Center for Human Reproduction, New York, NY 10021, USA.
J Assist Reprod Genet. 2013 Jan;30(1):49-62. doi: 10.1007/s10815-012-9890-z. Epub 2012 Dec 5.
To investigate whether androgen conversion rates after supplementation with dehydroepiandrosterone (DHEA) differ, and whether differences between patients with diminished ovarian reserve (DOR) are predictive of pregnancy chances in association with in vitro fertilization (IVF).
In a prospective cohort study we investigated 213 women with DOR, stratified for age (≤ 38 or >38 years) and ovarian FMR1 genotypes/sub-genotypes. All women were for at least 6 weeks supplemented with 75 mg of DHEA daily prior to IVF, between initial presentation and start of 1st IVF cycles. Levels of DHEA, DHEA-sulfate (DHEAS), total T (TT) and free T (FT) at baseline ((BL)) and IVF cycle start ((CS)) were then compared between conception and non-conception cycles.
Mean age for the study population was 41.5 ± 4.4 years. Forty-seven IVF cycles (22.1 %) resulted in clinical pregnancy. Benefits of DHEA on pregnancy rates were statistically associated with efficiency of androgen conversion from DHEA to T and amplitude of T gain. Younger women converted significantly more efficiently than older females, and selected FMR1 genotypes/sub-genotypes converted better than others. FSH/androgen and AMH/androgen ratios represent promising new predictors of IVF pregnancy chances in women with DOR.
DOR at all ages appears to represent an androgen-deficient state, benefitting from androgen supplementation. Efficacy of androgen supplementation with DHEA, however, varies depending on female age and FMR1 genotype/sub-genotype. Further clarification of FMR1 effects should lead to better individualization of androgen supplementation, whether via DHEA or other androgenic compounds.
研究补充脱氢表雄酮(DHEA)后雄激素转化率是否存在差异,以及 DOR 患者之间的差异是否与体外受精(IVF)相关的妊娠机会有关。
在一项前瞻性队列研究中,我们调查了 213 名 DOR 患者,按年龄(≤38 岁或>38 岁)和卵巢 FMR1 基因型/亚基因型分层。所有女性在初始就诊至第 1 次 IVF 周期开始前至少 6 周,每天补充 75mg DHEA。然后比较基线(BL)和 IVF 周期开始时(CS)的 DHEA、DHEA-硫酸盐(DHEAS)、总 T(TT)和游离 T(FT)水平,以及受孕和未受孕周期。
研究人群的平均年龄为 41.5±4.4 岁。47 个 IVF 周期(22.1%)导致临床妊娠。DHEA 对妊娠率的益处与雄激素从 DHEA 转化为 T 的效率和 T 增益幅度呈统计学相关。年轻女性的转化率明显高于年长女性,而某些 FMR1 基因型/亚基因型的转化率则高于其他基因型/亚基因型。FSH/雄激素和 AMH/雄激素比值是预测 DOR 女性 IVF 妊娠机会的有前途的新指标。
所有年龄段的 DOR 似乎都代表雄激素缺乏状态,受益于雄激素补充。然而,DHEA 补充雄激素的疗效因女性年龄和 FMR1 基因型/亚基因型而异。进一步阐明 FMR1 效应应导致更好的个体化雄激素补充,无论是通过 DHEA 还是其他雄激素化合物。