ESHRE guideline: number of embryos to transfer during IVF/ICSI†.

STUDY QUESTION: Which clinical and embryological factors should be considered to apply double embryo transfer (DET) instead of elective single embryo transfer (eSET)? SUMMARY ANSWER: No clinical or embryological factor per se justifies a recommendation of DET instead of eSET in IVF/ICSI. WHAT IS KNOWN ALREADY: DET is correlated with a higher rate of multiple pregnancy, leading to a subsequent increase in complications for both mother and babies. These complications include preterm birth, low birthweight, and other perinatal adverse outcomes. To mitigate the risks associated with multiple pregnancy, eSET is recommended by international and national professional organizations as the preferred approach in ART. STUDY DESIGN, SIZE, DURATION: The guideline was developed according to the structured methodology for development and update of ESHRE guidelines. Literature searches were performed in PUBMED/MEDLINE and Cochrane databases, and relevant papers published up to May 2023, written in English, were included. Live birth rate, cumulative live birth rate, and multiple pregnancy rate were considered as critical outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on the collected evidence, recommendations were discussed until a consensus was reached within the Guideline Development Group (GDG). A stakeholder review was organized after the guideline draft was finalized. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 35 recommendations on the medical and non-medical risks associated with multiple pregnancies and on the clinical and embryological factors to be considered when deciding on the number of embryos to transfer. These recommendations include 25 evidence-based recommendations, of which 24 were formulated as strong recommendations and one as conditional, and 10 good practice points. Of the evidence-based recommendations, seven (28%) were supported by moderate-quality evidence. The remaining recommendations were supported by low (three recommendations; 12%), or very low-quality evidence (15 recommendations; 60%). Owing to the lack of evidence-based research, the guideline also clearly mentions recommendations for future studies. LIMITATIONS, REASONS FOR CAUTION: The guideline assessed different factors one by one based on existing evidence. However, in real life, clinicians' decisions are based on several prognostic factors related to each patient's case. Furthermore, the evidence from randomized controlled trials is too scarce to formulate high-quality evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides health professionals with clear advice on best practice in the decision-making process during IVF/ICSI, based on the best evidence currently available, and recommendations on relevant information that should be communicated to patients. In addition, a list of research recommendations is provided to stimulate further studies in the field. STUDY FUNDING/COMPETING INTEREST(S): The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, the literature searches, and the dissemination of the guideline. The guideline group members did not receive payment. DPB declared receiving honoraria for lectures from Merck, Ferring, and Gedeon Richter. She is a member of ESHRE EXCO, and the Mediterranean Society for reproductive medicine and the president of the Croatian Society for Gynaecological Endocrinology and Reproductive Medicine. CDG is the past Chair of the ESHRE EIM Consortium and a paid deputy member of the Editorial board of Human Reproduction. IR declared receiving reimbursement from ESHRE and EDCD for attending meetings. She holds an unpaid leadership role in OBBCSSR, ECDC Sohonet, and AER. KAR-W declared receiving grants for clinical researchers and funding provision to the institution from the Swedish Cancer Society (200170F), the Senior Clinical Investigator Award, Radiumhemmets Forskningsfonder (Dnr: 201313), Stockholm County Council FoU (FoUI-953912) and Karolinska Institutet (Dnr 2020-01963), NovoNordisk, Merck and Ferring Pharmaceuticals. She received consulting fees from the Swedish Ministry of Health and Welfare. She received honoraria from Roche, Pfizer, and Organon for chairmanship and lectures. She received support from Organon for attending meetings. She participated in advisory boards for Merck, Nordic countries, and Ferring. She declared receiving time-lapse equipment and grants with payment to institution for pre-clinical research from Merck pharmaceuticals and from Ferring. SS-R received research funding from Roche Diagnostics, Organon/MSD, Theramex, and Gedeo-Richter. He received consulting fees from Organon/MSD, Ferring Pharmaceuticals, and Merck Serono. He declared receiving honoraria for lectures from Ferring Pharmaceuticals, Besins, Organon/MSD, Theramex, and Gedeon Richter. He received support for attending Gedeon Richter meetings and participated in the Data Safety Monitoring Board of the T-TRANSPORT trial. He is the Deputy of ESHRE SQART special interest group. He holds stock options in IVI Lisboa and received equipment and other services from Roche Diagnostics and Ferring Pharmaceuticals. KT declared receiving payment for honoraria for giving lectures from Merck Serono and Organon. She is member of the safety advisory board of EDQM. She holds a leadership role in the ICCBBA board of directors. ZV received reimbursement from ESHRE for attending meetings. She also received research grants from ESHRE and Juhani Aaltonen Foundation. She is the coordinator of EHSRE SQART special interest group. The other authors have no conflicts of interest to declare. DISCLAIMER: This guideline represents the views of ESHRE, 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 ESHRE 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. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (full disclaimer available at https://www.eshre.eu/Guidelines-and-Legal).

COVID-19-related uncertainty: fertility staff experiences of its sources, processing, responses, and consequences.

STUDY QUESTION: What are fertility staff experiences of managing COVID-19-related uncertainty after fertility clinics re-opened? SUMMARY ANSWER: Staff identified many COVID-19-related uncertainty sources, the main being the COVID-19 health threat, to which most clinics and staff responded effectively by implementing safety protocols and building strong collaborative environments that facilitated the acquisition and application of information to guide organizational responses during a rapidly changing situation, but with costs for staff and patients. WHAT IS KNOWN ALREADY: COVID-19 created significant disruption in fertility care delivery, including temporary clinic closure and treatment delay. Patients experienced significant distress, including concerns regarding the impact of COVID-19 and its vaccine on fertility and pregnancy. Multiple studies show that COVID-19-related uncertainty is a major threat and burden for healthcare staff, but this has not been investigated in reproductive medicine. STUDY DESIGN, SIZE, DURATION: A cross-sectional, online mixed-method bilingual (English, Spanish) survey (active 25 January-23 May 2021) was distributed to fertility staff across the UK, Latin America, and Africa. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligibility criteria were being a healthcare worker at a fertility clinic that had re-opened since its COVID-19-related closure, 18 years of age or older and ability to respond in English or Spanish. The survey was created in English, translated to Spanish, made available using Qualtrics, and consisted of four parts: (i) background and physical and mental wellbeing, (ii) open-ended questions regarding COVID-19 uncertainty, (iii) appraisal items regarding perceptions and impact of uncertainty, and (iv) changes in the workplace. The British Fertility Society and the African Network and Registry of Assisted Reproduction circulated the survey across the UK and Africa via email hyperlinks and social media platforms. The Argentinian Society of Reproductive Medicine and the Latin American Network of Assisted Reproduction distributed the survey across Latin America in the same manner. Thematic analysis was performed on responses from open-ended question to produce basic codes. Deductive coding grouped sub-themes across questions into themes related to the theory of uncertainty management. Descriptive statistics and repeated measures analysis of variance were used on the quantitative data. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 382 staff consented to the survey, 107 did not complete (28% attrition), and 275 completed. Sixty-three percent were women, 69% were physicians, and 79% worked at private clinics. Thematic analysis produced 727 codes, organized in 92 sub-themes, and abstracted into 18 themes and one meta-theme reflecting that uncertainty is stressful but manageable. The types of uncertainties related to the threat of COVID-19 (20.6%), unpredictability of the future (19.5%), failure of communication (11.4%), and change in the workplace (8.4%). Staff appraisals of negative and positive impact of uncertainty were significantly lower (P < 0.001) than appraisals of stress, controllability, and having what it takes to cope with uncertainty. To process uncertainty, clinics focused on information dissemination (30.8%) and building a collaborative work environment (5.8%), while staff employed proactive coping (41.8%) and emotional and cognitive processing (9.6%). Main organizational responses consisted on work restructuring (41.3%, e.g. safety protocols), adapting to adversity (9.5%, e.g. supplies, preparation), and welfare support (13.8%), though staff perceived lack of support (17.5%). Negative consequences of uncertainty were worse self- and patient welfare (12.1%) and worse communication due to virtual medicine and use of mask (9.6%). Positive consequences were work improvements (8.3%), organizational adaptation (8.3%), improved relationships (5.6%), and individual adaptation (3.2%). Ninety-two percent of participants thought changes experienced in the workplace due to COVID-19 were negative, 9.1% nor negative nor positive, and 14.9% positive. Most staff thought that their physical (92.4%) and mental health (89.5%) were good to excellent. LIMITATIONS, REASONS FOR CAUTION: Participants were self-selected, and most were physicians and embryologists working at private clinics based in Latin America. The study did not account for how variability in national and regional COVID-19 policy shaped staff experiences of uncertainty. WIDER IMPLICATIONS OF THE FINDINGS: To address COVID-19 uncertainty, clinics need to promote collaborative (clinic, staff, patients) processing of uncertainty, clear team coordination and communication, organizational flexibility, and provision of support to staff and patients, with an emphasis on cognitive coping to decrease threat of and increase tolerance to uncertainty. Uncertainty management interventions bespoke to fertility care that integrate these components may increase clinics resilience to COVID-19-related and other types of uncertainty. STUDY FUNDING/COMPETING INTERESTS: Cardiff University funded this research. S.G. reports consultancy fees from Ferring Pharmaceuticals A/S, speaker fees from Access Fertility, SONA-Pharm LLC, Meridiano Congress International, and Gedeon Richter, and grants from Merck Serono Ltd. F.Z.-H. reports speaker fees from Ferring Pharmaceuticals A/S and that he is a chair of the Latin American Registry of ART, Committee of Ethic and Public Policies, and Chilean Society of Obstetrics and Gynecology and a vice chair of the International Committee for monitoring ART. K.A., N.C., G.B., and J.B. report no conflict in relation to this work. TRIAL REGISTRATION NUMBER: N/A.