The Effect Of Dehydroepiandrosterone On Infertility Patients With Diminished Ovarian Reserve Undergoing In Vitro Fertilization

BackgroundDiminished ovarian reserve is a progressive decline of ovarian oocyte quality and quantity. Patients with DOR have high cancellation rate, low pregnancy rate, and high abortion rate during IVF.However, the early reports on DHEA supplement to the patients with DOR were still controversial because there was lack of large-scale, well-designed confirmatory studies. Given the controversial effect of DHEA, studies should be continued to support the use of DHEA and find the optimum treatment regimen in patients with DOR.Research indicated that pretreatment with estrogen may inhibit circulating FSH concentrations, restrict the depletion of follicles and therefore improve ovarian responsiveness. DHEA could up-regulated FSH receptors which may make remnant follicles more sensitivity to FSH administration. Patients with DOR characterized with an elevated basal follicle stimulating hormone(FSH) level and less antral follicle count. Therefore, we wonder whether DHEA /climen synergism can further augment beneficial effects on ovarian reserve. Objective1)To evaluate the effect of dehydroepiandrosterone(DHEA) on infertility patients with diminished ovarian reserve undergoing in vitro fertilization;2)To assess the effect of dehydroepiandrosterone(DHEA) plus climen(estradiol valerate and cyproterone acetate drug combination) supplementation in patients with diminished ovarian response(DOR). And determine whether it is superior to DHEA therapy on the effect of improving ovarian reserve. MethodsThis is a prospective randomized study. From March 2013 to October 2013, 105 patients with diminished ovarian reserve were included in this study. Of them, 52 patients were randomly allocated to the DHEA group, who received DHEA 75 mg daily for three consecutive menstrual cycles prior to IVF cycles, and 53 patients were allocated to the control group, who entered IVF cycles directly. All patients were treated with the same ovarian stimulation protocol. Follicular fluid samples from both groups were collected for bone morphogenetic protein-15(BMP-15) and growth differentiation factor-9(GDF-9). Fluid from the first aspirated follicle without any visible blood contamination was carefully collected. In addition, day 3 Blood samples were collected pre- and post-treatment of DHEA for serum anti-Mullerian hormone(AMH), follicle stimulating hormone(FSH) and estradiol(E2) in the DHEA group.Between November 2013 and July 2014, this prospective study included 147 women with DOR and randomized them into two groups. 72 patients received DHEA 75 mg plus climen 1 mg daily for 12 weeks prior to ovarian stimulation. 75 patients received DHEA 75 mg daily only for 12 weeks before In-vitro fertilization(IVF) cycles. AMH, FSH, E2 were detected before and after DHEA / DHEA plus climen supplementation in both groups. ResultsThe level of BMP-15 in follicular fluid samples from the DHEA group was significantly higher than that of the control samples(P = 0.000). Patients after DHEA treatment demonstrated a significantly higher level of AMH and a significantly lower level of FSH, E2 compared to themselves prior to DHEA therapy(P = 0.015; P = 0.036; P = 0.002; respectively). Moreover, the accumulated score of embryos was significantly higher in the DHEA group(P = 0.033).After 12 weeks pretreatment, the DHEA plus climen group demonstrated a significantly higher level of AMH(P = 0.000), and a significantly lower level of FSH(P = 0.016) as well as the DHEA group. When the two groups were divided into four subgroups based on FSH cut-off 10 mIU/mL, a significantly increase of AMH(0.57 ± 0.45 vs. 0.97 ± 0.75, P = 0.002) was found in the high-FSH DHEA plus climen group, while there was no significant difference in high-FSH DHEA group(0.82 ± 0.68 vs. 0.96 ± 1.12, P = 0.431). Moreover, a significantly higher accumulated sore of embryos was observed in low-FSH DHEA plus climen group when compared to low-FSH DHEA group(P = 0.032). Conclusion1) These observations confirm the beneficial effect of DHEA for infertility patients with diminished ovarian reserve; 2) DHEA together with climen before IVF cycles has better effects than addition of DHEA alone for infertility patients with diminished ovarian response.