Dreischor F, Dancet E A F, Lambalk C B, van Lunsen H W, Besselink D, van Disseldorp J, Boxmeer J, Brinkhuis E A, Cohlen B J, Hoek A, de Hundt M, Janssen C A H, Lambers M, Maas J, Nap A, Perquin D, Verberg M, Verhoeve H R, Visser J, van der Voet L, Mochtar M H, Goddijn M, Laan E, van Wely M, Custers I M
Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Public Health and Primary Care, KU Leuven-University of Leuven, Leuven, Belgium.
Hum Reprod. 2024 Dec 1;39(12):2711-2721. doi: 10.1093/humrep/deae220.
Does offering the Pleasure&Pregnancy (P&P) programme rather than expectant management improve naturally conceived ongoing pregnancy rates in couples diagnosed with unexplained infertility?
The P&P programme had no effect on the ongoing pregnancy rates of couples with unexplained infertility.
Underpowered studies suggested that face-to-face interventions targeting sexual health may increase pregnancy rates. The impact of an eHealth sexual health programme had yet to be evaluated by a large randomized controlled trial.
STUDY DESIGN, SIZE, DURATION: This is a nationwide multi-centre, unblinded, randomized controlled superiority trial (web-based randomization programme, 1:1 allocation ratio). This RCT intended to recruit 1164 couples within 3 years but was put on hold after having included 700 couples over 5 years (2016-2021). The web-based P&P programme contains psychosexual information and couple communication, mindfulness and sensate focus exercises aiming to help maintain or improve sexual health, mainly pleasure, and hence increase pregnancy rates. The P&P programme additionally offers information on the biology of conception and enables couples to interact online with peers and via email with coaches.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Heterosexual couples with unexplained infertility and a Hunault-prognosis of at least 30% chance of naturally conceiving a live-born child within 12 months were included, after their diagnostic work-up in 41 Dutch secondary and tertiary fertility centres. The primary outcome was an ongoing pregnancy, defined as a viable intrauterine pregnancy of at least 12 weeks duration confirmed by an ultrasound scan, conceived naturally within 6 months after randomization. Secondary outcomes were time to pregnancy, live birth, sexual health, and personal and relational well-being at baseline and after 3 and 6 months. The primary analyses were according to intention-to-treat principles. We calculated relative risks (RRs, pregnancy rates) and a risk difference (RD, pregnancy rates), Kaplan-Meier survival curves (live birth over time), and time, group, and interactive effects with mixed models analyses (sexual health and well-being).
Totals of 352 (one withdrawal) and 348 (three withdrawals) couples were allocated to, respectively the P&P group and the expectant management group. Web-based tracking of the intervention group showed a high attrition rate (57% of couples) and limited engagement (i.e. median of 16 visits and 33 min total visitation time per couple). Intention-to-treat analyses showed that 19.4% (n = 68/351) of the P&P group and 22.6% (n = 78/345) of the expectant management group achieved a naturally conceived ongoing pregnancy (RR = 0.86; 95% CI = 0.64-1.15, RD = -3.24%; 95% CI -9.28 to 2.81). The time to pregnancy did not differ between the groups (Log rank = 0.23). Live birth occurred in 18.8% (n = 66/351) of the couples of the P&P group and 22.3% (n = 77/345) of the couples of the expectant management group (RR = 0.84; 95% CI = 0.63-1.1). Intercourse frequency decreased equally over time in both groups. Sexual pleasure, orgasm, and satisfaction of women of the P&P group improved while these outcomes remained stable in the expectant management group. Male orgasm, intercourse satisfaction, and overall satisfaction decreased over time with no differences between groups. The intervention did not affect personal and relational well-being. Non-compliance by prematurely starting medically assisted reproduction, and clinical loss to follow-up were, respectively, 15.1% and 1.4% for the complete study population. Per protocol analysis for the primary outcome did not indicate a difference between the groups. Comparing the most engaged users with the expectant management group added that coital frequency decreased less, and that male sexual desire improved in the intervention group.
LIMITATIONS, REASONS FOR CAUTION: The intended sample size of 1164 was not reached because of a slow recruitment rate. The achieved sample size was, however, large enough to exclude an improvement of more than 8% of the P&P programme on our primary outcome.
The P&P programme should not be offered to increase natural pregnancy rates but may be considered to improve sexual health. The attrition from and limited engagement with the P&P programme is in line with research on other eHealth programmes and underlines the importance of a user experience study.
STUDY FUNDING/COMPETING INTEREST(S): Funded by The Netherlands Organisation for Health Research and Development (ZonMw, reference: 843001605) and Flanders Research Foundation. C.B.L. is editor-in-chief of Human Reproduction. H.W.L. received royalties or licences from Prometheus Publishers Springer Media Thieme Verlag. J.B. received support from MercK for attending the ESHRE course 'The ESHRE guideline on ovarian stimulation, do we have agreement?' J.v.D. reports consulting fees and lecture payments from Ferring, not related to the presented work, and support for attending ESHRE from Goodlife and for attending NFI Riga from Merck. A.H. reports consulting fees by Ferring Pharmaceutical company, The Netherlands, paid to institution UMCG, not related to the presented work. H.V. reports consulting fees from Ferring Pharmaceutical company, The Netherlands, and he is a member of the ESHRE guideline development group unexplained infertility and Chair of the Dutch guideline on unexplained infertility (unpaid). M.G. declares unrestricted research and educational grants from Ferring not related to the presented work, paid to their institution VU Medical Centre. The other authors have no conflicts to declare.
NTR5709.
4 February 2016.
DATE OF FIRST PATIENT’S ENROLMENT: 27 June 2016.
对于诊断为不明原因不孕症的夫妇，提供“愉悦与怀孕”（P&P）计划而非期待性管理是否能提高自然受孕的持续妊娠率？
P&P计划对不明原因不孕症夫妇的持续妊娠率没有影响。
样本量不足的研究表明，针对性健康的面对面干预可能会提高妊娠率。电子健康性健康计划的影响尚未通过大型随机对照试验进行评估。
研究设计、规模、持续时间：这是一项全国性多中心、非盲、随机对照优势试验（基于网络的随机化程序，分配比例为1:1）。该随机对照试验计划在3年内招募1164对夫妇，但在5年（2016 - 2021年）内纳入700对夫妇后暂停。基于网络的P&P计划包含性心理信息、夫妻沟通、正念和感官焦点练习，旨在帮助维持或改善性健康，主要是愉悦感，从而提高妊娠率。P&P计划还提供有关受孕生物学的信息，并使夫妇能够与同龄人在线互动以及通过电子邮件与教练交流。
参与者/材料、设置、方法：在荷兰41家二级和三级生育中心完成诊断检查后，纳入不明原因不孕症且Hunault预后显示在12个月内自然受孕活产几率至少为30%的异性恋夫妇。主要结局是持续妊娠，定义为经超声扫描确认的至少持续12周的宫内活胎妊娠，在随机分组后6个月内自然受孕。次要结局包括受孕时间、活产、性健康以及基线时、3个月和6个月后的个人及关系幸福感。主要分析遵循意向性分析原则。我们计算了相对风险（RRs，妊娠率）和风险差异（RD，妊娠率）、Kaplan - Meier生存曲线（随时间的活产情况）以及时间、组间和交互效应的混合模型分析（性健康和幸福感）。
分别有352对（1对退出）和348对（3对退出）夫妇被分配到P&P组和期待性管理组。对干预组基于网络的跟踪显示，脱落率较高（57%的夫妇）且参与度有限（即每对夫妇平均访问16次，总访问时间为33分钟）。意向性分析表明，P&P组19.4%（n = 68/351）和期待性管理组22.6%（n = 78/345）实现了自然受孕的持续妊娠（RR = 0.86；95%CI = 0.64 - 1.15，RD = -3.24%；95%CI -9.28至2.81）。两组的受孕时间没有差异（对数秩检验=0.23）。P&P组18.8%（n = 66/351）的夫妇和期待性管理组22.3%（n = 77/345）的夫妇实现了活产（RR = 0.84；95%CI = 0.63 - 1.1）。两组的性交频率随时间均同等下降。P&P组女性的性愉悦、性高潮和满意度有所改善，而期待性管理组这些结局保持稳定。男性性高潮、性交满意度和总体满意度随时间下降，两组之间没有差异。该干预未影响个人及关系幸福感。整个研究人群中，过早开始医学辅助生殖的不依从率和临床失访率分别为15.1%和1.4%。主要结局的符合方案分析未显示两组之间存在差异。将参与度最高的用户与期待性管理组进行比较发现，干预组的性交频率下降较少，且男性性欲有所改善。
局限性、谨慎理由：由于招募率缓慢，未达到预期样本量1164。然而，已达到的样本量足以排除P&P计划在我们的主要结局上有超过8%的改善。
不应提供P&P计划来提高自然妊娠率，但可考虑用于改善性健康。P&P计划的高脱落率和有限参与度与其他电子健康计划的研究一致，并强调了用户体验研究的重要性。
研究资金/利益冲突：由荷兰卫生研究与发展组织（ZonMw，参考文献：843001605）和弗拉芒研究基金会资助。C.B.L.是《人类生殖》的主编。H.W.L.从普罗米修斯出版社、施普林格媒体、蒂梅出版社获得版税或许可。J.B.获得默克公司的支持参加ESHRE课程“ESHRE卵巢刺激指南，我们达成共识了吗？”J.v.D.报告从辉凌公司获得咨询费和讲课费，与所展示的工作无关，以及从Goodlife获得支持参加ESHRE，从默克公司获得支持参加NFI里加会议。A.H.报告荷兰辉凌制药公司支付给机构UMCG的咨询费，与所展示的工作无关。H.V.报告从荷兰辉凌制药公司获得咨询费，他是ESHRE不明原因不孕症指南制定小组的成员以及荷兰不明原因不孕症指南的主席（无报酬）。M.G.声明从辉凌公司获得与所展示的工作无关的无限制研究和教育资助，支付给他们的机构VU医学中心。其他作者无利益冲突声明。
NTR5709。
2016年2月4日。
2016年6月27日。
