GynecologyGynecologyГинекология2079-56962079-5831Consilium Medicum3002510.26442/2079-5696_19.6.19-23ArticlesСтатьиResearch ArticleInduction of ovulation with letrozole in women with polycystic ovary syndromeИндукция овуляции летрозолом у женщин с синдромом поликистозных яичниковChernukhaG EЧернухаГалина Евгеньевна

д-р мед. наук, проф., отд-ние гинекологической эндокринологии

c-galina1@yandex.ruKaprinaE KКапринаЕлена Кайратовна

отд-ние гинекологической эндокринологии

kaprina_elena@mail.ruNaidukovaA AНайдуковаАлина Александровна

отд-ние гинекологической эндокринологии

aleeshka@mail.ruV.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian FederationФГБУ «НМИЦАГиП им. акад. В.И.Кулакова»15122017196VOL 19, NO6 (2017)ТОМ 19, №6 (2017)192309042020Copyright ©; 2017, Consilium MedicumCopyright ©; 2017, ООО "Консилиум Медикум"2017Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://gynecology.orscience.ru/2079-5831/article/view/30025

The aim of the study was to evaluate the effectiveness of the use of letrozole as an inducer of ovulation in women with polycystic ovary syndrome (PCOS) and anovulatory infertility and to determine possible clinical and laboratory predictors of the effect of therapy. Materials and methods: 61 women with anovulatory infertility and PCOS (mean age 28.5 ± 3.3 years, mean body mass index - BMI 21.8 ± 2.7 kg / m2) were included in the study. In order to induce ovulation, the patient received letrozole at a dose of 2.5-5 mg / day from day 3 to 7 of the menstrual cycle under the control of folliculometry, ultrasound m / pelvis on the 20-24 day cycle and the level of progesterone in the blood. Results: the frequency of ovulation per cycle was 77.2% (146/189), 98.4% for women, 24.9% for conception (47/189), 77% for women (47/61) , in 6 (12.8%) women the pregnancy was biochemical, in 1 (2.1%) ectopic, multiple pregnancy took place in 2 (5%) women with progressive uterine pregnancy, spontaneous abortion in the period up to 12 weeks of gestation occurred in 5 (12.5%) women, there was no case of ovarian hyperstimulation syndrome or other side effects. Comparative analysis revealed higher levels of BMI, the percentage of total adipose tissue by densitometry, and the number of antral follicles in the volume of the ovaries in the group with no pregnancy. Conclusion: letrozole is an effective medication for induction of ovulation and pregnancy in the treatment of infertility in patients with PCOS, characterized by good tolerability, low risk of multiple pregnancies and the absence of cases of ovarian hyperstimulation syndrome.

Цель исследования - оценить эффективность применения летрозола в качестве индуктора овуляции у женщин с синдромом поликистозных яичников (СПКЯ) и ановуляторным бесплодием и определить возможные клинико-лабораторные предикторы эффекта терапии. Материалы и методы. В исследование включена 61 женщина с ановуляторным бесплодием и СПКЯ (средний возраст 28,5±3,3 года, средний индекс массы тела 21,8±2,7 кг/м2). С целью индукции овуляции пациентки получали летрозол в дозе 2,5-5 мг/сут с 3 по 7-й день менструального цикла под контролем проведения фолликулометрии, ультразвукового исследования малого таза на 20-24-й день цикла и уровня прогестерона в крови. Результаты. Частота овуляции на цикл составила 77,2% (146/189) случаев, на число женщин - 98,4%, частота зачатия на цикл - 24,9% (47/189), на число женщин - 77% (47/61), у 6 (12,8%) женщин беременность оказалась биохимической, у 1 (2,1%) - внематочная, многоплодная беременность имела место у 2 (5%) женщин с прогрессирующей маточной беременностью, самопроизвольный выкидыш в сроке до 12 нед гестации произошел у 5 (12,5%) женщин, не наблюдалось случаев синдрома гиперстимуляции яичников или других побочных эффектов. Сравнительный анализ выявил более высокие уровни индекса массы тела, процента общего количества жировой ткани по денситометрии, количества антральных фолликулов в объеме яичников в группе с отсутствием беременности. Выводы. Летрозол является эффективным препаратом для индукции овуляции и наступления беременности при лечении бесплодия у пациенток с СПКЯ, характеризуется хорошей переносимостью, низким риском многоплодной беременности и отсутствием случаев синдрома гиперстимуляции яичников.

polycystic ovary syndromeinduction of ovulationletrozoleinfertilityсиндром поликистозных яичниковиндукция овуляциилетрозолбесплодиеThessaloniki ESHRE/ASRM-Sponsored PCOS Consensus WorkshopGroup. Consensus on infertility treatment related to polycystic ovarysyndrome. Hum Reprod 2008; 23: 462-77.Sirmans S.M, Pate K.A. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 2013; 6: 1-13.Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19-25.Dumesic D.A, Padmanabhan V, Abbott D.H. Polycystic ovary syndrome and oocytedevelopmental competence. Obstet Gynecol Surv 2007; 63: 39-48.Tuckerman E.M, Okon M.A, Li T, Laird S.M. Do androgens have a direct effect on endometrial function? An in vitro study. Fertil Steril 2000; 74: 771-9.Weenen C, Laven J.S, Von Bergh A.R. et al. Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004; 10: 77-83.Dewailly D, Andersen C.Y., Balen A. et al. The physiology and clinical utility of anti-Muellerian hormone in women. Hum Reprod Update 2014; 20 (3): 370-85.Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in infertile women: a committee opinion. Fertil Steril 2013; 100: 341-8.Mulders A.G., Laven J.S.E, Eijkemans M.J.C. et al. Patient predictors for outcome of gonadotrophin ovulation induction in women with normogonadotrophic anovulatory infertility: a meta-analysis. Hum Reprod Update 2003; 9: 429-49.Mitwally M.F.M, Casper R.F. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril 2001; 75: 305-9.Misso M.L, Wong J.L.A., Teede H.J. et al. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Hum Reprod Update 2012; 18: 301-12.Legro R.S, Arslanian S.A, Ehrmann D.A. et al. Endocrine Society Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline J Clin Endocrinol Metab 2013; 98 (12): 4565-92.Legro R.S., Brzyski R.G, Diamond M.P. et al. National Institute of Child Health and Human Development Reproductive Medicine Network. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 2014; 371: 119-29.Tulandi T, Martin J, Al-Fadhli R et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril 2006; 85 (6): 1761-5.Sharma S, Ghosh S, Singh S et al. Congenital malformations among babies born following letrozole or clomiphene for infertility treatment. PLoS One 2014; 9 (10): e108219.Tatsumi T, Jwa S.C, Kuwahara A. et al. No increased risk of major congenital anomalies or adverse pregnancy or neonatal outcomes following letrozole use in assisted reproductive technology. Hum Reprod 2017; 32 (1): 125-32.Diamond M.P, Legro R.S, Coutifaris C et al. Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) Trial: Baseline Characteristics. Fertil Steril 2015; 103 (4): 962-73.e4.Чернуха Г.Е., Иванец Т.Ю., Найдукова А.А., Каприна Е.К. Возрастные аспекты оценки уровня антимюллерова гормона при синдроме поликистозных яичников. Акушерство и гинекология. 2017; 3.Ghahiri A, Mogharehabed N, Mamourian M. Letrozole as the first-line treatment of infertile women with polycystic ovarian syndrome (PCOS) compared with clomiphene citrate: A clinical trial. Adv Biomed Res 2016; 5: 6.Liu C, Feng G, Huang W. et al. Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial. Gynecol Endocrinol 2017; 33 (11): 872-6.Franik S, Kremer J.A, Nelen W.L, Farquhar C. Aromatase inhibitors for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev 2014; 2: CD010287.Imani B, Eijkemans M.J, te Velde E.R.et al. Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropicoligoamenorrheic infertility. J Clin Endocrinol Metab 1999; 84: 1617-22.Imani B, Marinus J.S. Predictors of Patients Remaining Anovulatory during Clomiphene Citrate Induction of Ovulation in Normogonadotropic Oligoamenorrheic Infertility. J Clin Endocrinol Metab 1998; 83 (7).Piltonen T.T. Polycystic ovary syndrome: endometrialmarkers. Best Pract Res Clin Obstet Gynaecol 2016; 37: 66-79.Qiao J, Feng H.L. Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum Reprod Update 2011; 17: 17-33. DOI: 10.1093/humupd/dmq032