The clinical effectiveness of the Mind/Body Program for Infertility on wellbeing and assisted reproduction outcomes: a randomized controlled trial in search for active ingredients.

Does the Mind/Body Program for Infertility (MBPI) perform better, due to certain distinctive elements, than a partly matched support group in improving the wellbeing and medically assisted reproduction (MAR) outcomes of women with elevated distress levels in a clinical setting? While robust enhancements occurred in the wellbeing overall, the cognitive behavioural and formalized stress management elements of the MBPI allowed a significantly stronger improvement in trait anxiety, but not in other mental health and MAR outcomes, compared with a support group. Mind-body psychological programmes adjacent to MAR have been found to improve women's mental states and possibly increase chances of pregnancy. However, not enough is known about the programme's effectiveness among patients with elevated distress levels in routine clinical settings, nor is it clear which of its particular ingredients are specifically effective. A pre-post design, single-centre, randomized controlled trial was performed between December 2019 and October 2022 (start and end of recruitment, respectively). The sample size (n = 168) was calculated to detect superiority of the MBPI in improving fertility-related quality of life. Randomization was computer-based, with random numbers concealing identities of patients until after allocation. The trial was conducted at a large university teaching hospital. A total of 168 patients were randomly assigned to the mind-body (MBPI) group (n = 84) and the fertility support (FS) control group (n = 84). Patients received a 10-week, 135-min/week group intervention, with the FS group following the same format as the MBPI group, but with a less restricted and systematic content, and without the presumed effective factors. The number of patients analysed was n = 74 (MBPI) and n = 68 (FS) for post-intervention psychological outcomes, and n = 54 (MBPI) and n = 56 (FS) for pregnancy outcomes at a 30-month follow-up. Significant improvements occurred in both groups in all psychological domains (adjusted P < 0.001), except for treatment-related quality of life. Linear mixed-model regression analysis did not reveal significantly greater pre-post improvements in the MBPI group than in the FS group in fertility-related quality of life (difference in differences (DD) = 4.11 [0.42, 7.80], d = 0.32, adjusted P = 0.124), treatment-related quality of life (DD = -3.08 [-7.72, 1.55], d = -0.20, adjusted P = 0.582), infertility-specific stress (DD = -2.54 [-4.68, 0.41], d = -0.36, adjusted P = 0.105), depression (DD = -1.16 [3.61, 1.29], d = -0.13, adjusted P = 0.708), and general stress (DD = -0.62 [-1.91, 0.68], d = -0.13, adjusted P = 0.708), but it did show a significantly larger improvement in trait anxiety (DD = -3.60 [-6.16, -1.04], d = -0.32, adjusted P = 0.042). Logistic regression showed no group effect on MAR pregnancies, spontaneous pregnancies, or live births. The follow-up only covered MAR-related medical outcomes and no psychological variables, and their rates were not equal in the two groups. Biological factors other than age, aetiology, and duration of infertility may have confounded the study results. Loss to follow-up was between 5% and 10%, which may have led to some bias. The psychologically and medically heterogeneous sample, the normal clinical setting and the low attrition rate all raise the external validity and generalizability of our study. The MBPI works not only in controlled conditions, but also in routine MAR practice, where it can be introduced as a cost-effective, low-intensity psychological intervention, within the framework of stepped care. More studies are needed to further identify its active ingredients. The authors received no financial support for the research, authorship, and/or publication of this article. The authors have no conflict of interest to disclose. ClinicalTrials.gov NCT04151485. 5 November 2019. 15 December 2019.

Szigeti F J ，Kazinczi C ，Szabó G ，Sipos M ，Ujma PP ，Purebl G ... -  《-》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

The web-based Pleasure&Pregnancy programme in the treatment of unexplained infertility: a randomized controlled trial.

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. 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. 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. 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. 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. 27 June 2016.

Dreischor F ，Dancet EAF ，Lambalk CB ，van Lunsen HW ，Besselink D ，van Disseldorp J ，Boxmeer J ，Brinkhuis EA ，Cohlen BJ ，Hoek A ，de Hundt M ，Janssen CAH ，Lambers M ，Maas J ，Nap A ，Perquin D ，Verberg M ，Verhoeve HR ，Visser J ，van der Voet L ，Mochtar MH ，Goddijn M ，Laan E ，van Wely M ，Custers IM ... -  《-》

Psychosocial and physical wellbeing in women and male partners undergoing immediate versus postponed modified natural cycle frozen embryo transfer after ovarian stimulation and oocyte pick-up: a sub-study of a randomized controlled trial.

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)? 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. 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. 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. 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. 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. 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. 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. 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. ClinicalTrials.gov NCT04748874.

Bergenheim S ，Saupstad M ，Colombo C ，Møller JE ，Bogstad JW ，Freiesleben NC ，Behrendt-Møller I ，Prætorius L ，Oxlund B ，Nøhr B ，Husth M ，Løkkegaard E ，Sopa N ，Pinborg A ，Løssl K ，Schmidt L ... -  《-》

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

Elwenspoek MM ，Thom H ，Sheppard AL ，Keeney E ，O'Donnell R ，Jackson J ，Roadevin C ，Dawson S ，Lane D ，Stubbs J ，Everitt H ，Watson JC ，Hay AD ，Gillett P ，Robins G ，Jones HE ，Mallett S ，Whiting PF ... -  《-》