OBJECTIVE: Which clinical and embryological factors should be considered to apply double embryo transfer (DET) instead of elective single embryo transfer (eSET)?
CONCLUSIONS: No clinical or embryological factor per se justifies a recommendation of DET instead of eSET in IVF/ICSI.
BACKGROUND: 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.
METHODS: 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.
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.
RESULTS: 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.
CONCLUSIONS: 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.
CONCLUSIONS: 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.
BACKGROUND: 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.
CONCLUSIONS: 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).

OBJECTIVE: To provide agreed-upon guidelines on the management of a hyper-responsive patient undergoing ovarian stimulation (OS) METHODS: A literature search was performed regarding the management of hyper-response to OS for assisted reproductive technology. A scientific committee consisting of 4 experts discussed, amended, and selected the final statements. A priori, it was decided that consensus would be reached when ≥66% of the participants agreed, and ≤3 rounds would be used to obtain this consensus. A total of 28/31 experts responded (selected for global coverage), anonymous to each other.
RESULTS: A total of 26/28 statements reached consensus. The most relevant are summarized here. The target number of oocytes to be collected in a stimulation cycle for IVF in an anticipated hyper-responder is 15-19 (89.3% consensus). For a potential hyper-responder, it is preferable to achieve a hyper-response and freeze all than aim for a fresh transfer (71.4% consensus). GnRH agonists should be avoided for pituitary suppression in anticipated hyper-responders performing IVF (96.4% consensus). The preferred starting dose in the first IVF stimulation cycle of an anticipated hyper-responder of average weight is 150 IU/day (82.1% consensus). ICoasting in order to decrease the risk of OHSS should not be used (89.7% consensus). Metformin should be added before/during ovarian stimulation to anticipated hyper-responders only if the patient has PCOS and is insulin resistant (82.1% consensus). In the case of a hyper-response, a dopaminergic agent should be used only if hCG will be used as a trigger (including dual/double trigger) with or without a fresh transfer (67.9% consensus). After using a GnRH agonist trigger due to a perceived risk of OHSS, luteal phase rescue with hCG and an attempt of a fresh transfer is discouraged regardless of the number of oocytes collected (72.4% consensus). The choice of the FET protocol is not influenced by the fact that the patient is a hyper-responder (82.8% consensus). In the cases of freeze all due to OHSS risk, a FET cycle can be performed in the immediate first menstrual cycle (92.9% consensus).
CONCLUSIONS: These guidelines for the management of hyper-response can be useful for tailoring patient care and for harmonizing future research.

Pre-conception counselling and management of expectations about chance of success of IVF/ICSI treatments is an integral part of fertility care. Registry data are usually used to inform patients about expected success rates of IVF/ICSI treatment, as these data should best represent real-world populations and clinical practice. In registries, the success rate of IVF/ICSI treatments is conventionally reported per treatment cycle or per embryo transfer and estimated from data for which several treatment attempts per subject have been pooled (e.g. repetitive IVF/ICSI attempts or repetitive attempts of cryotransfer). This, however, may underestimate the true mean chance of success per treatment attempt, because treatment attempts of women with a poor prognosis will usually be over-represented in a pool of treatment cycle data compared to treatment events of women with a good prognosis. Of note, this phenomenon is also a source of potential bias when comparing outcomes between fresh transfers and cryotransfers, since women can undergo a maximum of only one fresh transfer after each IVF/ICSI treatment, but potentially several cryotransfers. Herein, we use a trial dataset from 619 women, who underwent one cycle of ovarian stimulation and ICSI, a Day 5 fresh transfer and/or subsequent cryotransfers (follow-up of all cryotransfers up to 1 year after the start of stimulation), to exemplify the underestimation of the live birth rate, when not accounting for repeated transfers in the same woman. Using mixed-effect logistic regression modelling, we show that the mean live birth rate per transfer per woman in cryocycles is underestimated by the factor 0.69 (e.g. live birth rate per cryotransfer of 36% after adjustment versus 25% unadjusted). We conclude that the average chance of success of treatment cycles of women of a given age, treated in a given centre, etc., when conventionally calculated per cycle or per embryo transfer from a pool of treatment events, do not apply to an individual woman. We suggest that patients are, especially at the outset of treatment, systematically confronted with mean estimates of success per attempt that are too low. Live birth rates per transfer from datasets encompassing multiple transfers from single individuals could be more accurately reported using statistical models accounting for the correlation between cycle outcomes within women.

Two-round Delphi study carried out in Spain. Three theme-based blocks were set out: 1) Patient profiles: therapeutic goal and parameters to be analysed according to POSEIDON patient profiles; 2) Ovarian stimulation protocols with antagonists: monotherapy (FSH) vs combined therapy (FSH + LH/HMG); 3) Safety and effectiveness of the devices. The antral follicle count and the anti-Müllerian hormone level were considered indicators that can be used to predict ovarian response. More than 80% of the participants agreed that FSH monotherapy is the recommended regimen in normal/hyper-responsive patients of < 35 years of age; that 150-300 IU is the dose to be used in ovarian stimulation in monotherapy depending on clinical parameters; and that FSH monotherapy improves patients\' comfort compared to two combined drugs. It was unanimously considered that the type of device used by the patient influences the comfort of the treatment.IMPACT STATEMENTWhat is already known on this subject? There is currently no consensus on the optimal treatment for controlled ovarian stimulation for patients undergoing IVF which leads to highly variable clinical practices.What the results of this study add? This study\'s strong point is that, since it is a consensus, it has been possible to include more topics than would normally be dealt with in a systematic review or guidelines, which are generally based on a strict method that restricts the scope of the research. Experts have reached a consensus on most of the statements and based on these they have issued consensus statements that will enable the optimal use of gonadotropins in IVF.What the implications are of these findings for clinical practice and/or further research? This Delphi consensus provides a real-life clinical perspective on gonadotropin usage in IVF.

BACKGROUND: Follitropin Delta (FD) is indicated exclusively for in-vitro fertilization however, being a gonadotropin it could be used for other purposes. A dosing algorithm exists for FD and IVF but is needed for intrauterine insemination (IUI) cycles. The objective of this study is to determine dosing for FD for the first controlled ovarian hyperstimulation (COH) cycle according to current stimulation guidelines.
RESULTS: A retrospective study of 157 subjects from a single university fertility center from January 2017 to March 2020, was performed. All patients stimulated with FD for IUI were included. The number of failed, normal, or overstimulation cycles was determined based on stimulating not more than 2 mature follicles. We then stratified the group based on the AFC, AMH, and body weight. Of 157 subjects, 49% stimulated correctly, 5.6% failed and 45.4% overstimulated. An analysis of the COH IUI cycles based on stratification and over or lack of stimulation per published guidelines found that women with a bodyweight < 80 kg or AMH ≥ 1.5 ng/ml or AFC ≥ 10 initially stimulate with FD 2.0 to 3.0mcg daily. For women with an AFC of 6-9 stimulate with Follitropin Delta 3.0mcg daily. For women with an AFC < 6 or serum AMH < 1.5 ng/ml stimulate with FD 3.0-4.0mcg daily. For women with body weight > 80 kg stimulate initially with daily with 4.0-6.0mcg FD.
CONCLUSIONS: Follitropin Delta can be used safely for controlled ovarian stimulation and insemination at doses easily dispensed by the current methods of delivery, within the current published guidelines for follicle development.

OBJECTIVE: International guidelines for the management of recurrent miscarriage (RM) do not provide detailed guidance for the care of women/couples with concurrent infertility. Research studies concerning the investigation and treatment of RM frequently omit this cohort. The aim of this study was to assess the care of women/couples with infertility attending a RM clinic in a large tertiary unit in the Republic of Ireland.
METHODS: We conducted an audit of women with RM and infertility attending our RM clinic from 2008 to 2020 against 110 established guideline-based key performance indicators (KPIs) for RM care, encompassing five categories: structure of care, counselling/supportive care, investigation, treatment and outcomes. Information was gathered from documentation from the RM clinic, hospital laboratory and electronic health records.
RESULTS: We identified 128 women with infertility and RM. Information provision in RM clinics regarding modifiable risk factors (71 %; 91/128) and unexplained RM (53 %; 69/128) could be improved. Most women were investigated in line with KPIs, except for pelvic ultrasound (40 %; 51/128), cytogenetic analysis (27 %; 34/128) and 3D ultrasound (2 %; 2/128). Immunotherapies were seldom prescribed (<1%); however, 98 % (125/128) of women received aspirin, 48 % LMWH (62/128) and 16 % corticosteroids (21/128). Surgical interventions were uncommon (5 %; 6/128)). The subsequent pregnancy rate was 70 % (89/128), with 36 % undergoing artificial reproductive technology (32/89). The livebirth rate was 63 % (56/89); 37 % had a further pregnancy loss (33/89), of which two were second-trimester miscarriages.
CONCLUSIONS: Women with RM and infertility received care largely in line with RM guideline-based KPIs. However, we identified areas for improvement, including the quality of information provision, and access to certain investigations. While guideline-based KPIs allow for internationally applicable and reproducible audit that can direct service improvements, the experiences and needs of service-users are not captured, meriting further qualitative research.

OBJECTIVE: To evaluate the oocyte potential to develop to blastocyst in Rotterdam consensus PCOS in women with hyper-responses requiring freeze-all embryos.
METHODS: Retrospective, single-academic center, cohort study of 205 patients who underwent freeze-all antagonist IVF cycles for OHSS risk between 2013 and 2019. Women in the PCOS group (n = 88) were diagnosed per the 2003 Rotterdam criteria. Control patients (n = 122) had no evidence of hyperandrogenism or menstrual disturbance. Data was compared by t-tests, chi-squared tests, or multivariate logistic regression (SPSS). Frozen blastocysts were Gardner\'s grade BB or better.
RESULTS: There was no difference in terms of number of oocytes collected (PCOS vs non-PCOS 27.7 ± 9.4 vs 25.9 ± 8.2, p = 0.157), number of MII (20.7 ± 8.0 vs 19.1 ± 6.6, p = 0.130), number of 2PN fertilized (15.6 ± 7.4 vs 14.4 ± 5.9, p = 0.220), and number of frozen blastocysts (7.8 ± 4.9 vs 7.1 ± 3.8, p = 0.272). In addition, fertilization rates (74 ± 17% vs 75 ± 17%, p = 0.730), blastulation rates per 2PN (51 ± 25% vs 51 ± 25%, p = 0.869), and blastulation rates per mature oocytes (37 ± 18% vs 37 ± 15%, p = 0.984) were all comparable between PCOS and controls, respectively. Moreover, there was no difference when comparing PCOS and controls in pregnancy rates (45/81 vs 77/122, p = 0.28) and clinical pregnancy rates (34/81 vs 54/122, p = 0.75), respectively. Multivariate logistic regression controlling for confounders failed to alter these results.
CONCLUSIONS: PCOS subjects do not seem to have altered oocyte potential as measured by number of MII oocytes collected, fertilization, and blastulation rates when compared to high-responder controls, with similar magnitude of stimulation.

OBJECTIVE: To evaluate the websites of Brazilian fertility clinics included in the 11th Report of the National Embryo Production System (SisEmbrio, 2017) for compliance with the 2004 American Society for Reproductive Medicine (ASRM) and the Brazilian Medical Council (Conselho Federal de Medicina, CFM) guidelines for advertising.
METHODS: We performed an online evaluation of the websites of clinics listed in the 11th SisEmbrio report based on criteria from the 2004 ASRM guidelines (publication of success rates, live birth rates (LBR), method of LBR calculation, success rates by age range and diagnosis, experimental/investigational nature of procedures and the practice of comparison marketing) and CFM guidelines (clinic director name and register visible on the website; no prices displayed, no photos of patients nor success stories with patient identification).
RESULTS: A total of 161 SiSEmbrio-registered clinics were evaluated: 153 (95.0%) had functional websites, and only seven were public clinics. Social media presence was as follows: 87 (54.03%) were on WhatsApp; 128 (79.5%) were on Facebook; and 122 (75.8%) were on Instagram. Seventy-five (46.6%) were on other social media platforms (YouTube, LinkedIn, and Twitter). Regarding CFM recommendations, 49 (30.4%) showed information of a registered director, 85 (52.8%) showed patient photos on their websites and/or social media accounts. Fifty-four clinics published success rates (33.5%) and 19 (11.8%) used their own data, whereas seven (4.3%) showed pregnancy rates by age. None reported LBR or advertised prices.
CONCLUSIONS: The information published online by Brazilian fertility clinics is heterogeneous in nature. A significant portion of the websites does not follow some of the ASRM and CFM guidelines for advertising.

There is moderate evidence that assisted hatching does not significantly improve live birth rates in fresh assisted reproductive technology cycles and insufficient evidence for the benefit of assisted hatching in patients with poor prognosis or undergoing frozen embryo transfer cycles. This document replaces the document of the same name published in 2014.

OBJECTIVE: To test the validity of the Vienna consensus laboratory key performance indicators (KPIs) to monitor the outcome of treatments involving women of different age ranges.
METHODS: The retrospective cohort study included 862 complete IVF/ICSI cycles carried out between January 2014 and May 2021. All embryos of each cycle cohort were subject to extended culture. The overall population was divided into two groups according to female age: the Vienna consensus (≤ 39 years) and older female age (≥ 40 years). We compared outcomes of a selection of the Vienna performance indicators (PIs) and KPIs, with a focus on measures relevant to embryo cleavage and blastocyst formation. A possible association between total good blastocyst development rate (TGBDR) and cumulative clinical pregnancy rate (CPR) was also assessed.
RESULTS: No differences were observed in fertilization and embryo cleavage KPIs between the Vienna consensus and the older female age group (standard IVF fertilization, 67.2 vs. 67.3; ICSI fertilization, 72.3 vs. 75.3; day 2 development, 57.6% vs 58.7%; day 3 development, 52.4% vs. 50.7%, respectively). TGBDR was lower in the older female age group (45.5% vs. 33.4% p < 0.001). Multivariate logistic regression analysis indicated female age as a factor independently associated with TGBDR. Clinical outcomes significantly decreased with increasing female age.
CONCLUSIONS: The study suggests that, while most laboratory outcome measures are reliably applicable irrespective of female age, KPIs describing extended embryo culture should be fine-tuned in consideration of older female age.