Department of Obstetrics, Gynecology and Reproductive Biology, Brigham & Women's Hospital and Harvard Medical School, 02115 Boston, MA, USA.
Hum Reprod. 2012 Nov;27(11):3198-207. doi: 10.1093/humrep/des308. Epub 2012 Sep 11.
Is the cytoskeletal and chromosomal organization of failed fertilized oocytes from severely obese patients (BMI ≥ 35 kg/m²) altered compared with that in patients with normal BMI (BMI 18.5-24.9 kg/m²)?
Compared with normal BMI patients, severe obesity was associated with a greater prevalence of spindle anomalies and non-aligned chromosomes in failed fertilized oocytes.
Obesity is associated with poor reproductive outcomes, but little is known regarding the underlying mechanisms. To address potential mechanisms, our study compared the cytoskeletal and chromosome organization in failed fertilized oocytes from severely obese and normal BMI patients.
The study population was drawn from IVF patients treated in a hospital-based infertility clinic between February 2010 and July 2011. The prevalence of meiotic spindle and chromosome alignment anomalies in failed fertilized oocytes from patients with severe obesity (i.e. Class II and III; BMI 35.0-50.1 kg/m²) was compared with those from patients with normal BMI (BMI 18.5-24.9 kg/m²). Oocytes were fixed and then labeled for tubulin, actin and chromatin. Spindle number and integrity, as well as chromosome alignment, were assessed using immunofluorescence microscopy and, in some cases, confocal microscopy. Generalized estimating equations were applied, which account for the correlation among oocytes from the same patient to estimate odds ratio (OR), 95% confidence intervals (CIs) and two-sided Wald P-values. Models were adjusted for continuous age at cycle start, cycle type (IVF or ICSI) and polycystic ovarian syndrome (PCOS) a priori.
University-affiliated infertility clinic. A total of 276 oocytes that failed to fertilize from 137 patients were evaluated: 105 oocytes from severely obese women (n = 47) and 171 oocytes from normal BMI patients (n = 90).
(i) Significantly more oocytes from the severely obese group exhibited two spindles compared with those from the normal BMI group (58.9 versus 35.1%; OR = 2.68, CI = 1.39-5.15, P-value = 0.003). (ii) Among oocytes with a single spindle, those from severely obese patients showed a significantly higher prevalence of disarranged spindles with non-aligned chromosomes compared with those from normal BMI patients (28.6 versus 8.6%; OR = 4.58, CI = 1.05-19.86, P-value = 0.04).
BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Inclusion of only failed fertilized oocytes, small sample size, unknown factors such as non-PCOS comorbidity.
For this study, by design, it is unclear whether the findings are generalizable to successfully fertilized oocytes, and whether this oocyte-level influence of obesity is generalizable to infertile women who do not undergo stimulation or, more broadly, to spontaneous conceptions in fertile women.
STUDY FUNDING/COMPETING INTEREST(S): none.
n/a.
严重肥胖（BMI≥35kg/m²）患者的失败受精卵的细胞骨架和染色体结构是否与正常 BMI（BMI 18.5-24.9kg/m²）患者的不同？
与正常 BMI 患者相比，严重肥胖与失败受精卵中纺锤体异常和染色体排列不齐的发生率更高有关。
肥胖与生殖结局不佳有关，但关于潜在机制知之甚少。为了解决潜在的机制问题，我们比较了严重肥胖和正常 BMI 患者的失败受精卵的细胞骨架和染色体结构。
该研究人群来自 2010 年 2 月至 2011 年 7 月在一家医院为不孕不育患者治疗的 IVF 患者。比较了严重肥胖（即 II 类和 III 类；BMI 35.0-50.1kg/m²）患者的失败受精卵中的减数分裂纺锤体和染色体排列异常的发生率与正常 BMI（BMI 18.5-24.9kg/m²）患者的发生率。使用免疫荧光显微镜检查固定后的卵母细胞，并用共聚焦显微镜检查卵母细胞的某些情况。应用广义估计方程来评估卵母细胞的纺锤体数量和完整性以及染色体排列情况，该方程考虑了来自同一患者的卵母细胞之间的相关性，以估计比值比（OR）、95%置信区间（CI）和双侧 Wald P 值。根据周期开始时的连续年龄、周期类型（IVF 或 ICSI）和多囊卵巢综合征（PCOS）预先调整模型。
大学附属不孕不育诊所。评估了 137 名患者中 276 个未受精的卵母细胞：105 个卵母细胞来自严重肥胖的女性（n=47），171 个卵母细胞来自正常 BMI 患者（n=90）。
（i）严重肥胖组中表现出两个纺锤体的卵母细胞明显多于正常 BMI 组（58.9%比 35.1%；OR=2.68，CI=1.39-5.15，P 值=0.003）。（ii）在具有单个纺锤体的卵母细胞中，严重肥胖患者的纺锤体排列紊乱且染色体排列不齐的比例明显高于正常 BMI 患者（28.6%比 8.6%；OR=4.58，CI=1.05-19.86，P 值=0.04）。
偏见、混杂因素和其他注意事项：仅纳入失败受精的卵母细胞，样本量小，未知因素如非 PCOS 合并症。
对于这项研究，由于设计原因，尚不清楚这些发现是否适用于成功受精的卵母细胞，以及肥胖对卵母细胞的这种影响是否适用于未接受刺激的不孕妇女，或者更广泛地说，是否适用于生育能力正常的妇女的自然受孕。
研究资金/利益冲突：无。
无。
