Effects of transdermal testosterone in poor responders undergoing IVF: systematic review and meta-analysis

Abstract

A systematic review and meta-analysis was performed to evaluate the effect of transdermal testosterone preceding ovarian stimulation in women with poor ovarian response undergoing IVF. Studies comparing pretreatment with transdermal testosterone versus standard ovarian stimulation among poor responders were included. The main outcome assessed was live birth. Three trials were included (113 women in the testosterone group, 112 in the control group). Testosterone-treated women achieved significantly higher live birth rate (risk ratio, RR, 1.91, 95% CI 1.01 to 3.63), clinical pregnancy rate (RR 2.07, 95% CI 1.13 to 3.78) and required significantly lower doses of FSH (RR -461.96, 95% CI -611.82 to -312.09). However, differences observed in clinical pregnancy per embryo transferred were not statistically significant (RR 1.72, 95% CI 0.91 to 3.26). No differences were observed regarding number and quality of the oocytes retrieved. In conclusion, transdermal testosterone significantly increases live birth and reduces the doses of FSH required. These findings support the theoretical synergistic role of androgens and FSH on folliculogenesis. The present data should be interpreted with caution because of the small number of trials and clinical heterogeneity. The identification of poor responders that could especially benefit from testosterone treatment should be addressed in further studies. The poor response to ovarian stimulation among women undergoing IVF is of great concern in reproductive medicine. Certain modalities have been tested to improve this response to gonadotrophin stimulation, although results from some studies have shown conflicting results. Hence, a systematic review and meta-analysis was performed in order to evaluate the effect of transdermal testosterone prior to ovarian stimulation among these women with poor ovarian response. The main outcome assessed was live birth rate. In all, three trials were included, which comprehended 113 women in the testosterone group and 112 in the control group. Women that were pretreated with transdermal testosterone achieved significantly higher live birth rate and clinical pregnancy rate and required significantly lower doses of exogenous FSH as compared with controls. However, when clinical pregnancy rate was adjusted per embryo transferred differences observed were not statistically significant. No differences were observed in the number and quality of the oocytes retrieved. In conclusion, transdermal testosterone prior to ovarian stimulation significantly increases live birth and reduces the doses of FSH required among poor responders. In addition, the identification of poor responders that could especially benefit from testosterone treatment should be addressed in further studies.

Basal serum testosterone levels correlate with ovarian response but do not predict pregnancy outcome in non-PCOS women undergoing IVF

“…In vitro data indicate that human granulosa cells possess sulfates activity, and that DHEAS can be used as a substrate for both estrogen and androstenedione synthesis [13,14]. Androgens can augment FSH receptor expression in granulosa cells and are thought to promote follicular growth and estrogen biosynthesis by amplifying the effects of FSH in rhesus monkeys [15]. Studies on murine models of conditional granulosa cell and oocyte-specific deletion of the androgen receptor found positive correlations between androgen receptor and FSH receptor expression, suggesting that androgens may prevent preantral follicle growth and atresia [16][17][18][19][20].…”

“…Androgens can augment FSH receptor expression in granulosa cells and are thought to promote follicular growth and estrogen biosynthesis by amplifying the effects of FSH in rhesus monkeys [15]. Studies on murine models of conditional granulosa cell and oocyte-specific deletion of the androgen receptor found positive correlations between androgen receptor and FSH receptor expression, suggesting that androgens may prevent preantral follicle growth and atresia [16][17][18][19][20]. Similarly, it has recently been shown that androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA expression in human granulosa cells from small antral follicles [21].…”

Adjuvants Therapies for Women Undergoing IVF: Is There Any Evidence of their Safety and Efficacy? An Updated Mini-Review

“…However, differences observed in clinical pregnancy per embryo transferred were not statistically significant (RR 1.72, 95% CI 0.91 to 3.26). Authors did not observe any difference regarding number and quality of the oocytes retrieved [19]. …”

“…Different RCTs report a beneficial effect of TT pre-treatment [16,17] and the meta-analysis from Bosdou et al [18] analyzing both trials conducted by Massin et al [16] and Kim et al [17] reported that pretreatment with transdermal testosterone was associated with an increase in clinical pregnancy (risk difference (RD): +15%, 95% confidence interval (CI): +3 to +26%) and live birth rates (RD: +11%, 95% CI: +0.3 to +22%) in poor responders undergoing ovarian stimulation for IVF. A second meta-analysis conducted by Gonzalez-Comadran et al [19] also reported that testosterone-treated women achieved a significantly higher live birth rate (risk ratio, RR, 1.91, 95% CI 1.01 to 3.63), clinical pregnancy rate (RR 2.07, 95% CI 1.13 to 3.78) and required significantly lower doses of FSH (RR -461.96, 95% CI -611.82 to -312.09). However, differences observed in clinical pregnancy per embryo transferred were not statistically significant (RR 1.72, 95% CI 0.91 to 3.26).…”

Is it possible to help patients of older reproductive age implement their reproductive function within the framework of IVF and PE programs backed by state support?

“…Наиболее хорошие результаты получены при использовании тестостерона в виде геля по 12,5-25 мг в течение 15-20 дней до вступления в программу или с 21-го дня преды-дущего цикла до момента назначения ГТ. Механизм положительного эффекта андрогенного прайминга у таких пациенток авторы связывают со способностью андрогенов активизировать ранний рекрутинг фоллику-лов в созревающую когорту, увеличить экспрессию рецепторов к ФСГ на клетках гранулезы малых антраль-ных фолликулов и поддерживать адекватную чувстви-тельность ФСГ-рецепторов на всех гормонально зависи-мых этапах фолликулогенеза [24,25].…”