The Benefits of Testosterone Therapy in Poor Ovarian Responders Undergoing In Vitro Fertilisation (IVF)

Abstract

Introduction: Poor ovarian responders are the most challenging patients in reproductive medicine and no successful treatment has been proposed. Androgens are thought to play an important role during early folliculogenesis and diminished levels are associated with decreased ovarian sensitivity to follicle-stimulating hormone. This study aimed to determine whether pretreatment with testosterone improves the results in poor responders undergoing in vitro fertilisation (IVF). Materials and methods: This observational pilot study enrolled 33 poor responders undergoing IVF. Eleven patients were pretreated with 250 mg intramuscular testosterone and compared to a control group of 22 patients. The participants were tested for free testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, and anti-mullerian hormone (AMH). Results: The two groups had similar baseline characteristics. Significant improvement was reached in the hormones free testosterone, dehydroepiandrosterone sulfate, and sex hormone binding globulin in the testosterone-pretreatment group. No difference was detected in antral follicle count (5.06 versus 4.24); AMH (0.51 versus 0.53), mature oocytes (2.2 versus 2.32), and the number of embryos (1.2 versus 1.33) between the study and control groups, respectively. There was a slow improvement in fertilisation rate but without any significance (62.97% versus 57.61%). However, the cancellation rate of the ovarian stimulation was much greater in the control group (18.18%) in comparison with the study group (0.0%). Pregnancy rate (PR) in the testosterone group was higher than controls (PR per cycle: 27.3% versus 4.6; p=0.09). Conclusion: Based on the limited number of patients studied, pretreatment with testosterone seems to improve PR and cancellation rate in poor responders but failed to affect antral follicle count, AMH, and the number of mature oocytes and embryos. Given these results, further research would provide more certainty.

The effect of methyltestosterone on in vitro fertilization outcomes: A randomized clinical trial on patients with low ovarian response

“…This finding aligns with previous studies suggesting a correlation between optimal endometrial thickness and improved IVF outcomes [17]. Furthermore, Andreeva et al [15] reported in their study that extended testosterone pretreatment could potentially enhance IVF treatment in patients with low ovarian response. Their results demonstrated an increase in pregnancy rates, which is consistent with our findings.…”

“…Their results demonstrated an increase in pregnancy rates, which is consistent with our findings. We observed a nearly significant difference between the patients who received testosterone pretreatment and the control group in terms of definitive pregnancy [15].…”

“…As the follicle matures, AR expression decreases, underscoring the importance of androgens during the initial stages of follicle development [13,14]. Many researchers now posit that androgens play a crucial role in follicular recruitment, promoting follicular growth, and reducing GC apoptosis, which in turn leads to an increase in the number of growing follicles [15]. A meta-analysis conducted by Noventa et al [16] suggested an increase in the total number of oocytes, M2 oocytes, and total embryos following testosterone therapy.…”

AOP key event relationship report: Linking decreased androgen receptor activation with decreased granulosa cell proliferation of gonadotropin-independent follicles

“…In humans, the importance of AR in follicular growth becomes evident with the beneficial effects of androgens in assisted reproductive technology outcomes [20][21][22][23][24][25][26][27]. Although the mechanism remains elusive, it has been suggested that androgen priming of women seeking fertility treatment promotes follicle growth resulting in an increase in the FSH-sensitive follicle pool [82].…”

“…Evidence for the importance of AR during the early stages of folliculogenesis derives from several mammalian species. In humans, the significance of the AR is highlighted by infertility treatment protocols that include androgens to promote follicular growth in women seeking fertility assistance [20][21][22][23][24][25][26][27][28]. In cases of hypoandrogenism, diminished ovarian reserve, premature ovarian aging, and reduced fertility have been observed, indicating that AR is essential for optimal ovarian health and function [29,30].…”