Laboratory for Reproductive Medicine and Immunology, San Francisco, CA, USA.
Am J Reprod Immunol. 2012 Nov;68(5):428-37. doi: 10.1111/j.1600-0897.2012.01179.x. Epub 2012 Jul 30.
Human embryos develop at varying rates in culture, with only a fraction of the eggs retrieved developing to 'transfer quality' embryos. We investigated whether the ratios between the number of eggs retrieved or the number of pro-nucleate embryos formed and the number of Day 3 embryos with ≥5 cells [oocyte 'die-off ratios' (DOR)] were correlated with the chance of IVF success, independent of other factors such as embryo grade score and patient's age. We also investigated what factors may be correlated with this ratio.
608 IVF fresh cycles in subfertile women were retrospectively evaluated. For each cycle, an oocyte DOR number was calculated as follows: Number of eggs retrieved divided by the number of Day 3 embryos with ≥5 cells. This number was correlated with the subsequent success rates for the index cycles. A 'post-fertilization' or 'embryo' die-off ratio (EDOR; the number of pro-nucleate embryos/the number of day 3 embryos ≥5 cells) was also calculated.
The oocyte DOR showed a reverse linear correlation with IVF live birth rate. Live birth rate = (-5.75; DOR) +71.6 (with DOR > 1; P ≤ 0.005; R = -0.87). In addition, the oocyte DOR continued to show an inverse correlation with success rates even when embryo quality and patient's age were held constant. The post-fertilization or EDOR also continued to show a statistically significant negative correlation with live birth rate (R = -0.91; P ≤ 0.01). The preconception TNF-α:IL-10 ratio, an immmunologic marker (drawn 3.3 ± 2.6 months preconception), was more strongly correlated with high oocyte DOR than either age or number of eggs retrieved (P = 0.04, 0.14, 0.72, respectively). When anti-TNF-α therapy (Humira) was given preconception, the oocyte DOR's negative effect on live birth rate was nearly eliminated (correlation coefficient between oocyte DOR and live birth rate: cycles using no Humira, R = -0.90, P ≤ 0.006; cycles using Humira, R = 0.25, P ≤ 0.55).
In subfertile women undergoing IVF, the oocyte DOR may help predict IVF success rates. This factor may offer an additional tool to help improve implantation rate, clinical pregnancy rate, live birth rate, and live birth rate per embryo transferred for an upcoming IVF cycle. Although many mechanisms may contribute to the oocyte DOR's negative effect on IVF success rates, its correlation with elevated preconception TNF-α:IL-10 ratio and correction with Humira suggests a strong immunologic component that may be treatable.
人类胚胎在培养过程中发育速度不同，只有一部分取回的卵子发育成“可移植质量”的胚胎。我们研究了取回的卵子数量或原核胚胎形成数量与第 3 天具有≥5 个细胞的胚胎数量之间的比例[卵母细胞“死亡比例”（DOR）]是否与 IVF 成功的机会相关，而不受胚胎等级评分和患者年龄等其他因素的影响。我们还研究了哪些因素可能与这个比例相关。
回顾性评估了 608 个不孕妇女的新鲜 IVF 周期。对于每个周期，计算卵母细胞 DOR 数如下：取回的卵子数除以第 3 天具有≥5 个细胞的胚胎数。这个数字与后续的指数周期成功率相关。还计算了“受精后”或“胚胎”死亡比例（EDOR；原核胚胎数/第 3 天具有≥5 个细胞的胚胎数）。
卵母细胞 DOR 与 IVF 活产率呈反向线性相关。活产率=（-5.75；DOR）+71.6（DOR>1；P≤0.005；R=-0.87）。此外，即使保持胚胎质量和患者年龄不变，卵母细胞 DOR 仍继续与成功率呈负相关。受精后或 EDOR 也继续与活产率呈统计学显著负相关（R=-0.91；P≤0.01）。受孕前 TNF-α：IL-10 比值（受孕前 3.3±2.6 个月抽取）与高卵母细胞 DOR 的相关性强于年龄或取回的卵子数量（P=0.04、0.14、0.72）。如果在受孕前给予抗 TNF-α 治疗（Humira），卵母细胞 DOR 对活产率的负面影响几乎消除（卵母细胞 DOR 与活产率之间的相关系数：未使用 Humira 的周期，R=-0.90，P≤0.006；使用 Humira 的周期，R=0.25，P≤0.55）。
在接受 IVF 的不孕妇女中，卵母细胞 DOR 可能有助于预测 IVF 成功率。该因素可能为提高即将到来的 IVF 周期的着床率、临床妊娠率、活产率和每个胚胎移植的活产率提供额外的工具。尽管许多机制可能导致卵母细胞 DOR 对 IVF 成功率的负面影响，但它与升高的受孕前 TNF-α：IL-10 比值相关，并且可以通过 Humira 纠正，这表明存在强烈的免疫成分，可能可以治疗。
