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

Annalisa Inversetti; Arianna Bossi; Martina Cristodoro; Alessandro Larcher; Andrea Busnelli; Giuseppe Grande; Andrea Salonia; Nicoletta Di Simone

doi:10.1111/andr.13540

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

Andrology. 2023 Oct 25. doi: 10.1111/andr.13540. Online ahead of print.

Authors

Annalisa Inversetti^{1

2}, Arianna Bossi¹, Martina Cristodoro¹, Alessandro Larcher³, Andrea Busnelli^{1

2}, Giuseppe Grande⁴, Andrea Salonia^{3

5}, Nicoletta Di Simone^{1

2}

Affiliations

¹ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
² IRCCS Humanitas Research Hospital, Rozzano, Italy.
³ Department of Urology and Division of Experimental Oncology, URI Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁴ Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy.
⁵ Division of Experimental Oncology/Unit of Urology, Vita-Salute San Raffaele University, Milan, Italy.

PMID: 37881014
DOI: 10.1111/andr.13540

Abstract

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.

Keywords: Recurrent pregnancy loss; male component; recurrent miscarriage; sperm DNA fragmentation; sperm parameters.

Publication types

Review