sildenafil-citrate and Abortion--Habitual

Endometrial thickness and uterine blood flow influence pregnancy continuation until term. Nifedipine, a type II calcium channel blocker, and Sildenafil, a type 5-specific phosphodiesterase inhibitor, have shown the potential to improve these factors. This study aims to compare the safety and efficacy of Nifedipine and Sildenafil in improving endometrial blood flow and thickness in Iraqi women with recurrent first-trimester miscarriages. Women with unexplained recurrent pregnancy loss in the first trimester (non-pregnant during the study) were randomly assigned to two groups. Transvaginal color Doppler ultrasound assessed uterine artery pulsatility, resistance indexes, and endometrial thickness during the second phase of the menstrual cycle (day 15 to day 25). The first group received oral Nifedipine (10 mg) twice daily, while the second group received oral Sildenafil citrate (20 mg) every 8 hours from day 5 to day 25. Baseline measurements showed no significant differences in pulsatility index between the groups (2.02±0.52 for Nifedipine, 2.03±0.49 for Sildenafil, p=0.927). Sildenafil treatment resulted in a more noticeable reduction in the pulsatility index. The resistive index had a significant difference in baseline readings (0.98±0.14 for Nifedipine, 1.06±0.14 for Sildenafil, p=0.033), with Sildenafil showing a more pronounced reduction. Post-treatment, Sildenafil demonstrated a greater improvement in endometrial thickness than Nifedipine (10.09±0.74 mm

Topics: Abortion, Habitual; Female; Humans; Nifedipine; Pregnancy; Pregnancy Trimester, First; Sildenafil Citrate

Many factors have been implicated in the pathogenesis of unexplained recurrent spontaneous miscarriage (URSM).. The objective of this preliminary clinical study was to verify whether intravaginal sildenafil citrate tablets (25 mg intravaginally, 4 times/day for 24 days) are effective as a novel treatment of threatened miscarriage in patients with a history of URSM (n=4). We also evaluated changes in the concentrations of some antioxidants, the percent expression of cells positive for tumor necrosis factor-alpha (TNF-alpha), CD56+T-cells [CD3+CD56+ natural killer cells (NKT cells) (cluster differentiation 3, 56 NKT cells)], which express one of the NK cell markers, and uterine artery pulsatility index (PI). We compared these results with healthy women in their first trimester of pregnancy (FTP n=4).. Sildenafil improved the measured antioxidants concentrations [total antioxidant capacity (TAC), glutathione S-transferase (GSH-S-T) and catalase (CAT), superoxide dismutase (SOD)], and improved oxidative stress by reducing malondialdehyde (MDA) and nitric oxide (NO) in the four patients under investigation. The improvement in antioxidants was close to concentrations seen in women in their FTP. The four patients had progressed to their third trimester of pregnancy using this novel application. The percentage of [CD3+CD56+ NKT cells] and TNF-alpha in peripheral blood was higher in URSM patients compared to women in their FTP. However, concentrations were greatly reduced and improved after sildenafil administration. We demonstrated that intravaginal sildenafil citrate tablets can reduce vasoconstriction by increasing blood flow through relaxation of uterine arteries as indicated from measured PI in URSM patients.. We conclude that intravaginal sildenafil citrate tablets used as suppositories might be a novel, interesting, safe antiabortive option in the treatment of threatened miscarriage in patients with a history of URSM. We are the first to report this novel clinical application in four case reports in Egypt.

Topics: Abortion, Habitual; Administration, Intravaginal; Adult; Egypt; Female; Humans; Piperazines; Pregnancy; Purines; Sildenafil Citrate; Sulfones; Tablets; Treatment Outcome; Young Adult

To evaluate the effect of sildenafil on peripheral natural killer (NK) cell activity in women with a history of recurrent miscarriage (RM).. Observational study.. University teaching hospital.. Thirty-eight nonpregnant women with a history of RM and 37 healthy women with previous successful pregnancy outcomes.. Patients self-administered sildenafil suppositories (25 mg intravaginally, four times a day) for 36 days.. Peripheral blood NK-cell activity before and after vaginal sildenafil therapy in the RM women was measured using flow cytometry. In addition, the influence of 10 microg and 400 ng sildenafil on NK-cell activity after in vitro culture were determined. Uterine artery blood flow and endometrial thickness were recorded using Doppler ultrasound with an intravaginal probe.. The NK-cell activity was significantly decreased after vaginal sildenafil therapy. Endometrial thickness was significantly increased after such therapy.. Vaginal sildenafil might be an interesting therapeutic option before conception in women with histories of reproductive failure.

Topics: Abortion, Habitual; Administration, Intravaginal; Adult; Arteries; Cells, Cultured; Endometrium; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Killer Cells, Natural; Live Birth; Piperazines; Pregnancy; Pregnancy Rate; Purines; Regional Blood Flow; Sildenafil Citrate; Sulfones; Suppositories; Treatment Failure; Ultrasonography, Doppler; Uterus

Does addition of Intralipid to sildenafil and enoxaparin immunotherapy improve pregnancy outcome?. Report of a striking case of a patient with history of 4 recurrent pregnancy losses (RPL) and IVF failures.. Adding of Intralipid resulted in giving birth to a healthy male baby in the 3th IVF cycle.. Combination therapy that includes Intralipid may generate successful IVF outcome, although this problem merits further study, especially regarding safety issues.

Topics: Abortion, Habitual; Adult; Enoxaparin; Female; Humans; Pregnancy; Pregnancy Outcome; Sildenafil Citrate; Treatment Outcome

Lipopolysaccharide (LPS) injections during pregnancy are well established as models for pregnancy complications, including fetal growth restriction (FGR), thrombophilia, preterm labor and abortion. Indeed, inflammation, as induced by LPS injection has been described as a pivotal factor in cases of miscarriage related to placental tissue damage. The phosphodiesterase-5 inhibitor sildenafil (Viagra®) is currently used to treat FGR cases in women, while low-molecular weight heparin (Fragmin®) is a standard treatment for recurrent miscarriage (RM). However, the pathways and cellular dynamics involved in RM are not completely understood. The aim of this study was to evaluate the protective effect of sildenafil and dalteparin in a mouse model of LPS-induced abortion. Histopathology, ultrastructural analysis and immunofluorescence for P-selectin were studied in two different placental cell types: trophoblast cells and labyrinth endothelial cells. Treatment with sildenafil either alone or in combination with heparin showed the best response against LPS-induced injury during pregnancy. In conclusion, our results support the use of these drugs as future therapeutic agents that may protect the placenta against inflammatory injury in RM events. Analyses of the ultrastructure and placental immunophysiology are important to understand the mechanism underlying RM. These findings may spark future studies and aid in the development of new therapies in cases of RM.

Topics: Abortion, Habitual; Animals; Anticoagulants; Dalteparin; Disease Models, Animal; Female; Lipopolysaccharides; Male; Mice; Phosphodiesterase 5 Inhibitors; Placenta; Pregnancy; Sildenafil Citrate; Trophoblasts

Recurrent pregnancy losses (RPL) are common women's health issues. Inflammatory and thrombotic events have been associated with RPL including excessive production of cytokines, in particular TNF-α. However, mechanisms behind gestational losses are not yet fully understood. Sildenafil inhibits phosphodiesterase Type-5 (PDE5). This drug increases intracellular cyclic guanosine monophosphate, having vasodilatory and, more recently described, anti-inflammatory properties. PDE5 is present in murine and human uterus and placenta. Sildenafil is already used clinically for treatment of human fetal growth restriction (FGR). Our objective was to determine if Sildenafil alone or in combination with Heparin had protective effects in pregnant Swiss albino challenged to abort by lipopolysaccharide (LPS).. Treatments (Sildenafil (50 mg/kg/day), Heparin (500 IU/Kg/day) or Sildenafil + Heparin at the same doses) were initiated the morning of copulation plug detection (gestational day (gd0)). On the 15th day of pregnancy, an intra-peritoneal injection of LPS (100 μg/kg) was administered. Untreated, pregnant mice challenged by LPS served as controls.. Assessments at 48 h after LPS revealed that Sildenafil + Heparin prevented fetal loss. Early assessments at 2 h after LPS indicated that the pretreatments prevented induction of inflammatory cytokine production (TNF-α, IL-1β/NF-κβ) and preserved placental histopathology.. Combined Sildenafil + Heparin therapy was superior to either treatment alone in most analyses. The known safety of Sildenafil and Heparin in human pregnancy suggests that usage of these combined agents may be of value for treatment of patients with impending pregnancy loss or prophylactically in women with a history of recurrent miscarriages.

Topics: Abortion, Habitual; Abortion, Spontaneous; Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Lipopolysaccharides; Male; Mice; Phosphodiesterase 5 Inhibitors; Placenta; Pregnancy; Sildenafil Citrate

The aim of the study was to determine serum concentrations of a proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α), in patients with recurrent abortions undergoing treatment with sildenafil or etanercept.. Serum TNF-α concentrations were determined for 24 patients with recurrent miscarriages (aged 32.7 ± 4.64 years) deemed eligible for sildenafil therapy and 7 patients treated with etanercept (aged 37.65 ± 5.45 years). Measurements were performed before and after therapy. The control group included 10 healthy women (aged 33.3 ± 5.49 years), who gave birth at least once without pregnancy-related complications. The levels of serum TNF-α were measured by Elisa.. Patients treated with etanercept had significantly elevated levels of TNF-α before therapy as compared to the control group (41.4 ± 28.4 vs. 16.6 ± 7.2 pg/ml). Moreover we found a tendency for the concentration of TNF-α to increase in sera of patients treated with sildenafil after therapy completion (19 ± 29 vs. 15.4 ± 26.7 pg/ml). Treatment with etanercept resulted in a significant reduction of serum TNF-α levels (41.4 ± 28.4 vs. 25.4 ± 3.2 pg/ml).. Therapy of recurrent abortions with anti-TNF-α drugs appears to be encouraging. Administration of blockers of phosphodiesterase type 5 or TNF-α blockers before conception seems to be a promising future therapy of immune-dependent recurrent miscarriages, limiting the teratogenic influence of the drugs on the fetus.

Topics: Abortion, Habitual; Adult; Enzyme-Linked Immunosorbent Assay; Etanercept; Female; Humans; Immunoglobulin G; Phosphodiesterase 5 Inhibitors; Piperazines; Pregnancy; Purines; Receptors, Tumor Necrosis Factor; Sildenafil Citrate; Sulfonamides; Treatment Outcome; Tumor Necrosis Factor-alpha