Mehmet BALASAR, Ali Sami GÜRBÜZ, Ahmet ŞALVARCI

Ten-year outcomes of patients who developed persistent azoospermia following chemotherapy associated with different oncological diagnoses: A retrospective cohort study from a different perspective

Background/aim: This study evaluated the treatment procedures for chemotherapy (CT)-induced persistent azoospermia and their outcomes from a different perspective. Materials and methods: In 63 patients (mean age: 30.16 ± 4.91 years) who had undergone CT 11 ± 5 years earlier, the semen volume, gonadotropins level, FSH level, genetics, micro-testicular sperm extraction (m-TESE) result, sperm DNA fragmentation index (SDFI), semen reactive oxidative stress (ROS) rate, duration of embryonic development, and pregnancy and baby take-home rates were examined. The correlations between the ROS rates and the SDFIs, m-TESE results, sperm motility, pathology scores, time-lapses, and baby take-home rates were evaluated. Results: The semen volumes were 3.5 ± 1.1/ml. The FSH level following CT was 17.87 ± 5.80 mIU/ml. A sperm rate of 34.9% was found from the m-TESE result. The mean SDFI and ROS rate were 4 () and 1.29 ± 0.51, respectively. The time-lapse was calculated as 5h. Pregnancy and live birth were achieved at 20.63% and 12.7%, respectively. In the patients with a low ROS (≤1.42) and SDFI (≤15), the m-TESE success rate was high, the FSH value was low, the pathological score and fertilization rate were elevated, the embryonic cleavage period was normal, and the pregnancy and baby take-home rates were high. Conclusion: The sperms may be detected using m-TESE in patients who develop persistent azoospermia associated with CT due to different oncological diagnoses. Our study revealed that a low FSH value and normal ejaculatory ROS rates are positive predictive factors of sperm detection before m-TESE. The motility of the sperms detected after m-TESE and normal SDFI rates were found to be positive predictive criteria of high fertilization, good embryonic cleavage, pregnancy, and live birth.

PDF

___

1. Sung H, Ferlay J, Siegel RL, Laversamme M, Soerjomataram I et al.Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians 2021;71(3):209- 249. doi: 10.3322/caac.21660
2. Schover LR, Rybicki LA, Martin BA , Bringelsen KA. Having children after cancer: A pilot survey of survivors’ attitudes and experiences. Cancer 1999;86:697-709. doi: 10.1002/(sici)1097- 0142(19990815)86:4<697::aid-cncr20>3.0.co;2-j
3. Agarwal A, Prabakaran S, Allamaneni SS . Relationship between oxidative stress, varicocele, and infertility: a metaanalysis. Reproductive Biomedicine Online 2006;12(5):630– 633. doi: 10.1016/s1472-6483(10)61190-x
4. Bui A, Sharma R, Henkel R, Agarwal A . Reactive oxygen species impact on sperm DNA and its role in male infertility. Andrologia 2018; 50(8):e13012. doi: 10.1111/and.13012
5. Spermon JR, Ramos L, Wetzels AM. Sperm integrity pre-and post-chemotherapy in men with testicular germ cell cancer. Human Reproduction 2006;21:1781-1786. doi: 10.1093/ humrep /del084
6. Shin T, Miyata A, Arai G, Okada H. Fertility in testicular cancer patients (in Japanese). Gan To Kagaku Ryoho (Japanese Journal of Cancer and Chemotherapy) 2015;42:267–271
7. Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J et al. Fertility Preservation in Patients with Cancer: ASCO Clinical Practice Guideline Update. Journal of Clinical Oncology 2018; 36(19):1994-2001. doi: 10.1200/JCO.2018.78.1914
8. Gorczyca W, Gong J, Darzynkiewicz Z. Detection of DNA strand breaks in individual apoptotic cells by the in situ terminal deoxynucleotidyl transferase and nick translation assays. Cancer Research 1993; 53: 1945-51
9. Agarwal A, Roychoudhury S, Sharma R, Gupta S, Majzoub A et al. Diagnostic application of oxidationreduction potential assay for measurement of oxidative stress: clinical utility in male factor infertility. Reproductive Biomedicine Online 2017;34(1):48-57. doi: 10.1016/j.rbmo. 2016. 10.008
10. Salvarci A, Gurbuz AS, Uzman S, Kaya M, Gorkemli H. Comparison of embryo morphokinetics following intracytoplasmic sperm injection in smoker and non-smoker couples: Are the results different? Journal of the Pakistan Medical Association 2017;67(10):1552-1557
11. Sigman M. Cancer treatment and male infertility: effects of therapy and current and future management options. Fertility and Sterility 2013; 100:11791186. doi: 10.1016/ j.fertnstert.2013.09.011
12. Schmidt KL, Larsen E, Bangsboll S, Meinertz H, Carlsen E et al. Assisted reproduction in male cancer survivors: Fertility treatment and outcome in 67 couples. Human Reproduction 2004;19:2806-2810. doi: 10.1093/humrep/deh518
13. Meseguer M, Garrido N, Remohí J, Pellicer A, Simon C et al. Testicular sperm extraction (TESE) and ICSI in patients with permanent azoospermia after chemotherapy. Human Reproduction 2003;18:1281–1285. doi: 10.1093 /humrep/ deg260
14. Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Human Reproduction 1999;14:131–135. 10.1093/humrep /14.1.131
15. Palermo G, Joris H, Devroey P, Van Steirtegman AC. Pregnancies after intracytoplasmic injection of single spermatozoa into an oocyte. Lancet 1992;340:17–18. doi: 10.1016/0140-6736(92)92425-f
16. Shin T, Kobayasahi T, Shimomura Y, Iwahata T, Suzuki K et al. Microdissection testicular sperm extraction in Japanese patients with persistent azoospermia after chemotherapy. International Journal of Clinical Oncology 2016; 21(6): 1167- 1171. doi: 10.1007/s10147-016-0998-5
17. Hsio W, Stahl P, Osterberg EC, Nejat E, Palermo GD et al. Successful treatment of post-chemotherapy azoospermia with microsurgical sperm extraction: the Weill Cornell experience. Journal of Clinical Oncology 2011; 20: 1607-11. doi: 10.1200/ JCO.2010. 33 .7808
18. Meistrich ML, Wilson G, Brown BW, Cunha MF . Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer 1992;70:2703- 2712. doi: 10.1002/1097-0142(19921201)70 :11<2703::aidcncr2820701123>3.0.co;2-x
19. Kenney LB, Laufer MR, Grant FD, Grier H, Diller L. High risk of infertility and long-term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer 2001;91:613-621. doi: 10.1002/1097-0142(20010201)91:3<613::aid-cncr1042> 3.0.co;2-r
20. Agarwal A, Buid AD. Oxidation-reduction potential as a new marker for oxidative stress: Correlation to male infertility. Investigative and Clinical Urology 2017;58(6):385-399. doi: 10.4111/icu. 2017.58.6.385
21. Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: a committee opinion. Fertility and Sterility 2015;103:e18–25. doi: 10.1016/j.fertnstert.2015.03.019
22. Moskovtsev SI, Jarvi K, Mullen JB, Cadesky KI, Hannam T et al. Testicular spermatozoa have statistically significantly lower DNA damage compared with ejaculated spermatozoa in patients with unsuccessful oral antioxidant treatment. Fertility and Sterility 2010; 93: 1142–1. doi: 10.1016/j. fertnstert.2008.11.005