Sildenafil citrate decreased natural killer cell activity and enhanced chance of successful pregnancy in women with a history of recurrent miscarriage

Malgorzata Jerzak, Monika Kniotek, Jaroslaw Mrozek, Andrzej Górski, Wlodzimierz Baranowski
Fertil Steril 90(5):6 (2008), PMID 18440513

Objective: To evaluate the effect of sildenafil on peripheral natural killer (NK) cell activity in women with a history of recurrent miscarriage (RM). Design: Observational study. Setting: University teaching hospital. Patient(s): Thirty-eight nonpregnant women with a history of RM and 37 healthy women with previous successful pregnancy outcomes. Intervention(s): Patients self-administered sildenafil suppositories (25 mg intravaginally, four times a day) for 36 days. Main Outcome Measure(s): 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 @mg 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. Result(s): The NK-cell activity was significantly decreased after vaginal sildenafil therapy. Endometrial thickness was significantly increased after such therapy. Conclusion(s): Vaginal sildenafil might be an interesting therapeutic option before conception in women with histories of reproductive failure.

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Małgorzata Jerzak, Tomasz Niemiec, Anna Nowakowska, Monika Klochowicz, Andrzej Górski, Włodzimierz Baranowski
Department of Gynecology and Gynecological Oncology, Military Institute of Health Services, Warsaw, Poland;
Problem Does addition of enoxaparin to sildenafil and etanercept immunotherapy improve IVF outcome? Methods Report of a striking case with 15 IVF failures. Result When enoxaparin was added, the 16th IVF cycle generated a healthy male baby. Conclusions Combination therapy that includes a heparin may allow successful IVF outcome and this issue merits further study.
Keywords: enoxaparin; sildenafil; ivf; etanercept; ivf cycle; fail ivf; immunotherapy; pregnancy; successful pregnancy; pregnancy after; first successful; cycle; ivf outcome; after addition; successful;
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Clin Chem Lab Med. 2009 ;47 (11):1433-8  19912049
Mohamed El-Far, Abd El-Gawad El-Motwally, Ikbal Abou Hashem, Nadia Bakry
Division of Biochemistry, Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt. elfarma2002@yahoo.com
BACKGROUND: Many factors have been implicated in the pathogenesis of unexplained recurrent spontaneous miscarriage (URSM). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
Keywords: sildenafil; sildenafil citrate; nkt; nkt cell; miscarriage; intravaginal; citrate; unexplain recurrent; recurrent spontaneou; spontaneou miscarriage; egypt; ftp; threaten miscarriage; tablet; antioxidant;
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A Polish study (1) – published in Fertility and Sterility – evaluated the effectiveness of sildenafil on peripheral natural killer (NK) cell activity in women who had experienced recurrent miscarriages (RM). In this study thirty eight women with recurrent losses and thirty seven healthy controls with prior successful pregnancies were followed. The treatment consisted of four 25 mg sildenafil suppositories per day for thirty six days.
In a further Egyptian study (2) sildenafil citrate tablets were applied as suppositories (25 mg 4 times/day for 24 days) to treat threatened miscarriage in women with a history of unexplained recurrent spontaneous miscarriage.
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