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 ... -  《-》

Particulate air pollution at the time of oocyte retrieval is independently associated with reduced odds of live birth in subsequent frozen embryo transfers.

Does exposure to particulate matter (PM) air pollution prior to oocyte retrieval or subsequent frozen embryo transfer (FET) affect the odds of live birth? Live birth rates are lower when particulate matter (PM2.5 and PM10) levels are higher prior to oocyte retrieval, regardless of the conditions at the time of embryo transfer. Exposure to air pollution is associated with adverse reproductive outcomes, including reduced fecundity and ovarian reserve, and an increased risk of infertility and pregnancy loss. It is uncertain whether the effect on ART outcomes is due to the effects of pollution on oogenesis or on early pregnancy. This retrospective cohort study included 3659 FETs in 1835 patients between January 2013 and December 2021, accounting for all FETs performed at a single clinic over the study period. The primary outcome was the live birth rate per FET. Outcome data were missing for two embryo transfers which were excluded. Daily levels of PM2.5, PM10, nitric oxide, nitrogen dioxide, sulphur dioxide, ozone and carbon monoxide were collected during the study period and calculated for the day of oocyte retrieval and the day of embryo transfer, and during the preceding 2-week, 4-week, and 3-month periods. Clinical and embryological outcomes were analysed for their association with pollution over 24 hours, 2 weeks, 4 weeks, and 3 months, with adjustment for repeated cycles per participant, age at the time of oocyte retrieval, a quadratic age term, meteorological season, year, and co-exposure to air pollutants. Multi-pollutant models were constructed to adjust for co-exposures to other pollutants. Median concentrations in pollutant quartiles were modelled as continuous variables to test for overall linear trends; a Bonferroni correction was applied to maintain an overall alpha of 0.05 across the four exposure periods tested. Increased PM2.5 exposure in the 3 months prior to oocyte retrieval was associated with decreased odds of live birth (linear trend P = 0.011); the odds of live birth when PM2.5 concentrations were in the highest quartile were reduced by 34% (OR 0.66, 95% CI 0.47-0.92) when compared to the lowest quartile. A consistent direction of effect was seen across other exposure periods prior to oocyte retrieval, with an apparent dose-dependent relationship. Increased exposure to PM10 particulate matter in the 2 weeks prior to oocyte retrieval was associated with decreased odds of live birth (linear trend P = 0.009); the odds of live birth were decreased by 38% (OR 0.62, 95% CI 0.43-0.89, P = 0.010) when PM10 concentrations were in the highest quartile compared with the lowest quartile. Consistent trends were not seen across other exposure periods. None of the gaseous pollutants had consistent effects, prior to either oocyte retrieval or embryo transfer. This was a retrospective cohort study, however, all FETs during the study period were included and data were missing for only two FETs. The results are based on city-level pollution exposures, and we were not able to adjust for all possible factors that may affect live birth rates. Results were not stratified based on specific patient populations, and it was not possible to calculate the cumulative live birth rate per commenced cycle. This is the first study to specifically analyse FETs to separate the effects of environmental exposures prior to oocyte retrieval from those around the time of embryo transfer. Our findings suggest that increased PM exposure prior to oocyte retrieval is associated with reduced live birth rate following FET, independent of the conditions at the time of embryo transfer. Importantly, the air quality during the study period was excellent, suggesting that even 'acceptable' levels of air pollution have detrimental reproductive effects during gametogenesis. At the low pollution levels in our study, exposure to gaseous pollutants did not appear to affect live birth rates. This has important implications for our understanding of the effects of pollution on reproduction, and highlights the urgent need for effective policies limiting pollution exposure to protect human health and reproduction. No funding was provided for this study. S.J.L. is supported by the Jean Murray Jones Scholarship from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, has received educational sponsorship from Besins, Ferring, Merck, and Organon, honoraria from Hologic and Organon, consulting fees from Merck unrelated to the current study, and is a member of the Reproductive Technology Council of Western Australia. S.J.L. and R.J.H. are board members of Menopause Alliance Australia. C.S.R., M.W., and E.N. have no conflicts of interest to declare. R.J.H. is the Medical Director of Fertility Specialists of Western Australia, the National Medical Director of City Fertility Australia, and a shareholder in CHA SMG. He chairs the Western Australian Minister's Expert Panel on ART and Surrogacy. R.J.H. has made presentations for and received honoraria from Merck, Merck-Serono, Origio, Igenomix, Gideon-Richter, and Ferring, and has received support for attending meetings from Merck, Organon, and Ferring. N/A.

Leathersich SJ ，Roche CS ，Walls M ，Nathan E ，Hart RJ ... -  《-》

Preterm birth in assisted reproduction: the mediating role of hypertensive disorders in pregnancy.

To what extent can hypertensive disorders in pregnancy (HDP) explain the higher risk of preterm birth following frozen embryo transfer (frozen-ET) and fresh embryo transfer (fresh-ET) in ART compared with naturally conceived pregnancies? HDP did not contribute to the higher risk of preterm birth in pregnancies after fresh-ET but mediated 20.7% of the association between frozen-ET and preterm birth. Risk of preterm birth is higher after ART compared to natural conception. However, there is also a higher risk of HDP in pregnancies after ART compared to natural conception, in particular after frozen-ET. HDP increases the risk of both spontaneous and medically indicated preterm birth. It is not known to what extent the higher risk of preterm birth in ART-conceived pregnancies is mediated through HDP. This registry-based cohort study included singleton pregnancies from the Committee of Nordic ART and Safety (CoNARTaS) cohort from Denmark (1994-2014), Norway (1988-2015), and Sweden (1988-2015). The analysis included 78 300 singletons born after fresh-ET, 18 037 after frozen-ET, and 4 426 682 after natural conception. The exposure was ART conception with either frozen-ET or fresh-ET versus natural conception. The main mediator of interest was any of the following HDP: gestational hypertension, preeclampsia, eclampsia, or chronic hypertension with superimposed preeclampsia. The main outcome was any preterm birth, defined as delivery <37 weeks of gestation. Secondary outcomes were spontaneous and medically indicated preterm birth, and different severities of preterm birth based on the gestational age threshold. We linked data from the national Medical Birth Registries, ART registries/databases, and the National Patient Registries in each country using the unique national identity number of the mother. Criteria for inclusion were singleton pregnancies with birth order 1-4 in women aged ≥20 years at delivery. We used logistic regression to estimate odds ratios (ORs) with 95% CIs of preterm birth and decomposed the total effect into direct and mediated (indirect) effects to estimate the proportion mediated by HDP. Main models included adjustment for the year of delivery, maternal age, parity, and country. Pregnancies following frozen-ET had a higher risk of any preterm birth compared to natural conception (occurrence 6.6% vs 5.0%, total effect OR 1.29, 95% CI 1.21-1.37) and 20.7% of the association was mediated by HDP (mediated effect OR 1.05, 95% CI 1.04-1.05). The mediation occurred primarily in medically indicated preterm births. Pregnancies following fresh-ET also had a higher risk of any preterm birth compared to naturally conceived pregnancies (occurrence 8.1% vs 5.0%, total effect OR 1.49, 95% CI: 1.45-1.53), but none of this could be mediated by HDP (mediated effect OR 1.00, 95%CI 1.00-1.00, proportion mediated 0.5%). Sensitivity analyses with extra confounder adjustment for body mass index and smoking, and restriction to primiparous women, were consistent with our main findings. Furthermore, the results were not driven by differences in ART procedures (intracytoplasmic sperm injection, culture duration, or the number of embryos transferred). Although we could adjust for some important confounders, we cannot exclude residual confounding, particularly from factors associated with infertility. This population-based mediation analysis suggests that some of the higher risk of preterm birth after ART treatment may be explained by the higher risk of HDP after frozen-ET. If causality is established, investigations into preventive strategies such as prophylactic aspirin in pregnancies after frozen-ET may be warranted. Funding was provided by NordForsk (project number: 71450), the Nordic Federation of Obstetrics and Gynaecology (project numbers NF13041, NF15058, NF16026, and NF17043), the Norwegian University of Science and Technology (project number 81850092), an ESHRE Grant for research in reproductive medicine (grant number 2022-2), and the Research Council of Norway's Centres of Excellence funding scheme (project number 262700). D.A.L.'s and A.E.'s contribution to this work was supported by the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreements No 101021566) and the UK Medical Research Council (MC_UU_00032/05). D.A.L. has received support from Roche Diagnostics and Medtronic Ltd for research unrelated to that presented here. Pinborg declares grants from Gedeon Richter, Ferring, Cryos, and Merck, consulting fees from IBSA, Ferring, Gedeon Richter, Cryos, and Merck, payments from Gedeon Richter, Ferring, Merck, and Organon,travel support from Gedeon Richter. All other authors declare no conflicts of interest related to this work. ISRCTN 35879.

Petersen SH ，Åsvold BO ，Lawlor DA ，Pinborg A ，Spangmose AL ，Romundstad LB ，Bergh C ，Wennerholm UB ，Gissler M ，Tiitinen A ，Elhakeem A ，Opdahl S ... -  《-》

Evidence-based guideline: premature ovarian insufficiency().

How should premature/primary ovarian insufficiency (POI) be diagnosed and managed based on the best available evidence from published literature? The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae, and treatment of POI. Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular, and cognitive health. Although hormone therapy (HT) can mitigate some of these effects, many questions still remain regarding the optimal management of POI. The guideline was developed according to the structured methodology for development of ESHRE guidelines. Key questions were determined by a group of experts and informed by a scoping survey of women and health care professionals. Literature searches and assessments were then performed. Papers published up to 30 January 2024 and written in English were included in the guideline. An integrity review was conducted for the randomized controlled trials (RCTs) on POI included in the guideline. Based on the collected evidence, recommendations were formulated and discussed within the guideline development group until consensus was reached. Women with lived experience of POI informed the recommendations in general, and particularly on those on provision of care. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline development group and the ESHRE Executive Committee. New data indicate a higher prevalence of POI, 3.5%, than was previously thought. This guideline aims to help health care professionals to apply best practice care for women with POI. The recent update of the POI guideline covers 40 clinical questions on diagnosis of the condition, the different sequelae, including bone, cardiovascular, neurological and sexual function, fertility and general well-being, and treatment options, including HT. The list of clinical questions was expanded from the previous iteration of the guideline (2015) based on the scoping survey and appreciation of emerging knowledge of POI. Questions were added on the role of anti-Müllerian hormone (AMH) in the diagnosis of POI, fertility preservation, muscle health, and specific considerations for HT in iatrogenic POI. Additionally, the topic on complementary treatments was extended with specific focus on non-hormonal treatments and lifestyle management options. Significant changes from the previous 2015 guideline include the recommendations that only one elevated FSH >25 IU is required for diagnosis of POI, and guidance that AMH testing, repeat FSH measurement, and/or AMH may be required where there is diagnostic uncertainty. Recommendations were also updated regarding genetic testing, estrogen doses and regimens, use of the combined oral contraceptive and testosterone therapy. Women with lived experience of POI informed the recommendations on provision of care. The guideline describes different management options, but it must be acknowledged that for most of these options, supporting evidence is limited for POI. The guideline provides health care professionals with clear advice on best practice in POI care, based on the best evidence currently available. In addition, a list of research recommendations is provided to guide further studies in POI. The guideline was developed and funded by ESHRE, American Society for Reproductive Medicine (ASRM), Centre for Research Excellence in Women's Health in Reproduction Life (CRE-WHiRL), and International Menopause Society (IMS), covering expenses associated with the guideline meetings, literature searches, and dissemination of the guideline. The guideline group members did not receive payments. N.P. declared grants from Bayer Pharma (research and consultancy) and NIHR-research POISE; consulting fees from Abbott, Astellas, Bayer, Besins, Lawley, Mithra, Theramex, Viatris; honoraria from Astellas, Bayer, Besins, Gedeon Richter, Theramex, Viatris; support for attending meetings and/or travel from Astellas, Bayer, Theramex, Viatris; President, International Menopause Society, Medical Advisory Committee member, British Menopause Society, Patron Daisy Network. A.J.V. declared grants from Amgen Australia, Australian NHMRC, and Australian MRFF; consulting fees from IQ Fertility; honoraria from the Australasian Menopause Society; participation on a Data Safety Monitoring Board or Advisory Board of Astellas; Board Member of the International Menopause Society (2020 to current) and Past president of the Australasian Menopause Society (2017-2019); R.A.A. declared grants from Roche (Research support, to institution), and participation on a Data Safety Monitoring Board of Bayer. M.C. declared grants from NHI; payments or honoraria from Up-to-Date (as editor/reviewer); Board Member of American Society of Reproductive Medicine, and of American Gynecological and Obstetrical Society. M.D. declared (NIHR-HTA Reference Number: NIHR133461; NIHR-HTA Reference Number: NIHR128757; Action Medical Research and Borne: GN2818) consulting fees from a small personal medical practice, support for attending meetings and/or travel from ESHRE, Bayer and UCLH special Trustees; Participation on the Advisory Board of the British Menopause Society, UKSTORE project, the Progress Educational Trust, and the Turner Syndrome Support Society UK; Leadership or fiduciary roles in the British Fertility Society (Trustee), Elizabeth Garrett Anderson Hospital Charity (chair of Trustees), and the Essex Wynter charitable trust (Trustee). C.E. declared being Chair of a SIG from the Royal Australian College of General Practitioners Integrative Medicine Specific Interest Group and Program Lead for Next Practice Western Sydney Integrative Health. C.H.G. declared grants from Novo Nordisk Foundation (Nos. NNF15OC0016474 and NNF20OC0060610), sygesikringen danmark (No 2022-0189), and the Independent Research Fund Denmark (Nos. 0134-00406 and 0134-00130B); consulting fees from Novo Nordisk, Merck, and Astra Zeneca. S.K. declared grants from Roche diagnostics. A.K. declared grants from NIH R01 5R01HD101475; consulting fees as Medical Reviewer for Flo and for Healthline; honoraria as Medical Consultant for Summus; support for attending meetings from the Reproductive Scientist Development Program; Society for Reproductive Investigation Council Member and Society for Assisted Reproduction Registry/Validation Chair; R.E.N. declared consulting fees from Astellas, Bayer Pharma, Besins Healthcare, Fidia, Theramex; honoraria from Abbott, Astellas, Exeltis, Fidia, Gedeon Richter, Merck & Co, Novo Nordisk, Shionogi Limited, Theramex, Viatris; payment for expert testimony from Vichy Laboratories; Participation in Data Safety Monitoring Board of Advisory board from Astellas and Bayer Healthcare; President elect of the International Menopause Society (IMS). H.T. declared a grant from NHMRC Centre for Research Excellence for women's health in reproductive life. A.B. declared being chair of the Daisy Network Charity. The other authors have no conflicts of interest to declare. This guideline represents the views of ESHRE, ASRM, CRE-WHiRL, and IMS, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. The collaborating societies make no warranty, expressed or implied, regarding the clinical practice guidelines and specifically exclude any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.).

Panay N ，Anderson RA ，Bennie A ，Cedars M ，Davies M ，Ee C ，Gravholt CH ，Kalantaridou S ，Kallen A ，Kim KQ ，Misrahi M ，Mousa A ，Nappi RE ，Rocca WA ，Ruan X ，Teede H ，Vermeulen N ，Vogt E ，Vincent AJ ，ESHRE, ASRM, CREWHIRL, and IMS Guideline Group on POI ... -  《-》

Psychosocial wellbeing shortly after allocation to a freeze-all strategy compared with a fresh transfer strategy in women and men: a sub-study of a randomized controlled trial.

Is the psychosocial wellbeing affected in women and men shortly after allocation to a freeze-all strategy with postponement of embryo transfer compared to a fresh transfer strategy? In general, psychosocial wellbeing (i.e. emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit) was similar in women and men allocated to a freeze-all versus those allocated to a fresh-transfer strategy 6 days after disclosure of treatment strategy (i.e. 4 days after oocyte retrieval), although women in the freeze-all group reported a slightly higher degree of depressive symptoms and mood swings compared to women in the fresh transfer group. The use of a freeze-all strategy, i.e. freezing of the entire embryo cohort followed by elective frozen embryo transfer in subsequent cycles has increased steadily over the past decade in assisted reproductive technology (ART). This strategy essentially eliminates the risk of ovarian hyperstimulation syndrome and has proven beneficial regarding some reproductive outcomes in subgroups of women. However, patients experience a longer time interval between oocyte retrieval and embryo transfer, hence a longer time to pregnancy, possibly adding additional stress to the ART treatment. So far, little focus has been on the possible psychosocial strains caused by postponement of embryo transfer. This is a self-reported questionnaire based sub-study of a multicentre randomized controlled trial (RCT) including 460 women and 396 male partners initiating their first, second, or third treatment cycle of invitro fertilisation or intracytoplasmic sperm injection (ICSI) from May 2016 to September 2018. This sub-study was included in the primary project protocol and project plan for the RCT, as psychosocial wellbeing was considered a secondary outcome. Women from eight public fertility clinics in Denmark and Sweden and one private clinic in Spain were randomized in a 1:1 ratio on the day of inclusion (menstrual cycle day 2 or 3) to either a freeze-all strategy with postponement of embryo transfer to a subsequent modified natural menstrual cycle or a fresh transfer strategy with embryo transfer in the hormone stimulated cycle. Treatment allocation was blinded until the day of the ovulation trigger. Women and their male partners were asked to complete a validated self-reported questionnaire 6 days after unblinding of treatment group allocation, corresponding to 4 days after oocyte retrieval, investigating their psychosocial wellbeing related to the treatment defined as emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit. The questionnaire included items from the Copenhagen Multi-Centre Psychosocial Infertility (COMPI) Fertility Problem Stress Scales and the COMPI Marital Benefit Measure. Baseline characteristics were comparable between the two groups for both women and men. In total, response rates were 90.7% for women and 90.2% for men. In the freeze-all group, 207 women and 179 men completed the questionnaire compared with 204 women and 178 men in the fresh transfer group. Men in the two treatment groups did not differ in any of the explored aspects of psychosocial wellbeing (i.e. emotional reactions to the treatment, quality-of-life, infertility-related stress, and marital benefit) 6 days after disclosure of treatment strategy. Women in the freeze-all group reported a slightly higher degree of depressive symptoms (P = 0.045) and mood swings (P = 0.001) (i.e. variables included in 'emotional reactions to treatment') compared to women in the fresh transfer group. When adjusted for multiple testing, depressive symptoms were no longer significantly different between the two groups. No additional differences in psychosocial wellbeing were found. Self-reported quality-of-life during treatment was also rated as similar between the two groups in both women and men, but was slightly lower than they would rate their quality-of-life when not in fertility treatment. Although response rates were high, selection bias cannot be excluded. As this study was an RCT, we assume that psychosocial characteristics of the participants were equally distributed in the two groups, thus it is unlikely that the identified psychosocial differences between the freeze-all and fresh transfer group were present already at baseline. Furthermore, the questionnaire was completed as a one-time assessment 4 days after oocyte retrieval, thus not reflecting the whole treatment process, whereas an assessment after the full completed treatment cycle is needed to draw firm conclusions about the psychosocial consequences of the whole waiting period. However, a question posted that late would be highly biased on whether or not a pregnancy had been achieved. The results indicate that individuals in the freeze-all group exhibited slightly higher levels of depressive symptoms and mood swings compared to those in the fresh transfer group. Nevertheless, it is important to note that any worries related to potential emotional strains stemming from delaying embryo transfer should not overshadow the adoption of a freeze-all approach in cases where it is clinically recommended. As long as patients are provided with comprehensive information about the treatment strategy before initiating the process, it is worth emphasising that other aspects of psychosocial wellbeing were comparable between the two groups. The study is part of the Reprounion collaborative study, co-financed by the European Union, Interreg V Öresund-Kattegat-Skagerrak. L.P. reports financial support from Merck A/S. H.S.N. reports grants from Freya Biosciences ApS, Ferring Pharmaceuticals, BioInnovation Institute, Ministry of Education, Novo Nordic Foundation, Augustinus Fonden, Oda og Hans Svenningsens Fond, Demant Fonden, Ole Kirks Fond and Independent Research Fund Denmark and personal fees from Ferring Pharmaceuticals, Merck A/S, Astra Zeneca, Cook Medical, IBSA Nordic and Gedeon Richter. H.S.N is founder and chairman of the Maternity Foundation and co-developed the Safe Delivery App (non-profit). N.C.F. reports grants from Gedeon Richter, Merck A/S, Cryos International and financial support from Ferring Pharmaceuticals, Merck A/S and Gedeon Richter. N.C.F. is chairman in the steering committee for the guideline groups for The Danish Fertility Society (non-profit). P.H. reports honoraria from Merch A/S, IBSA Nordic and Gedeon Richter. A.L.M.E. reports grants and financial support from Merck A/S and Gedeon Richter. A.P. reports grants from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S and personal fees from Preglem S.A., Novo Nordic Foundation, Ferring Pharmaceuticals, Gedeon Richter, Cryos International, Merch A/S, Theramex and Organon and the lend of embryoscope to the institution from Gedeon Richter. All other authors declare no conflict of interest. Clinicaltrials.gov NCT02746562.

Pilegaard SP ，Schmidt L ，Stormlund S ，Koert E ，Bogstad JW ，Prætorius L ，Nielsen HS ，la Cour Freiesleben N ，Sopa N ，Klajnbard A ，Humaidan P ，Bergh C ，Englund ALM ，Løssl K ，Pinborg A ... -  《-》