STUDY QUESTION Are there differences in psychosocial and physical wellbeing among women and male partners undergoing modified natural cycle (mNC) frozen embryo transfer (FET) in immediate compared to postponed cycles after ovarian stimulation (OS) and oocyte pick-up (OPU)? SUMMARY ANSWER Significantly more women in the immediate group reported physical symptoms than women in the postponed group whilst fewer were emotionally affected by waiting time, although the latter difference lost statistical significance after adjustment for multiple testing. WHAT IS KNOWN ALREADY Infertility and fertility treatment are known to cause psychosocial distress in women and couples longing for a child. The treatment may be long-term and delayed for various reasons, such as the elective postponement of FET after a fresh transfer without pregnancy or an elective freeze-all cycle, possibly further increasing the level of distress. STUDY DESIGN, SIZE, DURATION Sub-study of an ongoing multicentre randomized controlled, non-inferiority trial assessing the optimal timing for mNC-FET treatment after OS and OPU. Participants were randomized 1:1 to mNC-FET in the cycle immediately following OS or mNC-FET in a subsequent cycle. The study is based on data from the first women (N = 300) and male partners (N = 228) invited to answer a self-reported questionnaire assessing psychosocial and physical wellbeing. Data were collected from April 2021 to March 2024. PARTICIPANTS/MATERIALS, SETTING, METHODS Questionnaires were distributed to all randomized women and their male partners on cycle day 2–5 of mNC-FET cycles and returned before the administration of ovulation trigger. The questionnaire consisted of validated items originating from the Copenhagen Multicentre Psychosocial Infertility—Fertility Problem Stress Scale (COMPI-FPSS) and Marital Benefit Measure (COMPI-MBM). Emotional reactions to waiting time in fertility treatment, mental health, general quality-of-life, and physical symptoms were also assessed. MAIN RESULTS AND THE ROLE OF CHANCE Questionnaire response rates were 90.3% for women and 80.0% for male partners in the immediate group, and 82.3% for women and 57.3% for male partners in the postponed group. Approximately 90% of all women worried to some or a great extent about whether the treatment would be successful. More women in the postponed group reported that they were emotionally affected by the waiting time from OPU to blastocyst transfer to some or to a great extent (57.4% versus 73.9% in the immediate versus postponed group, P = 0.014), but the results were not significant after adjustment for multiple testing (P = 0.125). For male partners, no difference in emotional reactions to waiting time between groups was found. There was no significant difference in total infertility-related stress or symptoms of severe depression between the immediate and the postponed group for women or male partners, but women were generally more distressed than their partners. There was a significantly higher incidence of stomach and/or pelvic pain (24.0% versus 9.4%, adjusted P = 0.013), feeling of being bloated (33.8% versus 15.1%, adjusted P = 0.010) and swollen or tender breasts (24.8% versus 0.9%, P < 0.001) in the immediate group. LIMITATIONS, REASONS FOR CAUTION All items were self-reported. No assessment of psychosocial or physical wellbeing was performed before participant enrolment. The sample size of male partners was relatively small, and female partners were not included in this sub-study due to a very small number of participants in this group. WIDER IMPLICATIONS OF THE FINDINGS If immediate mNC-FET proves to be effective, physical and emotional factors may play a key role in choosing treatment strategy for the individual patient. This study demonstrated more physical symptoms related to OS in the immediate cycles. STUDY FUNDING/COMPETING INTEREST(S) The RCT was supported by Rigshospitalet’s Research Foundation and an independent research grant from Merck A/S (MS200497_0024). Merck A/S had no role in the design of this study and will not have any role during its execution, analyses, interpretation of data, or decision to submit results. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors. A.P. received grants from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S and Cryos as payment to the institution. A.P. received consulting fees from IBSA, Ferring Pharmaceuticals, Gedeon Richter, Cryos and Merck A/S, and honoraria from Organon, Ferring Pharmaceuticals, Gedeon Richter and Merck A/S. A.P. received support for meeting attendance from Gedeon Richter. M.S. benefitted from a grant from Gedeon Richter. S.B. and C.C. benefitted from a grant from Merck A/S. S.B. is currently employed by Novo Nordisk. N.C.F. received grants from Gedeon Richter, Merck A/S and Cryos as payment to the institution. N.C.F. received consulting fees from Merck A/S and support for meeting attendance from Merck A/S, Ferring Pharmaceuticals, IBSA, and Gedeon Richter. N.C.F. is chair of the steering committee for the guideline groups for The Danish Fertility Society. E.L. received a radiometer contract on blood gas validation as a payment to the institution. E.L. received honoraria from Pfizer and support for meeting attendance from Astella. B.N. received grants from IBSA, Ferring Pharmaceuticals, Merck A/S, and Gedeon Richter as payment to the institution. B.N. received honoraria from Merck A/S and Organon and support for meeting attendance from IBSA and Gedeon Richter. B.N. and L.P. participate in an Advisory Board at Ferring Pharmaceuticals. L.P. received support for meeting attendance from Merck A/S, Ferring Pharmaceuticals, and Gedeon Richter. L.P. declare stocks in Novo Nordisk. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT04748874

中文翻译：

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卵巢刺激和卵母细胞提取后立即与延迟改良自然周期冷冻胚胎移植的女性和男性伴侣的社会心理健康和身体健康：一项随机对照试验的子研究


研究问题：与卵巢刺激 （OS） 和卵母细胞提取 （OPU） 后的延迟周期相比，接受改良自然周期 （mNC） 冷冻胚胎移植 （FET） 的女性和男性伴侣在即刻接受心理社会和身体健康方面是否存在差异？摘要答案 直接组报告身体症状的女性明显多于延迟组的女性，而受等待时间影响的情绪影响的女性较少，尽管后者差异在调整多次测试后失去了统计学意义。众所周知，不孕症和生育治疗会导致渴望孩子的女性和夫妇的社会心理困扰。治疗可能是长期的，并且由于各种原因而延迟，例如在没有怀孕的新鲜转移后选择性推迟 FET 或选择性冻结全周期，这可能会进一步增加痛苦程度。研究设计、规模、持续时间 一项正在进行的多中心随机对照、非劣效性试验的子研究，该试验评估了 OS 和 OPU 后 mNC-FET 治疗的最佳时机。参与者在 OS 之后的周期中以 1：1 的比例随机分配到 mNC-FET，或在随后的周期中随机分配至 mNC-FET。该研究基于第一批女性 （N = 300） 和男性伴侣 （N = 228） 的数据，这些女性被邀请回答一份自我报告的评估社会心理和身体健康的问卷。数据收集时间为 2021 年 4 月至 2024 年 3 月。参与者/材料、设置、方法 在 mNC-FET 周期的第 2-5 周期第 2-5 天向所有随机分配的女性及其男性伴侣分发问卷，并在施用排卵触发器之前返回。 该问卷由源自哥本哈根多中心社会心理不孕症——生育问题压力量表 （COMPI-FPSS） 和婚姻福利测量 （COMPI-MBM） 的经过验证的项目组成。还评估了对生育治疗等待时间、心理健康、一般生活质量和身体症状的情绪反应。主要结果和机会的作用 问卷回复率为直接组女性 90.3%，男性伴侣 80.0%，推迟组女性 82.3%，男性 57.3%。大约 90% 的女性在一定程度上或在很大程度上担心治疗是否会成功。推迟组的更多女性报告说，她们在情绪上受到从 OPU 到囊胚移植的等待时间的影响或多或大程度 （57.4% 对即时组与推迟组的 73.9%，P = 0.014），但在调整多次测试后结果不显著 （P = 0.125）。对于男性伴侣，未发现组间对等待时间的情绪反应存在差异。女性或男性伴侣在即时组和延迟组之间，总不孕症相关应激或严重抑郁症状没有显著差异，但女性通常比其伴侣更痛苦。胃痛和/或盆腔疼痛的发生率 （24.0% 对 9.4%，校正 P = 0.013）、腹胀感 （33.8% 对 15.1%，校正 P = 0.010） 和乳房肿胀或压痛 （24.8% 对 0.9%，P < 0.001） 在直接组中显著升高。限制，谨慎原因 所有项目均为自我报告。在参与者入组之前没有进行社会心理健康或身体健康状况评估。 男性伴侣的样本量相对较小，由于该组参与者人数很少，女性伴侣未被纳入本子研究。研究结果的更广泛意义 如果立即使用 mNC-FET 被证明有效，则身体和情绪因素可能在为个体患者选择治疗策略时起关键作用。这项研究表明，在即时周期中，与 OS 相关的身体症状更多。研究资金/利益争夺 该研究试验得到了 Rigshospitalet 研究基金会和 Merck A/S （MS200497_0024） 独立研究资助的支持。Merck A/S 在本研究的设计中没有任何作用，在研究的执行、分析、数据解释或决定提交结果期间也不会有任何作用。作者对本手稿的内容负全部责任，出版物中描述的观点和意见仅代表作者的观点和意见。A.P. 收到了 Gedeon Richter、Ferring Pharmaceuticals、Merck A/S 和 Cryos 的赠款作为对该机构的付款。A.P. 从 IBSA、Ferring Pharmaceuticals、Gedeon Richter、Cryos 和 Merck A/S 获得了咨询费，并从 Organon、Ferring Pharmaceuticals、Gedeon Richter 和 Merck A/S 获得了酬金。A.P. 获得了 Gedeon Richter 对参加会议的支持。M.S. 受益于 Gedeon Richter 的资助。S.B. 和 CC 受益于默克 A/S 的赠款。S.B. 目前受雇于诺和诺德。NCF 收到了 Gedeon Richter、Merck A/S 和 Cryos 的赠款作为对该机构的付款。NCF 从 Merck A/S 获得了咨询费，并从 Merck A/S、Ferring Pharmaceuticals、IBSA 和 Gedeon Richter 获得了会议出席支持。NCF 是丹麦生育协会指南小组指导委员会主席。 E.L. 收到了一份关于血气验证的辐射计合同，作为支付给该机构的报酬。E.L. 收到了 Pfizer 的酬金和 Astella 的会议出席支持。B.N. 收到了 IBSA、Ferring Pharmaceuticals、Merck A/S 和 Gedeon Richter 的赠款作为对该机构的付款。B.N. 获得了 Merck A/S 和 Organon 的酬金，以及 IBSA 和 Gedeon Richter 对会议出席的支持。B.N. 和 L.P. 参加了 Ferring Pharmaceuticals 的顾问委员会。L.P. 获得了 Merck A/S、Ferring Pharmaceuticals 和 Gedeon Richter 对会议出席的支持。L.P. 申报 Novo Nordisk 的股票。试验注册号 临床试验。政府NCT04748874