Андрология и генитальная хирургия. 2023; 24: 56-65
Может ли оценка уровня антимюллерова гормона в семенной плазме и сыворотке крови быть полезной в диагностике мужского бесплодия? (Обзор литературы)
https://doi.org/10.17650/2070-9781-2023-24-3-56-65Аннотация
Введение. Антимюллеров гормон (АМГ) секретируется у мужчин клетками Сертоли и играет важную роль в развитии мужских половых органов. Высокая экспрессия АМГ в период эмбрионального развития способствует регрессии мюллеровых (парамезонефрических) протоков, при отсутствии АМГ мюллеровы протоки развиваются в женские внутренние половые органы. Клиническая ценность определения АМГ в сыворотке крови и семенной плазме во взрослом возрасте остается спорной. Предполагается, что АМГ как маркер функционального состояния клеток Сертоли может быть полезен в диагностике мужского бесплодия.
Цель исследования – определение клинической ценности измерения уровня АМГ в сыворотке крови и семенной плазме в диагностике мужского бесплодия посредством изучения текущей доказательной базы мировой литературы.
Материалы и методы. Проведен поиск публикаций, посвященных изучению роли определения уровня АМГ в диагностике мужского бесплодия, в международной базе данных PubMed, научной электронной библиотеке eLIBRARY.RU и поисковой системе Google Scholar. Ограничений в отношении статуса и периода публикации не устанавливали.
Результаты и заключение. Результаты проведенного анализа указывают на отсутствие значимой взаимосвязи между параметрами эякулята и сывороточной концентрацией АМГ, что не позволяет использовать данный показатель для оценки мужской фертильности. Определение уровня сывороточного АМГ не имеет какой-либо ценности для дифференциальной диагностики обструктивной и необструктивной азооспермии, прогнозирования результатов применения вспомогательных репродуктивных технологий и предсказания результатов биопсии яичка в общей популяции пациентов с необструктивной азооспермией. Вероятно, показатель сывороточного АМГ может быть полезен для прогнозирования результатов биопсии яичка у пациентов с синдромом Клайнфельтера и идиопатической необструктивной азооспермией.
Клиническое применение измерения уровня АМГ в семенной плазме ограничено высокой вариативностью данного показателя, вероятно обусловленной зависимостью от объема эякулята и воздействия протеолитических ферментов спермы. Данный показатель может быть полезен для дифференциальной диагностики обструктивной и необструктивной азооспермии. При обструктивной азооспермии АМГ не определяется в семенной плазме, но неопределяемые концентрации АМГ могут наблюдаться также у пациентов с необструктивной азооспермией, что снижает дифференциальную ценность данного показателя. Перспективным направлением является использование показателя концентрации АМГ в семенной плазме для прогнозирования восстановления подвижности сперматозоидов после криоконсервации.
Список литературы
1. Tran D., Muesy-Dessole N., Josso N. Anti-Müllerian hormone is a functional marker of foetal Sertoli cells. Nature 1977;269(5627):411–2. DOI: 10.1038/269411a0
2. Josso N., Lamarre I., Picard J.Y. et al. Anti-müllerian hormone in early human development. Early Hum Dev 1993;33(2):91–9. DOI: 10.1016/0378-3782(93)90204-8
3. Скриганюк А.А., Харламова А.Н. Антимюллеров гормон. Universum: медицина и фармакология 2019;1(56). Доступно по: https://7universum.com/ru/med/archive/item/7020/
4. Aksglaede L., Sørensen K., Boas M. et al. Changes in anti-Müllerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. J Clin Endocrinol Metab 2010;95(12):5357–64. DOI: 10.1210/jc.2010-1207
5. Chong Y.H., Dennis N.A., Connolly M.J. et al. Elderly men have low levels of anti-Müllerian hormone and inhibin B, but with high interpersonal variation: a cross-sectional study of the sertoli cell hormones in 615 community-dwelling men. PLoS One 2013;8(8):e70967. DOI: 10.1371/journal.pone.0070967
6. Ramezani Tehrani F., Mansournia M.A., Solaymani-Dodaran M. et al. Serum variations of anti-mullerian hormone and total testosterone with aging in healthy adult Iranian men: a population-based study. 2017;12(7):e0179634. DOI: 10.1371/journal.pone.0179634
7. Kolon T.F., Herndon C.D., Baker L.A. et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol 2014;192(2):337–45. DOI: 10.1016/j.juro.2014.05.005
8. Fénichel P., Rey R., Poggioli S. et al. Anti-Müllerian hormone as a seminal marker for spermatogenesis in non-obstructive azoospermia. Hum Reprod 1999;14(8):2020–4. DOI: 10.1093/humrep/14.8.2020
9. Sinisi A.A., Esposito D., Maione L. et al. Seminal anti-Müllerian hormone level is a marker of spermatogenic response during long-term gonadotropin therapy in male hypogonadotropic hypogonadism. Hum Reprod 2008;23(5):1029–34. DOI: 10.1093/humrep/den046
10. Xu H.Y., Zhang H.X., Xiao Z. et al. Regulation of anti-Müllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility. Asian J Androl 2019;21(2):109–14. DOI: 10.4103/aja.aja_83_18
11. Young J., Rey R., Couzinet B. et al. Antimüllerian hormone in patients with hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1999;84(8):2696–9. DOI: 10.1210/jcem.84.8.5972
12. Benderradji H., Barbotin A.L., Leroy-Billiard M. et al. Defining reference ranges for serum anti-Müllerian hormone on a large cohort of normozoospermic adult men highlights new potential physiological functions of AMH on FSH secretion and sperm motility. J Clin Endocrinol Metab 2022;107(7):1878–87. DOI: 10.1210/clinem/dgac218
13. Aksglaede L., Olesen I.A., Carlsen E. et al. Serum concentration of anti-Müllerian hormone is not associated with semen quality. Andrology 2018;6(2):286–92. DOI: 10.1111/andr.12456
14. Siow Y., Fallat M.E., Amin F.A., Belker A.M. Müllerian inhibiting substance improves longevity of motility and viability of fresh and cryopreserved sperm. J Androl 1998;19(5):568–72. PMID: 9796616.
15. Rey R.A., Grinspon R.P. Normal male sexual differentiation and aetiology of disorders of sex development. Best Pract Res Clin Endocrinol Metab 2011;25(2):221–38. DOI: 10.1016/j.beem.2010.08.013
16. Völkl T.M., Dörr H.G. McCune-Albright syndrome: clinical picture and natural history in children and adolescents. J Pediatr Endocrinol Metab 2006;19(Suppl 2):551–9. DOI: 10.1515/jpem.2006.19.s2.551
17. Edelsztein N.Y., Grinspon R.P., Schteingart H.F., Rey R.A. Anti-Müllerian hormone as a marker of steroid and gonadotropin action in the testis of children and adolescents with disorders of the gonadal axis. Int J Pediatr Endocrinol 2016;2016:20. DOI: 10.1186/s13633-016-0038-2
18. Stévant I., Kühne F., Greenfield A. et al. Dissecting cell lineage specification and sex fate determination in gonadal somatic cells using single-cell transcriptomics. Cell Rep 2019;26(12):3272–83. e3. DOI: 10.1016/j.celrep.2019.02.069
19. Xu H., Zhang M., Zhang H. et al. Clinical applications of serum anti-Müllerian hormone measurements in both males and females: an update. Innovation (Camb) 2021;2(1):100091. DOI: 10.1016/j.xinn.2021.100091
20. Al-Qahtani A., Muttukrishna S., Appasamy M. et al. Development of a sensitive enzyme immunoassay for anti-Müllerian hormone and the evaluation of potential clinical applications in males and females. Clin Endocrinol (Oxf) 2005;63(3):267–73. DOI: 10.1111/j.1365-2265.2005.02336.x
21. Goulis D.G., Iliadou P. K., Tsametis C. et al. Serum anti-Müllerian hormone levels differentiate control from subfertile men but not men with different causes of subfertility. Gynecol Endocrinol 2008;24(3):158–60. DOI: 10.1080/09513590701672314
22. El-Halawaty S., Azab H., Said T. et al. Assessment of male serum anti-Mullerian hormone as a marker of spermatogenesis and ICSI outcome. Gynecol Endocrinol 2011;27(6):401–5. DOI: 10.3109/09513590.2010.495433
23. Tüttelmann F., Dykstra N., Themmen A.P. et al. Anti-Müllerian hormone in men with normal and reduced sperm concentration and men with maldescended testes. Fertil Steril 2009;91(5):1812–9. DOI: 10.1016/j.fertnstert.2008.02.118
24. Al-Chalabi S.S., Al-Wattar Y.T., Algalili I.M. Anti-Mullerian hormone is a significant marker for male infertility. Tikret J Pharm Sci 2012;8(1):1–5. Available at: https://www.iasj.net/iasj/download/6c40eab0268cfb9d
25. Andersen J.M., Herning H., Witczak O., Haugen T.B. Anti-Müllerian hormone in seminal plasma and serum: association with sperm count and sperm motility. Hum Reprod 2016;31(8):1662–7. DOI: 10.1093/humrep/dew121
26. Appasamy M., Muttukrishna S., Pizzey A. et al. Relationship between male reproductive hormones, sperm DNA damage and markers of oxidative stress in infertility. Reprod Biomed Online 2007;14(2):159–65. DOI: 10.1016/s1472-6483(10)60783-3
27. Isikoglu M., Ozgur K., Oehninger S. et al. Serum anti-Müllerian hormone levels do not predict the efficiency of testicular sperm retrieval in men with non-obstructive azoospermia. Gynecol Endocrinol 2006;22(5):256–60. DOI: 10.1080/09513590600624366
28. Fujisawa M., Yamasaki T., Okada H., Kamidono S. et al. The significance of anti-Müllerian hormone concentration in seminal plasma for spermatogenesis. Hum Reprod 2002;17(4):968–70. DOI: 10.1093/humrep/17.4.968
29. Nery S.F., Vieira M.A.F., Dela Cruz C. et al. Seminal plasma concentrations of Anti-Müllerian hormone and inhibin B predict motile sperm recovery from cryopreserved semen in asthenozoospermic men: a prospective cohort study. Andrology 2014;2(6):918–23. DOI: 10.1111/andr.278
30. Mostafa T., Amer M.K., Abdel-Malak G. et al. Seminal plasma anti-Müllerian hormone level correlates with semen parameters but does not predict success of testicular sperm extraction (TESE). Asian J Androl 2007;9(2):265–70. DOI: 10.1111/j.1745-7262.2007.00252.x
31. Duvilla E., Lejeune H., Trombert-Paviot B. et al. Significance of inhibin B and anti-Müllerian hormone in seminal plasma: a preliminary study. Fertil Steril 2008;89(2):444–8. DOI: 10.1016/j.fertnstert.2007.03.032
32. Muttukrishna S., Yussoff H., Naidu M. et al. Serum anti-Müllerian hormone and inhibin B in disorders of spermatogenesis. Fertil Steril 2007;88(2):516–8. DOI: 10.1016/j.fertnstert.2006.11.110
33. Plotton I., Garby L., Morel Y., Lejeune H. Decrease of anti-Mullerian hormone in genetic spermatogenic failure. Andrologia 2012;44(5):349–54. DOI: 10.1111/j.1439-0272.2010.01092.x
34. Deng C., Liu D., Zhao L. et al. Inhibin B-to-anti-Mullerian hormone ratio as noninvasive predictors of positive sperm retrieval in idiopathic non-obstructive azoospermia. J Clin Med 2023;12(2):500. DOI: 10.3390/jcm12020500
35. Alfano M., Ventimiglia E., Locatelli I. et al. Anti-Mullerian hormone-to-testosterone ratio is predictive of positive sperm retrieval in men with idiopathic non-obstructive azoospermia. Sci Rep 2017;7(1):17638. DOI: 10.1038/s41598-017-17420-z
36. Benderradji H., Prasivoravong J., Marcelli F. et al. Contribution of serum anti-Müllerian hormone in the management of azoospermia and the prediction of testicular sperm retrieval outcomes: a study of 155 adult men. Basic Clin Androl 2021;31(1):15. DOI: 10.1186/s12610-021-00133-9
37. Mitchell V., Boitrelle F., Pigny P. et al. Seminal plasma levels of anti-Müllerian hormone and inhibin B are not predictive of testicular sperm retrieval in nonobstructive azoospermia: a study of 139 men. Fertil Steril 2010;94(6):2147–50. DOI: 10.1016/j.fertnstert.2009.11.046
Andrology and Genital Surgery. 2023; 24: 56-65
Can evaluation of seminal plasma and serum anti-Müllerian hormone be useful in the diagnosis of male infertility? (Literature review)
https://doi.org/10.17650/2070-9781-2023-24-3-56-65Abstract
Background. Anti-Müllerian hormone (AMH) is secreted in men by Sertoli cells and plays an important role in the development of the male reproductive organs. High expression of AMH during embryonic development contributes to the regression of the Müllerian (paramesonephric) ducts; in the absence of AMH, the Müllerian ducts develop into the female internal genital organs. In adulthood, the clinical value of measuring AMH in serum and seminal plasma remains controversial. It is assumed that AMH, as a marker of the functional state of Sertoli cells, can be useful in the diagnosis of male infertility.
Aim. To determine the clinical value of measuring serum and seminal plasma AMH levels in the diagnosis of male infertility by examining the current evidence base in the world literature.
Materials and methods. A search was made for publications devoted to the study of the role of AMH in the diagnosis of male infertility in the international database PubMed, in the scientific electronic library eLIBRARY.RU and in the Google Scholar search engine. There were no restrictions regarding the status and period of publication.
Results and conclusion. The results of the analysis indicate the absence of a significant relationship between the parameters of the ejaculate and the serum concentration of AMH, which does not allow using this indicator to assess male fertility. Serum AMH is of no value in the differential diagnosis of obstructive and non-obstructive azoospermia, the prediction of assisted reproductive technologies outcomes, and the prediction of testicular biopsy outcomes in the general non-obstructive azoospermia patient population. It is likely that serum AMH may be useful in predicting testicular biopsy results in patients with Klinefelter’s syndrome and idiopathic non-obstructive azoospermia.
The clinical application of measuring the level of AMH in seminal plasma is limited by the high variability of this indicator, probably due to the dependence on the volume of the ejaculate and exposure to semen proteolytic enzymes. This indicator may be useful for the differential diagnosis of obstructive and non-obstructive azoospermia. In obstructive azoospermia, AMH is not detected in seminal plasma, but undetectable AMH concentrations can also be observed in patients with non-obstructive azoospermia, which reduces the differential value of this indicator. A promising direction is the use of AMH concentration in seminal plasma to predict the recovery of sperm motility after cryopreservation.
References
1. Tran D., Muesy-Dessole N., Josso N. Anti-Müllerian hormone is a functional marker of foetal Sertoli cells. Nature 1977;269(5627):411–2. DOI: 10.1038/269411a0
2. Josso N., Lamarre I., Picard J.Y. et al. Anti-müllerian hormone in early human development. Early Hum Dev 1993;33(2):91–9. DOI: 10.1016/0378-3782(93)90204-8
3. Skriganyuk A.A., Kharlamova A.N. Antimyullerov gormon. Universum: meditsina i farmakologiya 2019;1(56). Dostupno po: https://7universum.com/ru/med/archive/item/7020/
4. Aksglaede L., Sørensen K., Boas M. et al. Changes in anti-Müllerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. J Clin Endocrinol Metab 2010;95(12):5357–64. DOI: 10.1210/jc.2010-1207
5. Chong Y.H., Dennis N.A., Connolly M.J. et al. Elderly men have low levels of anti-Müllerian hormone and inhibin B, but with high interpersonal variation: a cross-sectional study of the sertoli cell hormones in 615 community-dwelling men. PLoS One 2013;8(8):e70967. DOI: 10.1371/journal.pone.0070967
6. Ramezani Tehrani F., Mansournia M.A., Solaymani-Dodaran M. et al. Serum variations of anti-mullerian hormone and total testosterone with aging in healthy adult Iranian men: a population-based study. 2017;12(7):e0179634. DOI: 10.1371/journal.pone.0179634
7. Kolon T.F., Herndon C.D., Baker L.A. et al. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol 2014;192(2):337–45. DOI: 10.1016/j.juro.2014.05.005
8. Fénichel P., Rey R., Poggioli S. et al. Anti-Müllerian hormone as a seminal marker for spermatogenesis in non-obstructive azoospermia. Hum Reprod 1999;14(8):2020–4. DOI: 10.1093/humrep/14.8.2020
9. Sinisi A.A., Esposito D., Maione L. et al. Seminal anti-Müllerian hormone level is a marker of spermatogenic response during long-term gonadotropin therapy in male hypogonadotropic hypogonadism. Hum Reprod 2008;23(5):1029–34. DOI: 10.1093/humrep/den046
10. Xu H.Y., Zhang H.X., Xiao Z. et al. Regulation of anti-Müllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility. Asian J Androl 2019;21(2):109–14. DOI: 10.4103/aja.aja_83_18
11. Young J., Rey R., Couzinet B. et al. Antimüllerian hormone in patients with hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1999;84(8):2696–9. DOI: 10.1210/jcem.84.8.5972
12. Benderradji H., Barbotin A.L., Leroy-Billiard M. et al. Defining reference ranges for serum anti-Müllerian hormone on a large cohort of normozoospermic adult men highlights new potential physiological functions of AMH on FSH secretion and sperm motility. J Clin Endocrinol Metab 2022;107(7):1878–87. DOI: 10.1210/clinem/dgac218
13. Aksglaede L., Olesen I.A., Carlsen E. et al. Serum concentration of anti-Müllerian hormone is not associated with semen quality. Andrology 2018;6(2):286–92. DOI: 10.1111/andr.12456
14. Siow Y., Fallat M.E., Amin F.A., Belker A.M. Müllerian inhibiting substance improves longevity of motility and viability of fresh and cryopreserved sperm. J Androl 1998;19(5):568–72. PMID: 9796616.
15. Rey R.A., Grinspon R.P. Normal male sexual differentiation and aetiology of disorders of sex development. Best Pract Res Clin Endocrinol Metab 2011;25(2):221–38. DOI: 10.1016/j.beem.2010.08.013
16. Völkl T.M., Dörr H.G. McCune-Albright syndrome: clinical picture and natural history in children and adolescents. J Pediatr Endocrinol Metab 2006;19(Suppl 2):551–9. DOI: 10.1515/jpem.2006.19.s2.551
17. Edelsztein N.Y., Grinspon R.P., Schteingart H.F., Rey R.A. Anti-Müllerian hormone as a marker of steroid and gonadotropin action in the testis of children and adolescents with disorders of the gonadal axis. Int J Pediatr Endocrinol 2016;2016:20. DOI: 10.1186/s13633-016-0038-2
18. Stévant I., Kühne F., Greenfield A. et al. Dissecting cell lineage specification and sex fate determination in gonadal somatic cells using single-cell transcriptomics. Cell Rep 2019;26(12):3272–83. e3. DOI: 10.1016/j.celrep.2019.02.069
19. Xu H., Zhang M., Zhang H. et al. Clinical applications of serum anti-Müllerian hormone measurements in both males and females: an update. Innovation (Camb) 2021;2(1):100091. DOI: 10.1016/j.xinn.2021.100091
20. Al-Qahtani A., Muttukrishna S., Appasamy M. et al. Development of a sensitive enzyme immunoassay for anti-Müllerian hormone and the evaluation of potential clinical applications in males and females. Clin Endocrinol (Oxf) 2005;63(3):267–73. DOI: 10.1111/j.1365-2265.2005.02336.x
21. Goulis D.G., Iliadou P. K., Tsametis C. et al. Serum anti-Müllerian hormone levels differentiate control from subfertile men but not men with different causes of subfertility. Gynecol Endocrinol 2008;24(3):158–60. DOI: 10.1080/09513590701672314
22. El-Halawaty S., Azab H., Said T. et al. Assessment of male serum anti-Mullerian hormone as a marker of spermatogenesis and ICSI outcome. Gynecol Endocrinol 2011;27(6):401–5. DOI: 10.3109/09513590.2010.495433
23. Tüttelmann F., Dykstra N., Themmen A.P. et al. Anti-Müllerian hormone in men with normal and reduced sperm concentration and men with maldescended testes. Fertil Steril 2009;91(5):1812–9. DOI: 10.1016/j.fertnstert.2008.02.118
24. Al-Chalabi S.S., Al-Wattar Y.T., Algalili I.M. Anti-Mullerian hormone is a significant marker for male infertility. Tikret J Pharm Sci 2012;8(1):1–5. Available at: https://www.iasj.net/iasj/download/6c40eab0268cfb9d
25. Andersen J.M., Herning H., Witczak O., Haugen T.B. Anti-Müllerian hormone in seminal plasma and serum: association with sperm count and sperm motility. Hum Reprod 2016;31(8):1662–7. DOI: 10.1093/humrep/dew121
26. Appasamy M., Muttukrishna S., Pizzey A. et al. Relationship between male reproductive hormones, sperm DNA damage and markers of oxidative stress in infertility. Reprod Biomed Online 2007;14(2):159–65. DOI: 10.1016/s1472-6483(10)60783-3
27. Isikoglu M., Ozgur K., Oehninger S. et al. Serum anti-Müllerian hormone levels do not predict the efficiency of testicular sperm retrieval in men with non-obstructive azoospermia. Gynecol Endocrinol 2006;22(5):256–60. DOI: 10.1080/09513590600624366
28. Fujisawa M., Yamasaki T., Okada H., Kamidono S. et al. The significance of anti-Müllerian hormone concentration in seminal plasma for spermatogenesis. Hum Reprod 2002;17(4):968–70. DOI: 10.1093/humrep/17.4.968
29. Nery S.F., Vieira M.A.F., Dela Cruz C. et al. Seminal plasma concentrations of Anti-Müllerian hormone and inhibin B predict motile sperm recovery from cryopreserved semen in asthenozoospermic men: a prospective cohort study. Andrology 2014;2(6):918–23. DOI: 10.1111/andr.278
30. Mostafa T., Amer M.K., Abdel-Malak G. et al. Seminal plasma anti-Müllerian hormone level correlates with semen parameters but does not predict success of testicular sperm extraction (TESE). Asian J Androl 2007;9(2):265–70. DOI: 10.1111/j.1745-7262.2007.00252.x
31. Duvilla E., Lejeune H., Trombert-Paviot B. et al. Significance of inhibin B and anti-Müllerian hormone in seminal plasma: a preliminary study. Fertil Steril 2008;89(2):444–8. DOI: 10.1016/j.fertnstert.2007.03.032
32. Muttukrishna S., Yussoff H., Naidu M. et al. Serum anti-Müllerian hormone and inhibin B in disorders of spermatogenesis. Fertil Steril 2007;88(2):516–8. DOI: 10.1016/j.fertnstert.2006.11.110
33. Plotton I., Garby L., Morel Y., Lejeune H. Decrease of anti-Mullerian hormone in genetic spermatogenic failure. Andrologia 2012;44(5):349–54. DOI: 10.1111/j.1439-0272.2010.01092.x
34. Deng C., Liu D., Zhao L. et al. Inhibin B-to-anti-Mullerian hormone ratio as noninvasive predictors of positive sperm retrieval in idiopathic non-obstructive azoospermia. J Clin Med 2023;12(2):500. DOI: 10.3390/jcm12020500
35. Alfano M., Ventimiglia E., Locatelli I. et al. Anti-Mullerian hormone-to-testosterone ratio is predictive of positive sperm retrieval in men with idiopathic non-obstructive azoospermia. Sci Rep 2017;7(1):17638. DOI: 10.1038/s41598-017-17420-z
36. Benderradji H., Prasivoravong J., Marcelli F. et al. Contribution of serum anti-Müllerian hormone in the management of azoospermia and the prediction of testicular sperm retrieval outcomes: a study of 155 adult men. Basic Clin Androl 2021;31(1):15. DOI: 10.1186/s12610-021-00133-9
37. Mitchell V., Boitrelle F., Pigny P. et al. Seminal plasma levels of anti-Müllerian hormone and inhibin B are not predictive of testicular sperm retrieval in nonobstructive azoospermia: a study of 139 men. Fertil Steril 2010;94(6):2147–50. DOI: 10.1016/j.fertnstert.2009.11.046
