National Perinatal Epidemiology and Statistics Unit (NPESU), Centre for Big Data Research in Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.
School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.
Hum Reprod. 2022 May 3;37(5):1047-1058. doi: 10.1093/humrep/deac032.
In a country with supportive funding for medically assisted reproduction (MAR) technologies, what is the proportion of MAR births over-time?
In 2017, 6.7% of births were conceived by MAR (4.8% ART and 1.9% ovulation induction (OI)/IUI) with a 55% increase in ART births and a stable contribution from OI/IUI births over the past decade.
There is considerable global variation in utilization rates of ART despite a similar infertility prevalence worldwide. While the overall contribution of ART to national births is known in many countries because of ART registries, very little is known about the contribution of OI/IUI treatment or the socio-demographic characteristics of the parents. Australia provides supportive public funding for all forms of MAR with no restrictions based on male or female age, and thus provides a unique setting to investigate the contribution of MAR to national births as well as the socio-demographic characteristics of parents across the different types of MAR births.
STUDY DESIGN, SIZE, DURATION: This is a novel population-based birth cohort study of 898 084 births using linked ART registry data and administrative data including birth registrations, medical services, pharmaceuticals, hospital admissions and deaths. Birth (a live or still birth of at least one baby of ≥400 g birthweight or ≥20 weeks' gestation) was the unit of analysis in this study. Multiple births were considered as one birth in our analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included a total of 898 084 births (606 488 mothers) in New South Wales and the Australian Capital Territory, Australia 2009-2017. We calculated the prevalence of all categories of MAR-conceived births over the study period. Generalized estimating equations were used to examine the association between parental characteristics (parent's age, parity, socio-economic status, maternal country of birth, remoteness of mother's dwelling, pre-existing medical conditions, smoking, etc.) and ART and OI/IUI births relative to naturally conceived births.
The proportion of MAR births increased from 5.1% of all births in 2009 to 6.7% in 2017, representing a 30% increase over the decade. The proportion of OI/IUI births remained stable at around 2% of all births, representing 32% of all MAR births. Over the study period, ART births conceived by frozen embryo-transfer increased nearly 3-fold. OI/IUI births conceived using clomiphene citrate decreased by 39%, while OI/IUI births conceived using letrozole increased 56-fold. Overall, there was a 55% increase over the study period in the number of ART-conceived births, rising to 56% of births to mothers aged 40 years and older. In 2017, almost one in six births (17.6%) to mothers aged 40 years and over were conceived using ART treatment. Conversely, the proportion of OI/IUI births was similar across different mother's age groups and remained stable over the study period. ART children, but not OI/IUI children, were more likely to have parents who were socio-economically advantaged compared to naturally conceived children. For example, compared to naturally conceived births, ART births were 16% less likely to be born to mothers who live in the disadvantaged neighbourhoods after accounting for other covariates (adjusted relative risk (aRR): 0.84 [95% CI: 0.81-0.88]). ART- or OI/IUI-conceived children were 25% less likely to be born to immigrant mothers than births after natural conception (aRR: 0.75 [0.74-0.77]).
LIMITATIONS, REASONS FOR CAUTION: The social inequalities that we observed between the parents of children born using ART and naturally conceived children may not directly reflect disparities in accessing fertility care for individuals seeking treatment.
With the ubiquitous decline in fertility rates around the world and the increasing trend to delay childbearing, this population-based study enhances our understanding of the contribution of different types of MARs to population profiles among births in high-income countries. The parental socio-demographic characteristics of MAR-conceived children differ significantly from naturally conceived children and this highlights the importance of accounting for such differences in studies investigating the health and development of MAR-conceived children.
STUDY FUNDING/COMPETING INTEREST(S): This study was funded through Australian National Health and Medical Research Council (NHMRC) grant: APP1127437. G.M.C. is an employee of The University of New South Wales (UNSW) and Director of the National Perinatal Epidemiology and Statistics Unit (NPESU), UNSW. The NPESU manages the Australian and New Zealand Assisted Reproduction Database with funding support from the Fertility Society of Australia and New Zealand. C.V. is an employee of The University of New South Wales (UNSW), Director of Clinical Research of IVFAustralia, Member of the Board of the Fertility Society of Australia and New Zealand, and Member of Research Committee of School of Women's and Children's Health, UNSW. C.V. reports grants from Australian National Health and Medical Research Council (NHMRC), and Merck KGaA. C.V. reports consulting fees, and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript, writing or educational events or attending meeting or travel from Merck, Merck Sparpe & Dohme, Ferring, Gedon-Richter and Besins outside this submitted work. C.V. reported stock or stock options from Virtus Health Limited outside this submitted work. R.J.N. is an employee of The University of Adelaide, and Chair DSMC for natural therapies trial of The University of Hong Kong. R.J.N. reports grants from NHMRC. R.J.N. reports lecture fees and support for attending or travelling for lecture from Merck Serono which is outside this submitted work. L.R.J. is an employee of The UNSW and Foundation Director of the Centre for Big Data Research in Health at UNSW Sydney. L.R.J. reports grants from NHMRC. The other co-authors have no conflict of interest.
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在一个对医学辅助生殖技术(MAR)有支持性资金的国家,MAR 出生的比例随时间推移有何变化?
2017 年,6.7%的出生是通过 MAR 实现的(4.8%为 ART,1.9%为排卵诱导(OI)/IUI),ART 出生人数增加了 55%,而 OI/IUI 出生人数在过去十年中保持稳定。
尽管全球不孕患病率相似,但全球范围内 ART 的利用率存在相当大的差异。由于 ART 注册,许多国家都知道 ART 对国家出生总数的总体贡献,但对于 OI/IUI 治疗的贡献或 MAR 出生父母的社会人口特征知之甚少。澳大利亚为所有形式的 MAR 提供支持性公共资金,没有基于男性或女性年龄的限制,因此为研究 MAR 对国家出生的贡献以及不同类型的 MAR 出生的父母的社会人口特征提供了一个独特的环境。
研究设计、规模、持续时间:这是一项基于人群的出生队列研究,使用澳大利亚新南威尔士州和首都直辖区的 898084 次出生的 ART 登记数据和包括出生登记、医疗服务、药品、住院和死亡在内的行政数据。本研究的单位是出生(至少 400 克活产或至少 20 周妊娠的婴儿的活产或死产)。在我们的分析中,多胎被视为一次出生。
参与者/材料、设置、方法:这项研究共包括澳大利亚新南威尔士州和首都直辖区 2009-2017 年的 898084 次出生(606488 位母亲)。我们计算了 MAR 受孕出生的所有类别在研究期间的流行率。使用广义估计方程检查了父母特征(父母年龄、产次、社会经济地位、母亲出生地、母亲居住地的偏远程度、既往医疗状况、吸烟等)与 ART 和 OI/IUI 出生相对于自然受孕出生的关联。
MAR 出生的比例从 2009 年的所有出生的 5.1%增加到 2017 年的 6.7%,在十年内增加了 30%。OI/IUI 出生的比例保持在所有出生的 2%左右,占所有 MAR 出生的 32%。在研究期间,使用冷冻胚胎移植的 ART 出生人数增加了近 3 倍。使用枸橼酸氯米酚的 OI/IUI 出生人数减少了 39%,而使用来曲唑的 OI/IUI 出生人数增加了 56 倍。总体而言,研究期间 ART 受孕出生人数增加了 55%,到 40 岁及以上母亲的出生比例上升至 56%。2017 年,67.6%的 40 岁及以上母亲的分娩是通过 ART 治疗实现的。相反,不同母亲年龄组的 OI/IUI 出生比例相似,在研究期间保持稳定。与自然受孕的儿童相比,ART 儿童的父母在社会经济上更具优势,但 OI/IUI 儿童并非如此。例如,与自然受孕的出生相比,ART 出生的母亲居住在贫困社区的比例降低了 16%(校正后的相对风险(aRR):0.84[95%CI:0.81-0.88])。与自然受孕相比,ART 或 OI/IUI 受孕的儿童是移民母亲所生的可能性低 25%(aRR:0.75[0.74-0.77])。
局限性、谨慎的原因:我们观察到的 ART 出生的父母和自然受孕的儿童之间的社会不平等,可能并不能直接反映寻求治疗的个人获得生育护理的差异。
随着全球生育率的普遍下降和生育年龄的推迟,这项基于人群的研究增强了我们对高收入国家 MAR 对出生人口特征贡献的理解。MAR 受孕儿童的父母的社会人口特征与自然受孕儿童有显著差异,这凸显了在研究 MAR 受孕儿童的健康和发展时,考虑这些差异的重要性。
研究资金/利益冲突:这项研究由澳大利亚国家健康与医学研究理事会(NHMRC)资助:APP1127437。G.M.C. 是新南威尔士大学(UNSW)的员工,也是国家围产期流行病学和统计单位(NPESU)的主任,UNSW 管理澳大利亚和新西兰辅助生殖数据库,资金由澳大利亚和新西兰生殖学会(FSANZ)提供。C.V. 是新南威尔士大学(UNSW)的员工,是 IVFAustralia 的临床研究主任,是澳大利亚和新西兰生殖学会(FSANZ)的董事会成员,也是 UNSW 妇女与儿童健康学院研究委员会的成员。C.V. 报告了澳大利亚国家健康与医学研究理事会(NHMRC)的拨款,以及默克公司、默克夏普德和多赫姆、费林、格登-里希特和贝辛斯的咨询费、讲座、演讲、演讲厅、手稿、写作或教育活动或参加会议或旅行的费用或报酬。C.V. 报告了维图斯健康有限公司的股票或股票期权,该公司位于澳大利亚以外的提交工作。R.J.N. 是香港大学自然疗法试验的阿德莱德大学的员工,也是该试验的 DSMC 主席。R.J.N. 报告了 NHMRC 的拨款。R.J.N. 报告了 Merck Serono 的讲座费和出席或参加讲座的费用支持,这与提交的工作无关。L.R.J. 是 UNSW 的员工,也是 UNSW 悉尼分校大数据研究中心的创始主任。L.R.J. 报告了 NHMRC 的拨款。其他合著者没有利益冲突。
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