STUDY QUESTION Do antral follicle dynamics change in women with obesity and regular ovulatory cycles after a 6-month hypocaloric dietary intervention? SUMMARY ANSWER After a 6-month hypocaloric dietary intervention, women with obesity and regular ovulatory cycles displayed evidence of improved antral follicle dynamics defined by the emergence of more dominant follicles, larger ovulatory follicle diameter at selection, and increased luteal progesterone concentrations compared to pre-intervention. WHAT IS KNOWN ALREADY Precise events in antral folliculogenesis must occur in order for natural and regular monthly ovulation. In healthy women of reproductive age, antral follicles are recruited for growth in a wave-like fashion, wherein a subset of follicles are selected for preferential growth, and typically, one dominant follicle culminates in ovulation. Women with obesity and regular ovulatory cycles display evidence of suppressed antral follicle development, as evidenced by fewer recruitment events, fewer selectable and dominant follicles, smaller diameter of the ovulatory follicle at selection, and a higher prevalence of luteal phase defects. While improvements in gonadotropin and ovarian steroid hormone concentrations after weight loss have been documented in eumenorrheic women with obesity, the precise impact of weight loss on antral follicle dynamics has not been evaluated. STUDY DESIGN, SIZE, DURATION A pre–post pilot study of 12 women who participated in a 6-month hypocaloric dietary intervention. PARTICIPANTS/MATERIALS, SETTING, METHODS Twelve women with obesity (total body fat ≥35%) underwent transvaginal ultrasonography and venipuncture every-other-day for one inter-ovulatory interval (IOI) both before (baseline) and during the final month (Month 7) of a six-month hypocaloric dietary intervention. Participants were aged 24–34 years and had a self-reported history of regular menstrual cycles (25–35 days). Follicle number and diameter (≥2 mm) were quantified at each study visit, and individual growth profiles for all follicles ≥7 mm were determined. Blood samples were assayed for reproductive hormones. Follicle dynamics and reproductive hormone concentrations were compared pre- and post-intervention. Further, post-intervention follicle and endocrine dynamics (Month 7 IOI) were compared to an age-matched reference cohort of lean women with regular ovulatory cycles (total body fat <35%, N = 21). MAIN RESULTS AND THE ROLE OF CHANCE Participants lost an average of 11% of their original body weight with the hypocaloric dietary intervention. More dominant follicles were detected (≥10 mm) at Month 7 compared to baseline (0. 3 ± 0.4 versus 0.4 ± 0.5 follicles, P = 0.001), and ovulatory follicles were selected at larger diameters post-intervention (7.3 ± 2.0 versus 10.9 ± 2.6 mm, P = 0.007). Luteal progesterone concentrations were increased at Month 7 compared to baseline (5.3 ± 3.65 versus 6.3 ± 4.74 ng/ml, P < 0.0001). However, risk for luteal phase dysfunction as judged by the prevalence of a luteal phase length <10 days, integrated luteal progesterone levels <80 ng/ml or peak progesterone <10 ng/ml did not differ pre- versus post-intervention (all, P > 0.05). In Month 7, follicle dynamics and endocrine profiles were similar to the reference cohort across all measures. LIMITATIONS, REASONS FOR CAUTION This study does not inform on the earliest stages of ovarian follicle development and is limited to providing knowledge on the later stages of antral follicle development. This study cannot fully address causation between weight loss and sustained improvements in antral follicle dynamics. The data cannot be extrapolated to comment on potential improvements in fertility and fecundity with weight loss. The small group sizes limit statistical power. WIDER IMPLICATIONS OF THE FINDINGS The increasing prevalence of obesity necessitates an understanding of the mechanisms that underlie potential improvements in reproductive health outcomes with weight loss. Women with obesity and regular ovulatory cycles who undertook a 6-month hypocaloric dietary intervention demonstrated improvements consistent with benefits of lifestyle intervention on reproductive health even in those without overt signs of reproductive dysfunction. Potential improvements in the cellular makeup of follicles, which may underlie the restoration of normal follicle development and amelioration of subfertility, require further investigation. STUDY FUNDING/COMPETING INTEREST(S) Cornell University, President’s Council of Cornell Women, United States Department of Agriculture (Grant No. 8106), and National Institutes of Health (R01-HD0937848). B.Y.J. and H.V.B. were supported by doctoral training awards from the National Institutes of Health (T32-DK007158) and Canadian Institutes of Health Research (Grant No. 146182), respectively. The authors have no competing interests. TRIAL REGISTRATION NUMBER NCT01927432 and NCT01785719.

中文翻译：

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低热量饮食干预对月经正常肥胖女性窦卵泡动态的影响

研究问题 肥胖且排卵周期规律的女性在接受 6 个月的低热量饮食干预后，窦卵泡动态是否会发生变化？答案总结 经过 6 个月的低热量饮食干预后，肥胖且排卵周期规律的女性表现出窦卵泡动态改善的证据，即出现更多优势卵泡、选择时排卵卵泡直径更大以及与治疗前相比黄体孕酮浓度增加。干涉。已知的情况 为了每月自然、定期排卵，必须发生窦卵泡发生的精确事件。在育龄健康女性中，窦卵泡以波状方式募集生长，其中选择卵泡子集优先生长，并且通常，一个优势卵泡在排卵时达到顶峰。肥胖且排卵周期规律的女性表现出窦卵泡发育受到抑制的证据，表现为招募事件较少、可选择和优势卵泡较少、选择时排卵卵泡直径较小以及黄体期缺陷发生率较高。虽然已记录到月经正常的肥胖女性减肥后促性腺激素和卵巢类固醇激素浓度有所改善，但减肥对窦卵泡动态的确切影响尚未得到评估。研究设计、规模、持续时间 这是一项针对 12 名参与为期 6 个月低热量饮食干预的女性的事前试点研究。参与者/材料、环境、方法 12 名肥胖女性（全身脂肪≥35%）在排卵前（基线）和最后一个月（当月）期间每隔一天接受一次经阴道超声检查和静脉穿刺，持续一个排卵间隔（IOI） 7）为期六个月的低热量饮食干预。参与者年龄为 24-34 岁，并有定期月经周期（25-35 天）的自我报告史。每次研究访视时都会对卵泡数量和直径（≥2 毫米）进行量化，并确定所有≥7 毫米的卵泡的个体生长概况。检测血液样本中的生殖激素。比较干预前后的卵泡动态和生殖激素浓度。此外，将干预后卵泡和内分泌动态（第7个月的IOI）与年龄匹配的具有规律排卵周期的瘦女性参考队列（全身脂肪<35%，N=21）进行比较。主要结果和机会的作用 通过低热量饮食干预，参与者的体重平均减轻了 11%。与基线相比，第 7 个月时检测到更多优势卵泡 (≥10 mm)（0. 3 ± 0.4 与 0.4 ± 0.5 个卵泡，P = 0.001），并且在干预后选择直径较大的排卵卵泡（7.3 ± 2.0 与 10.9） ± 2.6 毫米，P = 0.007）。与基线相比，第 7 个月时黄体孕酮浓度有所增加（5.3 ± 3.65 与 6.3 ± 4.74 ng/ml，P < 0.0001）。然而，根据黄体期长度<10天、黄体孕酮综合水平<80ng/ml或峰值孕酮<10ng/ml的发生率来判断，黄体期功能障碍的风险在干预前与干预后没有差异（所有，P＞0.05)。第 7 个月，卵泡动态和内分泌特征在所有指标上均与参考队列相似。局限性和注意理由本研究不提供有关卵巢卵泡发育最早阶段的信息，仅限于提供有关窦状卵泡发育后期的知识。这项研究无法完全解决体重减轻和窦卵泡动态持续改善之间的因果关系。无法推断这些数据来评论体重减轻对生育力和生育能力的潜在改善。小群体规模限制了统计能力。研究结果的更广泛意义 肥胖症患病率的日益增加，需要了解减肥可能改善生殖健康结果的机制。患有肥胖症且排卵周期规律的女性在接受为期 6 个月的低热量饮食干预后，表现出与生活方式干预对生殖健康的益处一致的改善，即使对于那些没有明显生殖功能障碍迹象的女性也是如此。卵泡细胞构成的潜在改善可能是恢复正常卵泡发育和改善生育力低下的基础，需要进一步研究。研究资助/竞争利益：康奈尔大学、康奈尔妇女总统委员会、美国农业部（拨款号 8106）和美国国立卫生研究院（R01-HD0937848）。裴勇俊和 HVB 分别获得了美国国立卫生研究院 (T32-DK007158) 和加拿大卫生研究院 (批准号 146182) 的博士培训奖的支持。作者没有竞争利益。试用注册号 NCT01927432 和 NCT01785719。研究结果的更广泛意义 肥胖症患病率的日益增加，需要了解减肥可能改善生殖健康结果的机制。患有肥胖症且排卵周期规律的女性在接受为期 6 个月的低热量饮食干预后，表现出与生活方式干预对生殖健康的益处一致的改善，即使对于那些没有明显生殖功能障碍迹象的女性也是如此。卵泡细胞构成的潜在改善可能是恢复正常卵泡发育和改善生育力低下的基础，需要进一步研究。研究经费/竞争利益：康奈尔大学、康奈尔妇女总统委员会、美国农业部（拨款号 8106）和美国国立卫生研究院（R01-HD0937848）。裴勇俊和 HVB 分别获得了美国国立卫生研究院 (T32-DK007158) 和加拿大卫生研究院 (批准号 146182) 的博士培训奖的支持。作者没有竞争利益。试用注册号 NCT01927432 和 NCT01785719。研究结果的更广泛意义 肥胖症患病率的日益增加，需要了解减肥可能改善生殖健康结果的机制。患有肥胖症且排卵周期规律的女性进行了 6 个月的低热量饮食干预，结果显示出与生活方式干预对生殖健康的益处一致的改善，即使对于那些没有明显生殖功能障碍迹象的女性也是如此。卵泡细胞构成的潜在改善可能是恢复正常卵泡发育和改善生育力低下的基础，需要进一步研究。研究经费/竞争利益：康奈尔大学、康奈尔妇女总统委员会、美国农业部（拨款号 8106）和美国国立卫生研究院（R01-HD0937848）。裴勇俊和 HVB 分别获得了美国国立卫生研究院 (T32-DK007158) 和加拿大卫生研究院 (批准号 146182) 的博士培训奖的支持。作者没有竞争利益。试用注册号 NCT01927432 和 NCT01785719。