Introduction: This systematic review evaluates maternal tolerance and obstetric and perinatal outcomes following sildenafil citrate (SC) use in human pregnancy. Data Sources: Scopus, PubMed, Cochrane Library, Web of Science, Embase, and Google Scholar were searched. Relevant full-text studies including case series and reports in English were included. Publications were excluded if the pregnancy was terminated or if SC was used only at conception. Results: Sixteen studies were included (n = 165). Indications for use and outcomes were variably reported. Maternal outcomes reported were headache (45.8%, 49/107), visual disturbances (17.3%, 14/81), dyspepsia/epigastric pain (15.8%, 15/95), and hypotension (0%, 0/39). There were more caesarean (83.3%, 55/66) than vaginal deliveries (16.7%, 11/66) and postpartum haemorrhage occurred in 3.9% (3/76) of women exposed to SC. Neonatal outcomes including nursery admission (67.3%, 35/52), Apgar scores <7 at 5 min (7.1%, 4/56), and cord arterial pH <7.1 (0%, 0/17) were reported. Stillbirths (4.3%, 3/69) and neonatal deaths (3.9%, 5/129) were comparable to SC-naïve groups. There were no congenital malformations (0%, 0/35). Conclusions: Despite limited data, overall there does not appear to be any severe adverse maternal side effects nor any increase in the rate of stillbirths, neonatal deaths, or congenital anomalies attributed to SC.

1.
Mehrotra N, Gupta M, Kovar A, Meibohm B: The role of pharmacokinetics and pharmacodynamics in phosphodiesterase-5 inhibitor therapy. Int J Impot Res 2007;19:253-264.
2.
Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C: Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996;8:47-52.
3.
Sanchez Luna M, Franco ML, Bernardo B: Therapeutic strategies in pulmonary hypertension of the newborn: where are we now? Curr Med Chem 2012;19:4640-4653.
4.
Shah PS, Ohlsson A: Sildenafil for pulmonary hypertension in neonates. Cochrane Database Syst Rev 2011:CD005494.
5.
Iacovidou N, Syggelou A, Fanos V, Xanthos T: The use of sildenafil in the treatment of persistent pulmonary hypertension of the newborn: a review of the literature. Curr Pharm Des 2012;18:3034-3045.
6.
Bédard E, Dimopoulos K, Gatzoulis MA: Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J 2009;30:256-265.
7.
Običan SG, Cleary KL: Pulmonary arterial hypertension in pregnancy. Semin Perinatol 2014;38:289-294.
8.
Huang S, DeSantis ERH: Treatment of pulmonary arterial hypertension in pregnancy. Am J Health Syst Pharm 2007;64:1922-1926.
9.
Wareing M, Myers JE, O'Hara M, Baker PN: Sildenafil citrate (viagra) enhances vasodilatation in fetal growth restriction. J Clin Endocrinol Metab 2005;90:2550-2555.
10.
Wareing M, Myers JE, O'Hara M, Kenny LC, Warren AY, Taggart MJ, Skillern L, Machin I, Baker PN: Effects of a phosphodiesterase-5 (PDE5) inhibitor on endothelium-dependent relaxation of myometrial small arteries. Am J Obstet Gynecol 2004;190:1283-1290.
11.
Sher G, Fisch JD: Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF. Hum Reprod 2000;15:806-809.
12.
Dastjerdi MV, Hosseini S, Bayani L: Sildenafil citrate and uteroplacental perfusion in fetal growth restriction. J Res Med Sci 2012;17:632-636.
13.
El-Far M, El-Motwally AE-G, Hashem IA, Bakry N: Biochemical role of intravaginal sildenafil citrate as a novel antiabortive agent in unexplained recurrent spontaneous miscarriage: first clinical study of four case reports from Egypt. Clin Chem Lab Med 2009;47:1433-1438.
14.
Sher G, Fisch JD: Effect of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple IVF failures attributed to poor endometrial development. Fertil Steril 2002;78:1073-1076.
15.
Dilworth MR, Andersson I, Renshall LJ, Cowley E, Baker P, Greenwood S, Sibley CP, Wareing M: Sildenafil citrate increases fetal weight in a mouse model of fetal growth restriction with a normal vascular phenotype. PLoS One 2013;8:e77748.
16.
Subbaiah M, Kumar S, Roy KK, Sharma JB, Singh N: Pregnancy outcome in women with pulmonary arterial hypertension: single-center experience from India. Arch Gynecol Obstet 2013;288:305-309.
17.
Duarte AG, Thomas S, Safdar Z, Torres F, Pacheco LD, Feldman J: Management of pulmonary arterial hypertension during pregnancy: a retrospective, multicenter experience. Chest 2013;143:1330-1336.
18.
Kiely DGD: Improved survival in pregnancy and pulmonary hypertension using a multiprofessional approach. BJOG 2010;117:565-574.
19.
Goland S, Tsai F, Habib M, Janmohamed M, Goodwin TM, Elkayam U: Favorable outcome of pregnancy with an elective use of epoprostenol and sildenafil in women with severe pulmonary hypertension. Cardiology 2010;115:205-208.
20.
Ng WP, Yip WL: Successful maternal-foetal outcome using nitric oxide and sildenafil in pulmonary hypertension with atrial septal defect and HIV infection. Singapore Med J 2012;53:e3-e5.
21.
Molelekwa V, Akhter P, McKenna P, Bowen M, Walsh K: Eisenmenger's syndrome in a 27 week pregnancy-management with bosentan and sildenafil. Ir Med J 2005;98:87-88.
22.
Lacassie HJ, Germain AM, Valdes G, Fernandez MS, Allamand F, López H: Management of Eisenmenger syndrome in pregnancy with sildenafil and L-arginine. Obstet Gynecol 2004;103:1118-1120.
23.
Samangaya RA, Mires G, Shennan A, Skillern L, Howe D, McLeod A, Baker PN: A randomised, double-blinded, placebo-controlled study of the phosphodiesterase type 5 inhibitor sildenafil for the treatment of preeclampsia. Hypertens Pregnancy 2009;28:369-382.
24.
Trapani A Jr, Goncalves LF, Trapani TF, Vieira S, Pires M, Pires MM: Perinatal and hemodynamic evaluation of sildenafil citrate for preeclampsia treatment: a randomized controlled trial. Obstet Gynecol 2016;128:253-259.
25.
El-Far M, Hashem IMA: Novel biopharmaceutical use of sildenafil citrate in treatment of unexplained recurrent miscarriage: first longitudinal clinical study of 50 cases from Egypt. World J Pharm Pharmaceut Sci 2014;3:63-86.
26.
von Dadelszen P, Dwinnell S, Magee LA, Carleton BC, Gruslin A, Lee B, Lim KI, Liston RM, Miller SP, Rurak D, Sherlock RL, Skoll MA, Wareing MM, Baker PN; Research into Advanced Fetal Diagnosis and Therapy (RAFT) Group: Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628.
27.
Panda S, Das A, Nowroz HM: Sildenafil citrate in fetal growth restriction. J Reprod Infertil 2014;15:168.
28.
Lin T, Su Y, Shih J, Hsu H, Lee C: Resolution of high uterine artery pulsatility index and notching following sildenafil citrate treatment in a growth‐restricted pregnancy. Ultrasound Obstet Gynecol 2012;40:609-610.
29.
Trapani A, Gonçalves LF, Trapani TF, Franco MJ, Galluzzo RN, Pires MMS: Comparison between transdermal nitroglycerin and sildenafil citrate in intrauterine growth restriction: effects on uterine, umbilical and fetal middle cerebral artery pulsatility indices. Ultrasound Obstet Gynecol 2016;48:61-65.
30.
Ganzevoort W, Alfirevic Z, von Dadelszen P, Kenny L, Papageorghiou A, van Wassenaer-Leemhuis A, Gluud C, Mol BW, Baker PN: STRIDER: Sildenafil therapy in dismal prognosis early-onset intrauterine growth restriction - a protocol for a systematic review with individual participant data and aggregate data meta-analysis and trial sequential analysis. Syst Rev 2014;3:23.
31.
Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D: The care guidelines: consensus-based clinical case reporting guideline development. Headache 2013;53:1541-1547.
32.
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP: The strengthening the reporting of observational studies in epidemiology (strobe) statement: guidelines for reporting observational studies. Prev Med 2007;45:247-251.
33.
Moher D, Schulz KF, Altman DG: The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 2001;357:1191-1194.
34.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009;151:264-269.
35.
Carey TS, Boden SD: A critical guide to case series reports. Spine 2003;28:1631-1634.
36.
Bao Z, Zhang J, Yang D, Xu X: Analysis of high risk factors for patient death and its clinical characteristics on pregnancy associated with pulmonary arterial hypertension. Zhonghua Fu Chan Ke Za Zhi 2014;49:495-500.
37.
Sun X, Wang K, Wang W, Li B: Clinical study on sildenafil in treatment of pregnant women with pulmonary arterial hypertension. Zhonghua Fu Chan Ke Za Zhi 2014;49:414-418.
38.
Malinova M: Sildenafil - for treatment of preeclampsia and intrauterine growth restriction. Akush Ginekol (Sofiia) 2013;53:40-43.
39.
Taçoy G, Ekim NN, Çengel A: Dramatic response of a patient with pregnancy induced idiopathic pulmonary arterial hypertension to sildenafil treatment. J Obstet Gynaecol Res 2010;36:414-417.
40.
Abbott D, Comby P, Charuel C, Graepel P, Hanton G, Leblanc B, Lodola A, Longeart L, Paulus G, Peters C, Stadler J: Preclinical safety profile of sildenafil. Int J Impot Res 2004;16:498-504.
41.
Giuliano F, Jackson G, Montorsi F, Martin-Morales A, Raillard P: Safety of sildenafil citrate: review of 67 double-blind placebo-controlled trials and the postmarketing safety database. Int J Clin Pract 2010;64:240-255.
42.
Gresser U, Gleiter C: Erectile dysfunction: comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil - review of the literature. Eur J Med Res 2002;7:435-446.
43.
Brock GB, McMahon CG, Chen K, Costigan T, Shen W, Watkins V, Anglin G, Whitaker S: Efficacy and safety of tadalafil for the treatment of erectile dysfunction: results of integrated analyses. J Urol 2002;168:1332-1336.
44.
Hellstrom WJ, Gittelman M, Karlin G, Segerson T, Thibonnier M, Taylor T, Padma- Nathan H: Vardenafil for treatment of men with erectile dysfunction: efficacy and safety in a randomized, double-blind, placebo-controlled trial. J Androl 2002;23:763-771.
45.
Hellstrom WJ, Gittelman M, Karlin G, Segerson T, Thibonnier M, Taylor T, Padma-Nathan H, Group VS: Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial. Urology 2003;61:8-14.
46.
Galiè N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A: Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005;353:2148-2157.
47.
Ford JB, Patterson JA, Seeho SKM, Roberts CL: Trends and outcomes of postpartum haemorrhage, 2003-2011. BMC Pregnancy Childbirth 2015;15:334.
48.
Dunn L, Flenady V, Kumar S: Reducing the risk of fetal distress with sildenafil study (RIDSTRESS): a double-blind randomised control trial. J Transl Med 2016;14:15.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.