Sperm DNA Fragmentation in Recurrent Pregnancy Loss

Summary

Recurrent pregnancy loss (RPL) affects approximately 1–2% of couples and has traditionally focused on maternal causes. Increasing evidence recognises the male partner’s contribution, notably through sperm DNA fragmentation (SDF), as a critical factor in early embryonic development and implantation. SDF arises from single- or double-strand breaks in the sperm genome, compromising chromatin integrity and potentially leading to compromised embryo quality, implantation failure or early miscarriage. Oxidative stress, defective chromatin packaging and apoptosis during spermatogenesis are principal drivers of DNA breakage. Assessment of SDF using assays such as the sperm chromatin structure assay (SCSA) or terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) provides a complementary dimension to standard semen analysis. Clinically, elevated SDF has been associated with reduced fertilisation rates, poor embryo development and increased miscarriage rates. Interventions under investigation include antioxidant therapy, lifestyle modification and assisted reproduction strategies tailored to minimise DNA damage, such as intracytoplasmic sperm injection following testicular sperm extraction. A clearer understanding of SDF’s mechanisms and its integration into diagnostic pathways may improve counselling, risk stratification and therapeutic outcomes for couples experiencing RPL.

Research from Nature Portfolio

Recent cross-sectional data have elucidated an unexpected link between elevated sperm DNA fragmentation and male sexual function in couples with pregnancy loss. In a cohort of over 400 men attending a specialised clinic, those with high SDF exhibited more than a two-fold increased risk of erectile dysfunction and significantly reduced coital frequency compared with normozoospermic peers. Concurrent measures of anxiety were also higher in the high-fragmentation group. These findings highlight a psychosomatic dimension in which SDF not only reflects genomic integrity but may influence intimate behaviour and psychological well-being, thereby indirectly affecting conception and gestation outcomes. The work underscores the importance of holistic assessment—including sexual health and mental status—when evaluating male partners in RPL.

Sperm DNA Fragmentation in Recurrent Pregnancy Loss publication trend

The graph below shows the total number of articles in sperm dna fragmentation in recurrent pregnancy loss across all publications each year (not limited to Nature Index journals).

Technical terms

Recurrent Pregnancy Loss (RPL): The occurrence of two or more consecutive pregnancy losses before 20 weeks of gestation.

Sperm DNA Fragmentation (SDF): The presence of single- and double-strand breaks in sperm chromatin that can impair genomic integrity and embryonic development.

DNA Fragmentation Index (DFI): A quantitative measure of the proportion of sperm with fragmented DNA within a semen sample, often expressed as a percentage.

Oxidative Stress: An imbalance between production of reactive oxygen species and antioxidant defences, leading to potential cellular and DNA damage.

Sperm Chromatin Structure Assay (SCSA): A flow cytometric technique that assesses sperm DNA integrity by measuring susceptibility of DNA to acid-induced denaturation.

References

  1. The Role of Seminal Oxidative Stress in Recurrent Pregnancy Loss. Antioxidants (2023).
  2. Relationship Among Traditional Semen Parameters, Sperm DNA Fragmentation, and Unexplained Recurrent Miscarriage: A Systematic Review and Meta-Analysis. Frontiers in Endocrinology (2022).
  3. Seminal Oxidative Stress and Sperm DNA Fragmentation in Men from Couples with Infertility or Unexplained Recurrent Pregnancy Loss. Journal of Clinical Medicine (2024).
  4. Sexual dysfunction is more common among men who have high sperm DNA fragmentation or teratozoopermia. Scientific Reports (2022).
  5. Prospective reproductive outcomes according to sperm parameters, including DNA fragmentation, in recurrent pregnancy loss. Reproductive BioMedicine Online (2023).

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