Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Hum Reprod. 2013 Nov;28(11):2972-80. doi: 10.1093/humrep/det315. Epub 2013 Aug 6.
Are we able to develop a model to calculate the chances of pregnancy prior to the start of the first IVF cycle as well as after one or more failed cycles?
Our prediction model enables the accurate individualized calculation of the probability of an ongoing pregnancy with IVF.
To improve counselling, patient selection and clinical decision-making in IVF, a number of prediction models have been developed. These models are of limited use as they were developed before current clinical and laboratory protocols were established.
STUDY DESIGN, SIZE, DURATION: This was a cohort study. The development set included 2621 cycles in 1326 couples who had been treated with IVF or ICSI between January 2001 and July 2009. The validation set included additional data from 515 cycles in 440 couples treated between August 2009 and April 2011. The outcome of interest was an ongoing pregnancy after transfer of fresh or frozen-thawed embryos from the same stimulated IVF cycle. If a couple became pregnant after an IVF/ICSI cycle, the follow-up was at a gestational age of at least 11 weeks.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Women treated with IVF or ICSI between January 2001 and April 2011 in a university hospital. IVF/ICSI cycles were excluded in the case of oocyte or embryo donation, surgically retrieved spermatozoa, patients positive for human immunodeficiency virus, modified natural IVF and cycles cancelled owing to poor ovarian stimulation, ovarian hyperstimulation syndrome or other unexpected medical or non-medical reasons.
Thirteen variables were included in the final prediction model. For all cycles, these were female age, duration of subfertility, previous ongoing pregnancy, male subfertility, diminished ovarian reserve, endometriosis, basal FSH and number of failed IVF cycles. After the first cycle: fertilization, number of embryos, mean morphological score per Day 3 embryo, presence of 8-cell embryos on Day 3 and presence of morulae on Day 3 were also included. In validation, the model had moderate discriminative capacity (c-statistic 0.68, 95% confidence interval: 0.63-0.73) but calibrated well, with a range from 0.01 to 0.56 in calculated probabilities.
LIMITATIONS, REASONS FOR CAUTION: In our study, the outcome of interest was ongoing pregnancy. Live birth may have been a more appropriate outcome, although only 1-2% of all ongoing pregnancies result in late miscarriage or stillbirth. The model was based on data from a single centre.
The IVF model presented here is the first to calculate the chances of an ongoing pregnancy with IVF, both for the first cycle and after any number of failed cycles. The generalizability of the model to other clinics has to be evaluated more extensively in future studies (geographical validation). Centres with higher or lower success rates could use the model, after recalibration, by adjusting the intercept to reflect the IVF success rates in their centre.
STUDY FUNDING/COMPETING INTEREST(S): This project was funded by the NutsOhra foundation (Grant 1004-179). The NutsOhra foundation had no role in the development of our study, in the collection, analysis and interpretation of data; in writing of the manuscript, and in the decision to submit the manuscript for publication. There were no competing interests.
我们能否在开始第一个试管婴儿周期之前以及一个或多个失败周期后建立一个预测妊娠概率的模型？
我们的预测模型可以准确地对试管婴儿周期中的妊娠概率进行个体化计算。
为了改善试管婴儿中的咨询、患者选择和临床决策，已经开发了许多预测模型。这些模型的用途有限，因为它们是在当前的临床和实验室方案建立之前开发的。
研究设计、大小和持续时间：这是一项队列研究。开发集包括 2001 年 1 月至 2009 年 7 月期间接受试管婴儿或卵胞浆内单精子注射治疗的 1326 对夫妇的 2621 个周期。验证集包括 2009 年 8 月至 2011 年 4 月期间接受治疗的另外 440 对夫妇的 515 个周期的数据。感兴趣的结果是同一刺激试管婴儿周期中新鲜或冷冻解冻胚胎移植后的持续妊娠。如果一对夫妇在试管婴儿/卵胞浆内单精子注射周期后怀孕，那么随访时间至少为 11 周的妊娠周数。
参与者/材料、地点、方法：在一所大学医院接受 2001 年 1 月至 2011 年 4 月期间的试管婴儿或卵胞浆内单精子注射治疗的女性。如果存在卵子或胚胎捐赠、手术采集的精子、人类免疫缺陷病毒阳性、改良自然试管婴儿以及由于卵巢刺激不良、卵巢过度刺激综合征或其他意外的医学或非医学原因而取消的周期，则排除试管婴儿/卵胞浆内单精子注射周期。
最终预测模型中包含了 13 个变量。对于所有周期，这些变量包括女性年龄、不孕持续时间、以前的持续妊娠、男性不孕、卵巢储备减少、子宫内膜异位症、基础 FSH 和失败的试管婴儿周期数。在第一次周期后：受精、胚胎数量、第 3 天胚胎的平均形态评分、第 3 天 8 细胞胚胎的存在和第 3 天的桑椹胚的存在也被包括在内。在验证中，该模型具有中等的区分能力（c 统计量为 0.68，95%置信区间：0.63-0.73），但校准良好，计算概率的范围为 0.01 至 0.56。
局限性、谨慎的原因：在我们的研究中，感兴趣的结果是持续妊娠。活产可能是一个更合适的结果，尽管所有持续妊娠中只有 1-2%会导致晚期流产或死产。该模型基于单个中心的数据。
这里提出的试管婴儿模型是第一个可以计算试管婴儿周期中妊娠概率的模型，无论是第一次周期还是任何数量的失败周期后。该模型在其他诊所的推广性需要在未来的研究中更广泛地进行评估（地理验证）。成功率较高或较低的中心可以在调整截距以反映其中心的试管婴儿成功率后，使用该模型进行重新校准。
研究资金/利益冲突：该项目由 NutsOhra 基金会（1004-179 号赠款）资助。NutsOhra 基金会在我们的研究开发、数据收集、分析和解释、手稿撰写以及提交手稿出版的决定中没有任何利益。没有利益冲突。
