Pentoxifylline for the treatment of endometriosis‐associated pain and infertility

Background Endometriosis is a chronic inflammatory condition that occurs during the reproductive years. It is characterised by endometrium‐like tissue developing outside the uterine cavity. This endometriotic tissue development is dependent on oestrogen produced primarily by the ovaries and partially by the endometriotic tissue itself, therefore traditional management has focused on ovarian suppression. In this review we considered the role of modulation of the immune system as an alternative approach. This is an update of a Cochrane Review previously published in 2012. Objectives To determine the effectiveness and safety of pentoxifylline in the management of endometriosis. Search methods We searched the Cochrane Gynaecology and Fertility (CGF) Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, and AMED on 16 December 2020, together with reference checking and contact with study authors and experts in the field to identify additional studies. Selection criteria We included randomised controlled trials (RCTs) comparing pentoxifylline with placebo or no treatment, other medical treatment, or surgery in women with endometriosis. The primary outcomes were live birth rate and overall pain (as measured by a visual analogue scale (VAS) of pain, other validated scales, or dichotomous outcomes) per woman randomised. Secondary outcomes included clinical pregnancy rate, miscarriage rate, rate of recurrence, and adverse events resulting from the pentoxifylline intervention. Data collection and analysis Two review authors independently assessed studies against the inclusion criteria, extracted data, and assessed risk of bias, consulting a third review author where required. We contacted study authors as needed. We analysed dichotomous outcomes using Mantel‐Haenszel risk ratios (RRs), 95% confidence intervals (CIs), and a fixed‐effect model. For small numbers of events, we used a Peto odds ratio (OR) with 95% CI instead. We analysed continuous outcomes using the mean difference (MD) between groups presented with 95% CIs. We used the I2 statistic to evaluate heterogeneity amongst studies. We employed the GRADE approach to assess the quality of the evidence. Main results We included five parallel‐design RCTs involving a total of 415 women. We included one additional RCT in this update. Three studies did not specify details relating to allocation concealment, and two studies were not blinded. There were also considerable loss to follow‐up, with four studies not c