Clinical Research Directory

HMG Treatment Reduces Sperm DNA Fragmentation

Male factors account for approximately 50% of infertility cases. The principal etiologies of male infertility include sexual dysfunction, semen abnormalities arising from various etiologies, and idiopathic infertility. Semen analysis remains a key method for assessing male fertility, with semen abnormalities representing the most significant contributing factors. Common semen abnormalities include oligozoospermia, asthenozoospermia, and teratozoospermia. In recent years, elevated sperm DNA fragmentation (SDF) has emerged as an important and increasingly prevalent cause of male infertility. The World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen, Sixth Edition, likewise emphasizes the importance of sperm DNA integrity, presents several techniques, and outlines the role of SDF testing in male infertility In infertile couples, the male sperm DFI is significantly higher than that of men with normal fertility (24.5% vs 17%), and the proportion of DFI \> 30% among men in infertile couples is greater. DFI is significantly associated with recurrent pregnancy loss. A meta-analysis shows that SDF is associated with sporadic miscarriage. Recent animal studies indicate that SDF may lead to fragmentation and random distribution of paternal chromosomal segments in the developing embryo, resulting in mosaicism of different genotypes within cells. Collectively, these findings suggest that increased SDF may elevate the risk of embryonic abnormalities. In IUI cycles, low SDF is associated with higher clinical pregnancy and live birth rates. IVF-ET studies indicate a significant association between high SDF and poorer embryo quality. The clinical pregnancy rate in the higher sperm DFI group is significantly lower than that in the low-DFI group. Follicle-stimulating hormone (FSH) plays a well-established role in human spermatogenesis. In most cases of azoospermia due to hypogonadotropic hypogonadism (HH), spermatogenesis can be effectively initiated. For patients with oligoasthenoteratospermia (OAT) who have low FSH levels, FSH may be administered at the same dose used for HH, enabling these infertile men to benefit from gonadotropin-based therapy. However, in some countries, FSH is not approved for male infertility treatment. Several clinical trials have evaluated recombinant FSH therapy in men with primary infertility, showing significant improvements in sperm concentration but little or no effect on progressive motility. However, most previous studies focused on men with oligoasthenoteratozoospermia or hypogonadotropic hypogonadism. It remains unclear whether HMG therapy benefits infertile men with isolated DFI elevation but normal conventional sperm count and normal sex hormone levels. This patient subgroup represents a clinical dilemma, as treatment options are limited. Therefore, we conducted this trial to evaluate the efficacy of HMG in improving DFI in this specific population. This study aims to evaluate the efficacy of HMG treatment on sperm DFI and conventional parameters, sex hormone levels, and seminal plasma biochemical markers in infertile men with abnormal sperm DFI through a prospective controlled design.

Comparison of Two Different Sperm Processing Methods and Their Effects on Sperm DNA Fragmentation and Embryo Development

The goal of this clinical trial is to learn if the LensHooke CA0 device lowers DNA fragmentation in sperm samples compared to a gradient/swim-up technique. The main questions it aims to answer are: 1. Does the LensHooke® CA0 device reduce DNA fragmentation compared to the gradient/swim-up technique? 2. Does the LensHooke® CA0 device improve concentration, motility, and morphology compared to the gradient/swim-up technique? 3. Is sibling embryo fertilization and development the same? 4. Are pregnancy rates different between the 2 groups? 1 semen sample will be split between the 2 treatment techniques. Half of the partner's egg cohort will be injected via intra-cytoplasmic sperm using sperm processed by one technique and the other half of the cohort will be injected by the sperm processed by the other technique. Both methods will look at DNA fragmentation, concentration, motility, and morphology of the sperm. Both methods will be compared in the resulting embryos looking at fertilization, embryo development and pregnancy rates.

Nordic Sperm DNA Study

Introduction The goal of this prospective observational study with an embedded randomized controlled trial (RCT) is to investigate the prevalence and clinical significance of sperm DNA fragmentation (damage to the genetic material in sperm cells) (SDF) among men undergoing fertility treatment and to determine whether an individualized lifestyle programme can reduce SDF and improve pregnancy outcomes. The study includes approximately 800 men undergoing fertility treatment at a Danish fertility clinic. Objectives and methods The main research questions are: 1. How common is elevated SDF among Danish men undergoing fertility treatment? 2. Is elevated SDF associated with reduced live birth rates and increased early pregnancy loss? 3. Can a 3-month individualized lifestyle intervention reduce SDF in men with high SDF levels (above 20%)? The whole cohort will participate in the observational study. Participants with SDF above 20% will be invited to take part in the randomized controlled trial. In the RCT researchers will compare men randomized to an individualized lifestyle intervention with men receiving standard fertility care to determine whether the intervention reduces sperm DNA fragmentation and improves subsequent pregnancy outcomes. All participants will: * Provide semen samples for sperm DNA fragmentation testing and routine semen analysis. * Provide blood samples to measure hormones and other health markers On the basis of SDF results participants will either: * Have SDF of 20% or lower: Continue with routine fertility treatment and follow up. * Have SDF above 20%: Be randomly assigned to either a personalised 3-month lifestyle programme or standard fertility care. Participants in the lifestyle programme will receive personalised advice on diet, physical activity, smoking, alcohol, sleep, stress management and antioxidant supplements. Ethics and dissemination The study has been approved by the Regional Committee on health research ethics and complies with the General Data Protection Regulation. Written informed consent will be obtained from all participants before enrolment. Study findings will be disseminated through peer-reviewed scientific journals, conference presentations, trial registry reporting, and communication with participants and relevant stakeholders.

Royal Jelly Supplementation in Unexplained Male Infertility

This randomized, double-blind, placebo-controlled clinical trial investigates the effects of oral Royal Jelly supplementation on sperm DNA fragmentation and pregnancy rates in couples with unexplained infertility. While routine semen analysis appears normal (normozoospermia) in these patients, underlying Sperm DNA Fragmentation (SDF) and oxidative stress are believed to contribute to reproductive failure. Participants will be randomized to receive either 750 mg of lyophilized Royal Jelly or a placebo daily for a period of 3 months (90 days). The study aims to evaluate whether the antioxidant properties of Royal Jelly can improve sperm chromatin integrity, reduce oxidative stress markers, and increase spontaneous pregnancy rates compared to the control group

Clinical Thresholds of Double-strand Breaks in Sperm's DNA in ART

The goal of this prospective observational study is to learn about the impact of double-strand sperm DNA fragmentation (dsSDF) on assisted reproductive technology (ART) outcomes and to derive clinically relevant threshold values for dsSDF and global sperm DNA fragmentation (SDF) in couples undergoing intracytoplasmic sperm injection (ICSI). The main questions it aims to answer are: * Can clinically relevant threshold values of dsSDF and global SDF predict live birth rates following ICSI? * Does elevated dsSDF reduce live birth rates following ICSI? Participants undergoing ICSI as part of their routine fertility treatment will provide semen samples for global SDF and dsSDF assessment using the R10 Plus and R11 Plus kits, respectively, analysed using the LensHooke® X12 platform before and after sperm preparation. SDF and dsSDF assessments will be performed both prior to and following sperm washing for each participant. Embryos will be assessed from fertilization through embryo development, and following embryo transfer, participants will be prospectively followed for clinical outcomes ranging from biochemical pregnancy to live birth.

The EPIC Study: Exploring Paternal Age and the Influence on Blastocyst Culture

This study aims to assess the effect of age of the male partner and the reproductive ability of sperm prepared via sperm selection devices (Zymot) compared to routine embryologist selected sperm after density gradient centrifugation (DGC) preparation for intracytoplasmic sperm injection (ICSI) in patients undergoing in vitro fertilization treatment (IVF) of their infertility.