Hypothesis/aims of study. Poor ovarian response is still considered one of the most challenging tasks in reproductive medicine. Poor responders have decreased circulating androgens during spontaneous cycles. Androgens are known to play an important role in follicular growth and development. Hence, the use of various androgens and androgen inhibitors in poor responders undergoing ovarian stimulation for IVF has been proposed to improve efficacy of treatment. This study was aimed to examine the efficacy of aromatase inhibitors and androgens in infertility treatment in patients with poor response. Study design, materials and methods. This prospective cohort-controlled clinical trial included 204 patients under 42 years of age with infertility and poor response to ovarian stimulation. In vitro fertilization treatment with an antagonist FSH/hMG protocol with letrozole (5 mg/day) was administered in the first group of patients (n = 26) during the first 5 days of stimulation. Patients of the second group (n = 38) were applied testosterone (25 mg/day) transdermally, starting from the 5th day of the menstrual cycle preceding controlled ovarian stimulation for in vitro fertilization. The third group of patients (n = 18) was administered dehydroepiandrosterone (100 mg/day) for 3 months prior to controlled ovarian stimulation for in vitro fertilization. Results. Improved response to FSH stimulation with letrozole co-treatment was evidenced, with parameters of stimulation efficacy and embryo development being better in the testosterone group. No significant improvement in ovarian response markers, ovarian response to gonadotrophin stimulation and in vitro fertilization outcomes were found in poor responders receiving pre-treatment dehydroepiandrosterone. Conclusion. Further studies are necessary to improve approaches of testosterone and aromatase inhibitors use in poor responders undergoing in vitro fertilization.

■ Проблема «слабого» ответа яичников на стимуляцию существует с момента начала широкого применения экс-тракорпорального оплодотворения (ЭКО) с целью лечения бесплодия. От 9 до 25 % циклов ЭКО сопровождается недостаточной ответной реакцией яичников на вводимые извне гонадотропины. В опубликованной за последние годы литературе описано большое количество методов преодоления «слабого» ответа, но результаты исследо-вания их эффективности противоречивы, а единого подхода к выбору оптимального алгоритма лечения нет. В статье описываются возможные пути реализации лечебного действия ингибиторов ароматазы у пациенток со «слабым» ответом на стимуляцию. ■ Ключевые слова: стимуляция овуляции; ЭКО; «слабый» ответ; ингибиторы ароматазы. AROMATASE INHIBITORS IN "POOR" OVARIAN RESPONDERS UNDERGOING IN VITRO FERTILIZATION © A.I. MerkulovaSt Petersburg State University, Saint Petersburg, Russia ■ Since the IVF treatment expands worldwide, it has become apparent that a proportion of women responds suboptimally to controlled ovarian stimulation with exogenous gonadotrophins. There is still no consensus on the ideal controlled ovarian stimulation protocol for patients with "poor" ovarian response. Many strategies have been studied. However, no compelling advantage for one treatment protocol over another has been identified. The addition of aromatase inhibitors in "poor" responders stimulation protocols is described in this article.■ Keywords: ovarian stimulation; IVF; poor ovarian response; aromatase inhibitors.По мере того как экстракорпоральное опло-дотворение (ЭКО), как метод лечения беспло-дия, получало все более широкое распростра-нение, все более очевидным становилось то, что далеко не во всех случаях стимуляции супер-овуляции ответ яичников на вводимые извне гонадотропины является оптимальным [1, 2]. По различным данным, частота встречаемости этой проблемы в программах вспомогательных репродуктивных технологий (ВРТ) составляет от 9 до 25 %, и с каждым годом она увеличива-ется [3, 4]. В 2010 г. в Болонье рабочей группой Евро-пейского общества репродукции человека и эм-бриологии было дано определение «слабому» ответу яичников на стимуляцию и сформу-лированы критерии, позволяющие его про-гнозировать. До публикации этого консенсу-са в 2011 г. проблема недостаточного ответа яичников в программах ВРТ была очевидна, но не конкретизирована в диагностическом аспекте.Согласно Болонским критериям «слабого» ответа яичников на стимуляцию, применение этого определения правомочно при соблюде-нии двух из трех условий [5]: 1) возраст женщины 40 и более лет или нали-чие других факторов риска «слабого» ответа на стимуляцию; 2) сниженный овариальный резерв (число ан-тральных фолликулов < 5-7; антимюллеров гормон (АМГ) < 0,5-1,1 нг/мл); 3) предшествующий «слабый» ответ яичников на стимуляцию при использовании адекват-ных доз гонадотропинов (3 и менее получен-ных ооцитов или отмена протокола в связи с отсутствием ответа яичников на проводи-мую стимуляцию).

Hypothesis/aims of study. The management of poor responders to ovarian stimulation for in vitro fertilization (IVF) has always been a challenge. It is difficult for both doctors and patients to make decision to proceed to oocyte donation or abandon fertility treatment. More predictors of successful IVF treatment in poor responders are needed. The aim of this study was to assess hormonal ovarian function in poor responders undergoing ovarian stimulation and to identify predictors of the chance of clinical pregnancy after IVF cycle. Study design, materials and methods. The study included 45 infertile patients undergoing ovarian stimulation with poor ovarian response according to the Bologna criteria. All patients underwent standard IVF or IVF/ICSI protocol using gonadotropin releasing hormone antagonists. Letrozole (5 mg/day) was administered during the first 5 days of stimulation in standard antagonist FSH/hMG protocol to 13 of the patients included in the study, with standard antagonist FSH/hMG protocol being only administered to other 32 patients. Serum and follicular fluid were collected at the time of follicle aspiration, and the concentrations of total testosterone, estradiol and androstenedione were determined. Results. Follicular fluid concentrations of testosterone and androstenedione were higher and serum estradiol level was lower in the letrozole group. The serum concentrations of testosterone and androstenedione were comparable in both groups, while the serum estradiol/testosterone ratio was lower in the letrozole group. The threshold level of estradiol/testosterone ratio 1000 on the day of oocyte retrieval above which pregnancy and implantation rates were increased was 1532.68 (odds ratio 7.0 (95% CI 1.3935.35), р = 0.02). Conclusion. Evaluating of the serum estradiol / testosterone ratio has been shown to determine aromatase activity of ovarian preovulatory follicles and to predict IVF outcome in poor responders undergoing assisted reproductive technology.