Does recurrent implantation failure exist? Prevalence and outcomes of five consecutive euploid blastocyst transfers in 123 987 patients

Human Reproduction, Journal Year: 2024, Volume and Issue: 39(5), P. 974 - 980

Published: March 7, 2024

Abstract STUDY QUESTION What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures absence of another known factor that affects implantation? SUMMARY ANSWER The fourth fifth resulted similar 40% 53.3%, respectively, culminating a cumulative rate 98.1% (95% CI = 96.5–99.6%) five transfers. WHAT IS KNOWN ALREADY first blastocysts have implantation provide 92.6%. DESIGN, SIZE, DURATION An international multi-center retrospective study was conducted at 25 individual clinics. period spanned between January 2012 December 2022. A total 123 987 patients with 64 572 were screened for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients history any embryo transfer clinic, unscreened participating clinics, parental karyotype abnormalities, use donor oocytes or gestational carrier, untreated intracavitary uterine pathology (e.g. polyp, leiomyoma), congenital anomalies, adenomyosis, communicating hydrosalpinx, endometrial thickness <6 mm prior initiating progesterone, testicular sperm due non-obstructive azoospermia male partner, an reported intermediate chromosome copy number (i.e. mosaic), preimplantation genetic testing cycles monogenic disorders, structural rearrangements excluded. Ovarian stimulation protocols embryology laboratory procedures including trophectoderm biopsy followed usual practice each center. ploidy status determined comprehensive screening. Endometrial preparation centers included programmed cycles, natural modified cycles. MAIN RESULTS AND THE ROLE OF CHANCE 105 (0.085% population) met criteria least one additional failing achieve positive test consecutive Outcomes across centers. Overall, (40% vs relative risk 1.33, 95% 0.93–1.9, P value 0.14). Sensitivity analyses excluding biopsied on Day 7 postfertilization, BMI >30 kg/m2, using non-ejaculate sperm, double-embryo which day receptivity assay result yielded results. Where data available, had (relative 0.84, 0.58–1.21, 0.29). 96.5–99.6%). LIMITATIONS, REASONS FOR CAUTION Retrospective design has its own inherent limitations. continuing further dropping out from treatment failed can be systematically different, perhaps regard ovarian reserve economic status. WIDER IMPLICATION FINDINGS Implantation failure seems mainly embryonic factors. Given stable high blastocysts, unexplained recurrent should prevalence <2%. Proceeding best next step once etiology is ruled out. FUNDING/COMPETING INTEREST(s) None. TRIAL REGISTRATION NUMBER N/A.

Language: Английский

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Evolution of biotechnological advances and regenerative therapies for endometrial disorders: a systematic review

Human Reproduction Update, Journal Year: 2024, Volume and Issue: 30(5), P. 584 - 613

Published: May 25, 2024

Abstract BACKGROUND The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) intrauterine adhesions (IUA), or atrophy (EA) thin endometrium (TE), can either originate autonomously arise as a result from conditions (i.e. endometritis congenital hypoplasia), medical interventions (e.g. surgeries, hormonal therapies, uterine curettage radiotherapy). Affected patients may present an altered inadequate lining that hinders embryo implantation increases the risk poor outcomes miscarriage. In humans, AS/IUA EA/TE are mainly treated with surgeries pharmacotherapy, however reported efficacy these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, tissue engineering have emerged to improve reproductive outcomes. OBJECTIVE AND RATIONALE This review comprehensively summarizes methodologies emerging biotechnologies (cellular, acellular, bioengineering approaches) treat human pathologies. Regenerative therapies derived tissues blood which were studied in preclinical models (in vitro vivo) clinical trials discussed. SEARCH METHODS A systematic search full-text articles available PubMed Embase was conducted identify original peer-reviewed studies published English between January 2000 September 2023. terms included: human, uterus, endometrium, syndrome, adhesions, atrophy, endometritis, hypoplasia, curettage, radiotherapy, therapy, bioengineering, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, hormone, progesterone, estrogen. Preclinical cellular, strategies repair regenerate included. Additional identified through manual searches. OUTCOMES From total 4366 records identified, 164 (3.8%) included for review. Due heterogeneity study design measured outcome parameters both studies, findings evaluated qualitatively quantitatively without meta-analysis. Groups using cell-based treatments pathologies commonly employed mesenchymal cells (MSCs) bone marrow umbilical cord. Alternatively, acellular based plasma (PRP) extracellular vesicles gaining popularity. These accompanied by emergence matrix (ECM)-derived hydrogels synthetic biosimilars sustain local delivery reporting promising results. Combined target multiple aspects regeneration remain testing but shown translational value. highlights myriad material sources, administration methods, carriers been tested. WIDER IMPLICATIONS Therapies promote proliferation, vascular development, help restore function and, ultimately, fertility. Based existing evidence, cost, accessibility, availability we propose development triple-hit strategies, potentially combining high-yield MSCs cord) (PRP), possibly integrated ECM hydrogels. Advances together insights will pave way developing personalized treatment regimens infertility-causing disorders such AS/IUA, EA/TE, endometritis. REGISTRATION NUMBER https://osf.io/th8yf/

Language: Английский

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Associations between the artificial intelligence scoring system and live birth outcomes in preimplantation genetic testing for aneuploidy cycles

Reproductive Biology and Endocrinology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 17, 2024

Abstract Background Several studies have demonstrated that iDAScore is more accurate in predicting pregnancy outcomes cycles without preimplantation genetic testing for aneuploidy (PGT-A) compared to KIDScore and the Gardner criteria. However, effectiveness of with PGT-A has not been thoroughly investigated. Therefore, this study aims assess association between artificial intelligence (AI)-based (version 1.0) single-embryo transfer (SET) PGT-A. Methods This retrospective was approved by Institutional Review Board Chung Sun Medical University, Taichung, Taiwan. Patients undergoing SET ( n = 482) following at a single reproductive center January 2017 June 2021. The blastocyst morphology morphokinetics all embryos were evaluated using time-lapse system. blastocysts ranked based on scores generated iDAScore, which defined as AI scores, or D5 3.2) manufacturer’s protocols. A transferred after examining embryonic ploidy status next-generation sequencing-based platform. Logistic regression analysis generalized estimating equations conducted whether are associated probability live birth (LB) while considering confounding factors. Results revealed score significantly LB (adjusted odds ratio [OR] 2.037, 95% confidence interval [CI]: 1.632–2.542) when pulsatility index (PI) level types chromosomal abnormalities controlled. Blastocysts divided into quartiles accordance their (group 1: 3.0–7.8; group 2: 7.9–8.6; 3: 8.7–8.9; 4: 9.0–9.5). Group 1 had lower rate (34.6% vs. 59.8–72.3%) higher loss (26% 4.7–8.9%) other groups p < 0.05). receiver operating characteristic curve verified significant but limited ability predict (area under [AUC] 0.64); weaker than combination type abnormalities, PI (AUC 0.67). In comparison non-LB groups, both euploid (median: 8.6 8.8) mosaic 8.0 8.6) SETs. Conclusions Although its predictive can be further enhanced, cycles. Euploid low (≤ 7.8) rate, indicating potential annotation-free system decision-support tool deselecting poor

Language: Английский

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In Vitro Culture of Mammalian Embryos: Is There Room for Improvement?

Cells, Journal Year: 2024, Volume and Issue: 13(12), P. 996 - 996

Published: June 7, 2024

Preimplantation embryo culture, pivotal in assisted reproductive technology (ART), has lagged innovation compared to selection advancements. This review examines the persisting gap between vivo and vitro development, emphasizing need for improved culture conditions. While humans this is hardly estimated, animal models, particularly bovines, reveal clear disparities developmental competence, cryotolerance, pregnancy live birth rates vitro-produced (IVP) vivo-derived (IVD) embryos. Molecular analyses unveil distinct differences morphology, metabolism, genomic stability, underscoring refining conditions better ART outcomes. To end, a deeper comprehension of oviduct physiology transport crucial grasping embryo–maternal interactions’ mechanisms. Research on autocrine paracrine factors, extracellular vesicles tract interactions, elucidates vital communication networks successful implantation pregnancy. In vitro, confinement, density are key factors boost development. Advanced dynamic systems mimicking fluid mechanical stimulation oviduct, through vibration, tilting, microfluidic methods, use innovative softer substrates, hold promise optimizing

Language: Английский

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Predicting the risk of a high proportion of three/multiple pronuclei (3PN/MPN) zygotes in individual IVF cycles using comparative machine learning algorithms

European Journal of Obstetrics & Gynecology and Reproductive Biology, Journal Year: 2025, Volume and Issue: 306, P. 139 - 146

Published: Jan. 15, 2025

Language: Английский

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Oocyte and embryo cryopreservation in assisted reproductive technology: past achievements and current challenges

Fertility and Sterility, Journal Year: 2023, Volume and Issue: 120(3), P. 506 - 520

Published: June 7, 2023

Language: Английский

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A novel machine-learning framework based on early embryo morphokinetics identifies a feature signature associated with blastocyst development

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: March 15, 2024

Abstract Background Artificial Intelligence entails the application of computer algorithms to huge and heterogeneous amount morphodynamic data produced by Time-Lapse Technology. In this context, Machine Learning (ML) methods were developed in order assist embryologists with automatized objective predictive models able standardize human embryo assessment. study, we aimed at developing a novel ML-based strategy identify relevant patterns associated prediction blastocyst development stage on day 5. Methods We retrospectively analysed morphokinetics 575 embryos obtained from 80 women who underwent IVF our Unit. Embryo was registered using Geri plus® time-lapse system. Overall, 30 clinical, morphological morphokinetic variables related recorded combined. Some reached expanded 5 (BL Group, n = 210), some others did not (nBL 365). Results The EmbryoMLSelection framework following four-steps: Feature Selection, Rules Extraction, Selection Evaluation. Six rules composed combination 8 finally selected, provided power described an AUC 0.84 accuracy 81%. Conclusions herein new feature-signature high performance best developmental competence reach Clear clinically cut-offs identified for each considered variable, providing tool early

Language: Английский

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When the Embryo Meets the Endometrium: Identifying the Features Required for Successful Embryo Implantation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2834 - 2834

Published: Feb. 29, 2024

Evaluation of the optimal number embryos, their quality, and precise timing for transfer are critical determinants in reproductive success, although still remaining one main challenges assisted reproduction technologies (ART). Indeed, success vitro fertilization (IVF) treatments relies on a multitude events factors involving both endometrium embryo. Despite concerted efforts fronts, overall rates IVF techniques continue to range between 25% 30%. The role implantation has been recently recognized, leading hypothesis that “soil” “seed” play central successful pregnancy. In this respect, identification molecular signature endometrial receptivity together with selection best embryo become crucial ART. Currently, have made develop accurate, predictive, personalized tests identify window quality However, value these is debated, as conflicting results reported literature. purpose review summarize critically report available criteria optimize better understand current limitations potential areas improvement.

Language: Английский

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Diagnostic or prognostic? Decoding the role of embryo selection on in vitro fertilization treatment outcomes

Fertility and Sterility, Journal Year: 2024, Volume and Issue: 121(5), P. 730 - 736

Published: Jan. 5, 2024

Language: Английский

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Extracellular vesicles secreted by human aneuploid embryos present a distinct transcriptomic profile and upregulate MUC1 transcription in decidualised endometrial stromal cells

Human Reproduction Open, Journal Year: 2024, Volume and Issue: 2024(2)

Published: Jan. 1, 2024

Abstract STUDY QUESTION Do extracellular vesicles (EVs) secreted by aneuploid human embryos possess a unique transcriptomic profile that elicits relevant response in decidualized primary endometrial stromal cells (dESCs)? SUMMARY ANSWER Aneuploid embryo-derived EVs contain transcripts of PPM1J, LINC00561, ANKRD34C, and TMED10 with differential abundance from euploid induce upregulation MUC1 transcript dESCs. WHAT IS KNOWN ALREADY We have previously reported IVF secrete can be internalized ESCs, conceptualizing successful implantation to the endometrium is facilitated EVs. Whether these may additionally serve as biomarkers ploidy status unknown. DESIGN, SIZE, DURATION Embryos destined for biopsy preimplantation genetic testing aneuploidy (PGT-A) were grown under standard conditions. Spent media (30 μl) collected (n = 175) 140) at cleavage (Days 1–3) stage 187) 142) blastocyst 3–5) stage. Media samples n 35 cleavage-stage pooled order obtain five four pools. Similarly, blastocysts create one pool. ESCs obtained women undergoing diagnostic laparoscopy. PARTICIPANTS/MATERIALS, SETTING, METHODS isolated pools centrifugation EV-RNA sequencing was performed following single-cell approach circumvents RNA extraction. (estradiol: 10 nM, progesterone: 1 µM, cAMP: 0.5 mM twice every 48 h) incubated 24 h (50 ng/ml). on ESCs. MAIN RESULTS AND THE ROLE OF CHANCE less abundant fragments originating genes PPM1J (log2fc −5.13, P 0.011), LINC00561 −7.87, 0.010), ANKRD34C −7.30, 0.017) more 1.63, 0.025) compared embryos. Decidualization per se induced downregulation −0.54, 0.0028) prerequisite establishment receptive endometrium. The expression significantly increased treatment embryo-secreted 0.85, 0.0201). LARGE SCALE DATA Raw data been uploaded GEO (accession number GSE234338). LIMITATIONS, REASONS FOR CAUTION findings study will require validation utilizing second cohort EV samples. WIDER IMPLICATIONS FINDINGS discovery differs supports possibility develop non-invasive methodology PGT-A. dESCs embryo proposes new mechanism underlying failure. FUNDING/COMPETING INTEREST(S) supported Marie Skłodowska-Curie Actions fellowship awarded SM European Commission (CERVINO grant agreement ID: 79620) BIRTH research Theramex HQ UK Ltd. authors no conflicts interest declare.

Language: Английский

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