IVF/ICSI cumulative live birth rates per consumed oocyte remain comparable regardless of sperm DNA fragmentation by TUNEL

Hervás, Irene; Pacheco, A.; Rivera‐Egea, Rocío; Juliá, María Gil; Navarro-Gomezlechon, Ana; Garrido, Nicolás

doi:10.1016/j.rbmo.2022.02.010

Cited by 11 publications

(9 citation statements)

References 56 publications

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“…This could limit the reliability of our findings as DSB compared to single‐strand breaks (SSB) have a more significant impact on reproductive outcomes including both fecundity and miscarriage. Studies analyzing the same semen sample with different techniques for the assessment of SDF are thus welcomed not only to test the reliability of each method but also to further clarify the role of DSBs in the pathophysiology of RPL 30–32 …”

Section: Discussionmentioning

confidence: 99%

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Sperm DNA fragmentation and idiopathic recurrent pregnancy loss: Results from a multicenter case–control study

et al. 2023

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BackgroundSperm DNA fragmentation was hypothesized to have a role in the pathogenesis of recurrent pregnancy loss. Unfortunately, the quality of already published evidence is low.ObjectivesTo investigate the association between sperm DNA fragmentation and idiopathic recurrent pregnancy loss by limiting, as much as possible, the interference of confounding factors.Materials and methodsThis was a retrospective multicenter case–control study conducted in two Italian University Hospitals (i.e., Policlinico Gemelli, Rome and Humanitas S. Pio X, Milan) from July 2020 to March 2022. Cases were men belonging to couples affected by first trimester idiopathic recurrent pregnancy loss, defined as the previous loss of two or more pregnancies. Two control groups were selected: (i) men belonging to couples with proven fertility (i.e., at least two previous full‐term pregnancies) (control group A); (ii) men belonging to couples with proven infertility (i.e., the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse) (control group B). The sperm DNA fragmentation index was measured by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay.ResultsWe included 74 cases, 37 men with proven fertility (control group A) and 100 men belonging to infertile couples (control group B). The median sperm DNA fragmentation index was significantly lower in control group A (17%, interquartile range: 14.3%–20.6%) compared to both case group (24.5%, interquartile range: 17%–32%; p < 0.0001) and control group B (24%, interquartile range: 18.9%–30%; p = 0.001). The rate of subjects with sperm DNA fragmentation index greater than 30% was significantly higher in both case groups (28%, 95% confidence interval [18%–40%]) and control group B (26%, 95% confidence interval [18%, 36%]) compared to control group A (0%, 95% confidence interval [0%–10%]) (p < 0.001). Multivariate regression models yielded a significant association between sperm DNA fragmentation index and recurrent pregnancy loss (adjusted odds ratio 1.13, 95% confidence interval [1.04–1.23], p = 0.006), but failed to show an association between sperm DNA fragmentation index and infertility (adjusted odds ratio 1.13, 95% CI [1–1.29], p = 0.05).ConclusionsMen within couples affected by recurrent pregnancy loss or infertility had a significantly higher rate of sperm DNA fragmentation compared to fertile controls. However, after adjusting for covariates, sperm DNA fragmentation index was associated only with recurrent pregnancy loss.

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Section: Discussionmentioning

confidence: 99%

“…Studies analyzing the same semen sample with different techniques for the assessment of SDF are thus welcomed not only to test the reliability of each method but also to further clarify the role of DSBs in the pathophysiology of RPL. [30][31][32]…”

Section: Limitationsmentioning

confidence: 99%

Sperm DNA fragmentation and idiopathic recurrent pregnancy loss: Results from a multicenter case–control study

et al. 2023

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“…A recent large retrospective cohort study including 1339 women undergoing 2759 IVF/ICSI cycles reported that there was no significant difference in LBR per first ET between ≤15% and >15% SDF groups: 38.2% (95% CI 34.5–41.9; n = 665) versus 41.9% (95% CI 34.2–49.7; n = 155; OR 1.2; 95% CI 0.8–1.7; P = 0.4). Similarly, cumulative LBR was not significantly different between groups with high or low SDF ( Hervás et al , 2022 ). While SDF is suggested to be a contributing factor to RPL and unexplained infertility, data specifically in patients with RIF are scarce.…”

Section: Investigations For Rifmentioning

confidence: 87%

“…While SDF is suggested to be a contributing factor to RPL and unexplained infertility, data specifically in patients with RIF are scarce. Furthermore, there is no consensus on the cost-effectiveness of the test in general or in couples with RIF ( Minhas et al , 2021 ; Hervás et al , 2022 ).…”

Section: Investigations For Rifmentioning

confidence: 99%

ESHRE good practice recommendations on recurrent implantation failure

Cimadomo

Santos

Griesinger

et al. 2023

Human Reproduction Open

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STUDY QUESTION How should recurrent implantation failure (RIF) in patients undergoing ART be defined and managed? SUMMARY ANSWER This is the first ESHRE good practice recommendations paper providing a definition for RIF together with recommendations on how to investigate causes and contributing factors, and how to improve the chances of a pregnancy. WHAT IS KNOWN ALREADY RIF is a challenge in the ART clinic, with a multitude of investigations and interventions offered and applied in clinical practice, often without biological rationale or with unequivocal evidence of benefit. STUDY DESIGN, SIZE, DURATION This document was developed according to a predefined methodology for ESHRE good practice recommendations. Recommendations are supported by data from the literature, if available, and the results of a previously published survey on clinical practice in RIF and the expertise of the working group. A literature search was performed in PubMed and Cochrane focussing on ‘recurrent reproductive failure’, ‘recurrent implantation failure’, and ‘repeated implantation failure’. PARTICIPANTS/MATERIALS, SETTING, METHODS The ESHRE Working Group on Recurrent Implantation Failure included eight members representing the ESHRE Special Interest Groups for Implantation and Early Pregnancy, Reproductive Endocrinology, and Embryology, with an independent chair and an expert in statistics. The recommendations for clinical practice were formulated based on the expert opinion of the working group, while taking into consideration the published data and results of the survey on uptake in clinical practice. The draft document was then open to ESHRE members for online peer review and was revised in light of the comments received. MAIN RESULTS AND THE ROLE OF CHANCE The working group recommends considering RIF as a secondary phenomenon of ART, as it can only be observed in patients undergoing IVF, and that the following description of RIF be adopted: ‘RIF describes the scenario in which the transfer of embryos considered to be viable has failed to result in a positive pregnancy test sufficiently often in a specific patient to warrant consideration of further investigations and/or interventions'. It was agreed that the recommended threshold for the cumulative predicted chance of implantation to identify RIF for the purposes of initiating further investigation is 60%. When a couple have not had a successful implantation by a certain number of embryo transfers and the cumulative predicted chance of implantation associated with that number is greater than 60%, then they should be counselled on further investigation and/or treatment options. This term defines clinical RIF for which further actions should be considered. Nineteen recommendations were formulated on investigations when RIF is suspected, and 13 on interventions. Recommendations were colour-coded based on whether the investigations/interventions were recommended (green), to be considered (orange), or not recommended, i.e. not to be offered routinely (red). LIMITATIONS, REASONS FOR CAUTION While awaiting the results of further studies and trials, the ESHRE Working Group on Recurrent Implantation Failure recommends identifying RIF based on the chance of successful implantation for the individual patient or couple and to restrict investigations and treatments to those supported by a clear rationale and data indicating their likely benefit. WIDER IMPLICATIONS OF THE FINDINGS This article provides not only good practice advice but also highlights the investigations and interventions that need further research. This research, when well-conducted, will be key to making progress in the clinical management of RIF. STUDY FUNDING/COMPETING INTEREST(S) The meetings and technical support for this project were funded by ESHRE. N.M. declared consulting fees from ArtPRED (The Netherlands) and Freya Biosciences (Denmark); Honoraria for lectures from Gedeon Richter, Merck, Abbott, and IBSA; being co-founder of Verso Biosense. He is Co-Chief Editor of Reproductive Biomedicine Online (RBMO). D.C. declared being an Associate Editor of Human Reproduction Update, and declared honoraria for lectures from Merck, Organon, IBSA, and Fairtility; support for attending meetings from Cooper Surgical, Fujifilm Irvine Scientific. G.G. declared that he or his institution received financial or non-financial support for research, lectures, workshops, advisory roles, or travelling from Ferring, Merck, Gedeon-Richter, PregLem, Abbott, Vifor, Organon, MSD, Coopersurgical, ObsEVA, and ReprodWissen. He is an Editor of the journals Archives of Obstetrics and Gynecology and Reproductive Biomedicine Online, and Editor in Chief of Journal Gynäkologische Endokrinologie. He is involved in guideline developments and quality control on national and international level. G.L. declared he or his institution received honoraria for lectures from Merck, Ferring, Vianex/Organon, and MSD. He is an Associate Editor of Human Reproduction Update, immediate past Coordinator of Special Interest Group for Reproductive Endocrinology of ESHRE and has been involved in Guideline Development Groups of ESHRE and national fertility authorities. D.J.M. declared being an Associate Editor for Human Reproduction Open and statistical Advisor for Reproductive Biomedicine Online. B.T. declared being shareholder of Reprognostics and she or her institution received financial or non-financial support for research, clinical trials, lectures, workshops, advisory roles or travelling from support for attending meetings from Ferring, MSD, Exeltis, Merck Serono, Bayer, Teva, Theramex and Novartis, Astropharm, Ferring. The other authors had nothing to disclose. DISCLAIMER This Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and are based on the scientific evidence available at the time of preparation. ESHRE GPRs should be used for information and educational purposes. They should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care, or be exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, or variations based on locality and facility type. Furthermore, ESHRE GPRs do not constitute or imply the endorsement, or favouring, of any of the included technologies by ESHRE.

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“…Many studies focus on the effect of drugs on semen parameters or sperm fragmentation, with only a few studies including reproductive outcomes (fertilization rate, pregnancy rate, and live birth rate) as a primary outcome. This makes it difficult to assess the clinical relevance of these studies, particularly given recent publications that have found a lack of correlation between factors like sperm DNA fragmentation and live pregnancy rates [29 ▪ ]. In addition, pregnancy occurrence is multifactorial, and it would be unrealistic to fully attribute any pregnancy outcome to the administration of antioxidant therapy alone.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Medical management of male infertility: now and future

Chen

Kathrins

Ohlander

et al. 2022

Current Opinion in Urology

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Purpose of reviewMedical therapy for idiopathic male infertility has historically been empiric and based on small observational studies rather than larger well designed clinical trials. This review is timely and relevant because of the recent publication of several studies that are less susceptible to bias because of being placebo-controlled and more highly powered.Recent findingsThe largest proportion of recent publications covered antioxidants, with eight randomized controlled trials (RCTs) included in this review. The Males, Antioxidants, and Infertility (MOXI) trial is of particular interest, being a large multicenter RCT, which demonstrated no improvement in semen parameters or live-birth rates with antioxidant use. In addition, phosphodiesterase-5 inhibitors (PDE5i) have been shown to improve semen parameters, while duloxetine use was not associated with any adverse effects on sperm. Progress was also made in the realm of regenerative medicine, with the realization of the first successful primate model of sperm production from pluripotent stem cells.SummaryIt may be time to stop recommending antioxidants for idiopathic male infertility given recent studies suggesting lack of efficacy, but given their relative safety, it is reasonable to continue their use until the evidence is overwhelming. Otherwise, stem cell therapy is another anticipated area of research interest.

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IVF/ICSI cumulative live birth rates per consumed oocyte remain comparable regardless of sperm DNA fragmentation by TUNEL

Cited by 11 publications

References 56 publications

Sperm DNA fragmentation and idiopathic recurrent pregnancy loss: Results from a multicenter case–control study

Sperm DNA fragmentation and idiopathic recurrent pregnancy loss: Results from a multicenter case–control study

ESHRE good practice recommendations on recurrent implantation failure

Medical management of male infertility: now and future

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