Risk assessment of infertility due to cyclophosphamide use for premenopausal women with systemic lupus erythematosus: a meta-analysis

Background: Recent studies suggested an increased risk of infertility due to cyclophosphamide (CYC) use in premenopausal women with systemic lupus erythematosus (SLE). However, the odds ratio (OR) reported are various according to different studies. Purpose: A meta-analysis was performed regarding the influence of CYC on fertility of premenopausal women with SLE, in an effort to obtain the accurate risk arising from CYC use. Methods: We conducted PubMed, Google Scholar and Ovid database search, as well as Cochrane Library search (up to November 2015) for studies assessing the association between CYC and infertility. We performed fixed effects meta-analysis of odds ratios (OR). Heterogeneity was evaluated by Q statistics and I-2 statistic. Results: After study selection, 4 unique studies (6 comparisons) including 239 patients were available for this meta-analysis. Pooled analysis of overall infertility risk of CYC group versus Non-CYC group showed a significant increase in risk of infertility (OR=5.97; 95% CI, 3.08-11.58; P<0.00001), without any heterogeneity (I-2=0%). Stratified by study design, subgroup analysis with only randomized controlled studies revealed a significant increase of risk (OR=4.77; 95% CI, 2.17-10.48; P<0.0001) with little heterogeneity (I-2=19%). And subgroup analysis with only retrospective studies also revealed a significant increase of risk (OR=9.37; 95% CI, 2.68-32.85; P=0.0005) without heterogeneity (I-2=0%). Conclusions: This meta-analysis suggests a notably increased risk of infertility due to CYC use in the clinical practice. Physicians should carefully evaluate such risk factors for SLE patients before routinely prescribing CYC.