Ma Congcong, Long Xiaoyu, Yan Liying, Zhu Xiaohui, Chen Lixue, Li Rong, Wang Ying, Qiao Jie
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, China.
National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.
Hum Reprod Open. 2024 Oct 3;2024(4):hoae054. doi: 10.1093/hropen/hoae054. eCollection 2024.
Does ovarian stimulation and the ovarian response affect embryo euploidy?
Ovarian stimulation and the ovarian response in women undergoing preimplantation genetic testing for monogenic disorders (PGT-M) cycles did not affect the rates of blastocyst euploidy.
Whether or not ovarian stimulation in IVF-embryo transfer has potential effects on embryo euploidy is controversial among studies for several reasons: (i) heterogeneity of the study populations, (ii) biopsies being performed at different stages of embryo development and (iii) evolution of the platforms utilized for ploidy assessment. Patients who undergo PGT-M cycles typically have no additional risks of aneuploidy, providing an ideal study population for exploring this issue.
A retrospective cohort study including embryos undergoing PGT-M was conducted at a single academically affiliated fertility clinic between June 2014 and July 2021.
PARTICIPANTS/MATERIALS SETTING METHODS: A total of 617 women with 867 PGT-M cycles involving 12 874 retrieved oocytes and 3106 trophectoderm biopsies of blastocysts were included. The primary outcome of the study was median euploidy rate, which was calculated by dividing the number of euploid blastocysts by the total number of biopsied blastocysts for each cycle. Secondary outcomes included the median normal fertilization rate (two-pronuclear (2PN) embryos/metaphase II oocytes) and median blastulation rate (blastocyst numbers/2PN embryos).
Comparable euploidy rates and fertilization rates were observed across all age groups, regardless of variations in ovarian stimulation protocols, gonadotropin dosages (both the starting and total dosages), stimulation durations, the inclusion of human menopausal gonadotrophin supplementation, or the number of oocytes retrieved (all > 0.05). Blastulation rates declined with increasing starting doses of gonadotropins in women aged 31-34 years old ( = 0.005) but increased with increasing gonadotrophin starting doses in women aged 35-37 years old ( = 0.017). In women aged 31-34, 35-37, and 38-40 years old, blastulation rates were significantly reduced with increases in the number of oocytes retrieved ( = 0.001, <0.001, and 0.012, respectively).
Limitations include the study's retrospective nature and the relatively small number of patients of advanced age, especially patients older than 40 years old, leading to quite low statistical power. Second, as we considered euploidy rates as outcome measures, we did not analyze the effects of ovarian stimulation on uniform aneuploidy and mosaicism, respectively. Finally, we did not consider the effects of paternal characteristics on embryo euploidy status due to the fact that blastocyst aneuploidy primarily originates from maternal meiosis. However, sperm factors might have an effect on embryo development and the blastulation rate, and therefore also the number of blastocysts analyzed. The exclusion of patients with severe teratozoospermia and the fact that only ICSI was used as the insemination technique for women undergoing PGT-M contributed to minimize the effect of paternal factors.
Ovarian stimulation and response to stimulation did not affect blastocyst euploidy rates in women undergoing PGT-M cycles. However, in women aged 31-40 years old, there was a significant decline in blastulation rates as the number of retrieved oocytes increased.
STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Natural Science Foundation of China (Grant No. 81701407, 82301826); the National Key Research and Development Program of China (2022YFC2702901, 2022YFC2703004); China Postdoctoral Science Foundation (2022M710261), and China Postdoctoral Innovation Talent Support Program (BX20220020). There is no conflict of interest.
N/A.
卵巢刺激及卵巢反应是否会影响胚胎整倍体率？
在接受单基因疾病植入前基因检测（PGT-M）周期的女性中，卵巢刺激及卵巢反应并不影响囊胚整倍体率。
由于以下几个原因，体外受精-胚胎移植中的卵巢刺激是否对胚胎整倍体有潜在影响在各项研究中存在争议：（i）研究人群的异质性；（ii）在胚胎发育的不同阶段进行活检；（iii）用于倍性评估的平台的演变。接受PGT-M周期的患者通常不存在额外的非整倍体风险，这为探索该问题提供了理想的研究人群。
研究设计、规模、持续时间：2014年6月至2021年7月期间，在一家学术附属生育诊所进行了一项回顾性队列研究，纳入接受PGT-M的胚胎。
参与者/材料、设置、方法：共纳入617名女性，她们进行了867个PGT-M周期，涉及12874个取到的卵母细胞和3106个囊胚滋养外胚层活检。该研究的主要结局是中位整倍体率，通过每个周期中整倍体囊胚数量除以活检囊胚总数来计算。次要结局包括中位正常受精率（双原核（2PN）胚胎/中期II卵母细胞）和中位囊胚形成率（囊胚数量/2PN胚胎）。
在所有年龄组中均观察到了可比的整倍体率和受精率，无论卵巢刺激方案、促性腺激素剂量（起始剂量和总剂量）、刺激持续时间、是否添加人绝经促性腺激素，或取到的卵母细胞数量如何变化（均P>0.05）。在31 - 34岁的女性中，囊胚形成率随着促性腺激素起始剂量的增加而下降（P = 0.005），但在35 - 37岁的女性中，囊胚形成率随着促性腺激素起始剂量的增加而上升（P = 0.017）。在31 - 34岁、35 - 37岁和38 - 40岁的女性中，随着取到的卵母细胞数量增加，囊胚形成率显著降低（分别为P = 0.001、P<0.001和P = 0.012）。
局限性、谨慎的原因：局限性包括该研究的回顾性性质以及高龄患者数量相对较少，尤其是40岁以上的患者，导致统计效能相当低。其次，由于我们将整倍体率作为结局指标，我们没有分别分析卵巢刺激对均匀非整倍体和嵌合体的影响。最后，由于囊胚非整倍体主要源于母本减数分裂，我们没有考虑父本特征对胚胎整倍体状态的影响。然而，精子因素可能对胚胎发育和囊胚形成率有影响，进而也会影响分析的囊胚数量。排除严重畸形精子症患者以及仅将卵胞浆内单精子注射（ICSI）用作接受PGT-M女性的授精技术，有助于将父本因素的影响降至最低。
卵巢刺激及对刺激的反应并不影响接受PGT-M周期女性的囊胚整倍体率。然而，在31 - 40岁的女性中，随着取到的卵母细胞数量增加，囊胚形成率显著下降。
研究资金/利益冲突：本研究得到中国国家自然科学基金（项目编号81701407、82301826）；中国国家重点研发计划（2022YFC2702901、2022YFC2703004）；中国博士后科学基金（2022M710261），以及中国博士后创新人才支持计划（BX20220020）的资助。不存在利益冲突。
无。
