Vanni V S, Somigliana E, Reschini M, Pagliardini L, Marotta E, Faulisi S, Paffoni A, Vigano' P, Vegetti W, Candiani M, Papaleo E
Centro Scienze Natalità, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Fondazione IRCCS Ca'Granda, Ospedale Maggiore Policlinico, Milan, Italy.
PLoS One. 2017 May 17;12(5):e0176482. doi: 10.1371/journal.pone.0176482. eCollection 2017.
Cycles with progesterone elevation during controlled ovarian stimulation (COS) for IVF/ICSI are commonly managed with a "freeze-all" strategy, due to a well-recognized detrimental effect of high progesterone levels on endometrial receptivity. However, also a detrimental effect of elevated progesterone on day-3 embryo quality has recently been found with regards to top quality embryo formation rate. Because blastocyst culture and cryopreservation are largely adopted, we deemed relevant to determine whether this detrimental effect is also seen on blastocyst quality on day 5-6. This issue was investigated through a large two-center retrospective study including 986 GnRH antagonist IVF/ICSI cycles and using top quality blastocyst formation rate as the main outcome. Results showed that on multivariate analysis sperm motility (p<0.01) and progesterone levels at ovulation triggering (p = 0.01) were the only two variables that significantly predicted top quality blastocyst formation rate after adjusting for relevant factors including female age, BMI, basal AMH and total dose of FSH used for COS. More specifically, progesterone levels at induction showed an inverse relation with top quality blastocyst formation (correlation coefficient B = -1.08, 95% CI -1.9 to -0.02) and ROC curve analysis identified P level >1.49 ng/ml as the best cut-off for identification of patients at risk for the absence of top quality blastocysts (AUC 0.55, p<0.01). Our study is the first to investigate the top quality blastocyst formation rate in relation to progesterone levels in IVF/ICSI cycles, showing that increasing progesterone is associated with lower rates of top quality blastocyst. Hence, the advantages of prolonging COS to maximize the number of collected oocytes might eventually be hindered by a decrease in top quality blastocysts available for transfer, if increasing progesterone levels are observed. This observation extends the results of two recent studies focused on day-3 embryos and deserves further research.
在体外受精/卵胞浆内单精子注射（IVF/ICSI）的控制性卵巢刺激（COS）过程中，出现孕酮升高的周期通常采用“全冷冻”策略进行处理，这是因为人们清楚地认识到高孕酮水平对子宫内膜容受性有不利影响。然而，最近关于优质胚胎形成率的研究发现，孕酮升高对第3天胚胎质量也有不利影响。由于目前广泛采用囊胚培养和冷冻保存技术，我们认为有必要确定这种不利影响在第5 - 6天的囊胚质量上是否也存在。本研究通过一项大型的两中心回顾性研究来探讨这个问题，该研究纳入了986个促性腺激素释放激素（GnRH）拮抗剂IVF/ICSI周期，并将优质囊胚形成率作为主要观察指标。结果显示，在多因素分析中，调整了包括女性年龄、体重指数（BMI）、基础抗缪勒管激素（AMH）以及COS所用促卵泡生成素（FSH）总剂量等相关因素后，精子活力（p<0.01）和扳机日孕酮水平（p = 0.01）是仅有的两个能显著预测优质囊胚形成率的变量。更具体地说，扳机日孕酮水平与优质囊胚形成呈负相关（相关系数B = -1.08，95%可信区间 -1.9至 -0.02），并且ROC曲线分析确定孕酮水平>1.49 ng/ml是识别无优质囊胚风险患者的最佳临界值（曲线下面积0.55，p<0.01）。我们的研究首次探讨了IVF/ICSI周期中优质囊胚形成率与孕酮水平的关系，表明孕酮水平升高与优质囊胚率降低有关。因此，如果观察到孕酮水平升高，延长COS以最大化收集的卵母细胞数量的优势最终可能会因可用于移植的优质囊胚数量减少而受到阻碍。这一观察结果扩展了最近两项针对第3天胚胎的研究结果，值得进一步研究。
