Abstract

Abstract Study question Is insulin-like growth factor-I (IGF-I) a mediator of the effect of transdermal testosterone (TT) in poor responder (PR) patients? Summary answer IGF-I might be a mediator of the effect of TT in PR patients who undergo an IVF cycle What is known already Many strategies have been tried to improve the results in PR patients. Androgen supplementation with TT is the only that has significantly increased live birth rate in these patients. The mechanism by which TT might influence on the better results remains unclear but it is likely mediated or facilitated by IGF-I. Testosterone increases the number of primordial follicles, increase IGF-I by threefold and increase IGF-I receptor mRNA by fivehold in primordial follicles in primates. Some studies have suggested that IGF-I could be a parameter that reflects the endocrinological environment of mature follicles, which is correlated with oocyte and embryonic quality Study design, size, duration This prospective cohort study of 93 women PR according Bologna criteria treated with TT and IVF/ICSI was conducted between May 2015 and December 2016 Participants/materials, setting, methods Exogenous andogenization with TT for 5 days prior to ovarian stimulation was carried out. Hormonal parameters were evaluated: basal FSH, LH and Estradiol, AMH, IGF–1 pre and post TT. Ultrasound parameterswere also analysed: antral follicle count (AFC) and number of pre-ovulatory follicles the day of HCGr. We compared these parameters according to the ovarian response: adequate (> 4 oocytes) or insufficient (<3 oocytes), as well as the pregnancy was achieved or not. Main results and the role of chance Baseline characteristics of the patients were: 36.9 years, FSH 11.8, AMH 0.86 and RFA 5.3. In 83% of the patients the oocyte retrieval was carried out, obtaining an average of 3.8 MII oocytes and 2.9 embryos of 2pn with a clinical pregnancy rate per transfer of 33.3%. The FORT Test (AFC/pre-ovulatory follicles x100) was 70%, higher than that observed in other studies with patients with PR without TT (55%). In cases in which an insufficient response was obtained (<3 oocytes) or the cycle was canceled, a higher age and FSH and lower AMH were observed (p < 0.05). There were no differences in the rest of the parameters. Evaluating the hormonal and ultrasound parameters depending on whether or not pregnancy was achieved, a significant increase in IGF1 pre and post-TT was observed in the cases of pregnancy (31.5%) compared to those cases where there was no pregnancy (10.9%) (p = 0’01). There were no differences in the rest of the parameters. A significant correlation was found between AMH, AFC and increase in IGF-I levels (p < 0’05). Limitations, reasons for caution This a prospective cohort study with limited number of patients included. Wider implications of the findings: The significant increase in serum levels of IGF–1 in pregnant patients would indicate the existence of a more favorable clinical setting for the administration of testosterone, probably related to a more favorable ovarian reserve as demonstrated by its correlation with serum levels of AMH and with the AF. Trial registration number Not applicable

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