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夏季与新鲜体外受精/卵胞浆内单精子注射周期的较高活产率无关:一项基于全国人口的登记研究。

Summer is not associated with higher live birth rates in fresh IVF/ICSI cycles: a population-based nationwide registry study.

作者信息

Carlsson Humla Eva, Bergh Christina, Akouri Randa, Tsiartas Panagiotis

机构信息

Department of Obstetrics and Gynecology, Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

Hum Reprod Open. 2022 Aug 24;2022(4):hoac036. doi: 10.1093/hropen/hoac036. eCollection 2022.

Abstract

STUDY QUESTION

Is summer associated with a higher live birth rate after fresh IVF/ICSI?

SUMMARY ANSWER

There was no support for a higher live birth rate after fresh IVF/ICSI when treatment was performed during the summer season.

WHAT IS KNOWN ALREADY

Seasonal variations in human natural conception and birth rates are well described. It has been hypothesized that serum vitamin D, levels of which are associated with sun exposure, may have a role in human natural conception rates. However, the association between seasons and IVF outcomes has not yet been clarified and conflicting reports have been published. Furthermore, it has been suggested that women with normal vitamin D levels have a better pregnancy outcome after ART compared to those with vitamin D insufficiency.

STUDY DESIGN SIZE DURATION

A nationwide, register-based cohort study including all first-time fresh IVF/ICSI treatments (n = 52 788) leading to oocyte retrieval in Sweden between 2009 and 2018 was carried out.

PARTICIPANTS/MATERIALS SETTING METHODS: All first-time fresh IVF/ICSI cycles leading to oocyte retrieval were identified in the National Quality Registry of Assisted Reproduction. Data collected included patient characteristics as well as information about the treatment cycle and pregnancy outcome. The patients were divided into season subgroups, (summer, autumn, winter and spring) based on the date of oocyte retrieval. The primary outcome was live birth rate, which was defined as the number of live births per oocyte retrieval and embryo transfer (ET). Other outcomes included clinical pregnancy per ET and miscarriage per clinical pregnancy. Logistic regression with multiple imputation was performed to evaluate whether there was an association between season and IVF/ICSI outcomes, with summer as reference. Adjustments were made for woman's age, year of treatment, BMI, total FSH/hMG dose, type of treatment, fertilization type, embryonic stage at ET and number of embryos transferred.

MAIN RESULTS AND THE ROLE OF CHANCE

Live birth rate per oocyte retrieval ranged between 24% and 26% among seasons. A significantly higher live birth rate was seen for spring compared with summer, 26% versus 24%, respectively (adjusted odds ratio (OR) 1.08, 95% CI 1.02-1.16, =0.02). No significant association was seen when winter and autumn were compared with summer. Live birth rate per ET ranged between 29% and 31% among seasons. A significantly higher live birth rate was seen for spring and autumn compared with summer, at 31% and 31%, respectively versus 29% (adjusted OR 1.08, 95% CI 1.01-1.16, =0.04 and adjusted OR 1.09, 95% CI 1.01-1.16, =0.02), respectively. No significant association was seen when winter was compared with summer. Clinical pregnancy rate varied between 36% and 38% and miscarriage rate between 16% and 18%, with no significant seasonal associations.

LIMITATIONS REASONS FOR CAUTION

Possible limitations are the retrospective design of the study and unmeasured confounders. Another limitation is that a generalized estimating equation (GEE) model was not used. The use of a GEE model would have made it possible to include all started fresh IVF/ICSI cycles since it allows for correction for any dependence between cycles within women.

WIDER IMPLICATIONS OF THE FINDINGS

The results of this large registry study give no support for the hypothesis that IVF/ICSI treatments performed during summer season, with the highest degree of sunlight and vitamin D synthesis, is associated with higher pregnancy and live birth rates. In fact, our results showed significantly lower live birth rates during summer compared with spring and autumn. However, the magnitude of this difference was small and unlikely of clinical value. We suggest that season should not be taken into consideration when planning and performing fresh IVF/ICSI treatments.

STUDY FUNDING/COMPETING INTERESTS: Financial support was received through the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70 940) and grants from the Hjalmar Svensson's Research Foundation (HJSV2021019 and HJSV2021037). None of the authors declare any conflict of interest.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

新鲜胚胎体外受精/卵胞浆内单精子注射(IVF/ICSI)后,夏季与较高的活产率相关吗?

总结答案

当在夏季进行新鲜IVF/ICSI治疗时,没有证据支持其有更高的活产率。

已知信息

人类自然受孕和出生率的季节性变化已有充分描述。据推测,血清维生素D水平与阳光照射有关,可能在人类自然受孕率中发挥作用。然而,季节与IVF结果之间的关联尚未明确,且已有相互矛盾的报道发表。此外,有人提出,维生素D水平正常的女性与维生素D不足的女性相比,辅助生殖技术(ART)后的妊娠结局更好。

研究设计规模及持续时间

开展了一项全国性的基于登记的队列研究,纳入了2009年至2018年在瑞典进行的所有首次导致取卵的新鲜IVF/ICSI治疗(n = 52788)。

参与者/材料设置方法:在国家辅助生殖质量登记处识别出所有首次导致取卵的新鲜IVF/ICSI周期。收集的数据包括患者特征以及治疗周期和妊娠结局的信息。根据取卵日期将患者分为季节亚组(夏季、秋季、冬季和春季)。主要结局是活产率,定义为每次取卵和胚胎移植(ET)后的活产数。其他结局包括每次ET后的临床妊娠和每次临床妊娠后的流产。采用多重填补的逻辑回归来评估季节与IVF/ICSI结局之间是否存在关联,以夏季作为对照。对女性年龄、治疗年份、体重指数(BMI)、促卵泡生成素/人绝经期促性腺激素(FSH/hMG)总剂量、治疗类型、受精类型、ET时的胚胎阶段和移植胚胎数进行了调整。

主要结果及机遇的作用

各季节每次取卵后的活产率在24%至26%之间。春季与夏季相比,活产率显著更高,分别为26%和24%(调整后的优势比(OR)为1.08,95%置信区间(CI)为1.02 - 1.16,P = 0.02)。冬季和秋季与夏季相比,未发现显著关联。各季节每次ET后的活产率在29%至31%之间。春季和秋季与夏季相比,活产率显著更高,分别为31%和31%,而夏季为29%(调整后的OR为1.08,95%CI为1.01 - 1.16,P = 0.04;调整后的OR为1.09,95%CI为1.01 - 1.16,P = 0.02)。冬季与夏季相比,未发现显著关联。临床妊娠率在36%至38%之间,流产率在16%至18%之间,未发现显著的季节关联。

局限性及谨慎原因

可能的局限性在于研究的回顾性设计和未测量的混杂因素。另一个局限性是未使用广义估计方程(GEE)模型。使用GEE模型将有可能纳入所有开始的新鲜IVF/ICSI周期,因为它允许校正女性体内周期之间的任何相关性。

研究结果的更广泛影响

这项大型登记研究的结果不支持以下假设:在阳光照射和维生素D合成程度最高的夏季进行IVF/ICSI治疗与更高的妊娠率和活产率相关。事实上,我们的结果显示夏季的活产率显著低于春季和秋季。然而,这种差异的幅度很小,不太可能具有临床价值。我们建议在计划和进行新鲜IVF/ICSI治疗时不应考虑季节因素。

研究资金/利益冲突:通过瑞典政府与郡议会之间的协议,获得了瑞典国家的财政支持(ALF协议,ALFGBG - 70940)以及Hjalmar Svensson研究基金会的资助(HJSV2021019和HJSV2021037)。所有作者均未声明存在任何利益冲突。

试验注册号

无。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea7/9464094/436f6c36d73d/hoac036f1.jpg

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