Prospective reproductive outcomes according to sperm parameters, including DNA fragmentation, in recurrent pregnancy loss

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Research question
Are the prospective reproductive outcomes in couples experiencing recurrent pregnancy loss (RPL) related to the sperm DNA fragmentation index (DFI), as measured by sperm chromatin structure assay, sperm morphology and sperm concentration at referral?

Design
This prospective cohort study included 95 couples seen between 1 April 2018 and 1 December 2019 at the tertiary Copenhagen RPL Unit, Copenhagen University Hospital, Rigshospitalet and Hvidovre Hospital, Denmark. The couples had experienced three or more unexplained consecutive pregnancy losses or two late pregnancy losses (>12 weeks gestation). Follow-up was 12–31 months.

Results
Eighty-one of 95 (85.3%) couples achieved pregnancy after referral. In the first pregnancy after referral, 46 (56.8%) couples achieved a live birth, and 35 (43.2%) couples experienced another pregnancy loss. There was no significant difference in baseline DFI between couples that experienced pregnancy loss [median 11.7, interquartile range (IQR) 9.1–17.3] and couples that achieved a live birth (median 12.5, IQR 9.3–16.5; P = 0.971). Improving sperm morphology increased the odds of a live birth after referral (adjusted OR 1.26, 95% CI 1.05–1.52; P = 0.014). DFI and sperm concentration were not associated with the outcome of the first pregnancy after referral. Overall, 35.9% of the men had DFI ≥15 at inclusion. Couples that failed to achieve pregnancy had a higher median DFI of 17.7 (IQR 7.7–27.2) compared with the rest of the cohort (median 12.0, IQR 9.3–16.5; P = 0.041).

Conclusions
At referral, sperm DFI, morphology and concentration cannot be used to identify RPL couples at risk of another pregnancy loss. Increased baseline DFI was associated with difficulty achieving another pregnancy, and improving sperm morphology was associated with increased odds of a live birth.
OriginalsprogEngelsk
Artikelnummer103773
TidsskriftReproductive BioMedicine Online
Vol/bind49
Udgave nummer2
Antal sider11
ISSN1472-6483
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
The authors wish to thank the nurses at the Recurrent Pregnancy Loss Unit, Copenhagen University Hospitals, Rigshospitalet and Hvidovre Hospital (Louise Lun\u00F8e, Karen Kirchheiner and Marie Chonovitsch) and the laboratory staff at the Department of Growth and Reproduction, Rigshospitalet. The authors also wish to thank Preben Christensen, CEO of SPZ Laboratory, for his assistance with sample analyses and expertise. Finally, the authors wish to thank Professor Emeritus Anders Nyboe Andersen for critical revision of the manuscript. This work was supported by funding from Rigshospitalet's Research Funds [MCK (#E-22614-01 and #E-22614-02), AS (E-22614-04) and SB (#E-22222-06)]. JR was funded by a Novo Nordisk Pregraduate Scholarship (NNF 190C0058877). KA received funding from Innovation Fund Denmark (#14-2013-4). Establishment and infrastructure of the MiRPL cohort were funded by an unrestricted research grant from Ferring Pharmaceuticals. The MiRPL cohort is a collaboration in the Microbiome in Reproductive Health Consortium, with the Centre for Translational Microbiome Research, Karolinska Institute, Stockholm, Sweden as the primary collaborator. MCK, HSN and KA conceptualized and designed this study. MCK, JRN, AS and KVH included patients, collected samples and performed semen analyses. MCK analysed the data and wrote the first draft of the manuscript. DW is a bioinformatician and aided with statistical analyses of the data. HSN, AMK and SB collected samples and critically revised the manuscript. All authors critically discussed and revised the manuscript, and all authors approved the submitted version.

Funding Information:
This work was supported by funding from Rigshospitalet's Research Funds ( MCK [#E-22614-01 and #E-22614-02], AS [E-22614-04], SB [#E-22222-06 ]. JR was funded by a Novo Nordisk Pregraduate Scholarship ( NNF 190C0058877 ). KA received funding from Innovation Fund Denmark [ #14-2013-4 ]. The establishment and infrastructure of the MiRPL cohort were funded by an unrestricted research grant from Ferring Pharmaceuticals. The MiRPL cohort is a collaboration in The Microbiome in Reproductive Health Consortium with the Centre for Translational Microbiome Research, Karolinska Institute, Stockholm, Sweden as the primary collaborator.

Publisher Copyright:
© 2023 The Author(s)

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