How can male factors contribute to recurrent IVF failure?

Male factors can play a significant and sometimes under-recognised role in recurrent IVF failure, even when standard semen parameters appear normal. One of the most well-established contributors is sperm DNA fragmentation, which refers to damage within the genetic material of the sperm. Elevated DNA fragmentation has been associated with reduced blastocyst formation, impaired embryo development, and increased miscarriage risk (Sedo et al., 2017). Studies have shown that even when a good number of oocytes are retrieved, poor sperm DNA integrity can result in embryos that develop more slowly or arrest before reaching the blastocyst stage.

Although oocytes have some capacity to repair sperm DNA damage after fertilisation, this ability is limited and declines with increasing maternal age (Karabulut et al., 2025). As a result, the impact of sperm DNA damage becomes more pronounced in older female partners, were reduced oocyte quality further compromises embryo viability. This highlights the importance of considering both male and female factors together when evaluating recurrent IVF failure.

Beyond DNA fragmentation, several other male-related factors may contribute. Genetic abnormalities, such as chromosomal rearrangements or sperm aneuploidy, can have negative effects on embryo development and implantation (Zheng et al.,2017). Hormonal imbalances may affect spermatogenesis, while infections and oxidative stress can damage sperm function and DNA integrity. In addition, lifestyle factors,including smoking, obesity, alcohol consumption, and environmental exposures, have been linked to poorer sperm quality and adverse IVF outcomes. These factors should be carefully assessed as part of a comprehensive evaluation.

Physical causes should also be considered. For example, a varicocele can negatively affect sperm quality through increased scrotal temperature and oxidative stress, and in selected cases, surgical correction has been shown to improve semen parameters and potentially fertility outcomes (Fallara et al., 2023).

Importantly, identifying and addressing treatable male factors can improve the chances of success in subsequent IVF cycles. In cases where routine testing is normal but failure persists, advanced investigations may be warranted. Additionally, newer laboratory techniques, including sperm selection methods such as microfluidic sperm sorting, aim to isolate higher-quality sperm with better DNA integrity for use in IVF or ICSI.

In summary, male factors contribute meaningfully to recurrent IVF failure through a combination of genetic, functional, and environmental influences. A thorough and targeted assessment of the male partner is therefore essential, as identifying and managing these factors can help optimise outcomes and guide more personalised treatment strategies.

Alvarez Sedó C, Bilinski M, Lorenzi D, Uriondo H, Noblía F, Longobucco V, Lagar EV, Nodar F. Effect of sperm DNA fragmentation on embryo development: clinical and biological aspects. JBRA Assist Reprod. 2017 Dec 1;21(4):343-350. doi: 10.5935/1518-0557.20170061. PMID: 29116706; PMCID: PMC5714603.

Karabulut S, Kutlu P, Korkmaz O, Oria L. Impact of Maternal Age on the Repairing Capacity of Oocytes on Paternal DNA Damage. Reprod Sci. 2025 Jul;32(7):2397-2403. doi: 10.1007/s43032-025-01911-w. Epub 2025 Jun 12. PMID: 40504287; PMCID: PMC12271266.

Zheng WW, Song G, Wang QL, Liu SW, Zhu XL, Deng SM, Zhong A, Tan YM, Tan Y. Sperm DNA damage has a negative effect on early embryonic development following in vitro fertilization. Asian J Androl. 2018 Jan-Feb;20(1):75-79. doi: 10.4103/aja.aja_19_17. PMID: 28675153; PMCID: PMC5753558.

Fallara G, Capogrosso P, Pozzi E, Belladelli F, Corsini C, Boeri L, Candela L, Schifano N, Dehò F, Castiglione F, Muneer A, Montorsi F, Salonia A. The Effect of Varicocele Treatment on Fertility in Adults: A Systematic Review and Meta-analysis of Published Prospective Trials. Eur Urol Focus. 2023 Jan;9(1):154-161. doi: 10.1016/j.euf.2022.08.014. Epub 2022 Sep 20. PMID: 36151030.

What tests are used to assess male contribution in failed IVF cycles?

Assessing the male contribution in failed IVF cycles requires a more comprehensive and targeted approach than standard initial testing, as routine semen analysis alone may not detect underlying functional or genetic sperm defects. Advanced diagnostic testing can help identify subtle male factors that may be contributing to poor fertilisation, impaired embryo development, or repeated implantation failure.

One of the key investigations is sperm DNA fragmentation testing, which evaluates the integrity of sperm DNA. Elevated levels of DNA fragmentation have been associated with reduced fertilisation rates, poorer embryo quality, and increased miscarriage risk. This test is particularly valuable in cases of recurrent IVF or ICSI failure where standard semen parameters appear normal.

In addition, oxidative stress testing may be performed, as excessive reactive oxygen species can damage sperm DNA and cellular function. Identifying oxidative stress can guide the use of antioxidant therapy or lifestyle modifications to improve sperm quality.

Hormonal profiling (including testosterone, FSH, LH, and prolactin) is another important component, particularly if there are concerns about impaired spermatogenesis or endocrine dysfunction contributing to poor outcomes.

Genetic testing can also play a crucial role, especially in cases of repeated IVF failure. This may include karyotyping to detect chromosomal abnormalities, Y chromosome microdeletion testing, and, in selected cases, more advanced sperm aneuploidy testing. These investigations help identify genetic causes that may affect embryo viability or increase the risk of implantation failure and miscarriage.

Finally, testicular assessment, including physical examination and scrotal ultrasound, may be used to identify conditions such as varicocele or other structural abnormalities that could impact sperm production and quality.

Overall, these tests provide a more detailed understanding of sperm function and genetic integrity, enabling clinicians to refine treatment strategies, such as selecting ICSI over conventional IVF, considering sperm selection techniques, or addressing underlying male factor issues to improve the chances of successful outcomes.

When should the male partner be re-evaluated after IVF failure?

According to current UK and international guidance (including NICE, World Health Organization, and Human Fertilisation and Embryology Authority), the male partner should be re-evaluated in a structured and indication-based way after IVF failure, rather than automatically repeating all tests.

Firstly, guidance emphasises that male evaluation should be reconsidered after failed assisted reproductive technology (ART) cycles, particularly when there is recurrent IVF failure or poor embryo development. This reflects the understanding that male factors, especially subtle ones not detected on routine testing, may contribute to unsuccessful outcomes (ASRM).

From a UK perspective, NICE recommends that if an initial semen analysis is abnormal, it should be repeated after approximately 3 months (one full spermatogenic cycle) to confirm the findings (NICE). Similarly, World Health Organization guidance states that repeat semen analysis is only required if results are outside reference ranges and should be performed after a minimum of ~11 weeks (Esteves et al., 2026).

In the context of IVF failure, this translates into the following practical approach:

• If previous semen analysis was abnormal: The male partner should be re-evaluated with a repeat semen analysis after an appropriate interval (≈3 months), along with further investigations such as hormonal profiling or specialist andrology review if abnormalities persist.
• If semen analysis was normal but IVF has failed: Routine repetition is not always required under WHO guidance. However, re-evaluation is still clinically justified, particularly after repeated IVF failure, to investigate advanced or “hidden” male factors (e.g. sperm DNA damage, oxidative stress, or genetic abnormalities), which are not detected on standard testing.

In summary, the male partner should not be overlooked after IVF failure. Instead, reassessment should be timely, evidence-based, and guided by prior results and clinical context, ensuring that potentially correctable male factors are identified before proceeding with further treatment cycles.

DIAGNOSIS AND TREATMENT OF INFERTILITY IN MEN: AUA/ASRM GUIDELINE PART I (2021) ASRM.

Fertility problems: assessment and treatment, NICE guideline, Reference number: NG257, Published: 31 March 2026. NICE

Esteves SC. The WHO 2025 Guideline for the Prevention, Diagnosis and Treatment of Infertility: A Comprehensive Review with Focus on Male Reproductive Health. Int Braz J Urol. 2026 May-Jun;52(3):e20260121. doi: 10.1590/S1677-5538.IBJU.2026.0121. PMID: 41770990; PMCID: PMC13124196.