence of sideeffects such as hypotension and headaches by delivering the medication in close proximity to the target organ. 12 To our knowledge, despite case reports, 12,18,19 there has been only one study of SC in FET cycles and one study in fresh ET cycles, both in thin-EM patients, and the results failed to reach statistical significance in differences in reproductive outcomes due to the limited sample sizes.…”

Section: Introductionmentioning

confidence: 99%

<p>Adjuvant Vaginal Use of Sildenafil Citrate in a Hormone Replacement Cycle Improved Live Birth Rates Among 10,069 Women During First Frozen Embryo Transfers</p>

Tao¹,

Wang²

2020

DDDT

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Purpose: To investigate the effects of sildenafil citrate (SC) on live birth rates (LBR) during women undergoing their first frozen embryo transfers (FET) with hormone replacement therapy (HRT). Patients and Methods: This retrospective cohort study included a total of 10,069 infertile women with adequate endometrial thickness (≥7 mm when progesterone was initiated) in their first FET cycle with hormone replacement therapy. Women received either vaginal SC or no adjuvant during their first transfer cycle depending on patient or physician preference. In the sildenafil group, 1098 women underwent HRT FET with adjuvant vaginal use of SC, and 8971 women were included as controls. The primary outcome measure was LBR, defined as the likelihood of live birth per transfer cycle. Endometrial thickness (EMT), implantation, chemical pregnancy, clinical pregnancy, miscarriage, ongoing pregnancy, birth weight and preterm delivery (PTB) were also recorded. Results: Baseline characteristics were comparable between the two groups. In the crude analysis, the unadjusted LBR was significantly higher in the vaginal SC group (scHRT-FET) than in the control group (HRT-FET) (40.3% vs 36.1%). After adjustment for 12 pregnancy-related confounding factors, logistic regression analysis showed that LBR remained significantly higher in the scHRT-FET group than in the HRT-FET group (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.14-1.49). Furthermore, after adjustment, the ongoing pregnancy rate was significantly higher (aOR 1.29, 95% CI 1.13-1.47), and the miscarriage rate was significantly lower (aOR 0.58, 95% CI 0.43-0.77), in the scHRT-FET group compared to the HRT-FET group. Adjuvant vaginal use of SC did not increase the endometrial thickness and had no significant effect on birth weight or PTB. Conclusion: Adjuvant vaginal use of SC in HRT FET was associated with higher LBR and improved pregnancy outcomes in an infertile population with adequate endometrial thickness. The beneficial effect of SC may be due not to an increase in EMT but instead to improve endometrial blood flow and receptivity, which might merit clinicians' attention for improving general IVF practices.

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Sildenafil stimulates human trophoblast invasion through nitric oxide and guanosine 3′,5′-cyclic monophosphate signaling

Cited by 21 publications

References 60 publications

Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia

Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia

Oxidative Stress in Preeclampsia and Placental Diseases

<p>Adjuvant Vaginal Use of Sildenafil Citrate in a Hormone Replacement Cycle Improved Live Birth Rates Among 10,069 Women During First Frozen Embryo Transfers</p>

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