Urologist V.I. Kulakov National Medical Research Center
Introduction: Recurrent pregnancy loss and IVF failures may be attributed, among other factors, to sperm DNA fragmentation (SDF). Many conditions and lifestyle factors potentially cause sperm DNA damage, but it is currently unknown where exactly this damage occurs – in testis, epididymis or other portion of seminal tract. Various studies have demonstrated lower SDF index in testicular sperm when compared to ejaculated sperm. Intracytoplasmic testicular sperm injection (Testi-ICSI) is a controversial technique using surgically retrieved sperm from non-azoospermic men to improve IVF outcomes. We sought to evaluate histopathology of seminiferous tubules obtained during sperm retrieval for Testi-ICSI.
Methods: This is an ongoing prospective study. The inclusion criteria are: recurrent pregnancy loss or at least 2 IVF failures, elevated DNA fragmentation index (TUNEL > 15%). The exclusion criteria are: known female factor causing pregnancy loss or IVF failures, abnormal karyotype, oligozoospermia (concentration < 15 × 106; total sperm count < 39 × 106), treatable causes of increased SDF index, history of hormone therapy. Eighteen patients underwent testicular sperm extraction (TESE) for Testi-ICSI. A portion of extracted tissue was sent to pathology. Specimens taken from 5 patients undergoing TESE for obstructive azoospermia (duration of obstruction less than 5 years) were used as controls. Bergmann-Kliesch score (BKS) was used to assess seminiferous tubules histology. Fisher’s exact test and Mann-Whitney test were used as a part of statistical analysis.
Results: Median DNA fragmentation index for ejaculated sperm was 26% (interquartile range [IQR]: 23-30). Median percentage of seminiferous tubules containing elongated spermatids was 74% (IQR: 61-89), while in control specimens it was 92% (IQR: 90-95), which was a statistically significant difference (p = 0.0251). Median BKS in Testi-ICSI specimens was 7 (IQR: 6-9), which was significantly lower than in control specimens (median: 9; IQR: 9-10; p = 0.0271). Hypospermatogenesis was a dominant histological pattern in 10 of 18 Testi-ICSI specimens (55.5%), while all control specimens had features of normal spermatogenesis (p = 0.0457).
Conclusions: High prevalence of hypospermatogenesis in non-oligozoospermic patients was an unexpected finding. In theory, Testi-ICSI should work better in cases of post-testicular sperm DNA damage. However, we have found histological evidence of spermatogenic failure in some patients, which hints at probable testicular origin of SDF, which is yet to be correlated with Testi-ICSI outcomes.
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