Цель исследования – разработать клинико-лабораторные критерии, характерные для оккультной (скрытой) формы преждевременной недостаточности яичников. Материал и методы. В проспективное исследование включены 22 женщины до 40 лет с оккультной формой преждевременной недостаточности яичников (ПНЯ). Проведено комплексное клинико-лабораторное обследование, включающее: гормональный профиль на 2–3-й день менструального цикла (антимюллеров гормон, фолликулостимулирующий гормон, лютеинизирующий гормон, эстрадиол), уровни биохимических и генетических маркеров (число CGG-повторов в гене FMR1). Результаты. 22 пациентки при среднем возрасте 30±6,1 года были включены в исследование. В результате нами были приняты диагностические критерии преждевременного старения яичников, на основании возможностей современных клинико-лабораторных маркеров овариального резерва, отражающие примордиальный пул фолликулов и предикторов, принимающих участие в прогнозировании наступления самопроизвольной беременности и преждевременного старения яичников. Заключение. На сегодняшний день нет единого мирового консенсуса в отношении наилучшего теста точной оценки количества и качества яйцеклеток, а также нет единого мнения в отношении стадийности преждевременного старения яичников, а также этиологии заболевания. Необходимо проведение полномасштабных многоцентровых проспективных рандомизированных контролируемых исследований, результаты которых облегчили бы консультирование пациенток и помогли бы клиницисту составить индивидуальный план лечения.
Purpose of the study. To develop clinical and laboratory criteria characteristic of the occult (hidden) form of premature ovarian failure. Material and methods. A prospective study included 22 women under 40 years old with an occult form of premature ovarian failure (POF). A comprehensive clinical and laboratory examination included: a hormonal profile on the 2–3rd day of the menstrual cycle (Anti-Muller hormone, Follicle-stimulating hormone, Luteinizing hormone, Estradiol), levels of biochemical and genetic markers (number of CGG repeats in the FMR1 gene). Results. 22 patients with an average age of 30±6.1 years were included in the study. As a result, we adopted diagnostic criteria for premature aging of the ovaries, based on the capabilities of modern clinical and laboratory markers of ovarian reserve, reflecting the primordial pool of follicles and predictors involved in predicting the onset of spontaneous pregnancy and premature aging of the ovaries. Conclusion. To date, there is no global consensus on the best test for an accurate assessment of the quantity and quality of eggs, and there is no consensus on the staging of premature ovarian aging, and the etiology of the disease. It is necessary to conduct full-scale multicenter, prospective, randomized, controlled studies, the results of which facilitated counseling patients and helping the clinician create an individualized treatment plan.
1. Cameron IT, O’Shea FC, Rolland JM et al. Occult ovarian failure: a syndrome of infertility, regular menses, and elevated follicle-stimulating hormone concentrations. J Clin Endocrinol Metab 1988; 6 (67): 1190–4.
2. Welt CK. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin Endocrinol 2008; 4 (68): 499–509.
3. European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI, Webber L, Davies M et al. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod 2016; 5 (31): 926–37.
4. Bidet M et al. Resumption of Ovarian Function and Pregnancies in 358 Patients with Premature Ovarian Failure. J Clin Endocrinol Metab 2011; 96: 3864–72.
5. Cohen J, Chabbert-Buffet N, Darai E. Diminished ovarian reserve, premature ovarian failure, poor ovarian responder – a plea for universal definitions. J Assist Reprod Gene 2015; 12 (32): 1709–12.
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10. Harlow SD, Gass M, Hall JE et al. Executive summary of the Stages of Reproductive Aging Workshop+10: addressing the unfinished agenda of staging reproductive aging. Menopause 2012; 4 (19): 387–95.
11. Klusek J et al. Curvilinear Association Between Language Disfluency and FMR1 CGG Repeat Size Across the Normal, Intermediate, and Premutation Range. Front Genet 2018; 9: 344.
12. Guzel Y, Aba YA, Yakin K et al. Menstrual cycle characteristics of young females with occult primary ovarian insufficiency at initial diagnosis and one-year follow-up with serum amh level and antral follicle count. PloS One 2017; 11 (12): e0188334.
13. Izhar R, Husain S, Tahir S et al. Occult Form of Premature Ovarian Insufficiency in Women with Infertility and Oligomenorrhea as Assessed by Poor Ovarian Response Criteria. J Reprod Infertil 2017; 4 (18): 361–7.
14. Shestakova IG, Radzinsky VE, Khamoshina MB. Occult form of premature ovarian insufficiency. Gynecol Endocrinol 2016; 32 (Suppl. 2): 30–2.
15. Streuli I, Fraisse T, Ibecheole V et al. Intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency. Fertil Steril 2009; 2 (92): 464–70.
16. Gleicher N, Weghofer A, Barad DH. A pilot study of premature ovarian senescence: I correlation of triple CGG repeats on the FMR1 gene to ovarian reserve parameters FSH and anti-Müllerian hormone. Fertil Steril 2009; 91 (5): 1700–6.
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1. Cameron IT, O’Shea FC, Rolland JM et al. Occult ovarian failure: a syndrome of infertility, regular menses, and elevated follicle-stimulating hormone concentrations. J Clin Endocrinol Metab 1988; 6 (67): 1190–4.
2. Welt CK. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin Endocrinol 2008; 4 (68): 499–509.
3. European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI, Webber L, Davies M et al. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod 2016; 5 (31): 926–37.
4. Bidet M et al. Resumption of Ovarian Function and Pregnancies in 358 Patients with Premature Ovarian Failure. J Clin Endocrinol Metab 2011; 96: 3864–72.
5. Cohen J, Chabbert-Buffet N, Darai E. Diminished ovarian reserve, premature ovarian failure, poor ovarian responder – a plea for universal definitions. J Assist Reprod Gene 2015; 12 (32): 1709–12.
6. Naidukova A.A., Kaprina E.K., Ivanets T.Iu. Vozrastnye aspekty otsenki urovnia antimiullerova gormona pri sindrome polikistoznykh iaichnikov. Akusherstvo i ginekologiia. 2017; 3: 95–100. [in Russian]
7. Gleicher N, Barad DH. The FMR1 gene as regulator of ovarian recruitment and ovarian reserve. Obstetl Gynecol Surv 2010; 8 (65): 523–30.
8. Shamilova N.N. Kliniko-prognosticheskoe znachenie molekuliarno-biologicheskikh markerov pri prezhdevremennoi nedostatochnosti iaichnikov. Dis. … kand. med. nauk. M., 2009; s. 60–128. [in Russian]
9. Iureneva S.V., Il'ina L.M., Smetnik V.P. Starenie reproduktivnoi sistemy zhenshchin: ot teorii k klinicheskoi praktike. Ch. I. Endokrinnye i klinicheskie kharakteristiki stadii reproduktivnogo stareniia zhenshchin. Akusherstvo i ginekologiia. 2014; 3: 21–7. [in Russian]
10. Harlow SD, Gass M, Hall JE et al. Executive summary of the Stages of Reproductive Aging Workshop+10: addressing the unfinished agenda of staging reproductive aging. Menopause 2012; 4 (19): 387–95.
11. Klusek J et al. Curvilinear Association Between Language Disfluency and FMR1 CGG Repeat Size Across the Normal, Intermediate, and Premutation Range. Front Genet 2018; 9: 344.
12. Guzel Y, Aba YA, Yakin K et al. Menstrual cycle characteristics of young females with occult primary ovarian insufficiency at initial diagnosis and one-year follow-up with serum amh level and antral follicle count. PloS One 2017; 11 (12): e0188334.
13. Izhar R, Husain S, Tahir S et al. Occult Form of Premature Ovarian Insufficiency in Women with Infertility and Oligomenorrhea as Assessed by Poor Ovarian Response Criteria. J Reprod Infertil 2017; 4 (18): 361–7.
14. Shestakova IG, Radzinsky VE, Khamoshina MB. Occult form of premature ovarian insufficiency. Gynecol Endocrinol 2016; 32 (Suppl. 2): 30–2.
15. Streuli I, Fraisse T, Ibecheole V et al. Intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency. Fertil Steril 2009; 2 (92): 464–70.
16. Gleicher N, Weghofer A, Barad DH. A pilot study of premature ovarian senescence: I correlation of triple CGG repeats on the FMR1 gene to ovarian reserve parameters FSH and anti-Müllerian hormone. Fertil Steril 2009; 91 (5): 1700–6.
Авторы
Л.А.Марченко*, Р.И.Машаева
ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова» Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4
*l.a.marchenko@yandex.ru
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L.A.Marchenko*, R.I.Mashaeva
V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Akademika Oparina, d. 4
*l.a.marchenko@yandex.ru