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

Background: Recurrent 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. Methods: Pooled 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). Results: Results 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. Conclusion: In 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 summary: We 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.