БИОХИМИЧЕСКИЕ И УЛЬТРАЗВУКОВЫЕ ДЕТЕРМИНАНТЫ ОВАРИАЛЬНОГО РЕЗЕРВА (ЛИТЕРАТУРНЫЙ ОБЗОР)
Основное содержимое статьи
Аннотация
Цель исследования – провести анализ современных данных литературы, посвященных методам оценки овариального резерва, их диагностической ценности, преимуществам и ограничениям.
Материалы и методы. Проведен анализ научной литературы с использованием баз данных Web of Science, Scopus, PubMed, eLibrary.ru, научной поисковой системы Google Scholar и клинической справочной системы UpToDate по ключевым словам на русском и английском языках. В обзор включены клинические рекомендации, систематические обзоры, метаанализы, проспективные и ретроспективные исследования. Основную часть источников составили публикации последнего десятилетия; были включены отдельные более ранние исследования с учетом их значимости для рассматриваемой темы.
Результаты. Установлено, что антимюллеров гормон (АМГ) и количество антральных фолликулов являются основными маркерами овариального резерва. При этом отмечается внутрицикловая и межцикловая вариабельность уровня АМГ. Использование гормональных контрацептивов сопровождается снижением концентрации АМГ в зависимости от метода контрацепции, а после их отмены показатель восстанавливается в течение нескольких месяцев. Несоответствие между уровнем АМГ и фактическим овариальным резервом отмечается среди пациенток с бесплодием. Овариальный резерв имеет прямую корреляционную зависимость с показателями интраовариального кровотока.
Заключение. Несмотря на высокую диагностическую ценность антимюллерова гормона и подсчета количества антральных фолликулов, ни один из существующих маркеров не обладает абсолютной прогностической точностью. Оценка интраовариального кровотока может дополнить существующие методы и требует дальнейшего изучения.
Ключевые слова
Информация о статье
Информация о финансировании и конфликте интересов
Авторы заявляют об отсутствии явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.
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Список литературы
1. Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2020; 114(6): 1151-1157. doi: 10.1016/j.fertnstert.2020.09.134
2. Hariton E, Shirazi TN, Douglas NC, Hershlag A, Briggs SF. Anti-Müllerian hormone levels among contraceptive users: evidence from a cross-sectional cohort of 27,125 individuals. Am J Obstet Gynecol. 2021; 225(5): 515.e1–515.e10. doi: 10.1016/j.ajog.2021.06.052
3. Werner L, van der Schouw YT, de Kat AC. A systematic review of the association between modifiable lifestyle factors and circulating anti-Müllerian hormone. Hum Reprod Update. 2024; 30(3): 262-308. doi: 10.1093/humupd/dmae004
4. Yin WW, Huang CC, Chen YR, Yu DQ, Jin M, Feng C. The effect of medication on serum anti-müllerian hormone (AMH) levels in women of reproductive age: a meta-analysis. BMC Endocr Disord. 2022; 22(1): 158. doi: 10.1186/s12902-022-01065-9
5. Chu C, Tsuprykov O, Chen X, Elitok S, Krämer BK, Hocher B. Relationship Between Vitamin D and Hormones Important for Human Fertility in Reproductive-Aged Women. Front Endocrinol (Lausanne). 2021; 12: 666687. doi: 10.3389/fendo.2021.666687
6. Melado L, Lawrenz B, Sibal J, Abu E, Coughlan C, Navarro AT, Fatemi HM. Anti-müllerian Hormone During Natural Cycle Presents Significant Intra and Intercycle Variations When Measured With Fully Automated Assay. Front Endocrinol (Lausanne). 2018; 9: 686. doi: 10.3389/fendo.2018.00686
7. Şükür YE, Aslan B, Kaplan NB, Doğru M, Özmen B, Sönmezer M, et al. Inter-cycle variability of anti-Müllerian hormone: implications for predicting controlled ovarian stimulation cycle outcomes. J Ovarian Res. 2024; 17(1): 209. doi: 10.1186/s13048-024-01517-x
8. Hadlow N, Brown SJ, Habib A, Wardrop R, Joseph J, Gillett M, et al. Quantifying the intraindividual variation of antimüllerian hormone in the ovarian cycle. Fertil Steril. 2016; 106(5): 1230-1237. doi: 10.1016/j.fertnstert.2016.06.009
9. Biniasch M, Laubender RP, Hund M, Buck K, De Geyter C. Intra- and inter-cycle variability of anti-Müllerian hormone (AMH) levels in healthy women during non-consecutive menstrual cycles: the BICYCLE study. Clin Chem Lab Med. 2021; 60(4): 597-605. doi: 10.1515/cclm-2021-0698
10. Kissell KA, Danaher MR, Schisterman EF, Wactawski-Wende J, Ahrens KA, Schliep K, et al. Biological variability in serum anti-Müllerian hormone throughout the menstrual cycle in ovulatory and sporadic anovulatory cycles in eumenorrheic women. Hum Reprod. 2014; 29(8): 1764-1772. doi: 10.1093/humrep/deu142
11. Barbouni K, Jotautis V, Metallinou D, Diamanti A, Orovou E, Liepinaitienė A, et al. When Weight Matters: How Obesity Impacts Reproductive Health and Pregnancy-A Systematic Review. Curr Obes Rep. 2025; 14(1): 37. doi: 10.1007/s13679-025-00629-9
12. Lin XH, Wang H, Wu DD, Ullah K, Yu TT, Ur Rahman T, Huang HF. High Leptin Level Attenuates Embryo Development in Overweight/Obese Infertile Women by Inhibiting Proliferation and Promotes Apoptosis in Granule Cell. Horm Metab Res. 2017; 49(7): 534-541. doi: 10.1055/s-0043-107617
13. Punchoo R, Bhoora S. Variation in the Measurement of Anti-Müllerian Hormone - What Are the Laboratory Issues? Front Endocrinol (Lausanne). 2021; 12: 719029. doi: 10.3389/fendo.2021.719029
14. Su HI, Sammel MD, Homer MV, Bui K, Haunschild C, Stanczyk FZ. Comparability of antimüllerian hormone levels among commercially available immunoassays. Fertil Steril. 2014; 101(6): 1766-1772.e1. doi: 10.1016/j.fertnstert.2014.02.046
15. Arvis P, Rongières C, Pirrello O, Lehert P. Reliability of AMH and AFC measurements and their correlation: a large multicenter study. J Assist Reprod Genet. 2022; 39(5): 1045-1053. doi: 10.1007/s10815-022-02449-5
16. Zhang Y, Xu Y, Xue Q, Shang J, Yang X, Shan X, et al. Discordance between antral follicle counts and anti-Müllerian hormone levels in women undergoing in vitro fertilization. Reprod Biol Endocrinol. 2019; 17(1): 51. doi: 10.1186/s12958-019-0497-4
17. Ng EH, Chan CC, Yeung WS, Ho PC. Effect of age on ovarian stromal flow measured by three-dimensional ultrasound with power Doppler in Chinese women with proven fertility. Hum Reprod. 2004; 19(9): 2132-2137. doi: 10.1093/humrep/deh387
18. Kupesic S, Kurjak A, Bjelos D, Vujisic S. Three-dimensional ultrasonographic ovarian measurements and in vitro fertilization outcome are related to age. Fertil Steril. 2003; 79(1): 190-197. doi: 10.1016/s0015-0282(02)04567-3
19. Toniyan KA, Dukhin AO, Boyarintsev VV. Physiological Aspects of the Reabilitation of the Reproductive Function in Patients after Acute Gynecological Diseases. Human Physiology. 2020; 46(5): 91-99. Russian (Тониян К.А., Духин А.О., Бояринцев В.В. Физиологические аспекты восстановления репродуктивной функции у пациенток после перенесённых острых гинекологических заболеваний //Физиология человека. 2020. Т. 46, № 5. С. 91-99.) doi: 10.31857/S0131164620050136
20. Dubinskaya ED, Gasparov AS, Dutov AA, Lapteva NV, Pyatykh NS. Ovarian reserve and endometrioid ovarian cysts: clinical and ultrasound aspects. Gynecology, Obstetrics and Perinatology. 2017; 16(4): 27-34. Russian (Дубинская Е.Д., Гаспаров А.С., Дутов А.А., Лаптева Н.В., Пятых Н.С. Овариальный резерв и эндометриоидные кисты яичников: клинические и ультразвуковые аспекты //Вопросы гинекологии, акушерства и перинатологии. 2017. Т. 16, № 4. С. 27-34.) doi: 10.20953/1726-1678-2017-4-27-34
21. Mashaeva RI, Marchenko LA, Olimpieva SP, Gus AI, Kostyukov KV, Chernukha GE. Morphofunctional characteristics of ovaries determined by 2D and 3D power Doppler sonography in different clinical forms of premature ovarian failure. Obstetrics and Gynecology. 2020; 12: 129-1362020; (12):129-136. Russian (Машаева Р.И., Марченко Л.А., Олимпиева С.П., Гус А.И., Костюков К.В., Чернуха Г.Е. Анализ морфофункционального состояния яичников при различных клинических формах преждевременной недостаточности яичников с использованием энергетической допплерометрии в режиме 2D/3D //Акушерство и гинекология. 2020. № 12. С. 129-136.) doi: 10.18565/aig.2020.12.129-136
22. Jayaprakasan K, Campbell B, Hopkisson J, Clewes J, Johnson I, Raine-Fenning N. Establishing the intercycle variability of three-dimensional ultrasonographic predictors of ovarian reserve. Fertil Steril. 2008; 90(6): 2126-2132. doi: 10.1016/j.fertnstert.2007.10.028
23. Wang X, Jin L, Mao YD, Shi JZ, Huang R, Jiang YN, et al. Evaluation of Ovarian Reserve Tests and Age in the Prediction of Poor Ovarian Response to Controlled Ovarian Stimulation-A Real-World Data Analysis of 89,002 Patients. Front Endocrinol (Lausanne). 2021; 12: 702061. doi: 10.3389/fendo.2021.702061
24. Rombauts L, Lambalk CB, Schultze-Mosgau A, van Kuijk J, Verweij P, Gates D, et al. Intercycle variability of the ovarian response in patients undergoing repeated stimulation with corifollitropin alfa in a gonadotropin-releasing hormone antagonist protocol. Fertil Steril. 2015; 104(4): 884-890.e2. doi: 10.1016/j.fertnstert.2015.06.027
25. Leader B, Hegde A, Baca Q, Stone K, Lannon B, Seifer DB, et al. High frequency of discordance between antimüllerian hormone and follicle-stimulating hormone levels in serum from estradiol-confirmed days 2 to 4 of the menstrual cycle from 5,354 women in U.S. fertility centers. Fertil Steril. 2012; 98(4): 1037-1042. doi: 10.1016/j.fertnstert.2012.06.006
26. Evers JL, Slaats P, Land JA, Dumoulin JC, Dunselman GA. Elevated levels of basal estradiol-17beta predict poor response in patients with normal basal levels of follicle-stimulating hormone undergoing in vitro fertilization. Fertil Steril. 1998; 69(6): 1010-1014. doi: 10.1016/s0015-0282(98)00080-6
27. Demır MB, Çopuroğlu M, Çevik Kaya F, Yüksek Ş. Correlation between serum AMH, AFC, AND histologically quantified primordial follicles: a prospective study in premenopausal women. J Ovarian Res. 2025; 18(1): 226. doi: 10.1186/s13048-025-01807-y
28. Haadsma ML, Groen H, Fidler V, Bukman A, Roeloffzen EMA, Groenewoud ER, et al. The predictive value of ovarian reserve tests for spontaneous pregnancy in subfertile ovulatory women. Hum Reprod. 2008; 23(8): 1800-1807. doi: 10.1093/humrep/den234
29. Ignatieva RE, Gustovarova TA, Dmitrieva EV, inventors; Smolensk State Medical University, assignee. Method for assessing the state of ovarian reserve. Russian Federation patent RU 2646572 C1. 2018 Mar 5. Russian (Игнатьева Р.Е., Густоварова Т.А., Дмитриева Е.В. Способ оценки состояния овариального резерва яичников: патент РФ RU 2646572 C1; опубликован 05.03.2018)
30. Ata B, Bosch E, Broer S, Griesinger G, Grynberg M, Kolibianakis E, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI: an update in 2025. Hum Reprod. 2026; 41(4): 498-514. doi: 10.1093/humrep/deag018
31. National Institute for Health and Care Excellence (NICE). Fertility problems: assessment and treatment [Internet]. London: National Institute for Health and Care Excellence; 2026 Mar 31 [cited 2026 Oct 19]. (NICE guideline; NG257). Available from: https://www.nice.org.uk/guidance/ng257
32. Bessow C, Donato R, de Souza T, Chapon R, Genro V, Cunha-Filho JS. Antral follicle responsiveness assessed by follicular output RaTe (FORT) correlates with follicles diameter. J Ovarian Res. 2019; 12(1): 48. doi: 10.1186/s13048-019-0522-4
33. Nelson SM, Klein BM, Arce JC. Comparison of antimüllerian hormone levels and antral follicle count as predictor of ovarian response to controlled ovarian stimulation in good-prognosis patients at individual fertility clinics in two multicenter trials. Fertil Steril. 2015; 103(4): 923-930.e1. doi: 10.1016/j.fertnstert.2014.12.114
34. Jeppesen JV, Anderson RA, Kelsey TW, Christiansen SL, Kristensen SG, Jayaprakasan K, et al. Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection. Mol Hum Reprod. 2013; 19(8): 519-527. doi: 10.1093/molehr/gat024
35. Kim C, Slaughter JC, Wang ET, Appiah D, Schreiner P, Leader B, et al. Anti-Müllerian hormone, follicle stimulating hormone, antral follicle count, and risk of menopause within 5 years. Maturitas. Author manuscript. 2017; 102: 18-25. doi: 10.1016/j.maturitas.2017.04.018
36. Ruth KS, Soares ALG, Borges MC, Eliassen AH, Hankinson SE, Jones ME, et al. Genome-wide association study of anti-Müllerian hormone levels in pre-menopausal women of late reproductive age and relationship with genetic determinants of reproductive lifespan. Hum Mol Genet. 2019; 28(8): 1392-1401. doi: 10.1093/hmg/ddz015
37. Chen Y, Ye B, Yang X, Zheng J, Lin J, Zhao J. Predicting the outcome of different protocols of in vitro fertilization with anti-Mullerian hormone levels in patients with polycystic ovary syndrome. J Int Med Res. 2017; 45(3): 1138-1147. doi: 10.1177/0300060517704140
38. Yuwen T, Yang Z, Cai G, Feng G, Liu Q, Fu H. Association between serum AMH levels and IVF/ICSI outcomes in patients with polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2023; 21(1): 95. doi: 10.1186/s12958-023-01153-y
39. Delamuta LC, Fassolas G, Dias Júnior JA, Henrique LFO, Izzo FPM, Izzo CR. Antimullerian hormone levels and IVF outcomes in polycystic ovary syndrome women: a scoping review. JBRA Assist Reprod. 2024; 28(2): 299-305. doi: 10.5935/1518-0557.20230059
40. Sacha CR, Chavarro JE, Williams PL, Ford J, Zhang L, Donahoe PK, et al. Follicular fluid anti-Mullerian hormone (AMH) concentrations and outcomes of in vitro fertilization cycles with fresh embryo transfer among women at a fertility center. J Assist Reprod Genet. 2020; 37(11): 2757-2766. doi: 10.1007/s10815-020-01956-7
41. Dai X, Wang Y, Yang H, Gao T, Yu C, Cao F, et al. AMH has no role in predicting oocyte quality in women with advanced age undergoing IVF/ICSI cycles. Sci Rep. 2020; 10(1): 19750. doi: 10.1038/s41598-020-76543-y
42. Bungum L, Tagevi J, Jokubkiene L, Bungum M, Giwercman A, Macklon N, et al. The Impact of the Biological Variability or Assay Performance on AMH Measurements: A Prospective Cohort Study With AMH Tested on Three Analytical Assay-Platforms. Front Endocrinol (Lausanne). 2018; 9: 603. doi: 10.3389/fendo.2018.00603
43. Chen D, Zhu X, Wu J. Can polymorphisms of AMH/AMHR2 affect ovarian stimulation outcomes? A systematic review and meta-analysis. J Ovarian Res. 2020; 13(1): 103. doi: 10.1186/s13048-020-00699-4
44. Moridi I, Chen A, Tal O, Tal R. The Association between Vitamin D and Anti-Müllerian Hormone: A Systematic Review and Meta-Analysis. Nutrients. 2020; 12(6): 1567. doi: 10.3390/nu12061567
45. Mirsharifi MS, Shirdel S, Ghaderi E, Javedani Masroor M. Impact of Vitamin D Supplementation on IVF Outcomes in Vitamin D-Deficient Poor Responders: a Randomized Controlled Trial. Reprod Sci. 2025; 33(1): 141-149. doi: 10.1007/s43032-025-02022-2
46. Melado L, Kumar A, Kalra B, Kalafat E, Lawrenz B, Fatemi H. How to enhance prediction of clinical outcomes in poor responders: integrating high-specific assays for anti-mullerian hormone with antral follicle count. Front Endocrinol (Lausanne). 2025; 16: 1654365. doi: 10.3389/fendo.2025.1654365
47. Kazemi M, Jarrett BY, Vanden Brink H, Lin AW, Hoeger KM, Spandorfer SD, Lujan ME. Obesity, Insulin Resistance, and Hyperandrogenism Mediate the Link between Poor Diet Quality and Ovarian Dysmorphology in Reproductive-Aged Women. Nutrients. 2020; 12(7): 1953. doi: 10.3390/nu12071953
48. Melado L, Lawrenz B, Edades J, Kumar A, Fatemi H. A novel antimüllerian gene mutation in a woman with high antral follicle count and extremely low serum antimüllerian hormone levels. F S Rep. 2024; 5(2): 152-156. doi: 10.1016/j.xfre.2024.01.006