Abstract
Patients with poor ovarian response (POR) to exogenous gonadotropins stimulation for assisted reproductive technology (ART) have decreased circulating androgens during spontaneous cycles. The Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) is a 4-tier stratification of women with POR to controlled ovarian stimulation (COH) based on age and biomarkers of ovarian reserve has been proposed to maximize the clinical management of this group for ART. The aim of the present study was to characterize the levels of androgens during COH in follicular fluid (FF) and serum in POSEIDON subgroups and compared them with women of normal ovarian response. Sixty nine consecutive patients undergoing ART were included and testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), estradiol, sex hormone-binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1) were measured in serum and FF collected at the time of oocyte pick-up. The number of retrieved oocytes was registered for each patient for their allocation to the respective POSEIDON subgroup. The control group comprised 19 women and the POSEIDON group 1 (age < 35, normal ovarian reserve biomarkers) n = 14, group 2 (age ≥ 35, normal ovarian reserve biomarkers) n = 8, group 3 (age < 35, poor ovarian reserve biomarkers) n = 6 and group 4 (age ≥ 35, poor ovarian reserve biomarkers) n = 22. Serum levels of total testosterone, androstenedione and DHEA-S were not different in group 1 vs. control but significantly decreased in group 3 vs. control. DHEA-S in FF was also significantly decreased in group 3 vs. control. In addition, serum testosterone was decreased in groups 2 and 4 vs. control; and serum androstenedione and estradiol were reduced in group 4 vs. control. No differences were observed for estradiol, SHBG and IGF-1 in FF. Finally, a high correlation between serum and FF DHEA-S was observed when data from samples of all groups were pooled. Group 1 did not show hypoandrogenemia however group 3 had low levels of all measured androgens in serum and DHEA-S in FF. Such differences might help to better characterize and/or improve the clinical management of women with POR according to their respective POSEIDON stratification.
Highlights
Controlled ovarian hyperstimulation (COH) is a key factor predicting reproductive outcomes in Assisted Reproductive Technology (ART), since the simultaneous development of multiple follicles increases the chances of transferring embryos with the highest potential to progress to a successful pregnancy
According to the ART results, 14 women were assigned to group 1, 8 were assigned to group 2 (35 or more years old with normal ovarian reserve and poor response to COH), 6 of the women corresponded to group 3, 22 women were assigned to group 4 (35 or more years old with low ovarian reserve and poor response to COH), and 19 women were included in the control group
Since dehydroepiandrosterone sulfate (DHEA-S) levels were decreased both in Follicular fluid (FF) and serum in POSEIDON group 3 (Table 4), we performed a scatter plot analyzing the correlation between serum and FF DHEA-S in all samples because it has been suggested that serum and follicular fluid testosterone concentrations do not correlate, questioning the potential effect of androgen supplementation to improve the follicular endocrine milieu [14]
Summary
Controlled ovarian hyperstimulation (COH) is a key factor predicting reproductive outcomes in Assisted Reproductive Technology (ART), since the simultaneous development of multiple follicles increases the chances of transferring embryos with the highest potential to progress to a successful pregnancy. Major progress has been achieved in ART, around 20% of women present an insufficient response to gonadotropins administered during COH [1], which have been classified as patients with impaired or poor ovarian response (POR). Its relevance in clinical trials has been questioned because it encompasses a large heterogeneous population that differs significantly in biologic characteristics but have in common, a reduced number of oocytes that can be obtained, with consequent poor results in assisted reproductive technology cycles [3]. Several intervention strategies have been tested for improving the results in women with POR; the respective randomized control trials as well as the derived meta-analyses from these studies present inconsistent results [5]
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