M Elena Ter Welle-Butalid, Josien G Derhaag, Bo E van Bree, Ingeborg J H Vriens, Mariëtte Goddijn, Eva M E Balkenende, Catharina C M Beerendonk, Anna M E Bos, Irene Homminga, Sofie H Benneheij, H C van Os, Jesper M J Smeenk, Marieke O Verhoeven, Casandra C A W van Bavel, Vivianne C G Tjan-Heijnen, Ron J T van Golde
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引用次数: 0
摘要
研究问题:在荷兰,冷冻保存卵母细胞或胚胎的患者的生育结果如何?这项研究表明,经过 10 年的随访,使用冷冻保存的卵母细胞或胚胎尝试怀孕的利用率为 25.5%,胚胎移植后每位患者的累计活产率为 34.6%:通过冷冻卵母细胞或胚胎来保存生育能力是一种成熟的治疗方法,适用于有卵巢早衰风险(由良性疾病或肿瘤引起)或与年龄有关的生理性生育能力下降的妇女。人们对冷冻保存的成功率、卵母细胞或胚胎的利用率或活产率知之甚少:在荷兰进行了一项回顾性观察研究。数据收集于2017年至2019年期间,来自荷兰10家试管婴儿中心的1112名女性,她们在2年多前的生育力保存背景下冷冻了卵母细胞或胚胎:本研究共纳入了 1112 名女性。研究使用医疗档案和患者数据库提取数据。根据保留生育能力的指征对妇女进行分类:肿瘤、良性或非医学指征。统计差异采用 t 检验或 Mann-Whitney U 检验。时间终点采用卡普兰-梅耶分析法,统计差异采用对数秩分析法。研究方案已获医学伦理委员会批准:多年来,荷兰的生育力保存周期越来越多。最初,每年进行的周期不到 10 个,10 年后增加到每年 300 多个。最初,胚胎冷冻是在生育力保存的背景下进行的。后来,冷冻保存卵母细胞成为标准方法。冷冻保存卵母细胞和胚胎的结果是,用于移植的胚胎数量相当(中位数为 2 个),活产率相当(分别为 33.9% 和 34.6%)。5 年使用率为 12.3%,10 年使用率为 25.5%。每位患者的累计临床妊娠率为 35.6%,累计活产率为 34.6%。因良性疾病而进行生育力保存的患者较早返回使用其冷冻保存的胚胎或卵细胞:本研究中,不同患者接受生育力保存术后的随访时间各不相同,而且在本研究结束时,并非所有冷冻卵母细胞或胚胎都已使用。这可能导致本研究中报告的结果被低估。此外,由于本研究中未包括开始生育力保存程序但未成功(因反应低而取消)的妇女,因此无法完全确定治疗意向:本研究提供了各种生育力保存适应症后的生殖结果数据。这些知识可为专业人士和未来的患者提供参考,以改善在保留生育力的情况下有关卵巢刺激的咨询和知情决策:本研究未获得任何资助。作者不存在与本研究相关的利益冲突。V.T.H. 从阿斯利康(AstraZeneca)、吉利德(Gilead)、诺华(Novartis)、礼来(Eli Lily)、辉瑞(Pfizer)和第一三共(Daiichi Sankyo)那里获得了资助,用于本研究之外的研究。V.T.H.从 Eli Lily 公司获得了本次研究之外的咨询费。M.G.从加柏公司(Guerbet)和菲林公司(Ferring)获得了本研究之外的研究补助金。E.M.E.B.接受了荷兰生育力保护网络(The Dutch Network of Fertility Preservation)的资助,用于本研究之外的一项研究:不详。
Outcomes of female fertility preservation with cryopreservation of oocytes or embryos in the Netherlands: a population-based study.
Study question: What are the reproductive outcomes of patients who cryopreserved oocytes or embryos in the context of fertility preservation in the Netherlands?
Summary answer: This study shows that after a 10-year follow-up period, the utilization rate to attempt pregnancy using cryopreserved oocytes or embryos was 25.5% and the cumulative live birth rate after embryo transfer was 34.6% per patient.
What is known already: Fertility preservation by freezing oocytes or embryos is an established treatment for women with a risk of premature ovarian failure (caused by a benign or oncological disease) or physiological age-related fertility decline. Little is known about the success of cryopreservation, the utilization rate of oocytes or embryos, or the live birth rates.
Study design, size, duration: A retrospective observational study was performed in the Netherlands. Data were collected between 2017 and 2019 from 1112 women who cryopreserved oocytes or embryos more than 2 years ago in the context of fertility preservation in 10 IVF centers in the Netherlands.
Participants/materials, setting, methods: A total of 1112 women were included in this study. Medical files and patient databases were used to extract data. Women were categorized based on indication of fertility preservation: oncological, benign, or non-medical. To indicate statistical differences the t-test or Mann-Whitney U test was used. Kaplan-Meier analyses were used for time endpoints, and log-rank analyses were used to assess statistical differences. The study protocol was approved by the medical ethics committee.
Main results and the role of chance: Fertility preservation cycles have been performed increasingly over the years in the Netherlands. In the first years, less than 10 cycles per year were performed, increasing to more than 300 cycles per year 10 years later. Initially, embryos were frozen in the context of fertility preservation. In later years, cryopreservation of oocytes became the standard approach. Cryopreservation of oocytes versus embryos resulted in comparable numbers of used embryos (median of 2) for transfer and comparable live birth rates (33.9% and 34.6%, respectively). The 5-year utilization rate was 12.3% and the 10-year utilization rate was 25.5%. The cumulative clinical pregnancy rate was 35.6% and the cumulative live birth rate was 34.6% per patient. Those who had fertility preservation due to benign diseases returned earlier to use their cryopreserved embryos or oocytes.
Limitations, reasons for caution: The follow-up period after the fertility preservation procedure varied between patients in this study and not all frozen oocytes or embryos had been used at the end of this study. This might have led to underestimated outcomes reported in this study. Furthermore, intention to treat cannot be fully determined since women who started the fertility preservation procedure without success (cancellation due to low response) were not included in this study.
Wider implications of the findings: This study provides data on the reproductive outcomes after various indications of fertility preservation. This knowledge can be informative for professionals and future patients to improve counseling and informed decision making regarding ovarian stimulation in the context of fertility preservation.
Study funding/competing interest(s): No funding was obtained for this study. The authors have no conflicts of interest to declare related to this study. V.T.H. received grants paid to the institute for studies outside the present work from AstraZeneca, Gilead, Novartis, Eli Lily, Pfizer, and Daiichi Sankyo. V.T.H. received consulting fees from Eli Lily outside the present work. M.G. received grants paid to the institute for studies outside the present work from Guerbet and Ferring. E.M.E.B. received a grant from The Dutch Network of Fertility Preservation for a study outside the present work.
期刊介绍:
Human Reproduction features full-length, peer-reviewed papers reporting original research, concise clinical case reports, as well as opinions and debates on topical issues.
Papers published cover the clinical science and medical aspects of reproductive physiology, pathology and endocrinology; including andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, early pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues.