Recurrent pregnancy loss: a male crucial factor—A systematic review and meta‐analysis

Abstract

AbstractBackgroundRecurrent pregnancy loss (RPL), defined as two or more failed clinical pregnancies, affects 1%–3% of couples trying to conceive. Nowadays up to 50% of cases remain idiopathic. In this context, paternal factors evaluation is still very limited. The aim is to address the topic of the male factor in RPL with a broad approach, analyzing collectively data on sperm DNA fragmentation (SDF) and semen parameters. We systematically searched in Pubmed/MEDLINE and Google Scholar from inception to February 2023. A protocol has been registered on PROSPERO (ID number CRD42022278616). PRISMA guidelines were followed.MethodsPooled results from 20 studies revealed a higher DNA fragmentation rate in the RPL group compared to controls (mean difference [MD] 9.21, 95% CI 5.58–12.85, p < 0.00001, I2 98%). Age, body mass index (BMI), smoking, and alcohol intake were not associated with DNA fragmentation. Subgroup analysis by different SDF assays (TUNEL and COMET at a neutral pH vs. indirect assessment with other assays) and ethnicity did not highlight different results (p = 0.25 and 0.44).ResultsResults pooled from 25 studies showed a significant difference comparing RPL and control groups regarding ejaculation volume (MD −0.24, 95% CI −0.43; −0.06, p 0.01, I2 66%), total sperm number (MD −10.03, 95% CI −14.65; −5.41, p < 0.0001, I2 76%), total sperm motility (MD −11.20, 95% CI −16.15; −6.25, p < 0.0001, I2 96%), progressive sperm motility (MD −7.34, 95% CI −10.87; −3.80, p < 0.0001, I2 97%), and normal sperm morphology (MD −5.99, 95% CI −9.08; −2.90, p 0.0001, I2 98%). A sub‐analysis revealed that Asian and Africans, but not white‐European RPL men had lower progressive sperm motility compared to controls.ConclusionIn conclusion, current review and meta‐analysis findings suggested that SDF and some specific semen parameters were associated with RPL in a multi‐ethnic evaluation. This effort opens future direction on a growing awareness of, first, how the male factor plays a key role and, second, how appropriate would be to establish a direct dialogue between the gynecologist and the urologist.Patient summaryWe performed a systematic review and meta‐analysis on the male component of RPL. We found that sperm DNA fragmentation and some specific sperm parameters are significantly associated with RPL.