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Андрология и генитальная хирургия. 2023; 24: 85-94

Изолированное повышение уровня фолликулостимулирующего гормона как прогностический фактор негативного результата microTESE

Гамидов С. И., Шатылко Т. В., Попова А. Ю., Гасанов Н. Г., Дружинина Н. К.

https://doi.org/10.17650/2070-9781-2023-24-2-85-94

Аннотация

Цель исследования – описать взаимосвязь между изолированным повышением уровня фолликулостимулирующего гормона (иФСГ) и неудачей при проведении экстракции сперматозоидов путем микродиссекции яичек (microTESE) у пациентов с азооспермией.

Материалы и методы. Проведен ретроспективный анализ результатов microTESE у 565 пациентов с необструктивной формой азооспермии (НОА). Гистологическое заключение выставляли на основании доминирующей гистологической картины и показателя по шкале Бергмана–Клиш (BKS). Описательная статистика была представлена для пациентов с иФСГ. Уровень ингибина В, частота получения сперматозоидов (ЧПС) и значение BKS сравнивали у пациентов с иФСГ и остальных пациентов.

Результаты. Общая ЧПС составила 33,3 % при попытке microTESE, медиана BKS – 0,6 балла (межквартильный диапазон – 0–2). Из всей выборки пациентов с НОА у 132 пациентов было выявлено иФСГ. Процедура microTESE была успешной только у 11 пациентов с иФСГ, при этом ЧПС составила 8,3 %, в то время как у других пациентов с НОА ЧПС составила 38,1 % (р <0,001). Чувствительность иФСГ как предиктора негативных результатов при проведении microTESE составила 32,1 % (95 % доверительный интервал 27,4–36,8), специфичность – 94,1 % (95 % доверительный интервал 90,8–97,5).

Заключение. Пациенты с иФСГ могут иметь характерный тестикулярный фенотип, ассоциированный с неудачными процедурами microTESE.

Список литературы

1. Schlegel P.N., Li P.S. Microdissection TESE: sperm retrieval in non-obstructive azoospermia. Hum Reprod Update 1998;4(4):439. DOI: 10.1093/humupd/4.4.439

2. Berookhim B.M., Palermo G.D., Zaninovic N. et al. Microdissection testicular sperm extraction in men with Sertoli cell-only testicular histology. Fertil Steril 2014;102(5):1282–6. DOI: 10.1016/j.fertnstert.2014.08.007

3. Li H., Chen L.P., Yang J. et al. Predictive value of FSH, testicular volume, and histopathological findings for the sperm retrieval rate of microdissection TESE in nonobstructive azoospermia: a metaanalysis. Asian J Androl 2018;20(1):30–6. DOI: 10.4103/aja.aja_5_17

4. Ramasamy R., Lin K., Gosden L.V. et al. High serum FSH levels in men with nonobstructive azoospermia does not affect success of microdissection testicular sperm extraction. Fertil Steril 2009;92(2):590–3. DOI: 10.1016/j.fertnstert.2008.07.1703

5. Esteves S.C., Miyaoka R., Agarwal A. An update on the clinical assessment of the infertile male. Clinics (Sao Paulo) 2011; 66(4):691–700. DOI: 10.1590/s1807-59322011000400026

6. Zegers-Hochschild F., Adamson G.D., de Mouzon J. et al. The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary on ART terminology, 2009. Fertil Steril 2009;92(5):1520–4. DOI: 10.1016/j.fertnstert.2009.09.009

7. Cooper T.G., Aitken J., Auger J. et al. WHO laboratory manual for the examination and processing of human semen. 5th edn. Geneva: WHO Press, 2010.

8. Bergmann M.N., Kliesch S. Hodenbiopsie. In: Andrologie. Ed. by W. Krause, W. Weidner. Stuttgart: Enke Verlag, 1998. Pp. 66–71.

9. Meduri G., Bachelot A., Cocca M.P. et al. Molecular pathology of the FSH receptor: new insights into FSH physiology. Mol Cell Endocrinol 2008;282(1–2):130–42. DOI: 10.1016/j.mce.2007.11.027

10. Simoni M., Gromoll J., Nieschlag E. The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr Rev 1997;18(6):739–73. DOI: 10.1210/edrv.18.6.0320

11. Themmen A.P.N., Huhtaniemi I.T. Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 2000;21(5):551–83. DOI: 10.1210/edrv.21.5.0409

12. Yang Q., Huang Y.P., Wang H.X. et al. Follicle-stimulating hormone as a predictor for sperm retrieval rate in patients with nonobstructive azoospermia: a systematic review and meta-analysis. Asian J Androl 2015;17(2):281–4. DOI: 10.4103/1008-682X.139259

13. Zeadna A., Khateeb N., Rokach L. et al. Prediction of sperm extraction in non-obstructive azoospermia patients: a machinelearning perspective. Hum Reprod 2020;35(7):1505–14. DOI: 10.1093/humrep/deaa109

14. Kelsey T.W., McConville L., Edgar A.B. et al. Follicle stimulating hormone is an accurate predictor of azoospermia in childhood cancer survivors. PLoS One 2017;12(7):e0181377. DOI: 10.1371/journal.pone.0181377

15. Amer M.K., Ahmed A.R., Abdel Hamid A.A., GamalEl Din S.F. Can spermatozoa be retrieved in non-obstructive azoospermic patients with high FSH level? A retrospective cohort study. Andrologia 2019;51(2):e13176. DOI: 10.1111/and.13176

16. Marques P., Skorupskaite K., Rosario K.S. et al. Physiology of GnRH and gonadotropin secretion. In: Endotext [Internet]. Ed. by K.R. Feingold, B. Anawalt, M.R. Blackman et al. South Dartmouth (MA): MDText.com, Inc., 2000. Available at: https://www.ncbi.nlm.nih.gov/books/NBK279070/

17. Namwanje M., Brown C.W. Activins and inhibins: roles in development, physiology, and disease. Cold Spring Harb Perspect Biol 2016;8(7):a021881. DOI: 10.1101/cshperspect.a021881

18. Yu Y., Xi Q., Wang R. et al. Intraoperative assessment of tubules in predicting microdissection testicular sperm extraction outcome in men with Sertoli cell-only syndrome. J Int Med Res 2019;47(2):722–9. DOI: 10.1177/0300060518809257

19. Gnessi L., Scarselli F., Minasi M.G. et al. Testicular histopathology, semen analysis and FSH, predictive value of sperm retrieval: supportive counseling in case of reoperation after testicular sperm extraction (TESE). BMC Urol 2018;18(1):63. DOI: 10.1186/s12894-018-0379-7

20. Liu Y.P., Qi L., Zhang N.N. et al. Follicle-stimulating hormone may predict sperm retrieval rate and guide surgical approach in patients with non-obstructive azoospermia. Reprod Biol 2020;20(4):573–9. DOI: 10.1016/j.repbio.2020.10.006

21. Zhu Z.G., Zhao Z.G., Pang Q.Y. et al. Predictive significance of serum inhibin B on testicular haploid gamete retrieval outcomes in nonobstructive azoospermic men. Asian J Androl 2019;21(2):137–42. DOI: 10.4103/aja.aja_94_18

22. Zhang H., Xi Q., Zhang X. et al. Prediction of microdissection testicular sperm extraction outcome in men with idiopathic nonobstruction azoospermia. Medicine (Baltimore) 2020;99(18):e19934. DOI: 10.1097/MD.0000000000019934

23. Chen S.C., Hsieh J.T., Yu H.J., Chang H.C. Appropriate cut-off value for follicle-stimulating hormone in azoospermia to predict spermatogenesis. Reprod Biol Endocrinol 2010;8:108. DOI: 10.1186/1477-7827-8-108

24. Das A., Halpern J.A., Darves-Bornoz A.L. et al. Sperm retrieval success and testicular histopathology in idiopathic nonobstructive azoospermia. Asian J Androl 2020;22(6):555–9. DOI: 10.4103/aja.aja_137_19

25. Kiserud C.E., Fosså A, Bjøro T. et al. Gonadal function in male patients after treatment for malignant lymphomas, with emphasis on chemotherapy. Br J Cancer 2009;100(3):455–63. DOI: 10.1038/sj.bjc.6604892

26. Veldhuis J.D., Iranmanesh A., Demers L.M., Mulligan T. Joint basal and pulsatile hypersecretory mechanisms drive the monotropic follicle-stimulating hormone (FSH) elevation in healthy older men: concurrent preservation of the orderliness of the FSH release process: a general clinical research center study. J Clin Endocrinol Metab 1999;84(10):3506–14. DOI: 10.1210/jcem.84.10.6076

Andrology and Genital Surgery. 2023; 24: 85-94

Isolated follicle-stimulating hormone elevation as a prognostic factor for negative microTESE outcome

Gamidov S. I., Shatylko T. V., Popova A. Yu., Gasanov N. G., Druzhinina N. K.

https://doi.org/10.17650/2070-9781-2023-24-2-85-94

Abstract

Aim. This study aimed to describe a distinct subpopulation of azoospermic patients with isolated elevation of follicle-stimulating hormone (iFSH) and poor outcomes of microdissection testicular sperm extraction (microTESE).

Materials and methods. A retrospective analysis of microTESE outcomes was conducted among 565 patients with non-obstructive azoospermia (NOA). Testicular pathology was assessed by the dominant histological pattern and Bergmann–Kliesch  score (BKS). Descriptive statistics were presented for the iFSH subgroup. Inhibin B levels, the sperm retrieval rate (SRR), and BKS were compared in iFSH patients and other NOA patients.

Results. The overall SRR was 33.3 % per microTESE attempt. The median BKS was 0.6 (interquartile range 0–2). Of all NOA patients, 132 had iFSH, and microTESE was successful only in 11 of those cases, with an SRR of 8.3 %, while the total SRR in other NOA patients was 38.1 % (p <0.001). iFSH had a sensitivity of 32.1 % (95 % confidence interval 27.4–36.8) and specificity of 94.1 % (95 % confidence interval 90.8–97.5) as a predictor of negative microTESE outcomes.

Conclusion. Patients with iFSH may harbor a distinct testicular phenotype with total loss of the germ cell population and poor outcomes of surgical sperm retrieval.

References

1. Schlegel P.N., Li P.S. Microdissection TESE: sperm retrieval in non-obstructive azoospermia. Hum Reprod Update 1998;4(4):439. DOI: 10.1093/humupd/4.4.439

2. Berookhim B.M., Palermo G.D., Zaninovic N. et al. Microdissection testicular sperm extraction in men with Sertoli cell-only testicular histology. Fertil Steril 2014;102(5):1282–6. DOI: 10.1016/j.fertnstert.2014.08.007

3. Li H., Chen L.P., Yang J. et al. Predictive value of FSH, testicular volume, and histopathological findings for the sperm retrieval rate of microdissection TESE in nonobstructive azoospermia: a metaanalysis. Asian J Androl 2018;20(1):30–6. DOI: 10.4103/aja.aja_5_17

4. Ramasamy R., Lin K., Gosden L.V. et al. High serum FSH levels in men with nonobstructive azoospermia does not affect success of microdissection testicular sperm extraction. Fertil Steril 2009;92(2):590–3. DOI: 10.1016/j.fertnstert.2008.07.1703

5. Esteves S.C., Miyaoka R., Agarwal A. An update on the clinical assessment of the infertile male. Clinics (Sao Paulo) 2011; 66(4):691–700. DOI: 10.1590/s1807-59322011000400026

6. Zegers-Hochschild F., Adamson G.D., de Mouzon J. et al. The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary on ART terminology, 2009. Fertil Steril 2009;92(5):1520–4. DOI: 10.1016/j.fertnstert.2009.09.009

7. Cooper T.G., Aitken J., Auger J. et al. WHO laboratory manual for the examination and processing of human semen. 5th edn. Geneva: WHO Press, 2010.

8. Bergmann M.N., Kliesch S. Hodenbiopsie. In: Andrologie. Ed. by W. Krause, W. Weidner. Stuttgart: Enke Verlag, 1998. Pp. 66–71.

9. Meduri G., Bachelot A., Cocca M.P. et al. Molecular pathology of the FSH receptor: new insights into FSH physiology. Mol Cell Endocrinol 2008;282(1–2):130–42. DOI: 10.1016/j.mce.2007.11.027

10. Simoni M., Gromoll J., Nieschlag E. The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr Rev 1997;18(6):739–73. DOI: 10.1210/edrv.18.6.0320

11. Themmen A.P.N., Huhtaniemi I.T. Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 2000;21(5):551–83. DOI: 10.1210/edrv.21.5.0409

12. Yang Q., Huang Y.P., Wang H.X. et al. Follicle-stimulating hormone as a predictor for sperm retrieval rate in patients with nonobstructive azoospermia: a systematic review and meta-analysis. Asian J Androl 2015;17(2):281–4. DOI: 10.4103/1008-682X.139259

13. Zeadna A., Khateeb N., Rokach L. et al. Prediction of sperm extraction in non-obstructive azoospermia patients: a machinelearning perspective. Hum Reprod 2020;35(7):1505–14. DOI: 10.1093/humrep/deaa109

14. Kelsey T.W., McConville L., Edgar A.B. et al. Follicle stimulating hormone is an accurate predictor of azoospermia in childhood cancer survivors. PLoS One 2017;12(7):e0181377. DOI: 10.1371/journal.pone.0181377

15. Amer M.K., Ahmed A.R., Abdel Hamid A.A., GamalEl Din S.F. Can spermatozoa be retrieved in non-obstructive azoospermic patients with high FSH level? A retrospective cohort study. Andrologia 2019;51(2):e13176. DOI: 10.1111/and.13176

16. Marques P., Skorupskaite K., Rosario K.S. et al. Physiology of GnRH and gonadotropin secretion. In: Endotext [Internet]. Ed. by K.R. Feingold, B. Anawalt, M.R. Blackman et al. South Dartmouth (MA): MDText.com, Inc., 2000. Available at: https://www.ncbi.nlm.nih.gov/books/NBK279070/

17. Namwanje M., Brown C.W. Activins and inhibins: roles in development, physiology, and disease. Cold Spring Harb Perspect Biol 2016;8(7):a021881. DOI: 10.1101/cshperspect.a021881

18. Yu Y., Xi Q., Wang R. et al. Intraoperative assessment of tubules in predicting microdissection testicular sperm extraction outcome in men with Sertoli cell-only syndrome. J Int Med Res 2019;47(2):722–9. DOI: 10.1177/0300060518809257

19. Gnessi L., Scarselli F., Minasi M.G. et al. Testicular histopathology, semen analysis and FSH, predictive value of sperm retrieval: supportive counseling in case of reoperation after testicular sperm extraction (TESE). BMC Urol 2018;18(1):63. DOI: 10.1186/s12894-018-0379-7

20. Liu Y.P., Qi L., Zhang N.N. et al. Follicle-stimulating hormone may predict sperm retrieval rate and guide surgical approach in patients with non-obstructive azoospermia. Reprod Biol 2020;20(4):573–9. DOI: 10.1016/j.repbio.2020.10.006

21. Zhu Z.G., Zhao Z.G., Pang Q.Y. et al. Predictive significance of serum inhibin B on testicular haploid gamete retrieval outcomes in nonobstructive azoospermic men. Asian J Androl 2019;21(2):137–42. DOI: 10.4103/aja.aja_94_18

22. Zhang H., Xi Q., Zhang X. et al. Prediction of microdissection testicular sperm extraction outcome in men with idiopathic nonobstruction azoospermia. Medicine (Baltimore) 2020;99(18):e19934. DOI: 10.1097/MD.0000000000019934

23. Chen S.C., Hsieh J.T., Yu H.J., Chang H.C. Appropriate cut-off value for follicle-stimulating hormone in azoospermia to predict spermatogenesis. Reprod Biol Endocrinol 2010;8:108. DOI: 10.1186/1477-7827-8-108

24. Das A., Halpern J.A., Darves-Bornoz A.L. et al. Sperm retrieval success and testicular histopathology in idiopathic nonobstructive azoospermia. Asian J Androl 2020;22(6):555–9. DOI: 10.4103/aja.aja_137_19

25. Kiserud C.E., Fosså A, Bjøro T. et al. Gonadal function in male patients after treatment for malignant lymphomas, with emphasis on chemotherapy. Br J Cancer 2009;100(3):455–63. DOI: 10.1038/sj.bjc.6604892

26. Veldhuis J.D., Iranmanesh A., Demers L.M., Mulligan T. Joint basal and pulsatile hypersecretory mechanisms drive the monotropic follicle-stimulating hormone (FSH) elevation in healthy older men: concurrent preservation of the orderliness of the FSH release process: a general clinical research center study. J Clin Endocrinol Metab 1999;84(10):3506–14. DOI: 10.1210/jcem.84.10.6076