IVI Murcia Clinic

BackgroundThe aims of this study were to gather expert agreement about essential aspects of clear aligner therapy (CAT) and to determine what research areas need further investigation.Materials and methodsA steering committee performed literature selection and compiled a list of 25 statements. This study used a modified Delphi method involving a panel of 23 international orthodontic experts. Six essential areas of CAT were investigated: treatment efficacy, quality of life, side effects, management of growing patients, treatment with extraction, and treatment of periodontal patients. A panel of experts assessed 25 statements using a 5-point Likert scale throughout 3 rounds of the study. A steering committee adjusted statements that failed to achieve consensus through either revision, splitting, merging, or complete removal.ResultsAfter the third round, 22 statements achieved consensus while 3 statements were rejected. The panel agreed that aligners could be used effectively in some types of malocclusions, such as those with mild or moderate crowding or open bite cases. The experts reached a consensus on the biomechanical limits of clear aligners. However, they agreed on the benefits in terms of improved quality of life during treatment and easier maintenance of oral hygiene maneuvers. Regarding specific patient categories, the panelists supported the use of aligners in periodontal patients with tooth migration requiring tipping movements. They also agreed on the advantages of using a rapid palatal expander over aligners in growing patients.ConclusionsThe panel members reached agreement on most topics. However, they acknowledged limitations in the current literature regarding root resorption and orthodontic relapse with CAT compared to fixed appliances. The absence of agreement on treatment duration, effects on skeletal growth, and the management of periodontally compromised patients highlights significant evidence gaps that warrant further research.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40510-025-00575-1.

Abstract Study question Does the administration of micronutrients and probiotics supplement during an oocyte donation program improve fertilization rate, blastocyst development, and pregnancy outcomes? Summary answer Micronutrients and probiotics supplementation in oocyte donors does not influence fertilization or blastocyst rates, but significantly improved pregnancy outcomes of recipients that used vitrified oocytes. What is known already Micronutrient supplementation could have a positive impact on IVF clinical results. Evidence about its role in improving oocytes’ quality and reproductive outcomes in normoresponders patients are still lacking. The OvoVid double-blind, randomized, controlled trial Phase 1 suggested that a micronutrients-probiotics supplementation enhances oocyte yield and quality in normoresponder oocyte donors. A significantly higher number of total oocytes retrieved and mature MII were achieved in the supplement group, which also showed a better follicular response to controlled ovarian hyperstimualtion (COH) than placebo in term of more follicles at the end of COH, despite a similar initial antral follicle count. Study design, size, duration Multicentric, double-blind, randomized controlled trial involving 130 oocyte donors and 107 recipients during a two-year period involving three Fertility Clinics in Spain. Oocyte donors were randomized in supplement or placebo group, taking one tablet a day at least for 30 days before and during COH. The micronutrients-probiotc supplement was a combination of Myoinositol+d-chiro-inositol (ratio 40:1), folic acid, melatonin, coenzyme Q10, vitamin D3, B6, B12, E, iron, zinc, Lactobacillus Gasseri and Crispatus. Participants/materials, setting, methods The Ovovid Phase 2 study analyzed the reproductive outcomes of 107 oocyte donation treatments in recipients, classified in supplement (n = 62) or placebo (n = 45) group depending on the oocytes’ origin, realized with donors’ oocytes of Ovovid Phase 1. Primary outcomes included fertilization and blastocyst development rates, while secondary outcomes encompassed pregnancy rates and oocyte survival after thawing. Statistical analysis was performed using Fisher’s exact test and Mann-Whitney U test, with significance set at p<0.05. Main results and the role of chance No significant differences were observed in fertilization rate (76,7% vs. 78%, p > 0,05) comparing supplement and placebo group, as well as in blastulation development (43,4% vs. 45,4%, p = 0,61), despite similar number of inseminated oocytes (6,7 ± 1,3 vs. 6,3 ± 1,2, p = 0,13). When vitrified oocytes were used, similar survival rate after thawing were described in the two groups (94,3% vs. 93,8%, p = 0,3). Pregnancy rate was similar regardless of multivitamin-probiotics supplement use (44,4% vs. 68,2%, p = 0,07). However, in the sub-analysis for type of oocyte, pregnancy rates with vitrified oocytes (Supplement n = 24; Placebo n = 18) were significantly higher in the supplement group compared to placebo (50% vs. 0%, p = 0,02). No significant differences were found for fresh oocytes (n = 65; Supplement n = 38; Placebo n = 27) outcomes. Limitations, reasons for caution The study was limited by the relatively small sample size for subgroup analyses and the lack of long-term follow-up for pregnancy outcomes. Further studies are warranted to confirm these observations and optimize supplementation strategies in oocyte donation programs and assisted reproductive technologies. Wider implications of the findings Micronutrients and probiotics supplementation during oocyte donors’ COH did not seem to improve overall fertilization or blastulation rates. However, it may be a valuable adjunct in improving recipients’ pregnancy outcomes with vitrified oocytes, suggesting a role in enhancing oocyte competence during vitrification, potentially optimizing outcomes for specific protocols. Trial registration number No

Does the use of preimplantation genetic testing for aneuploidies (PGT-A), personalized embryo transfer with endometrial receptivity assay (pET-ERA), or the use of donated oocytes modify the incidence of biochemical pregnancy loss (BPL) in frozen single embryo transfer (FSET)? Following FSET, BPL incidence does not differ between own and donated oocytes, and the use of PGT-A with euploid embryo transfer or pET-ERA results in a similar incidence of BPL compared to cycles without embryo or endometrial analysis. BPL occurs frequently after IVF, and many factors have been associated with its incidence. The etiology of BPL is not well known, but the most probable cause seems to be either a low-quality embryo or impaired endometrial maintenance. The impact of techniques diagnosing embryonic ploidy or endometrial receptivity on BPL incidence and the BPL incidence between own and donated oocytes have not been analyzed. This is a retrospective cohort study analyzing the incidence of BPL over 3741 cycles of FSET derived from own (2399 cycles) and donated (1342 cycles) oocytes between January 2013 and January 2022 in 1736 of which PGT-A, pET-ERA, or both were applied. We defined BPL as a pregnancy diagnosed only by serum β-hCG > 10 UI/l followed by a decrease that does not result in a clinical pregnancy. Clinical pregnancy was defined as the presence of gestational sac on transvaginal ultrasound. We compared BPL rates among patients undergoing 2399 FSETs from own oocytes, which comprised 1310 cycles of embryos analyzed by PGT-A, 950 cycles of untested embryos, 30 cycles of untested embryos with pET-ERA, and a subgroup of 109 cycles analyzed by both PGT-A and pET-ERA. We also included a total of 1342 FSET cycles from donated oocytes comprising 132, 1055, 140, and 15 cycles in the same groups, respectively. In FSET from own oocytes, the overall BPL rate per embryo transfer was 8.2% (95% CI [7.09-9.33]). In untested embryo transfers, the BPL rate was 7.5% [5.91-9.37]. In the PGT-A group, the BPL rate was 8.8% [7.32-10.47]. In the pET-ERA group, the rate was 6.7% [0.82-22.07]. In the PGT-A+ERA group, the rate was 6.5% [2.65-12.90]. No significant differences were found (P = 0.626). A multivariate analysis considering clinically meaningful variables that were significantly different among groups, taking the untested embryos/endometrium group as a reference, showed comparable incidences among groups. For PGT-A, the adjusted odds ratio (AdjOR) was 1.154 [0.768-1.735] (P = 0.49) and for PGT-A+ERA 0.885 [0.330-2.375] (P = 0.808). Because of a low number of registered cases in the pET-ERA group, and to prevent statistical errors and convergence issues, this group was excluded from further analysis. In FSET of donated oocytes, the overall BPL rate per embryo transfer was 4.9% [3.76-6.14]. In the PGT-A group, the BPL rate was 6.8% [3.16-12.55]. In the pET-ERA group, the rate was 5.0% [2.03-10.03]. In untested embryo transfers, the rate was 4.7% [3.46-6.10]. No cases occurred in the PGT-A+ERA group, and no significant differences were found (P = 0.578). The multivariate analysis showed comparable incidences among groups. For PGT-A the AdjOR was 1.669 [0.702-3.972] (P = 0.247) and for pET-ERA 1.189 [0.433-3.265] (P = 0.737). The PGT-A+ERA group was eliminated from the model to prevent statistical errors and convergence issues because no BPL cases were registered in this group. In the multivariate analysis, when the sources of oocytes were compared, own versus donated, no significant differences were found in the incidence of BPL. This was a retrospective cohort study with potential biases. In addition, we were unable to control differences among groups due to modifications in medical or laboratory protocols during this long time period, which may modify the relationships being addressed. Factors previously associated with BPL, such as immunological conditions other than thyroid autoimmunity, were not considered in this study. Limited sample sizes of some groups may limit the statistical power for finding differences that can be present in the general population. BPL may be related to a mechanism not associated with the chromosomal constitution of the embryo or the transcriptome of the endometrium. More studies are needed to explore the factors associated with this reproductive issue. No specific funding was available for this study. None of the authors have a conflict of interest to declare with regard to this study. This trial was registered at clinicaltrials.gov (NCT04549909).

To review the rebound effect after cessation of different myopia control treatments. A systematic review that included full-length randomised controlled studies (RCTs), as well as post-hoc analyses of RCTs reporting new findings on myopia control treatments rebound effect in two databases, PubMed and Web of Science, was performed according to the PRISMA statement. The search period was between 15 June 2023 and 30 June 2023. The Cochrane risk of bias tool was used to analyse the quality of the selected studies. A total of 11 studies were included in this systematic review. Unifying the rebound effects of all myopia control treatments, the mean rebound effect for axial length (AL) and spherical equivalent refraction (SER) were 0.10 ± 0.07 mm [-0.02 to 0.22] and -0.27 ± 0.2 D [-0.71 to -0.03] after 10.2 ± 7.4 months of washout, respectively. In addition, spectacles with highly aspherical lenslets or defocus incorporated multiple segments technology, soft multifocal contact lenses and orthokeratology showed lower rebound effects compared with atropine and low-level light therapy, with a mean rebound effect for AL and SER of 0.04 ± 0.04 mm [0 to 0.08] and -0.13 ± 0.07 D [-0.05 to -0.2], respectively. It appears that the different treatments for myopia control produce a rebound effect after their cessation. Specifically, optical treatments seem to produce less rebound effect than pharmacological or light therapies. However, more studies are required to confirm these results.

Abstract A 3‐year‐old, neutered, female, mix‐breed dog was presented with a history of acute haemorrhagic vomiting, diarrhoea, anorexia and lethargy. The patient had a hyperkinetic pulse, pale mucous membranes, bilateral hyphema and the capillary refill time was increased. Coagulation testing showed increased values. Abdominal ultrasound revealed diffuse thickening of the submucosal layer with hyperechoic peritoneum and enlargement of the gastric lymph node. The presumptive diagnosis was gastric wall haemorrhage secondary to rodenticide intoxication. The dog responded to treatment and was discharged after 48 hours. Fifteen days later, the thickness and layering of the stomach wall was normal. Gastric wall haemorrhage is a rare condition in dogs with rodenticide intoxication, which requires a biopsy for confirmation. However, the risk of haemorrhage does not make this feasible. In this case, the authors suspect that submucosal gastric thickening was secondary to anticoagulant rodenticide intoxication based on history, clinical examination, haematological analysis and coagulation testing.

This cross-sectional study aimed to quantify the impact of implant-related complications on perceived pain, functional impairment, concern, quality of life (QoL) and confidence which were the study's primary outcomes. Patients were recruited in five centres over 19 months. They completed a structured ad hoc questionnaire scoring pain, chewing ability, concern, QoL and confidence in future implant treatment. Some potential independent variables were also recorded. The data were analysed descriptively and with a multiple-stepwise regression model for correlations of the five primary variables with the other data. The sample consisted of 408 patients, with prosthesis mobility being the most common complication (40.7%). Most patients (79.2%) consulted because of a complication, while 20.8% were asymptomatic and consulted regularly. Pain was correlated with symptoms at consultation and in biological/mixed complications (p < .001; R2 = 44.8%). Chewing impairment with implant loss, prosthesis fracture and removable implant-supported or total prostheses (p < .001; R2 = 42.8%); patient concern was correlated with the clinical symptoms and removable implant-supported prostheses (p < .001; R2 = 36.1%); impact on QoL was correlated with implant loss, prosthesis fracture and removable implant-supported prostheses (p < .001; R2 = 41.1%). Patient confidence was relatively independent and only impact on quality of life significantly influenced it (r = 0.73). Implant-related complications moderately impaired patients' perceptions of pain, chewing ability, concern and QoL. Nevertheless, complications only slightly reduced their confidence in future implant treatment.

Does culture in a high relative humidity atmosphere improve clinical outcomes when using a time-lapse integrated incubator and single-step culture medium? Using an integrated time-lapse system and single-step culture medium, culture in a high relative humidity atmosphere increases the likelihood of embryos, especially those subjected to preimplantation genetic testing for aneuploidies, to achieve a pregnancy compared to those cultured in dry conditions. The use of a humid atmosphere inside incubators can reduce changes in culture media osmolality, which has been reported to have a significant effect on embryo quality and morphokinetics. Studies assessing the effect of humid culture (HC) in clinical outcomes are, however, scarce and inconclusive, mostly due to a high variability in culture conditions and reduced sample size. Retrospective cohort study performed over 1627 ICSI cycles performed during 3 consecutive years in which embryo cohorts were cultured in a time-lapse incubator with three dry and three humidified chambers, and using single-step culture medium. Clinical outcomes were compared between treatments in which embryo cohorts were cultured in either humid (n = 833) or dry (n = 794) conditions. The study includes autologous treatments, with (N = 492) and without (N = 372) preimplantation genetic testing for aneuploidies (PGT-A) and ovum donation treatments (N = 763), performed in three university-affiliated private IVF centres. Stimulation, oocyte pickup and fertilization were performed according to the standard procedures of the clinic. All embryo cohorts were cultured in the same model of time-lapse incubator, distributed to either a dry or humidified chamber, while the rest of the culture variables remained equal. The population was weighted by the inverse probability of treatment to control for all measured confounders. The association between HC and the main outcome was assessed by logistic regression over the weighted population. The E-value was reported as a way of considering for unmeasured confounders. Differences in embryo development and other secondary outcomes between the study groups were assessed by Pearson Chi-squared test, ANOVA test and Kaplan-Meier survival analysis. An univariable logistic regression analysis, weighted by the inverse probability of treatment, determined that embryos cultured in humid conditions are more likely to achieve a clinical pregnancy than those cultured in dry conditions (odds ratio (OR) = 1.236 (95% CI 1.009-1.515), P = 0.041, E = 1.460). Through stratification, it was determined that said effect is dependent on the type of treatment: no improvement in clinical pregnancy was present in ovum donation or autologous treatments, but a statistically significant positive effect was present in treatments with preimplantation genetic testing (OR = 1.699 (95% CI 1.084-2.663), P = 0.021, E = 1.930). Said increase does not relate with an improvement in later outcomes. Differences were also found in variables related to embryo developmental morphokinetics. The retrospective nature of the study makes it susceptible to some bias linked to the characteristics of the treatments. To lessen the effect of possible biases, cases were weighted by the inverse probability of treatment prior to the evaluation of the outcome, as means to assess for measured confounders. In addition, the E-value of the weighted OR was calculated as a sensitivity analysis for unmeasured confounders. A randomized prospective study could be performed for further assessing the effect of humid conditions in clinical outcome. These results support that embryo culture under conditions of high relative humidity contributes to optimize clinical results in undisturbed culture in a time-lapse incubator with single-step medium. To our knowledge, this is the largest study on the matter and the first performing a propensity score-based analysis. This work was supported by the ''Centro para el Desarrollo Tecnologico Industrial'' from the Spanish Ministry of Science, Innovation, and Universities (CDTI-20170310) and Generalitat Valenciana and European Social Fund (ACIF/2019/264). None of the authors have any competing interest to declare. N/A.

Abstract Study question What is the relationship between qualitative and quantitative morphokinetic parameters automatically annotated using CHLOE(Fairtility), an AI-based tool? Summary answer CHLOE score is associated with ploidy. DUC embryos have lower blastulation, form fewer good blastocysts, have increased fragmentation, slower development, lower implantation than non-DUCs. What is known already The introduction of time-lapse technologies in IVF has led to the discovery of quantitiative and qualitative morphokinetic parameters which are predictive of embryo viability (ESHRE Workshop group, 2020). The challenges of annotating videos manually remain: (i)operator variation, (ii)time-consuming; (iii)complexity of how to prioritise numerous features when determining which embryos to transfer, freeze or discard. CHLOE (Fairtility) is an AI-based tool designed to automatically capture these parameters from the time-lapse videos, removing the “black box” associated with AI, and, instead, bringing transparency and support to the embryologist responsible for the decision, thus, enhancing personalisation of care down to each individual embryo. Study design, size, duration Prospective cohort analysis on time-lapse data retrospectively collected at a single private fertility clinic in Spain between 2018-2020. 693 videos were automatically annotated (without training) using the CHLOE Artificial Intelligence (AI) tool for the following quantitative features: tPNa,tPNf,t2,t3,t4,t5,t6,t7,t8,t9,tM,tsB,tB,teB, size of ICM; and the following qualitative parameters: number of pronucleates, morphological quality of Inner Cell Mass and Trophectoderm (CHLOE Morphological scoring), identification of unusual embryo cleavages i.e. Direct Uneven Cleavage (DUCs), amongst other features. Participants/materials, setting, methods All embryos were cultured using the Embryoscope (Vitrolife) incubator. Using a range of algorithms, CHLOE generated a prediction of blastulation (at 30hpi) and implantation which were compared to outcome (blastocysts vs non-blastocysts; euploids vs Aneuploids&amp;Mosaics; Mosaics vs euploids&amp;aneuploids). Embryos identified as DUCS by CHLOE were compared with non-DUCs in terms of outcomes and in terms of endpoints generated by CHLOE (parametric continuous data assessed using 2-tail t-test, categorical data using chi-square). Main results and the role of chance Within all cleaved embryos analysed (n = 693), 29% were DUCs. DUC embryos were less likely to blastulate (DUCvsNonDUCs: 25vs50%,p&amp;lt;0.001), had a higher proportion of embryos with severe fragmentation (26% vs 3%,p&amp;lt;0.001), less likely to be suitable for biopsy (23vs87%, p &amp;lt; 0.001) lower blastulation prediction score (0.53vs0.76,p&amp;lt;0.001), lower implantation prediction score (0.21vs0.48,p&amp;lt;0.001) and slower embryo development across the all morphokinetic time-points assessed(p &amp;lt; 0.001), except for t5 (NS); than non-DUCs. DUCs and non-DUCs had similar proportion of 1,2,3PNs(5,83,5%vs 7,84,3%, NS). Within embryos that blastulated (n = 581), 25% were DUCs. DUC blastocysts were less likely to have a good quality ICM (7vs33%,p&amp;lt;0.001) or a good quality trophectoderm (9vs35%,p&amp;lt;0.05), lower implantation score (0.29vs0.52,p&amp;lt;0.05) and slower embryo development across the following morphokinetics time-points than non-DUC blastocysts. DUCs (n = 38) and non-DUC (n = 292) blastocysts had similar euploidy rate (50vs43%,NS), mosaicism rate (8vs11%,NS), and similar ratio of Euploids:Aneuploid:Mosaics (19:16:3vs126:133:33, NS). One DUC embryo was transferred, leading to an ongoing clinical pregnancy. Blastulation score was predictive of blastulation (AUC of 0.91, p &amp;lt; 0.001). Mosaic embryos had similar implantation score to non-mosaics (0.61vs0.67, NS). Euploid embryos had a higher implantation score than aneuploid blastocysts (0.71bs0.62, p &amp;lt; 0.02), so implantation score was predictive of ploidy. Limitations, reasons for caution This study involved the validation of (i) a specific AI based tool which may not be generalised across other AI tools; (ii) in a single centre. Results obtained did not involve training, suggestive of CHLOE’s ability to generalise across clinics. Presenting a framework for responsibly incorporating AI into clinical practice. Wider implications of the findings CHLOE can simplify the processing of time-lapse data to effectively, consistently, and efficiently quantify parameters that can help explain a comprehensive prediction of embryo viability. This provides a useful tool which will ultimately assist clinicians with selecting the most optimal embryos for transfer and avoid wastage from discarding viable embryos. Trial registration number not applicable

Expanded hemodialysis (HDx), using medium cut‐off membrane, is a novel therapy that effectively clears middle molecules (MMs). We aimed to compare HDx to hemodiafiltration (HDF) in an open randomized clinical study. Patients currently on HDF (age 18–80 years; on HDF >3 months) were randomized to switch to HDx (N = 21) or continue HDF (N = 22) with a 24‐week follow‐up. Pre‐ to post‐dialysis reduction ratios (RR) and changes in pre‐dialysis levels over time were evaluated for MMs and clinical biomarkers. Use of erythropoiesis‐stimulating agents (ESAs) was assessed. HDx showed greater RR for YKL‐40 while RR appeared similar between groups for beta2‐microglobulin, FGF‐23, and free light chains. Intradialytic changes in inflammatory biomarkers (IL‐6, CRP, PTX3) did not differ between therapies. Changes from baseline to 12 and 24 weeks did not differ between groups for MMs, inflammatory markers, albumin, fibrinogen, hemoglobin, PTH, and phosphorus. Use of ESAs tended to decrease in HDx arm while remaining stable in HDF arm. HDx appeared safe with similar clinical effectiveness as HDF. With fewer requirements and resource needs, HDx provides an attractive alternative to HDF.