Investigating the Effect of Transdermal Testosterone Gel Administration on Ovarian Response Rate in Infertile Women with Poor Response to Conventional Assisted Reproductive Methods

Current advances in infertility treatment have given hope to the treatment of different types of infertility. Considering that the administration of high doses of gonadotropins is used in the treatment of infertility, the lack of response to gonadotropins leads to fertility failure. Various factors may affect women's response to gonadotropins. One of these factors is aging. Increasing age will lead to a Decrease in Follicular Recess and a decrease in response to gonadotropin. However, the reason for the poor ovarian response in women younger than 41 years is not clearly understood. The most common criteria to describe a poor ovarian response are a small number of developed follicles or retrieved oocytes and low levels of estradiol after using a standard ovarian stimulation protocol. According to the Two Cell/Two Gonadotropins theory, androgens play an important role in ensuring adequate steroid levels. A large number of studies have been conducted to treat these patients and various techniques have been proposed, but none of them were able to increase the response to gonadotropin completely. Androgens have important physiological roles in women and act both as precursors of estrogen biosynthesis and directly as androgen receptors. It is known that plasma Dehydroepiandrosterone and testosterone are relatively high in reproductive age and decrease with age. Various effects of androgens on the steroidogenesis process in Granulosa cells have also been investigated, which includes balancing and regulating the activity of the Aromatase enzyme based on the level of maturation in the follicles. A large number of studies have been conducted on the process of folliculogenesis, but the results have not been fully established. Androgen excess usually causes atresia of developing follicles in rodents. However, it may have a synergistic effect with Follicle-stimulating Hormones to promote follicular recruitment in mammals. In animal studies on monkeys, it has been determined that the administration of testosterone leads to an increase in the expression of FSH receptors, which causes the start of follicular growth and an increase in the number of pre-antral and small antral follicles. Several different studies on primates and humans have shown the role of androgens in controlling follicular growth and follicular sensitivity to FSH. These studies show that a temporary increase in testosterone concentration increases the follicular response to LH, FSH, HCG, and DHEA. Most of these studies have been conducted on the effect of testosterone administration on the folliculogenesis process in women who did not respond successfully to fertility treatments, but the results are quite different. Since there is little information about prescribing testosterone gel to infertile women, it is important to conduct research in this field. Therefore, the aim of this study was to investigate the effect of testosterone gel administration on infertile women with poor ovarian response who had previously used the usual methods of assisted reproduction.

This clinical trial was conducted at Shahid Beheshti Infertility Center of Isfahan from April to March 2013. In this study, 64 infertile women referred to the infertility clinic of Shahid Beheshti Hospital and Isfahan Infertility Research Center from April 2013 to March 2013 were selected. Patients who underwent routine IVF/ICSI in their last cycle and had a poor response to these fertility treatments were selected. Inclusion criteria included age 30-42 years, willingness to participate in the study, poor response to ovarian stimulation in previous IVF and ICSI attempts, evidence of ovarian follicular reserves and no previous ovarian surgery, and ovarian endometriosis. , endocrine and metabolic disorders, and breast cancer. The exclusion criteria were: pregnancy, any evidence of drug side effects or sensitivity to the applied treatment, not following the study protocol, and inability to follow up with the patient. Among the 64 participants who were selected in this study, 56 patients who met the inclusion criteria were randomly assigned to two intervention or control groups (28 people in each group). Finally, 49 patients were examined. The number of patients in the intervention and control groups was 23 and 26, respectively. The intervention group received transdermal testosterone gel and the control group received a placebo. After the period of using the gel, patients were evaluated based on the number of Antral follicles and hormone levels, including FSH and testosterone. t-dependent and independent t-statistical methods were used to analyze the data.

Based on the findings of this study, the serum level of testosterone increased significantly in the intervention group, but the total number of follicles was not significantly different between the two groups on the third day of the control cycle. All patients were monitored during the study for possible side effects of using the gel. 4 patients in the intervention group reported itching, 1 case of scaling, and 1 case of acne. No other side effects were reported by the patients. 3 patients in the placebo group also reported itching. No other side effects were reported by patients in this group.

This study showed that topical testosterone administration does not increase ovarian response to FSH in women with long-term infertility histories and poor responses to common fertility treatments. Indeed, increasing plasma testosterone concentration before FSH administration in fertility treatments such as IVF did not affect ovarian response. The results of the present study showed that the use of testosterone gel before the administration of FSH in assisted reproductive treatments does not have a significant effect on increasing the ovarian response to FSH and the success rate of these treatments. This level of testosterone plasma concentration is not enough to increase the Folliculogenesis process and improve fertility treatments. Therefore, more studies should be conducted using this assessment. The results of this study can have different reasons. The most important of these is the normal plasma testosterone concentration in our participants from baseline, and it may be necessary to conduct several future studies that specifically evaluate the effect of testosterone administration on women with low plasma testosterone concentrations.