Griesinger Georg, Trevisan Silvia, Cometti Barbara
Department of Gynecological Endocrinology and Reproductive Medicine, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany.
IBSA Institut Biochimique SA, via del Piano, 6915 Pambio-Noranco, Switzerland.
Hum Reprod Open. 2018 Jan 29;2018(1):hox031. doi: 10.1093/hropen/hox031. eCollection 2018.
What is the independent contribution of endometrial thickness (EMT) on day of embryo transfer to achieving an ongoing pregnancy and live birth after IVF treatment?
EMT is a poor predictor of IVF success and has only little independent prognostic value.
In a number of previous studies, pregnancy rates have been found to be lower in patients with thin endometrium.
This is a retrospective analysis of data from two large, randomized phase III studies (conducted in Europe and the USA) comparing s.c. progesterone with vaginal progesterone for luteal phase support. The studies were very similar in design, patient population and outcome, and the study data were combined and analysed on an individual patient level.
PARTICIPANTS/MATERIALS SETTING METHOD: Subjects were infertile patients with an indication for IVF/ICSI, aged between 18 and 42 years, BMI <30 kg/m, <3 prior ART cycles and ≥ 3 oocytes after controlled ovarian stimulation with GnRH-agonist or GnRH-antagonist. EMT was assessed on day of embryo transfer ( = 1401). The association of EMT and ongoing pregnancy rate was determined by comparison of outcomes by quantiles of EMT. The predictive capacity of EMT for ongoing pregnancy achievement was assessed at each millimeter cut-off. Finally, a regression model was built to determine the contribution of EMT among other confounders, such as age and oocyte numbers, on the likelihood of ongoing pregnancy and live birth.
In univariate analysis, ongoing pregnancy rates correlate to EMT. In patients above a cut-off of ≥9 mm EMT, the chance of pregnancy was higher as compared to patients with an EMT of 3-8 mm (odds ratio (OR) = 1.69, 95% CI: 1.23-2.35, = 0.001; sensitivity 88.89%, specificity 17.52%, positive predictive value 39.02%, negative predictive value 72.64% and likelihood ratio 1.08). In multivariate regression analysis, after controlling for trial, female age and oocyte numbers, EMT was a statistically significant predictor of live birth (OR = 1.05, 95% CI: 1.00-1.10; = 0.0351). If EMT indeed is an independent factor affecting outcome, this finding implies that at a baseline live birth rate of 20% an increase of 2 mm in EMT should result in an increase of the live birth rate of ~1.6%.
The independent contribution of EMT to live birth likelihood is small and may result from (undetermined) confounding. The EMT on day of embryo transfer is usually higher as compared to the EMT on day of triggering final oocyte maturation when it is conventionally assessed during routine cycle monitoring. Furthermore, endometrial lining pattern and/or subendometrial Doppler flow have not been assessed and, accordingly, the conclusions of this work are limited to only the thickness of the endometrium.
EMT can be ignored during cycle monitoring of the majority of IVF patients and only the extremes of EMT deserve further diagnostic work-up.
STUDY FUNDING/COMPETING INTERESTS: The study was supported by IBSA. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott, Gedeon-Richter as well as personal fees from VitroLife, NMC Healthcare, ReprodWissen, BioSilu and ZIVA. S.T. and B.C. are employees of IBSA.
NCT00827983 and NCT00828191 (clinicaltrials.gov).
23 January 2009 (NCT00827983 and NCT00828191).
DATE OF FIRST PATIENT’S ENROLMENT: January 2009 (NCT00827983 and NCT00828191).
胚胎移植日的子宫内膜厚度（EMT）对体外受精（IVF）治疗后实现持续妊娠和活产有何独立贡献？
EMT对IVF成功的预测能力较差，且仅有很小的独立预后价值。
在之前的多项研究中，已发现子宫内膜薄的患者妊娠率较低。
研究设计、规模、持续时间：这是一项对两项大型随机III期研究（在欧洲和美国开展）数据的回顾性分析，该研究比较了皮下注射黄体酮与阴道用黄体酮进行黄体期支持的效果。两项研究在设计、患者群体和结果方面非常相似，研究数据在个体患者层面进行合并和分析。
参与者/材料、环境、方法：受试者为有IVF/卵胞浆内单精子注射（ICSI）指征的不孕患者，年龄在18至42岁之间，体重指数（BMI）<30kg/m²，既往ART周期<3次，经促性腺激素释放激素（GnRH）激动剂或GnRH拮抗剂控制性卵巢刺激后获卵≥3枚。在胚胎移植日评估EMT（n = 1401）。通过按EMT分位数比较结果来确定EMT与持续妊娠率的关联。在每个毫米截点评估EMT对实现持续妊娠的预测能力。最后，建立回归模型以确定EMT在年龄和卵母细胞数量等其他混杂因素中对持续妊娠和活产可能性的贡献。
在单因素分析中，持续妊娠率与EMT相关。EMT≥9mm的患者与EMT为3 - 8mm的患者相比，妊娠几率更高（优势比（OR）= 1.69，95%置信区间（CI）：1.23 - 2.35，P = 0.001；敏感性88.89%，特异性17.52%，阳性预测值39.02%，阴性预测值72.64%，似然比1.08）。在多因素回归分析中，在控制试验、女性年龄和卵母细胞数量后，EMT是活产的统计学显著预测因素（OR = 1.05，95%CI：1.00 - 1.10；P = 0.0351）。如果EMT确实是影响结局的独立因素，这一发现意味着在基线活产率为20%时，EMT增加2mm应导致活产率增加约1.6%。
局限性、谨慎原因：EMT对活产可能性的独立贡献较小，可能源于（未确定的）混杂因素。与在常规周期监测中传统评估的触发最终卵母细胞成熟日的EMT相比，胚胎移植日的EMT通常更高。此外，未评估子宫内膜的内膜形态和/或内膜下多普勒血流，因此，本研究的结论仅限于子宫内膜厚度。
在大多数IVF患者的周期监测中可忽略EMT，只有EMT的极端情况值得进一步诊断检查。
研究资助/利益冲突：该研究由IBSA资助。G.G.从默克雪兰诺（MSD）、辉凌（Ferring）、默克 - 雪兰诺（Merck - Serono）、Finox、梯瓦（TEVA）、IBSA、Glycotope、雅培（Abbott）、吉德昂 - 里奇特（Gedeon - Richter）获得个人费用和非财务支持，以及从VitroLife、NMC Healthcare、ReprodWissen、BioSilu和ZIVA获得个人费用。S.T.和B.C.是IBSA的员工。
NCT00827983和NCT00828191（clinicaltrials.gov）。
2009年1月23日（NCT00827983和NCT00828191）。
2009年1月（NCT00827983和NCT00828191）。
