Sildenafil Supplementation for Women Undergoing Infertility Treatments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Loris Marin,Amerigo Vitagliano,Francesco Dessole,Giampiero Capobianco,Alessandra Andrisani,Luciana Bordin,Guido Ambrosini,Marco Noventa

doi:10.3390/jcm10194346

Loris Marin, Amerigo Vitagliano + Show 6 more

Open Access

https://doi.org/10.3390/jcm10194346

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Abstract

The aim of this systematic review and meta-analysis is to summarize data on the effectiveness of Sildenafil supplementation for women undergoing assisted reproduction techniques. This meta-analysis of randomized controlled trials (RCTs) evaluates the effects of Sildenafil administration during infertility treatments compared with a control group in infertile women. Outcomes evaluated were endometrial thickness (ETh) and the clinical pregnancy rate (CPR). The chemical pregnancy rate (ChPR) was also evaluated. Pooled results were expressed as the risk ratio (RR) or mean differences (MD) with a 95% confidence interval (95% CI). Women undergoing ovulation induction who received Sildenafil showed higher ETh and a higher CPR in comparison to controls. In this group, both the ETh and ChPR resulted in significantly higher values only with delayed start administration. Women undergoing fresh or frozen embryo transfer who received Sildenafil showed no significant advantages regarding ETh and CPR in comparison to controls. In this group, we found a significantly higher ChPR in women receiving Sildenafil. A subgroup analysis revealed significant advantages regarding ETh with oral administration for women undergoing fresh or frozen embryo transfer. Sildenafil therapy appears to improve endometrial thickness and pregnancy rate in women undergoing timed intercourses but it resulted not effective in IUI and IVF treatments. Further RCTs with rigorous methodology are still mandatory.

Highlights

Despite advances in assisted reproductive technologies (ARTs), the cumulative success rate of the procedures remains suboptimal, with an estimated overall pregnancy rate of around 30% [1]
We found no significant increase in the clinical pregnancy rate (CPR) in the intervention group compared to controls analyzing together (RR 1.45, 95% confidence interval (95% CI) 0.93–2.25) and separately by in vitro fertilization (IVF) and FET group
Concerning chemical pregnancy rate (ChPR), analyzing together IVF fresh-ET and frozen-ET, we found a significantly higher ChPR in the intervention group compared to controls (RR 1.47, 95% CI 1.0–2.13, p = 0.05), with no heterogeneity (I2 = 0%)

Summary

Introduction

Despite advances in assisted reproductive technologies (ARTs), the cumulative success rate of the procedures remains suboptimal, with an estimated overall pregnancy rate of around 30% [1]. Several strategies (including hormonal and non-hormonal adjuvants) have been tested with the purpose of increasing ETh in women undergoing infertility treatments, with conflicting results [7,8,9,10,11,12,13,14,15,16,17]. One of the adjuvants that showed potential beneficial effects on endometrial thickening in women undergoing infertility treatments is sildenafil citrate, a 5-phosphodiesterase inhibitor widely used for male erectile dysfunction [18]. Due to its supposed action of favoring implantation both through the increase in endometrial thickness [19] and through the immune action [20], this type of add-therapy has been studied on different types of infertile women, both those with a thin endometrium and those without an apparent endometrial problem. Implantation does not occur in about 1/3 of transfers of euploid blastocyst in women without an apparent endometrial abnormality [21]

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