Sildenafil Group Research Articles

Screening sexual performance enhancing compounds and their analogues in counterfeit and illicit erectile dysfunction drugs by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry

The growth of the counterfeit and illicit drugs market is attributable in part to phosphodiesterase type–5 inhibitor (PDE–5is) medications for erectile dysfunction (ED). PDE–5is and their analogues are being increasingly supplied as counterfeit and illicit drugs marketed to enhance sexual performance. Herein, we screened and confirmed a total of 181 such counterfeit and illicit drugs used to date to enhance sexual performance by high-performance liquid chromatography (HPLC) and liquid chromatography–tandem mass spectrometry (LC–MS/MS). Out of 181 samples, PDE–5is and their analogues were detected in 156 samples, with 49.4% containing two or more components in a single sample. Sildenafil, tadalafil, and miscellaneous group were detected a rates of 64.1%, 34.4%, and 1.5% times and concentrations of 0.04–496 mg/g, 0.02–147 mg/g, and 0.54–16.4 mg/g, respectively with multiple compound groups also detected in single samples. Overdosing on these drugs can lead to adverse effects, the toxicities of combined administrations have not been researched, and administering multiple components in a single sample can be fatal. We recommend that counterfeit and illicit drugs for enhancing sexual performance be continuously controlled and supervised for the protection of public health, and more studies into toxicity and side effects are required.

Sildenafil’s Early, Late Impact on Ventricular Septal Repair: Older Children Using the Double Patch

BackgroundDelayed diagnosis in children with a ventricular septal defect (VSD) is common in low- and middle-income countries. Consequently, these children present with elevated pulmonary vascular resistance (PVR) and pulmonary arterial hypertension (PAH). The study investigators introduced the double-flap valve VSD patch closure technique (DFV) in 1996 to reduce early postoperative risk. Long-term results are presented in this report. MethodsThis was a retrospective single-institution study of patients who underwent DFV between May 1996 and July 2015. Beginning in 2005, all candidates for DFV received sildenafil preoperatively and postoperatively. Preoperative catheterization data and operative, postoperative, hospital, and follow-up data were analyzed. ResultsA total of 40 patients underwent the DFV procedure. Patients’ demographics were comparable between the sildenafil and nonsildenafil groups. One of 39 patients (2.6%) was lost to follow-up. Early mortality was 2.5% (1 of 40), and late mortality was 2.6% (1 of 38). Sildenafil improved preoperative oxygen saturation, improved preoperative hemodynamics, and shortened postoperative ventilation time. In both groups, abnormal hemodynamic values improved with a 100% oxygen challenge. The median age at late follow-up was 26.3 years (interquartile range [25%, 75%], 20.9, 29.9 years), and the median time since operation was 19.2 years (interquartile range, 11.4, 22.7 years). Current discharge survival was 97.3%. A total of 18% of patients had severe PAH in late follow-up. Multivariate analysis revealed only a baseline PVR-to–systemic vascular resistance ratio of 0.8 or greater as a significant predictor of late severe PAH. ConclusionsLong-term follow-up demonstrated that 60% of the patients will achieve normal or nearly normal pulmonary artery pressures. Furthermore, the study demonstrated that sildenafil improves preoperative hemodynamics and postoperative management. Children with VSD, elevated PVR, and PAH should not be denied operation.

The Effect of Sildenafil Citrate on Poor Endometrium in Patients Undergoing Frozen-Thawed Embryo Transfer following Resection of Intrauterine Adhesions: A Retrospective Study

Background: The recent studies have shown that sildenafil citrate can enhance estrogen-induced proliferation of the endometrium in infertile women. Objective: This study was aimed to investigate whether sildenafil citrate could affect pregnancy outcomes in infertile women receiving frozen-thawed embryo transfer (FET) after resection of intrauterine adhesions (IUAs). Materials and Methods: A total of 310 subjects who met the inclusion criteria were recruited and divided into the control group (group A) and the sildenafil citrate group (or the SC group, group B). The 2 groups were, respectively, divided into 2 subgroups based on the severity of reformed adhesions: (1) group A1 (with mild IUAs) and group A2 (with moderate to severe IUAs) and (2) group B1 (with mild IUAs) and group B2 (with moderate to severe IUAs). Therapeutic effects of sildenafil citrate on the cases were evaluated after resection of IUAs during FET cycles. Endometrial thickness, endometrial pattern, and pregnancy outcomes were evaluated and compared between the 2 groups. Results: There was no significant difference in the number of embryos transferred between the 2 groups. The endometrial thickness in group B (0.80 [0.68–0.90] cm) was significantly higher than that in group A (0.73 [0.35–0.80] cm). Besides, the biochemical pregnancy rate, clinical pregnancy rate, and live birth rate (LBR) were 71.60, 50.83, and 39.17% in group B, which were significantly higher than those in group A, namely, 57.36, 34.73, and 23.68%, respectively (p < 0.05). The univariate analysis and multivariate logistic regression showed that the LBR in either subgroups of group B after vaginal sildenafil treatment was significantly higher than that in the corresponding control group (p < 0.05). Conclusions: It was observed that the administration of sildenafil citrate during FET could effectively improve the poor endometrial conditions after FET following the resection of IUAs.

Sildenafil in endotoxin-induced pulmonary hypertension: an experimental study

BackgroundSepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. MethodsTwenty pigs were randomly assigned to Control group (n.ß=.ß10), which received saline solution; or to Sildenafil group (n.ß=.ß10), which received sildenafil orally (100.ßmg). After 30.ßminutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4.ß..g.kg-1.h-1) for 180.ßminutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNF.., IL-1.., IL6, and IL10) and troponin I response. ResultsSignificant hemodynamic alterations were observed after 30.ßminutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19.ß...ß2.ßmmHg to LPS30 52.ß...ß4.ßmmHg, p.ß<.ß0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411.ß...ß29 to LPS180 334.ß...ß49, p.ß<.ß0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35.ß...ß4.ßmmHg at LPS30, p.ß<.ß0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. ConclusionSildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.

Systematic review and cost-effectiveness of bosentan and sildenafil as therapeutic drugs for pediatric pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare disease in children, with significant mortality. Because of the limited research on pediatric PAH, first, systematic review of related drugs is conducted, and then economic evaluation of PAH drug treatment programs is conducted, which to provide a reference for the choice of more cost-effective treatment options. The search includes electronic databases such as Pubmed, ScienceDirect, and Embase. Through inclusion and exclusion criteria, screen high-quality randomized controlled trials. We used TreeAge Pro 2011 software to construct the markov model, that to simulate the total medical cost and quality-adjusted life years (QALYs), and to calculate the incremental cost-effectiveness ratio. Sensitivity analysis of transfer probability, utility, and cost was carried out. Incorporate two studies that meet the criteria, one compared the therapeutic effects of bosentan and placebo on pediatric PAH, the other compared therapeutic effects of sildenafil and placebo on pediatric PAH, both articles were of good quality. Compared with the sildenafil group (3.38QALYs and $161,120.14), the QALY of the bosentan treatment group (3.33QALYs and $257,411.29) was reduced by 0.05, and the cost increased by $96,291.15. The estimated improvement to quality of life and reduced costs result in an estimate of economic dominance for sildenafil over bosentan. This dominant result persisted probabilistic analyses. Based on this model, a more cost-effective treatment drug for PAH in children is sildenafil.

Comparison between the effect of sildenafil and endometrial scratch injury on the outcome of (ICSI) cycle.

Background: The main aim of the study, is to compare the effect of sildenafil therapy and endometrial scratch injury as methods for improving endometrial receptivity on the outcome of ICSI cycle. Patients and methods: This was a prospective randomized controlled study which was done in private based ICSI centers, where a total of 150 patients were included. These were divided into 3 groups; Control group(n=50), endometrial scratch injury group(n=50) ,and sildenafil group(n=50). Endometrial scratch injury was done on 21th day of the spontaneous cycle before ICSI-ET treatment using a pipelle endometrium sampler. received sildenafil citrate( 25mg tablets 3 times daily intravaginally) staring from the first day of FSH stimulation. Beta-HCG titter was done for detection of pregnancy. Results: There was a statistically significant difference regarding the pregnancy rate between the control group and those who received endometrial scratch( Pvalue 0.0405) with a pregnancy rate of 56% (N=28) in comparison to the control group with 46% (N=23). On the other hand, there was no significant difference regarding the sildenafil group P value 0.067 with pregnancy rate of 48% (N=24). In the control group, all the pregnant patients showed positive fetal pulsations, while in the endometrial scratch group 92.8% showed positive fetal pulsations (N=26), and in the sildenafil group 95.8% showed positive fetal pulsations (N=23). Conclusion: Endometrial scratch injury was a safe and cheap method to improve pregnancy rate in ICSI cycles, however using it routinely needs more studies comparing it to other methods of improving endometrial receptivity.

Clinical and hemodynamic effects of oral sildenafil on biventricular function on patients with left ventricular systolic dysfunction.

We explore the dual benefits of sildenafil on bi-ventricular functions in the form of improvement of ejection fraction, pulmonary vascular resistance and functional capacity of systolic heart failure patients either related to dilated or ischemic cardiomyopathy. To evaluate the effect of oral sildenafil on biventricular function in patients with left ventricular systolic dysfunction. The prospective randomised case-control study included 80 patients with left ventricular systolic dysfunction resulting from dilated or ischemic cardiomyopathy were equally randomised to one of the treatment groups in (1:1) who were collected from the outpatient clinic of cardiac care unit (CCU) of Beni-Suef University hospital; each group contained 40 patients: The first group (control group): received the guideline-recommended treatment of heart failure with reduced ejection fraction which consists of [angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), beta-blockers, aldosterone receptor antagonist, digoxin]. The second group (sildenafil group): received the previously mentioned guideline-recommended treatment in the control group plus sildenafil 25mg three times per day. All patients were subjected to detailed history taking, baseline transthorathic echocardiography and exercise ECG using the Naughton protocol. Follow-up transthorathic echocardiography and exercise ECG was conducted after 3months. Sildenafil improves heart failure symptoms such as dyspnea or orthopnea or increasing the functional capacity of myocardium which is measured by estimated metabolic equivalents of task (METS) (P=.017), and exercise duration (P=.013). Sildenafil increased cardiac output (P=.033), which is considered one of the desirable targets in heart failure patients. In patients with left ventricular systolic dysfunction secondary to dilated or ischemic cardiomyopathy, relatively small doses of sildenafil significantly enhances exercise period and functional ability, with substantial improvement in left ventricular systolic function irrespective of the existence of major pulmonary hypertension.

Comparison of the efficacy and safety of low-intensity extracorporeal shock wave therapy versus on-demand sildenafil for erectile dysfunction.

BackgroundLow-intensity extracorporeal shock wave therapy (Li-ESWT) is an effective therapy for erectile dysfunction (ED) but is not widely recognized and applied. This prospective nonrandomized study aimed to investigate the efficacy and safety of Li-ESWT.MethodsAfter a 4-week washout period of past ED treatment, patients entered one of 2 active treatment groups, either 9-week Li-ESWT or 100 mg on-demand sildenafil. Patients were evaluated in the first- and third-month following initiation of treatment. The Li-ESWT protocol comprised 2 sessions per week for 3 weeks, which were repeated after a 3-week interval. Patients in the drug group took self-administered sildenafil at a dose of 100 mg before intercourse. The primary outcome was the effectiveness of Li-ESWT measured by the International Index of Erectile Function-5 (IIEF-5) scores. Other measurements included erection hardness score (EHS) and Self-Esteem And Relationship (SEAR).ResultsA total of 78 participants completed the study (46 in the Li-ESWT group and 32 in the sildenafil group). Overall, 26.9% of the participants (21/78) included were psychogenic. In the third month, the outcome measured by IIEF-5 was 21.52 in the Li-ESWT group and 21.26 in the sildenafil group (P>0.05). Proportion of improvement defined by minimal clinically important difference (MCID) criteria was 52.2% in the Li-ESWT group and 59.4% in the sildenafil group (P>0.05). The EHS and SEAR improvement was similar in the 2 groups (P>0.05 at baseline and third month). Transient and mild adverse events were observed in both groups.ConclusionsIn our study, a similar treatment efficacy and safety was shown by the application of Li-ESWT as on demand sildenafil.

The protective effects of phosphodiesterase-5 inhibitor, sildenafil on post-resuscitation cardiac dysfunction of cardiac arrest: by regulating the miR-155-5p and miR-145-5p

BackgroundMiRNA-155 and miRNA-145 have been demonstrated to function as a key regulator in the development of the cardiovascular system. Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.MethodsThirty-two male pigs (weighing 30 ± 2 kg) were randomly divided into 4 groups, sildenafil group (n = 8), sildenafil +NG-nitro-l-arginine methyl ester (L-NAME) (20 mg/kg L) group (n = 8), saline (SA group, n = 8); and sham operation group (sham group, n = 8). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC), and the hearts were removed and analyzed under electron microscopy, quantitative real-time polymerase chain reaction and ultra structural analysis were performed to evaluate myocardial injury.ResultsCompared with the sildenafil + L-NAME and saline groups, the sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, and attenuated myocardial injury; In this study, CA pigs showed evidently increased levels of miR-155-5p and miR-145-5p, while the sildenafil treatment decreased the levels of miR-155-5p and miR-145-5p in CA pigs. In addition, the levels of eNOS was decreased in CA pigs, validating sildenafil attenuating post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.ConclusionsSildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, inhibited the increases in the miR-155-5p and miR-145-5p levels and attenuated myocardial injury in a porcine model of CA and resuscitation.

Effects of adipose tissue-derived mesenchymal stem cells and/or sildenafil citrate in experimental colon anastomosis model.

This study aimed to evaluate the healing effects of adipose tissue-derived mesenchymal stem cells (AT-MSC) and sildenafil citrate alone or in combination of colon anastomosis experimental model. A total of 40 female Wistar rats were randomly distributed to four groups: Control (without any intervention post-anas-tomosis), stem cell (AT-MSC injection on the anastomosis site), SIL (oral gavage of 10 mg/kg sildenafil citrate), and stem cell + SIL (AT-MSC injection and oral administration of sildenafil citrate) groups. Rats were euthanized 5 days post-anastomosis. Intra-abdominal adhesion status and anastomotic burst pressure were measured to assess anastomotic healing. Hydroxyproline and TNF-α level, neu-trophil leukocyte infiltration, epithelial regeneration, and necrosis in the anastomosis tissue were examined. Anastomosis leakage and anastomosis burst pressure were not different among the groups. Treatment with sildenafil, stem cell, and stem cell + SIL reduced the degree of perianastomotic adhesions compared to control (p<0.05). A significant increase was noted in hydroxyproline in the stem cell and stem cell + SIL groups (p=0.001). AT-MSC injection alone or in combination with sildenafil citrate reduced the TNF-α concentration at the anastomosis site (p=0.001). Histopathological examination revealed that all treatments enhanced the clearance of the necrotic debris, reduced leukocytes infiltration, and accelerated the retraction of anastomo-sed ends except control (p=0.001). Epithelial regeneration was more pronounced in the stem cell group than other groups (p=0.001). Macrophage density was lower in groups treated with the SIL or stem cell groups than the control and stem cell + SIL groups (p=0.001). Sildenafil citrate and/or AT-MSC in the anastomosed rats promoted the anastomosis healing that was more pro-nounced in groups receiving stem cell injections.

The determination of the protective role of sildenafil administration in rats with sepsis-in duced liver injury.

Sepsis is a complex syndrome which comes out after infection, characterized by activation of inflammation and infection and has a high morbidity and mortality. Sildenafil (SLD) is a selective Phosphodiesterase Type 5 (PDE-5) enzyme inhibitor and is used in the treatment of erectile dysfunction effectively all over the world. In this study, we investigated whether sildenafil had protective effect or not by studying the effect of sildenafil on reactive oxygen species and antioxidants in Cecal Ligation and Puncture (CLP) polymicrobial sepsis model in rat liver histopathologically and biochemically. Rats were divided into four groups: 1) 10 mg/kg SLD given CLP group; 2) 20 mg/kg SLD given CLP group; 3) CLP group; 4) SHAM operated group. CLP polymicrobial sepsis model was applied to the rats. All rats in our study were sacrificed by overdose general anesthetic after 16 hours (thiopental sodium, 50 mg/kg). Specimens of rat liver were analyzed histopathologically and biochemically. In the study, Superoxide Dismutase (SOD) and Glutathione (GSH) parameters were measured to indicate the antioxidant activity in liver during sepsis. To evaluate the oxidant activity, Myeloperoxidase (MPO) and Lipid Peroxidation (LPO) parameters were measured in liver tissue. SOD and MPO activities and GSH and LPO levels were high in CLP polymicrobial sepsis model when compared to SHAM group (P<0.05). In all sildenafil groups, GSH levels were high when compared to CLP group. In 20 mg/kg sildenafil given sepsis group, high GSH levels were observed according to SHAM group. In addition, while all sildenafil dose groups had a significant decrease versus CLP group in LPO levels (P<0.05), they had a significant increase in MPO activities. In 20 mg/kg sildenafil administrated rats, an improvement observed in biochemical parameters. In this study, SOD and MPO activities which were low in SHAM group increased in CLP polymicrobial sepsis model. When SLD administrated, MPO activity increased in both SHAM and CLP groups. In this study, GSH and LPO levels also increase in septic liver tissue. When SLD administrated to SHAM group, it increased protective GSH level and decreased detrimental LPO level. In histopathological examination, it was observed that 10 mg/kg sildenafil administration had a curative effect in liver tissue partly. In conclusion, it was shown that acute sildenafil administration decreased liver damage in septic rats dose-dependently in this study. In addition, it was observed that it corrected the broken oxidant-antioxidant balance. This might mediate the protective effect of sildenafil in liver. But we believe that new experimental and clinical studies should be in future to understand the protective effect of sildenafil in liver.

Nephroprotective effect of coadministration of curcumin and sildenafil in adenine-induced chronic renal failure in rats

BackgroundChronic renal failure (CRF) is a major public health problem worldwide. The pathophysiological basis of the disease and its complication include inflammation and oxidative stress, which are similar in humans and animals. In this study, we seek to develop new therapeutic modalities for CRF.ObjectiveThis study aimed to investigate the nephroprotective effects of curcumin (CUR) and/or sildenafil in adenine (AD) model of CRF.Materials and methodsRats were divided into five groups as follows: control naive group, AD group received AD 200 mg/kg/day orally to induce CRF, CUR group received CUR 200 mg/kg/day in addition to AD, sildenafil group received sildenafil 0.5 mg/kg/day in addition to AD, and combination group received combination of CUR 200 mg/kg/day and sildenafil 0.5 mg/kg/day in addition to AD. After consecutive 28 days of treatment, body weight, kidney index, and Doppler on renal artery assessments were done for all groups. In addition, kidney function tests and markers of oxidative stress were evaluated. Histopathological assessment of renal tissues and immunohistochemical staining for tumor necrosis factor-α were performed.ResultsCUR, sildenafil, and their combination significantly decreased body weight loss and urine volume and improved renal hemodynamic changes caused by AD. In addition, they significantly improved kidney function tests and biomarkers of oxidative stress. A significant down-regulation of tumor necrosis factor-α immunohistochemical expression was noted. They also brought histopathological changes induced by AD toward normal.ConclusionCUR and sildenafil may play a role in renal protection in AD-induced nephrotoxicity. The combined treatment showed better nephroprotective effect than either treatment alone did.

Role of Sildenafil in Improvement of Endometrial Receptivity Markers in Fresh ICSI Cycles

Receptivity of endometrial is a series of events which enhance implantation of the embryo. It is controlled by several growth factors, cytokines and steroid hormones. The current study aims to assess the influences of vaginally managed sildenafil in ICSI patients on the thickness of endometrial, sub endometrial resistance index and pulsatility index, serum level of vascular endothelial growth factor (VEGF) and pregnancy outcome. The study was planned as a controlled randomized trial (interventional experimental study) involved a total of sixty women who attend High Institute of Infertility Diagnosis and Assisted Reproductive Technologies who undergo ICSI cycle. Enrolled patients divided into two groups: 1) Study group: thirty (30) infertile women had received sildenafil 25mg tablet intravaginally four times daily form the day of stopping blood of menstrual cycle to the day of hCG injection. 2) Control group: thirty (30) infertile women had not treated by sildenafil. In our study, we found the following results: the level of vascular endothelial growth factor was highly significant in the study group. The sub endometrial Doppler study, the mean pulsatility index was significantly lower in the study group, while no significant difference in the resistant index and mean systolic to the diastolic ratio between study and control groups. The thickness of endometrial on the same day of ova pickup was higher in the study group, although statistically not significant. The pregnancy rate of sildenafil group was higher. However, the difference was not statistically significant. We concluded the using vaginal sildenafil during fresh ICSI cycle improve endometrial receptivity by enhancing sub endometrial blood flow through reducing pulsatility index and increasing vascular endothelial growth factor.

Prenatal Use of Sildenafil in Fetal Growth Restriction and Its Effect on Neonatal Tissue Oxygenation-A Retrospective Analysis of Hemodynamic Data From Participants of the Dutch STRIDER Trial.

Objective: Sildenafil is under investigation as a potential agent to improve uteroplacental perfusion in fetal growth restriction (FGR). However, the STRIDER RCT was halted after interim analysis due to futility and higher rates of persistent pulmonary hypertension and mortality in sildenafil-exposed neonates. This hypothesis-generating study within the Dutch STRIDER trial sought to understand what happened to these neonates by studying their regional tissue oxygen saturation (rSO2) within the first 72 h after birth.Methods: Pregnant women with FGR received 25 mg placebo or sildenafil thrice daily within the Dutch STRIDER trial. We retrospectively analyzed the cerebral and renal rSO2 monitored with near-infrared spectroscopy (NIRS) in a subset of neonates admitted to two participating neonatal intensive care units, in which NIRS is part of standard care. Secondarily, blood pressure and heart rate were analyzed to aid interpretation. Differences in oxygenation levels and interaction with time (slope) between placebo- and sildenafil-exposed groups were tested using mixed effects analyses with multiple comparisons tests.Results: Cerebral rSO2 levels were not different between treatment groups (79 vs. 77%; both n = 14) with comparable slopes. Sildenafil-exposed infants (n = 5) showed lower renal rSO2 than placebo-exposed infants (n = 6) during several time intervals on day one and two. At 69–72 h, however, the sildenafil group showed higher renal rSO2 than the placebo group. Initially, diastolic blood pressure was higher and heart rate lower in the sildenafil than the placebo group, which changed during day two.Conclusions: Although limited by sample size, our data suggest that prenatal sildenafil alters renal but not cerebral oxygenation in FGR neonates during the first 72 post-natal hours. The observed changes in renal oxygenation could reflect a vasoconstrictive rebound from sildenafil. Similar changes observed in accompanying vital parameters support this hypothesis.

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

PurposeTo 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 MethodsThis 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.ResultsBaseline 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.ConclusionAdjuvant 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.

Cadmium-induced adrenal cortical autophagy in rats: possible modulation by sildenafil.

The link between autophagy, inflammatory bowel disease, ischaemic injury and cancer had been established. Reasonable evidence is available for cadmium to be related to certain cancers. Sildenafil had been investigated to modulate oxidative stress mechanisms. The aim of this study is to investigate cadmium-induced adrenal cortical autophagy and to declare possible modulation by sildenafil. Twenty four Wistar rats weighing 150-200 g were randomly and equally assigned into: control group, sildenafil (20 mg/kg/day orally) exposed group, cadmium group (cadmium chloride 1 mg/kg/day SC), cadmium + sildenafil group (rats received cadmium concomitant with sildenafil). Euthanasia was done 4 weeks from the beginning of experiment; adrenal glands were subjected to biochemical, histological, ultrastructural and immunnohistochemical assessment. Control and sildenafil exposed groups exhibited nearly similar results. Cadmium had produced adrenal cortical apoptosis and ultrastructural derangement of cell organelles. Cadmium-induced autophagy was detected by ultrastructural abundance of enlarged lysosomes and significant (p < 0.05) increase in the optical density of lysosomal associated membrane protein 2 immunoexpression. Sildenafil taken with cadmium had decreased adrenal cortical autophagy, significantly modulated the adrenal gland superoxide dismutase and malondialdehyde compared to cadmium group. Also, the optical density of nuclear factor kappa B (NF-kB) and caspase-3 immunoexpression was significantly decreased in cadmium + sildenafil compared to cadmium group. Cadmium might induce adrenal cortical autophagy in rats and sildenafil might show an ameliorating effect probably through enhancement of antioxidant defence mechanism and modulation of NF-kB.

Effect of sildenafil citrate on treatment of infertility in women with a thin endometrium: a systematic review and meta-analysis.

ObjectiveEndometrial thickness is a prognostic factor for successful pregnancy. This meta-analysis aimed to examine the role of sildenafil citrate on infertile women with a thin endometrium.MethodsTwo investigators independently searched the literature on sildenafil citrate and infertile women with a thin endometrium from PubMed, EMBASE, and the Cochrane Controlled Trials Register Database from inception to January 2019.ResultsNine studies involving 1452 patients were included for analysis in our study. We found that endometrial thickness in patients who received sildenafil citrate was significantly higher than that in the control group (placebo or no treatment) (weighted mean difference: 1.22; 95% confidence interval [CI]: 1.07–1.38). The radial artery resistance index was significantly lower (weighted mean difference: −0.12; 95% CI: −0.17 to −0.06), and the clinical pregnancy rate (risk ratio: 1.31; 95% CI: 1.11–1.53) and biochemical pregnancy rate (risk ratio: 1.45; 95% CI: 1.11–1.89) were significantly higher in the sildenafil citrate group compared with the control group.ConclusionSildenafil citrate is effective in improving endometrial thickness, the clinical pregnancy rate, and the biochemical pregnancy rate in women who have a thin endometrium. This treatment is a potential therapeutic intervention for a thin endometrium.

Safety and effect of sildenafil on treating paediatric pulmonary arterial hypertension: a meta-analysis on the randomised controlled trials.

Efficacy of sildenafil in treating paediatric pulmonary arterial hypertension is controversial. This systematic review aimed to explore the safety and effect of sildenafil on treating paediatric pulmonary arterial hypertension (PAH) through meta-analysis. In this study, the electronic databases, including the Cochran Library database, EMBASE, and MEDLINE were systemically retrieved to identify the related randomised controlled trials (RCTs). Two reviewers had independently completed study selection, data collection, and assessment of the bias risk. Amongst 938 articles researched according to our retrieval strategy, 15 papers that involved 673 cases had been screened. Relative to control group, the sildenafil group had markedly reduced mortality (RR = 0.25, 95% CI: 0.12-0.51; p < 0.0001), but difference within the mortality was not statistically significant between high- and low-dose sildenafil groups (p = 0.152). Nonetheless, difference of the mean pulmonary arterial pressure between sildenafil as well as control group was of no statistical significance. Differences in the length of hospital stay and the incidences of pulmonary hypertensive crisis between children with PAH and controls were of no statistical significance. However, the summary estimate favoured that sildenafil reduced the duration of mechanical ventilation time, as well as the length of ICU stay and inotropic support. Sildenafil therapy reduces the mortality of PAH patients, but its effects on the haemodynamic outcomes and other clinical outcomes are still unclear.

Benefits of perioperative sildenafil therapy in children with a ventricular septal defect with pulmonary artery hypertension on early surgical outcomes.

Pulmonary hypertension is a common association in children with nonrestrictive ventricular septal defect. It increases perioperative mortality and morbidity. Oral sildenafil is an effective pulmonary vasodilator. In this study, we assessed effects of perioperative oral sildenafil therapy on pulmonary artery pressure and early surgical outcomes. This was a single centre, prospective randomized control study. Thirty children with nonrestrictive ventricular septal defects with pulmonary hypertension were divided into two groups. In the sildenafil group (n = 15, mean age 23.3 months), oral sildenafil was administered two weeks before surgery. In the control group (n = 15, mean age 36 months), preoperative sildenafil was not given. Sildenafil was continued postoperatively in both groups, provided the postoperative pulmonary artery pressure was over 50% of systemic pressure. There was no perioperative mortality, pulmonary hypertensive crisis and there were no intolerable side effects related to sildenafil in either group. Mean pulmonary artery pressure showed a reduction in both groups. Sildenafil group showed statistically significant improvement in duration of cardiopulmonary bypass (100.27 ± 21.09 minvs. 125.40 ± 26.83 min, p = .008), mechanical ventilation requirement (22.79 ± 17.13 hvs. 30.53 ± 13.05 h; p = .04), epinephrine requirement (22% patients vs. 48% patients; p = .03) and hospital stay (6.13 ± 1.40 days vs. 7.53 ± 1.92 days; p = .05). Oral Sildenafil therapy is an inexpensive and well-tolerated method for reducing pulmonary hypertension secondary to non-restrictive ventricular septal defect. It has noteworthy advantages regarding early surgical outcomes like reduced cardiopulmonary bypass time, improved mechanical ventilation time, lower inotrope requirement and shorter hospital stay if used preoperatively in select patient population.

Comparative Study between Nifedipine Alone Versus Nifedipine Combined with Sildenafil Citrate for Cases with Threatened Preterm Labour

Background: Preterm labour (PTL) is any delivery after 20 weeks and before the completion of 37 weeks’ gestation. In preterm labour , the efficacy of tocolytic drugs has been proven to prolong pregnancy. A commonly used tocolytic drug is nifedipine which appears to be more effective than β2-adrenergic-receptor agonists and magnesium sulfate. The aim of the present study was to study the tocolytic action of nifedipine combined with sildenafil citrate and if the combination is superior to nifedipine alone in inhibiting threatened preterm labour. Methods: This interventional Study was conducted at Obstetrics and Gynecology Department, Zagazig University, from April 2019 to Febrile 2020. Included 96 pregnant women who suffered from threatened preterm labor. They were divided into two groups, group (A) included 48 cases who received Nifedipine only and group (B) included 48 cases who received Nifedipine with sildenafil. Results: our study showed that a statistically significant difference regarding maternal heart rate and mean blood pressure (mm Hge) before and after treatment in Nifedipine with sildenafil group group. But in Nifedipine only group, there was no statistically significant difference regarding maternal heart rate before and after treatment. There was statistically significant difference between the two studied groups in delivery 24,48 and 72 hours after admission with less early deliveries among the Nifedipine with sildenafil group. Regarding mode of delivery, there was no statistical significant deference between nifedipine and Nifedipine with sildenafil groups. Conclusions: Vaginal sildenafil citrate (SC) combined with nifedipine is an effective option for tocolytic therapy during threatened PTL.