School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK.
Institute of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK.
Hum Reprod. 2017 Nov 1;32(11):2287-2297. doi: 10.1093/humrep/dex293.
In women undergoing IVF/ICSI who miscarry in their first complete cycle, what is the chance of a live birth in subsequent complete cycles, and how does this compare with those whose first complete cycle ends with live birth or without a pregnancy?
After two further complete cycles of IVF/ICSI, women who had miscarried or had a live birth in their first complete cycle had a higher chance of live birth (40.9 and 49.0%, respectively) than those who had no pregnancies (30.1%).
Cumulative live birth rates (CLBRs) after one or more complete cycles of IVF have been reported previously, as have some of the risk factors associated with miscarriage, both in general populations and in those undergoing IVF. Chances of cumulative live birth after a number of complete IVF cycles involving replacement of fresh followed by frozen embryos after an initial miscarriage in a population undergoing IVF treatment have not been reported previously.
STUDY DESIGN, SIZE, DURATION: National population-based cohort study of 112 549 women who started their first IVF treatment between 1999 and 2008.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from the UK Human Fertilisation and Embryology Authority (HFEA) register on IVF/ICSI treatments, using autologous gametes were analysed. CLBRs were estimated in women who (i) had miscarriage (and no live birth), (ii) at least one live birth or (iii) no pregnancy in their first complete cycle of IVF/ICSI (including fresh and frozen embryo transfers following a single oocyte retrieval episode). A multivariable analysis was performed to assess the effect of first complete cycle outcome on subsequent CLBRs after adjusting for confounding factors such as female age, duration of infertility and cause of infertility.
In their first complete cycle, 9321 (8.3%) women had at least one miscarriage (and no live birth); 33 152 (29.5%) had at least one live birth and 70 076 (62.3%) had no pregnancies. After two further complete cycles, conservative CLBRs (which assume that women who discontinued treatment subsequently never had a live birth) were 40.9, 49.0 and 30.1%, while optimal CLBRs (which assume that women who discontinue have the same chance of live birth as those treated) were 49.5, 57.9 and 38.4% in the miscarriage, live birth and no pregnancy groups respectively. Odds of cumulative live birth for women who miscarried in their first complete cycle were 42% higher than those who had no pregnancy [odds ratio (95% CI) = 1.42 (1.34, 1.50)], and twice as high for live birth versus no pregnancy [2.04 (1.89, 2.20)]. Negative predictors for live birth in all women included tubal infertility [0.88 (0.82, 0.94)] and increasing age [18-40 years = 0.94 (0.94, 0.95); >40 years = 0.63 (0.59, 0.66) per year].
CLBRs could not be estimated for treatments occurring after September 2008 due to potentially incomplete data following regulatory changes regarding consent for data use in research. Additionally, covariates not included in the HFEA database (including BMI, smoking, previous history of miscarriage and gestational age at miscarriage) could not be adjusted for in our analysis.
Miscarriage following IVF can be devastating for couples who are uncertain about their ultimate prognosis. Our findings will provide reassurance to these couples as they consider their options for continuing treatment.
STUDY FUNDING/COMPETING INTEREST(S): N.J.C. received an Aberdeen Summer Research Scholarship funded by the Institute of Applied Health Sciences (University of Aberdeen), through the Aberdeen Clinical Academic Training Scheme. This work was supported by a Chief Scientist Office Postdoctoral Training Fellowship in Health Services Research and Health of the Public Research (Ref PDF/12/06). The views expressed here are those of the authors and not necessarily those of the Chief Scientist Office or the University of Aberdeen. The funders did not have any role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. None of the authors has any conflicts of interest to declare.
在首次完整周期中流产的接受 IVF/ICSI 的女性中，随后的完整周期中活产的机会是多少，与首次完整周期结束时活产或无妊娠的女性相比如何？
在两次进一步的 IVF/ICSI 完整周期后，与首次完整周期无妊娠的女性相比，首次完整周期中流产或活产的女性活产的机会更高（分别为 40.9%和 49.0%）。
之前已经报道了一个或多个 IVF 完整周期后的累积活产率 (CLBR)，以及在一般人群和接受 IVF 的人群中与流产相关的一些风险因素。在接受 IVF 治疗的人群中，在初始流产后，新鲜胚胎移植后紧接着是冷冻胚胎移植，涉及替换初始卵母细胞的多次 IVF 周期后，累积活产的机会尚未被报道。
研究设计、大小和持续时间：这是一项针对 1999 年至 2008 年间首次接受 IVF 治疗的 112549 名女性的全国性基于人群的队列研究。
参与者/材料、设置、方法：使用自体配子对英国人类受精和胚胎管理局 (HFEA) 登记册上的 IVF/ICSI 治疗数据进行了分析。在首次 IVF/ICSI 完整周期中（包括单次卵母细胞采集后新鲜和冷冻胚胎移植）经历（i）流产（且无活产）、（ii）至少一次活产或（iii）无妊娠的女性中，估计 CLBR。进行了多变量分析，以评估首次完整周期结果对随后 CLBR 的影响，调整了混杂因素，如女性年龄、不孕持续时间和不孕原因。
在首次完整周期中，9321 名（8.3%）女性至少有一次流产（且无活产）；33152 名（29.5%）至少有一次活产，70076 名（62.3%）无妊娠。在两次进一步的完整周期后，保守的 CLBR（假设停止治疗的女性随后从未有过活产）分别为 40.9%、49.0%和 30.1%，而最佳的 CLBR（假设停止治疗的女性具有与接受治疗的女性相同的活产机会）分别为 49.5%、57.9%和 38.4%，在流产、活产和无妊娠组中。与无妊娠组相比，首次完整周期中流产的女性累积活产的几率高 42%[比值比（95%CI）=1.42（1.34，1.50）]，而与活产相比，几率高 2 倍[2.04（1.89，2.20）]。所有女性活产的负面预测因素包括输卵管性不孕[0.88（0.82，0.94）]和年龄增长[18-40 岁=0.94（0.94，0.95）；>40 岁=0.63（0.59，0.66）每增加 1 年]。
由于监管变更后关于数据用于研究的同意问题，可能导致数据不完整，因此无法在 2008 年 9 月后进行的治疗中估计 CLBR。此外，我们的分析中无法调整 HFEA 数据库中未包含的协变量（包括 BMI、吸烟、既往流产史和流产时的孕龄）。
IVF 后流产对不确定最终预后的夫妇来说是毁灭性的。我们的发现将为这些夫妇提供安慰，因为他们考虑继续治疗的选择。
研究资助/利益冲突：NJC 获得了由应用健康科学研究所（阿伯丁大学）通过阿伯丁临床学术培训计划资助的 Aberdeen 暑期研究奖学金。这项工作得到了首席科学家办公室博士后培训奖学金在卫生服务研究和公众健康研究（参考 PDF/12/06）的支持。这里表达的观点是作者的观点，不一定是首席科学家办公室或阿伯丁大学的观点。资助者在研究设计、数据的收集、分析和解释、报告的撰写或提交论文进行发表方面没有任何作用。作者均无利益冲突。
