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.