47 results on '"Pellicer, N."'
Search Results
2. P-800 Autologous stem cell ovarian transplant induced long-lasting effects on the plasma proteome of women with premature ovarian insufficiency
- Author
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Buigues, A, primary, Ramírez-Martin, N, additional, Martinez, J, additional, Pellicer, N, additional, Meseguer, M, additional, Pellicer, A, additional, and Herraiz, S, additional
- Published
- 2023
- Full Text
- View/download PDF
3. Macro and micromechanics analysis of short fiber composites stiffness: The case of old newspaper fibers–polypropylene composites
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Serrano, A., Espinach, F.X., Tresserras, J., del Rey, R., Pellicer, N., and Mutje, P.
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- 2014
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4. Study on the technical feasibility of replacing glass fibers by old newspaper recycled fibers as polypropylene reinforcement
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Serrano, A., Espinach, F.X., Tresserras, J., Pellicer, N., Alcala, M., and Mutje, P.
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- 2014
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5. O-142 COVID19-free endometrium: Undetectable viral RNA in endometrial biopsies from positive symptomatic SARS-CoV-2 women
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De Miguel-Gómez, L, primary, Romeu, M, additional, Pellicer, N, additional, Faus, A, additional, Pellicer, A, additional, and Cervelló, I, additional
- Published
- 2021
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6. Novel therapeutic targets to improve IVF outcomes in endometriosis patients: a review and future prospects
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Corachán A, Pellicer N, Pellicer A, and Ferrero H
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IVF, angiogenic factors, cell cycle, embryo quality, endometriosis, infertility, inflammation, oocyte quality, oxidative stress, steroidogenesis - Abstract
Patients with endometriosis often experience infertility and have poor IVF outcomes, with low fertilization and pregnancy rates. Although many theories have tried to explain the mechanisms underlying infertility in these patients, none of them is conclusive.
- Published
- 2021
7. Undetectable viral RNA from SARS-CoV-2 in endometrial biopsies from women with COVID-19: a preliminary study
- Author
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de Miguel-Gómez L, Romeu M, Castells-Ballester J, Pellicer N, Faus A, Mullor JL, Pellicer A, and Cervelló I
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ACE2, COVID-19, Endometrium, SARS-CoV-2 - Published
- 2021
8. Pathways and factors regulated by bone marrow-derived stem cells in human ovarian tissue
- Author
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Buigues A, Diaz-Gimeno P, Sebastian-Leon P, Pellegrini L, Pellicer N, Pellicer A, and Herraiz S
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sense organs ,Female infertility, gene expression, growth factors, ovarian reserve, stem cells ,skin and connective tissue diseases - Abstract
To describe molecular and paracrine signaling changes produced by human bone marrow-derived stem cells (BMDSC) in human ovarian cortex.
- Published
- 2021
9. Treatment potential of bone marrow-derived stem cells in women with diminished ovarian reserves and premature ovarian failure
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Herraiz, S, Pellicer, N, Romeu, M, and Pellicer, A
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endocrine system ,premature ovarian insufficiency ,endocrine system diseases ,stem cell ovarian transplant ,follicular rescue ,adult stem cell ,diminished ovarian reserve - Abstract
Purpose of review We review the techniques recently tested in both animal models and humans to provide a state-of-the-art on adult stem cell ovarian transplant to achieve ovarian rejuvenation in patients with diminished ovarian reserves. Recent findings As the firsts reports of spontaneous pregnancies achieved after bone marrow transplantation in oncologic women with primary ovarian insufficiency, increasing evidence supports the regenerative effects of stem cell-based therapies in the ovarian niche. Adult stem cells from several origins promote follicular development, increase ovarian local vascularization, increase follicle and stromal cell proliferation and reduce cell apoptosis and follicular atresia, although they do not modify embryo quality. Therefore, residual quiescent follicles of aged or damaged ovaries might produce competent oocytes in an adequate ovarian environment. Nevertheless, further research is needed to properly evaluate underlying mechanisms, identify best cell sources and design less invasive infusion techniques. Summary Stem cells may be a relevant therapeutic alternative for ovary regeneration and follicular development in patients with impaired ovaries, such as poor ovarian responders or women diagnosed with primary ovarian insufficiency.
- Published
- 2019
10. Identification of targetable mutations for differential molecular diagnosis of uterine leiomyomas versus leiomyosarcomas using next generation sequencing
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Mas, A., primary, Alonso, R., additional, Jimenez Almazan, J., additional, Martin, J., additional, Ayala, G.L., additional, Pellicer, N., additional, Monleon, J., additional, and Simon, C., additional
- Published
- 2018
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11. Strategy for the Simulation of the ITER Toroidal Field Coil Case Welding Distortion With Finite-Element Method
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Jimenez, Marc, primary, Cornelis, M., additional, Damone, M., additional, Kostopoulos, C., additional, Libens, K., additional, Heikkinen, S., additional, Harrison, R., additional, Hernandez, A., additional, LoBue, A., additional, Pellicer, N., additional, Poncet, L., additional, Bellesia, B., additional, Veredas, G., additional, Viladiu, E., additional, Malpica, O., additional, Barbero, P., additional, Bolla, M., additional, Francone, R., additional, Spagnolo, M., additional, Falcitelli, G., additional, Cornella, J., additional, Aprili, P., additional, Barbero, E., additional, Batista, R., additional, Oliva, A. Bonito, additional, Boter, E., additional, and Casas, P., additional
- Published
- 2018
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12. Completion and Test of the First ITER TF Coil Winding Pack by Europe
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Bonito-Oliva, Alessandro, primary, Aprili, P., additional, Soto, E. Barbero, additional, Batista, R., additional, Bellesia, B., additional, Robello, E. Boter, additional, Caballero, J., additional, Lino, M. Casas, additional, Cornelis, M., additional, Damone, M., additional, Harrison, R., additional, Cornella, J., additional, Kostopoulos, C., additional, Jimenez, M., additional, Libens, K., additional, Malpica, O., additional, Moreno, A., additional, Pellicer, N., additional, Poncet, L., additional, Tarrago, S., additional, Viladu, E., additional, Dormicchi, O., additional, Valle, N., additional, Lucas, J., additional, Felipe, A., additional, Francone, R., additional, Barbero, P., additional, Ribeiro, J. Silva, additional, Thyssen, E., additional, Devred, A., additional, Koczorowski, S., additional, and Mitchell, N., additional
- Published
- 2018
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13. Bacterial and fungal contamination risks in human oocyte and embryo cryopreservation: open versus closed vitrification systems
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Molina I, Mari M, Martínez JV, Novella-Maestre E, Pellicer N, and Pemán J
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vitrification systems ,liquid nitrogen ,Cross-contamination ,fungi ,open and closed devices ,bacteria - Abstract
Objective: To study the contamination risk in open and closed vitrification devices for oocyte/embryo cryopreservation by evaluating the contaminants present (bacteria and fungi) in the thaw medium and in liquid nitrogen (LN) storage containers. Design: Retrospective study. Setting: Human reproduction unit. Patient(s): None. Intervention(s): Retrospective study of vitrification device safety and LN sterility performed from July to October 2014. Main Outcome Measure(s): From each bank container, both open and closed vitrification devices, devitrification media and LN in the containers and as supplied by the company were evaluated for contaminants. An automated system and the corresponding susceptibility to antibiotics were used for bacteria identification. Fungus detection was performed by evaluating the colony morphology and their microscopic characteristics. Result(s): No bacteria or fungi were observed in any of the devitrification media regardless of the type of device used, nor in the LN supplied by the company. No fungi were observed in any of the LN samples tested. Stenotrophomonas maltophilia and Bacillus spp. were found in all oocyte/ embryo bank LN containers. There was no relationship between the number of samples or the time that each container had been used and the presence of microbiologic contaminants in the LN. At the container's bottom, Acinetobacter lwoffii, Alcaligenes faecalis ssp. faecalis, and Sphingomonas paucimobilis were found. Conclusion(s): Bacteria cross-contamination may not occur in oocyte/embryo banking in either open or closed storage devices. However, microorganisms can survive in LN. The bacteria cross-contamination risk is no greater for open than for closed containers. Storage containers should be cleaned periodically owing to the risk of lost straws or small particles of contaminated material. (C) 2016 by American Society for Reproductive Medicine.
- Published
- 2016
14. New methods to improve the safety assessment of cryopreserved ovarian tissue for fertility preservation in breast cancer patients
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Rodríguez-Iglesias B, Novella-Maestre E, Herraiz S, Díaz-García C, Pellicer N, and Pellicer A
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Breast cancer ,MGB1 ,ovarian cortex cryopreservation ,SBEM ,GCDFP15 - Abstract
Objective: To develop a novel molecular panel of markers to detect breast cancer (BC) disseminated malignant cells in ovarian tissue, and to improve the safety of ovarian tissue transplantation. Design: Experimental study. Setting: University hospital. Patient(s): Ten ovarian biopsies from healthy patients, 13 biopsies with diagnosed BC metastasis, and 4 biopsies from primary BC tumor for designing a diagnostic panel of BC cell contamination; 60 ovarian biopsies from BC patients undergoing fertility preservation for validating the panel. Animal(s): Female nude mice. Intervention(s): A novel panel for BC malignant cell detection by reverse-transcription polymerase chain reaction (RT-PCR), inmmunohistochemical analysis, in vitro invasion assay and xenotransplantation assayed in ovarian tissue from BC patients. Main Outcome Measure(s): Expression of GCDFP15, MGB1, SBEM, MUC1, WT-1, and NY-BR-01, selected as markers, assessed by quantitative RT-PCR in samples with confirmed BC metastasis. The most sensitive markers were confirmed by immunohistochemistry, and tested in vitro and in vivo. Result(s): GCDFP15, MGB1, and SBEM were the most sensitive and specific markers to detect BC metastatic cells when at least one was expressed by quantitative RT-PCR. The panel was validated in 60 patients and confirmed in an in vitro invasion assay, where no invasive cells were observed. Samples negative for BC cells cannot develop disease when xenografted. Conclusion(s): GCDFP15, MGB1, and SBEM were the most sensitive molecules to create a diagnostic panel for BC malignant cell contamination, which may make ovarian tissue cryopreservation and transplantation a safe technique for fertility preservation in BC patients. (C) 2015 by American Society for Reproductive Medicine.
- Published
- 2015
15. Dopamine agonist inhibits vascular endothelial growth factor protein production and secretion in granulosa cells
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Ferrero H, García-Pascual CM, Pellicer N, Simón C, Pellicer A, and Gómez R
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Granulosa cells ,OHSS ,Dopamine receptor-2 agonist ,VEGF ,Dopamine receptor 2 - Abstract
Background: Dopamine receptor 2 agonists (D2-ags) inhibit vascular endothelial growth factor (VEGF) secretion in luteinized granulosa cells (LGCs) both in vitro and in vivo. However, the mechanism of D2 regulation of the VEGF/ VEGF Receptor 2 (VEGFR-2) pathway remains to be elucidated. We sought to determine the effects of D2 signaling on VEGF transcription and translation in LGCs, with the expectation of identifying potential D2-ag-based therapies for ovarian hyperstimulation syndrome (OHSS). Findings: LGCs from egg donors were cultured with chorionic gonadotropin (hCG) in the presence of Actinomycin-D (ActD) or Brefeldin-A (BFA) to evaluate the effects of a D2-ag, cabergoline (Cb2), on VEGF secretion. The contribution of the conventional G(i)/G(o), G(z) and AKT/beta-Arrestin pathways in the VEGF regulation was assessed by adding pertussis toxin (PTX), phorbol 12-myristate 13-acetate (PMA), or wortmannin (WT). While Cb2 inhibited VEGF secretion by interfering with VEGF peptide translation and secretion, inhibition of conventional D2 transduction pathways did not reverse Cb2-mediated inhibition of VEGF secretion. Conclusions: The effects of D2-ag on VEGF translation and secretion are mediated by D2 signaling pathways that have yet to be described. We found that D2-ag inhibits VEGF secretion at the post-transcriptional level, suggesting that D2-ag treatment should be combined with therapies that inhibit VEGF transcription, such as the employment of LH or GnRH for triggering ovulation, to improve the efficacy of OHSS prevention.
- Published
- 2015
16. Sustainability in the wine sector: a case study from the Abruzzo region in Italy
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Valente, Francesca, Chiodo, Emilio, and SANJUAN PELLICER, N.
- Published
- 2013
17. Strategy for the Simulation of the ITER Toroidal Field Coil Case Welding Distortion With Finite-Element Method.
- Author
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Marc Jimenez, Bellesia, B., Cornell'a, J., Aprili, P., Barbero, E., Batista, R., Bonito Oliva, A., Boter, E., Casas, P., Cornelis, M., Damone, M., Kostopoulos, C., Libens, K., Heikkinen, S., Harrison, R., Hernandez, A., LoBue, A., Pellicer, N., Poncet, L., and Veredas, G.
- Subjects
SUPERCONDUCTORS ,SOLDER & soldering ,WELDING ,FINITE element method ,MAGNETIC fields - Abstract
The first European superconducting winding pack (WP) and the first set of coil cases [toroidal field coil cases (TFCC)] for ITER are going to be delivered in 2017. The TFCC are steel structures that provide structural integrity to the WP, contribute to neutron shielding capacity, provide support to operating forces, and offer interface connections with the rest of the ITER machine. The TFCC assembly is formed by four main parts: two sectors with U-shaped section and two closure plates, which, after being welded together, enclose the WP. Each TFCC weights about 150 t and presents a wall thickness from 60 to 120 mm. The presence of distortions when welding such thick structures is particularly problematic in these components, which require tight tolerances and include several interfaces with other parts of the machine. In order to compensate the distortions, extra material is present in the critical areas to allow postwelding machining. The amount of extra material has to be optimized to reduce machining time and therefore the cost of the manufacturing. Thus, the evaluation of the welding-caused distortions is essential in order to confirm the extra-material strategy. In this scenario, an experimental and simulation campaign has been set up to predict the deformation of the TFCC during welding. First, welding coupons were welded in representative configurations. Then, these data were used to build a preliminary finite element method (FEM) model tool, using ANSYS software, which was then benchmarked against a "blind test" coupon and three TFCC-like mock-ups of 1-m length. Finally, a full FEM model was constructed using the previous outputs and is currently under assessment to predict the deformation of the TFCC during the welding process. This paper presents the numerical and experimental activities carried out so far, being EnginSoft S.p.A. the developer of FEM models, SIMIC S.p.A. the responsible of welding processes and data acquisition, and Fusion for Energy the contractual and technical supervisor. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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18. Machining processes time calculating tool integrated in computer aided process planning (CAPP) for small and medium enterprises (SMEs)
- Author
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Blanch, R., primary, Pellicer, N., additional, G.-Romeu, M. L., additional, and Ciurana, J., additional
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- 2011
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19. Influence of Process Parameters and Electrode Geometry on Feature Micro-Accuracy in Electro Discharge Machining of Tool Steel
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Pellicer, N., primary, Ciurana, J., additional, and Ozel, T., additional
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- 2009
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20. Measurement of the external surface area of powders by a permeametric method
- Author
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Casal, J., primary, Arnaldos, J., additional, and Pellicer, N., additional
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- 1989
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21. Predicting risk of endometrial failure: a biomarker signature that identifies a novel disruption independent of endometrial timing in patients undergoing hormonal replacement cycles.
- Author
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Diaz-Gimeno P, Sebastian-Leon P, Spath K, Marti-Garcia D, Sanchez-Reyes JM, Vidal MDC, Devesa-Peiro A, Sanchez-Ribas I, Martinez-Martinez A, Pellicer N, Wells D, and Pellicer A
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- Humans, Female, Adult, Prospective Studies, Pregnancy, Biomarkers metabolism, Infertility, Female genetics, Infertility, Female therapy, Infertility, Female diagnosis, Infertility, Female metabolism, Pregnancy Rate, Hormone Replacement Therapy, Risk Assessment, Time Factors, Transcriptome, Embryo Transfer, Risk Factors, Luteal Phase metabolism, Gene Expression Profiling, Predictive Value of Tests, Endometrium metabolism, Endometrium drug effects, Endometrium pathology
- Abstract
Objective: To propose a new gene expression signature that identifies endometrial disruptions independent of endometrial luteal phase timing and predicts if patients are at risk of endometrial failure., Design: Multicentric, prospective study., Setting: Reproductive medicine research department in a public hospital affiliated with private fertility clinics and a reproductive genetics laboratory., Patients: Caucasian women (n = 281; 39.4 ± 4.8 years old with a body mass index of 22.9 ± 3.5 kg/m
2 ) undergoing hormone replacement therapy between July 2018 and July 2021. Endometrial samples from 217 patients met RNA quality criteria for signature discovery and analysis., Intervention(s): Endometrial biopsies collected in the mid-secretory phase., Main Outcome Measure(s): Endometrial luteal phase timing-corrected expression of 404 genes and reproductive outcomes of the first single embryo transfer (SET) after biopsy collection to identify prognostic biomarkers of endometrial failure., Results: Removal of endometrial timing variation from gene expression data allowed patients to be stratified into poor (n = 137) or good (n = 49) endometrial prognosis groups on the basis of their clinical and transcriptomic profiles. Significant differences were found between endometrial prognosis groups in terms of reproductive rates: pregnancy (44.6% vs. 79.6%), live birth (25.6% vs. 77.6%), clinical miscarriage (22.2% vs. 2.6%), and biochemical miscarriage (20.4% vs. 0%). The relative risk of endometrial failure for patients predicted as a poor endometrial prognosis was 3.3 times higher than those with a good prognosis. The differences in gene expression between both profiles were proposed as a biomarker, coined the endometrial failure risk (EFR) signature. Poor prognosis profiles were characterized by 59 upregulated and 63 downregulated genes mainly involved in regulation (17.0%), metabolism (8.4%), immune response, and inflammation (7.8%). This EFR signature had a median accuracy of 0.92 (min = 0.88, max = 0.94), median sensitivity of 0.96 (min = 0.91, max = 0.98), and median specificity of 0.84 (min = 0.77, max = 0.88), positioning itself as a promising biomarker for endometrial evaluation., Conclusion(s): The EFR signature revealed a novel endometrial disruption, independent of endometrial luteal phase timing, present in 73.7% of patients. This EFR signature stratified patients into 2 significantly distinct and clinically relevant prognosis profiles providing opportunities for personalized therapy. Nevertheless, further validations are needed before implementing this gene signature as an artificial intelligence (AI)-based tool to reduce the risk of patients experiencing endometrial failure., Competing Interests: Declaration of Interests P.D.-G., P.S.-L., and A.P. report planned European patent IVI RMA GLOBAL. K.S. has nothing to disclose. D.M.-G. has nothing to disclose. J.M.S.-R. has nothing to disclose. M.D.C.V. has nothing to disclose. A.D.-P. has nothing to disclose. I.S.-R. has nothing to disclose. A.M.-M. has nothing to disclose. N.P. has nothing to disclose. D.W. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
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22. The effectiveness of cervical cerclage in twin pregnancies with a mid-trimester short cervix: A retrospective cohort study.
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Ferro J, Diago V, Diago DM, Pellicer N, Olmo I, Vázquez S, Lara C, Perales A, and Serra V
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- Pregnancy, Infant, Newborn, Female, Humans, Pregnancy, Twin, Cervix Uteri, Retrospective Studies, Birth Weight, Pregnancy Outcome, Infant, Very Low Birth Weight, Cerclage, Cervical methods, Premature Birth prevention & control
- Abstract
Objective: To analyze the effectiveness of cerclage in twin pregnancies with a short cervix., Study Design: Retrospective cohort study performed in two University Institutions in Valencia (Spain) with two different protocols for the management of asymptomatic dichorionic diamniotic twin pregnancies with mid-trimester cervical length ≤ 25 mm: treatment with indomethacin, antibiotics and cerclage (cerclage group) (N = 43) versus expectant management (control group) (N = 37)., Results: The initial cervical length was similar in both groups but detection of a short cervix was performed earlier in the cerclage group (21.6 vs 24.1 weeks, p < 0.001). Women with cerclage had a greater pregnancy latency (12.5 vs. 7.7 weeks, p < 0.001); higher gestational age at delivery (34.1 vs. 31.8 weeks, p < 0.04); less spontaneous preterm birth (SPB) < 28 weeks (11.6 % vs 37.8 %, p < 0.009); higher birthweight (2145 vs 1733 g, p < 0.001); lower birthweight < 1500 g (12.5 % vs 40.0 %, p < 0.001); less admissions to the neonatal intensive care unit (NICU) (24.1 % vs 43.3 %, p < 0.03); shorter stay at NICU (25.6 vs 49.4 days, p < 0.02); lower respiratory distress requiring mechanical ventilation (14.9 % vs 36.5 %, p < 0.02); fewer patent ductus arteriosus (8.9 % vs 26.9 %, p < 0.008); and lower composite adverse neonatal outcome (26.6 % vs. 44.8 %, p < 0.03). Cerclage and gestational age at diagnosis were the only independent predictors of SPB < 32 and < 28 weeks by multivariate analysis. The cumulative data in the literature show promising beneficial effects of cerclage., Conclusion: Our data suggest that cerclage in asymptomatic twin pregnancies with a short cervix may reduce the earliest SPB and may improve neonatal outcome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2024
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23. Systemic changes induced by autologous stem cell ovarian transplant in plasma proteome of women with impaired ovarian reserves.
- Author
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Buigues A, Ramírez-Martin N, Martínez J, Pellicer N, Meseguer M, Pellicer A, and Herraiz S
- Subjects
- Pregnancy, Humans, Female, Aged, Proteome, Proteomics, Stem Cells metabolism, Ovarian Reserve, Primary Ovarian Insufficiency therapy, Primary Ovarian Insufficiency metabolism
- Abstract
Patients with poor ovarian response (POR) and premature ovarian insufficiency (POI) are challenging to treat, with oocyte donation remaining as the only feasible option to achieve pregnancy in some cases. The Autologous stem cell ovarian transplantation (ASCOT) technique allows follicle development, enabling pregnancies and births of healthy babies in these patients. Previous results suggest that growth factors and cytokines secreted by stem cells are partially responsible for their regenerative properties. Indeed, ASCOT beneficial effects associate with the presence of different bone marrow derived stem cell- secreted factors in plasma. Therefore, the aim of this study was to assess whether ASCOT induce any modifications in the plasma proteomic profile of patients with impaired ovarian reserves. Discriminant analysis highlighted clear distinctions between the plasma proteome before (PRE), during stem cell mobilization and collection (APHERESIS) and three months after ASCOT (POST) in patients with POR and POI. Both the stem cell mobilization and ASCOT technique induced statistically significant modifications in the plasma composition, reversing some age-related protein expression changes. In the POR group, functional analysis revealed an enrichment in processes related to the complement cascade, immune system, and platelet degranulation, while in the POI group, enriched processes were also associated with responses to oxygen-containing compounds and growth hormones, and blood vessel maturation. In conclusion, our findings highlight the potential proteins and biological processes that may promote the follicle activation and growth observed after ASCOT. Identifying plasma proteins that regenerate aged or damaged ovaries could lead to more effective, targeted and/or preventive therapies for patients.
- Published
- 2023
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24. Deciphering reproductive aging in women using a NOD/SCID mouse model for distinct physiological ovarian phenotypes.
- Author
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Marchante M, Ramirez-Martin N, Buigues A, Martinez J, Pellicer N, Pellicer A, and Herraiz S
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- Humans, Female, Mice, Animals, Mice, SCID, Mice, Inbred NOD, Mice, Inbred C57BL, Disease Models, Animal, Proteomics, Aging physiology
- Abstract
Female fertility is negatively correlated with age, with noticeable declines in oocyte quantity and quality until menopause. To understand this physiological process and evaluate human approaches for treating age-related infertility, preclinical studies in appropriate animal models are needed. Thus, we aimed to characterize an immunodeficient physiological aging mouse model displaying ovarian characteristics of different stages during women's reproductive life. NOD/SCID mice of different ages (8-, 28-, and 36-40-week-old) were employed to mimic ovarian phenotypes of young, Advanced Maternal Age (AMA), and old women (~18-20-, ~36-38-, and >45-years-old, respectively). Mice were stimulated, mated, and sacrificed to recover oocytes and embryos. Then, ovarian reserve, follicular growth, ovarian stroma, mitochondrial dysfunction, and proteomic profiles were assessed. Age-matched C57BL/6 mice were employed to cross-validate the reproductive outcomes. The quantity and quality of oocytes were decreased in AMA and Old mice. These age-related effects associated spindle and chromosome abnormalities, along with decreased developmental competence to blastocyst stage. Old mice had less follicles, impaired follicle activation and growth, an ovarian stroma inconducive to growth, and increased mitochondrial dysfunctions. Proteomic analysis corroborated these histological findings. Based on that, NOD/SCID mice can be used to model different ovarian aging phenotypes and potentially test human anti-aging treatments.
- Published
- 2023
- Full Text
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25. Reproductive outcomes of oocyte donation in patients with uterine Müllerian anomalies.
- Author
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Muñoz E, Fernández I, Pellicer N, Mariani G, Pellicer A, and Garrido N
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- Pregnancy, Humans, Female, Oocyte Donation adverse effects, Retrospective Studies, Pregnancy Rate, Uterus, Live Birth, Fertilization in Vitro adverse effects, Abortion, Spontaneous epidemiology, Abortion, Spontaneous etiology, Infertility, Female diagnosis, Infertility, Female epidemiology, Infertility, Female therapy
- Abstract
Objective: To evaluate live-birth rates per embryo transfer in patients with uterine Müllerian anomalies (UMAs). Secondary objectives were to compare reproductive outcomes between the normal uterus group, the different UMA types, and UMA subgroups with and without required surgery., Design: This retrospective study compared two cohorts, one with UMAs and other with normal uteri of our oocyte donation program at 12 Instituto Valenciano De Infertilidad/Reproductive Medicine Associates University affiliated clinics from January 2000 to 2020. The oocyte donation reduces confounding because of differences in embryo quality. The primary outcome was the live-birth rate per embryo transfer. Secondary outcomes included the rates of implantation, clinical pregnancy, miscarriage, and ongoing pregnancy. We calculated odds ratios with 95% confidence intervals., Patients: Infertile women undergoing oocyte donation with UMAs., Intervention: None., Main Outcome Measures: The rates of implantation, clinical pregnancy, miscarriage, ongoing pregnancy, and live birth., Results: We analyzed 58,337 cycles of oocyte donation: 57,869 patients had no uterine malformation, and 468 women had UMAs. Compared with patients with normal uteri, patients with UMAs had lower rates of live births (36.67% [32.84-40.65] vs. 38.1% [95% confidence intervals {CI}: 37.82-38.42]) and ongoing pregnancy (39.74% [35.93-43.66] vs. 41.5% [41.24-41.83]). The miscarriage rate was higher in patients with UMAs (19.5% [16.55-22.85] vs. 16.6% [16.47-16.92]). Specifically, patients with a unicornuate uterus (n=29) had lower rates of implantation (24.07% [13.49-37.64] vs. 42.85% [95% CI: 42.6-43.09]), pregnancy (41.86% [27.01-57.87] vs. 59.51% [59.22-59.81]), ongoing pregnancy (16.67% [6.97-31.36] vs. 41.54% [41.24-41.83]), and live births (16.67% [6.97-31.36] vs. 38.12% [37.83-38.42]). In addition, patients with a partial septate uterus (n=91) had a higher miscarriage rate (26.50% [18.44-34.89] vs. 16.7% [16.47-16.92]). Compared with the normal uterus group, the live-birth rates were lower in the UMA without surgery group (33.09% [27.59-38.96] vs. 38.12% [37.83-38.42])., Conclusion: Among patients who received embryos derived from donated oocytes, live birth and ongoing pregnancy rates were lower in patients with UMAs compared with patients with normal uteri. A higher miscarriage rate was found in patients with UMAs. Patients with a unicornuate uterus had worse reproductive outcomes. Our results show that the uterus is less competent in patients with UMAs., Trial Registration: This study was registered at clinicaltrial.gov (NCT04571671)., Competing Interests: Declaration of interests E.M. has nothing to disclose. I.F. has nothing to disclose. N.P. has nothing to disclose. G.M. has nothing to disclose. A.P. has nothing to disclose. N.G. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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26. Deciphering a shared transcriptomic regulation and the relative contribution of each regulator type through endometrial gene expression signatures.
- Author
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Parraga-Leo A, Sebastian-Leon P, Devesa-Peiro A, Marti-Garcia D, Pellicer N, Remohi J, Dominguez F, and Diaz-Gimeno P
- Subjects
- Female, Humans, Transcriptome, Progesterone, Endometrium, Estrogens, MicroRNAs genetics, Infertility
- Abstract
Backgorund: While various endometrial biomarkers have been characterized at the transcriptomic and functional level, there is generally a poor overlap among studies, making it unclear to what extent their upstream regulators (e.g., ovarian hormones, transcription factors (TFs) and microRNAs (miRNAs)) realistically contribute to menstrual cycle progression and function. Unmasking the intricacies of the molecular interactions in the endometrium from a novel systemic point of view will help gain a more accurate perspective of endometrial regulation and a better explanation the molecular etiology of endometrial-factor infertility., Methods: An in-silico analysis was carried out to identify which regulators consistently target the gene biomarkers proposed in studies related to endometrial progression and implantation failure (19 gene lists/signatures were included). The roles of these regulators, and of genes related to progesterone and estrogens, were then analysed in transcriptomic datasets compiled from samples collected throughout the menstrual cycle (n = 129), and the expression of selected TFs were prospectively validated in an independent cohort of healthy participants (n = 19)., Results: A total of 3,608 distinct genes from the 19 gene lists were associated with endometrial progression and implantation failure. The lists' regulation was significantly favoured by TFs (89% (17/19) of gene lists) and progesterone (47% (8 /19) of gene lists), rather than miRNAs (5% (1/19) of gene lists) or estrogen (0% (0/19) of gene lists), respectively (FDR < 0.05). Exceptionally, two gene lists that were previously associated with implantation failure and unexplained infertility were less hormone-dependent, but primarily regulated by estrogen. Although endometrial progression genes were mainly targeted by hormones rather than non-hormonal contributors (odds ratio = 91.94, FDR < 0.05), we identified 311 TFs and 595 miRNAs not previously associated with ovarian hormones. We highlight CTCF, GATA6, hsa-miR-15a-5p, hsa-miR-218-5p, hsa-miR-107, hsa-miR-103a-3p, and hsa-miR-128-3p, as overlapping novel master regulators of endometrial function. The gene expression changes of selected regulators throughout the menstrual cycle (FDR < 0.05), dually validated in-silico and through endometrial biopsies, corroborated their potential regulatory roles in the endometrium., Conclusions: This study revealed novel hormonal and non-hormonal regulators and their relative contributions to endometrial progression and pathology, providing new leads for the potential causes of endometrial-factor infertility., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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27. Bioaccumulation of Non-Essential Trace Elements Detected in Women's Follicular Fluid, Urine, and Plasma Is Associated with Poor Reproductive Outcomes following Single Euploid Embryo Transfer: A Pilot Study.
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Palomar A, Gonzalez-Martin R, Quiñonero A, Pellicer N, Fernandez-Saavedra R, Rucandio I, Fernandez-Martinez R, Conde-Vilda E, Quejido AJ, Zuckerman C, Whitehead C, Scott RT, and Dominguez F
- Subjects
- Male, Female, Humans, Pilot Projects, Bioaccumulation, Barium, Follicular Fluid, Prospective Studies, Semen, Embryo Transfer, Aneuploidy, Trace Elements
- Abstract
This study aims to determine the association of non-essential trace elements present in follicular fluid, plasma, and urine with reproductive outcomes of women undergoing intracytoplasmic sperm injection (ICSI), preimplantation genetic testing for aneuploidies (PGT-A) and single frozen euploid embryo transfer (SET/FET). This single-center, prospective cohort study included sixty women undergoing ICSI with PGT-A and SET/FET between 2018 and 2019. Urine, plasma and follicular fluid samples were collected on the vaginal oocyte retrieval day to simultaneously quantify ten non-essential trace elements (i.e., Ba, Sr, Rb, Sn, Ti, Pb, Cd, Hg, Sb, and As). We found several associations between the levels of these non-essential trace elements and clinical IVF parameters. Specifically, the increased levels of barium in follicular fluid were negatively associated with ovarian function, pre-implantation development and embryo euploidy, while elevated strontium concentrations in this biofluid were negatively associated with impaired blastulation and embryo euploidy. Elevated plasma strontium levels were negatively associated with ovarian function, fertilization and blastulation. Enhanced presence of other trace elements in plasma (i.e., rubidium and arsenic) were associated with a diminished ovarian function and limited the number of recovered oocytes, mature oocytes and zygotes, respectively. Fully adjusted models suggested significantly lower odds of achieving a live birth when increased concentrations of barium and tin were found in urine.
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- 2023
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28. Preimplantation genetic testing for aneuploidy is not related to adverse obstetric and neonatal outcomes in singleton pregnancies.
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Cozzolino M, Cecchino GN, Garcia Velasco JA, Pellicer N, Galliano D, and Pellicer A
- Subjects
- Female, Humans, Infant, Newborn, Pregnancy, Retrospective Studies, Risk Assessment, Male, Aneuploidy, Genetic Testing methods, Pregnancy Outcome epidemiology
- Abstract
Study Question: What is the potential impact of preimplantation genetic testing for aneuploidy (PGT-A) on obstetric and neonatal outcomes?, Summary Answer: PGT-A is not associated with increased rates of adverse maternal and neonatal outcomes in singleton pregnancies following IVF/ICSI cycles., What Is Known Already: PGT-A pregnancies may be associated with increased risks of lower birthweight, preterm delivery, and hypertensive disorders compared with natural pregnancies. In a recent meta-analysis, the overall obstetric and neonatal outcomes of PGT-A pregnancies were favorable compared with those of IVF/ICSI pregnancies, although PGT-A pregnancies were associated with a higher risk of hypertensive disorders., Study Design, Size, Duration: A multicenter retrospective cohort study was performed in University-affiliated infertility centers. Single live births following IVF/ICSI between October 2016 and January 2021 were included in the study., Participants/materials, Setting, Methods: A total of 7146 live births after single embryo transfers with (n = 3296) or without (n = 3850) PGT-A were included. The primary outcome was pre-eclampsia and secondary outcomes included gestational diabetes, low birthweight and very low birthweight, cesarean section delivery, emergency cesarean section, as well as preterm birth, birthweight, congenital abnormalities, neonatal sex, Apgar score at 5 min, and neonatal intensive care unit admission. In a subgroup analysis, were included only blastocysts screened with next-generation sequencing (NGS)., Main Results and the Role of Chance: Univariate analysis showed that pre-eclampsia, cesarean section incidence, and low Apgar score were higher in women undergoing PGT-A. However, after performing multivariate logistic and linear regression models accounting for many possible confounders, pregnancies that had been conceived after embryo biopsy showed no increase in adverse obstetric and neonatal outcomes. The subgroup analysis including patients with blastocysts screened by NGS showed a decreased risk of preterm birth in the group undergoing PGT-A., Limitations, Reasons for Caution: Caution should be used when interpreting the data because of its limitations, mainly related to its retrospective design. Although this is a large multicenter study, data acquisition included self-reporting questionnaires, and the deliveries occurred in different institutions with distinct protocols., Wider Implications of the Findings: The current study does not show any major adverse clinical outcomes after PGT-A. Efforts should be made to promote good quality research on embryo biopsy in terms of neonatal and obstetric outcomes, as well as its long-term consequences., Study Funding/competing Interest(s): No specific funding was obtained for this study. The authors declare no conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2023
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29. Increased cytotoxic natural killer cells in the endometrium alone cannot be considered the immunological cause of recurrent miscarriage.
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Cuadrado-Torroglosa I, Pacheco A, Barrio A, Garrido N, Aparicio P, Pellicer N, García-Velasco JA, and Alecsandru D
- Subjects
- Female, Humans, Genotype, HLA-C Antigens metabolism, Prospective Studies, Receptors, KIR genetics, Pregnancy, Abortion, Habitual etiology, Abortion, Habitual immunology, Endometrium pathology, Killer Cells, Natural pathology
- Abstract
Objective: To study the distribution and gene expression of endometrial immune cell populations, especially natural killer (NK) subsets, between assisted reproductive technology patients and healthy donors and explore a possible relationship of these results with patients' killer cell immunoglobulin-like receptor (KIR) genotypes and KIR-human antigen leukocyte-C (HLA-C) binding., Design: Prospective observational cohort study., Setting: Clinic and university laboratories., Patient(s): Participants included 39 women with recurrent miscarriages who had undergone in vitro fertilization cycles with donated oocytes and 21 healthy oocyte donors with proven fertility., Intervention(s): Endometrial biopsy samples were collected from both patients and donors, and the KIR genotypes of the assisted reproductive technology patients were analyzed., Main Outcome Measure(s): Endometrial gene expression (cluster of differentiation [CD] antigens and anti-inflammatory and proinflammatory interleukins) and the number and percentage of regulatory T and NK cell populations in patients and donors were determined. Subsequently, the results obtained were categorized in the group of patients by KIR genotype. Killer cell immunoglobulin-like receptor-HLA-C binding was also examined in patients, considering their KIRs., Result(s): A higher percentage of CD56
dim CD16+ NK cells were observed in patients than those in healthy donors. Nevertheless, when categorizing patients by KIR genotype and comparing the KIR AA (35.9%), AB (43.6%), and BB (20.5%) groups, no statistically significant difference was observed in either endometrial gene expression or any of the immune cell populations analyzed. Finally, no differences in binding between KIR and HLA-C molecules were registered among these 3 sets of patients., Conclusion(s): The reported increase in the number of NK cells with a cytotoxic profile in the endometrium of women with a history of recurrent miscarriages cannot alone explain these events because no relationship is observed between such cellular increase and the KIR genotypes, which individually, and in combination with the different HLA-C alleles, have also been associated, by previous studies, with negative reproductive outcomes., Clinical Trial Registration Number: 1405-MAD-025-JG., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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30. The Impact of Essential Trace Elements on Ovarian Response and Reproductive Outcomes following Single Euploid Embryo Transfer.
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Gonzalez-Martin R, Palomar A, Quiñonero A, Pellicer N, Fernandez-Saavedra R, Conde-Vilda E, Quejido AJ, Whitehead C, Scott RT Jr, and Dominguez F
- Subjects
- Pregnancy, Female, Humans, Copper analysis, Manganese, Molybdenum, Lithium, Zinc analysis, Chromium analysis, Embryo Transfer, Trace Elements
- Abstract
Essential trace elements are required in extremely small amounts and obtained through diet. This research focuses on detecting major trace elements in different biofluids of sixty women undergoing ICSI with PGT-A and SET/FET at IVI-RMA, New Jersey, and assessing their impact on their IVF outcomes. Urine, plasma, and follicular fluid samples were collected on the vaginal oocyte retrieval day to measure the concentrations of eight essential trace elements (copper, zinc, molybdenum, lithium, selenium, manganese, chromium, and iron) using ICP-MS. After analysis, ovarian response and preimplantation outcomes had significant positive associations with both copper alone and the copper/zinc ratio in the follicular fluid and plasma, in addition to plasma manganese. Alternatively, elevated follicular fluid lithium concentrations were significantly associated with poor preimplantation outcomes while the urinary molybdenum concentration was significantly associated with a lower probability of implantation, clinical pregnancy, and live birth. Urinary lithium and chromium concentrations were significantly associated with a lower probability of achieving a live birth. Our results suggest that the essential trace elements present in follicular fluid, plasma, and urine of women are directly associated with their reproductive outcomes, with copper and manganese exerting positive effects and lithium and molybdenum exerting negative effects.
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- 2023
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31. Phytoestrogens Present in Follicular Fluid and Urine Are Positively Associated with IVF Outcomes following Single Euploid Embryo Transfer.
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Gonzalez-Martin R, Palomar A, Quiñonero A, Pellicer N, Zuckerman C, Whitehead C, Scott RT Jr, and Dominguez F
- Subjects
- Pregnancy, Female, Humans, Follicular Fluid, Prospective Studies, Embryo Transfer methods, Pregnancy Rate, Retrospective Studies, Fertilization in Vitro methods, Phytoestrogens
- Abstract
The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and IVF outcomes continues to be hotly debated. In this prospective cohort study, 60 women attending IVI-RMA New Jersey undergoing IVF with single frozen embryo transfer (SET/FET) of good-quality euploid blastocyst after PGT-A analysis were recruited. Concentrations of two phytoestrogens (daidzein and genistein) in follicular fluid (FF) and urine (U) were measured by UPLC-MSMS, both collected on vaginal oocyte retrieval day. These measurements correlated with IVF clinical outcomes. In models adjusted for age, BMI, race/ethnicity, and smoking status, higher FF phytoestrogen concentrations were significantly associated with higher serum estradiol, enhanced probability of implantation, clinical pregnancy, and live birth. Moreover, higher urine phytoestrogen concentrations were significantly associated with improved oocyte maturation and fertilization potential and increased probability of clinical pregnancy and live birth. Finally, higher FF and urine phytoestrogen concentrations were associated with a higher probability of live birth from a given IVF cycle. Our results suggest that dietary phytoestrogens improved reproductive outcomes of women undergoing IVF treatment. However, additional prospective studies are needed to optimize the use of phytoestrogens to further enhance reproductive outcomes and/or protect against reproductive insults.
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- 2023
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32. Single intraovarian dose of stem cell- and platelet-secreted factors mitigates age-related ovarian infertility in a murine model.
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Marchante M, Buigues A, Ramirez-Martin N, Martinez J, Pellicer N, Pellicer A, and Herraiz S
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- Animals, Female, Humans, Mice, Disease Models, Animal, Oocytes, Proteomics, Stem Cells, Random Allocation, Infertility, Ovary
- Abstract
Background: Systemic administration of soluble factors from bone marrow-derived stem cells combined with activated platelet-rich plasma (SC-PRP) restored ovarian function, mediated through paracrine signaling, in murine models of chemotherapy-induced ovarian damage and human tissue from poor responder patients. However, the effects against age-related infertility and the efficacy of local administration have not been evaluated yet., Objective: This study aimed to assess whether a single intraovarian dose of stem cells combined with activated platelet-rich plasma can recover ovarian function, oocyte quality, and developmental competence in older mice., Study Design: The effects of stem cells combined with activated platelet-rich plasma against age-related infertility were assessed following controlled ovarian stimulation in an aging murine model reproducing 3 physiological stages of women's reproductive life, namely young, advanced maternal age, and menopausal (n=12 animals per group). Female mice were randomized to receive a single intraovarian injection (10 μL/ovary) of either saline, activated platelet-rich plasma, or stem cells combined with activated platelet-rich plasma. Seven days later, the mice were stimulated, naturally mated, and sacrificed to harvest their ovaries for histologic assessment and molecular analysis and their oviducts to evaluate oocyte maturation and to assess early embryo development., Results: A single intraovarian injection of stem cells combined with activated platelet-rich plasma promoted follicle activation and development in young, advanced maternal age, and old mice. Furthermore, stem cells combined with activated platelet-rich plasma rescued fertility in older mice by enhancing the quantity and quality of ovulated mature oocytes and supporting early embryo development to the blastocyst stage in all the evaluated ages. These fertility outcomes were positively associated with mitochondrial quality, treatment-increased mitochondrial DNA copy numbers, and reduced oxidative damage and apoptosis. Finally, the effects observed by histologic analysis were supported at the proteomic level. Functional proteomic analyses revealed molecular mechanisms involved in oocyte maturation and quality, mitochondrial function, and recovery of the ovarian stroma., Conclusion: Bone marrow-derived stem cells combined with activated platelet-rich plasma is a promising treatment with the potential to improve the reproductive outcomes of women with age-related infertility, exceeding the restorative effects of platelet-rich plasma alone. Although further research in human ovarian samples is still required, the autologous nature of stem cell factors collected by noninvasive mobilization, their combination with platelet-rich plasma, and the local administration route suggest that stem cells combined with activated platelet-rich plasma treatment could be a potentially effective and safe application for future clinical practice., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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33. Ovarian rescue in women with premature ovarian insufficiency: facts and fiction.
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Pellicer N, Cozzolino M, Diaz-García C, Galliano D, Cobo A, Pellicer A, and Herraiz S
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- Humans, Female, Ovarian Follicle physiology, Oocytes, Primary Ovarian Insufficiency therapy, Menopause, Premature, Ovarian Diseases, Ovarian Reserve physiology
- Abstract
The ovary has a comparatively short functional lifespan compared with other organs, and genetic and pathological injuries can further shorten its functional life. Thus, preserving ovarian function should be considered in the context of women with threats to ovarian reserve, such as ageing, premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR). Indeed, one-third of women with POI retain resting follicles that can be reactivated to produce competent oocytes, as proved by the in-vitro activation of dormant follicles. This paper discusses mechanisms and clinical data relating to new therapeutic strategies using ovarian fragmentation, stem cells or platelet-rich plasma to regain ovarian function in women of older age (>38 years) or with POI or DOR. Follicle reactivation techniques show promising experimental outcomes and have been successful in some cases, when POI is established or DOR diagnosed; however, there is scarce clinical evidence to warrant their widespread clinical use. Beyond these contexts, also discussed is how new insights into the biological mechanisms governing follicular dynamics and oocyte competence may play a role in reversing ovarian damage, as no technique modifies oocyte quality. Additional studies should focus on increasing follicle number and quality. Finally, there is a small but important subgroup of women lacking residual follicles and requiring oocyte generation from stem cells., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
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34. Pituitary suppression with GnRH agonists before ART may be insufficient to treat women with severe adenomyosis.
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Cozzolino M, Pellicer N, Galliano D, and Pellicer A
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- Pregnancy, Humans, Female, Letrozole therapeutic use, Aromatase Inhibitors therapeutic use, Ovulation Induction, Pregnancy Rate, Estrogens, Estradiol, Fertilization in Vitro, Gonadotropin-Releasing Hormone, Adenomyosis drug therapy
- Abstract
Research Question: Does aromatase inhibitor improve IVF outcomes by reducing local oestrogen production in patients with adenomyosis undergoing long-term gonadotrophin-releasing hormone agonist (GnRHa) treatment?, Design: Four patients with severe adenomyosis who failed to improve after long-term treatment (≥3 months) with depot GnRHa received treatment with an aromatase inhibitor for 21 days. Blood oestradiol concentrations were monitored after GnRHa treatment both before and after treatment with an aromatase inhibitor. Women received a transfer of IVF autologous or donor oocytes. Pregnancy and ongoing pregnancy rates were the primary outcomes. Blood oestradiol concentration after treatment with an aromatase inhibitor was a secondary outcome., Results: Patients with severe adenomyosis presented with hyperestrogenism due to local production from the lesions even after long-term treatment with GnRHa. Treatment with an aromatase inhibitor reduced hyperestrogenism and improved clinical outcomes in adenomyosis patients who have experienced previous embryo transfer failures., Conclusion: Women with severe adenomyosis would benefit from letrozole or a combination of GnRHa plus letrozole before receipt of treatment with assisted reproductive technology. For women with severe adenomyosis, GnRHa treatment alone may be insufficient to suppress oestrogen production by adenomyotic lesions. Thus, it should be mandatory to test for oestradiol concentrations in patients with severe adenomyosis who have received long-term GnRHa treatment. Also, GnRHa may not always be the sole strategy for medical management of adenomyotic lesions. Letrozole is safe and can improve IVF outcomes for patients with adenomyosis., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
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35. Adjustment of progesterone administration after endometrial transcriptomic analysis does not improve reproductive outcomes in women with adenomyosis.
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Juárez-Barber E, Cozzolino M, Corachán A, Alecsandru D, Pellicer N, Pellicer A, and Ferrero H
- Subjects
- Pregnancy, Humans, Female, Progesterone metabolism, Transcriptome, Retrospective Studies, Cohort Studies, Embryo Implantation physiology, Endometrium metabolism, Abortion, Spontaneous, Adenomyosis complications, Adenomyosis drug therapy, Adenomyosis genetics
- Abstract
Research Question: Do patients with adenomyosis present a dysregulated endometrial receptivity that can be reversed with personalized embryo transfer (PET) by transcriptomic-based progesterone adjustment, improving IVF outcomes?, Design: A multicentre, retrospective, cohort study that transcriptomically analysed the endometrial receptivity of the endometrium in patients with adenomyosis (n = 81) and healthy women (n = 231). Subsequently, implantation, biochemical and clinical miscarriage, and live birth rates between adenomyosis patients with one previous implantation failure using donor oocytes who received (n = 59) or did not receive (n = 66) PET based on endometrial receptivity, were observed to evaluate if adjusted progesterone improves reproductive outcomes of adenomyosis patients., Results: Patients with adenomyosis significantly presented an altered endometrial receptivity (non-receptive) compared with healthy patients (53.1% versus 37.2%, P = 0.0179), elevating the risk of adenomyosis patients having a non-receptive endometrium 42.59% higher (95% CI 41.50 to 44.45). No significant differences were found in implantation (62.7% versus 78.8%, P = 0.0514), biochemical (13.5% versus 3.9%, P = 0.1223) and clinical (10.8% versus 15.4%, P = 0.7543) miscarriage, or live birth rates (75.7% versus 80.8%, P = 0.6066), in patients with PET compared with those without PET., Conclusions: Women with adenomyosis presented an altered expression of genes involved in decidualization, and a higher rate of non-receptive endometrial statuses than controls. Although progesterone is indispensable for implantation, adjusting progesterone before PET, using endometrial transcriptomic signatures, does not improve IVF outcomes in patients with adenomyosis. Other molecular mechanisms beyond progesterone regulation may be involved in implantation failure., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2023
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36. Endometrial gene expression differences in women with coronavirus disease 2019.
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de Miguel-Gómez L, Sebastián-León P, Romeu M, Pellicer N, Faus A, Pellicer A, Díaz-Gimeno P, and Cervelló I
- Subjects
- Female, Humans, Pilot Projects, Endometrium pathology, Transcriptome, RNA, COVID-19 diagnosis, COVID-19 genetics
- Abstract
Objective: To study the potential effect of coronavirus disease (COVID-19) on the endometrial transcriptome of affected, symptomatic women for the detection of altered gene expression., Design: Pilot study of the endometrial transcriptomes of women manifesting COVID-19 compared with those of women without COVID-19 undergoing hysteroscopic procedures for benign gynecologic disorders using RNA sequencing., Setting: Hospital and university laboratories., Patient(s): Women with (n = 14) and without a COVID-19 (n = 10) diagnosis based on a nasopharyngeal swab analysis using quantitative reverse-transcription polymerase chain reaction. The endometrium of the patients with COVID-19 had previously been tested for severe acute respiratory syndrome coronavirus 2 infection, revealing the absence of the virus in this tissue., Intervention(s): Endometrial biopsy sample collection., Main Outcomes Measure(s): Endometrial gene expression and functional analysis of symptomatic patients with COVID-19 vs. individuals without the infection., Result(s): The systemic disease COVID-19 altered endometrial gene expression in 75% of the women, with the patients exhibiting a preponderance of 163 up-regulated (e.g., UTS2, IFI6, IFIH1, and BNIP3) and 72 down-regulated genes (e.g., CPZ, CDH3, and IRF4) (false discovery rate<0.05). A total of 161 dysregulated functions (36 up-regulated and 125 down-regulated) were typically enriched in the endometria of the patients with COVID-19, including up-regulation in pathways involved in the development of immune responses to viruses and cytokine inflammation, reflecting elicitation of a COVID-19 response pathway., Conclusion(s): Coronavirus disease 2019 affects endometrial gene expression despite the absence of severe acute respiratory syndrome coronavirus 2 RNA in endometrial tissues., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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37. Hysterosalpingography is obsolete: hysterosalpingo-contrast foam sonography should be the alternative.
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Ramos J, Pellicer N, and Fernández-Sánchez M
- Subjects
- Female, Humans, Hysterosalpingography methods, Fallopian Tube Patency Tests methods, Fallopian Tubes diagnostic imaging, Ultrasonography methods, Laparoscopy, Infertility, Female diagnostic imaging
- Abstract
Current evidence suggests that the hysterosalpingo-foam sonography test (HyFoSy) has emerged as a new option to make Fallopian tube assessment easier. Several published studies have compared the different types of tubal patency test available with the accepted gold standard, laparoscopy and dye, endorsing the advantages of HyFoSy over the other techniques. However, the authors wonder why professionals nowadays do not indicate HyFoSy as a first-choice diagnostic tool, with X-ray hysterosalpingography as still the most recommended procedure in outpatients. The aim of this article is to highlight the latest updates on this topic in order to raise awareness of the benefits of hysterosalpingo-contrast sonography as well as provide some tips for performing HyFoSy to obtain the maximum information in a single consultation., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2022
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38. Undetectable viral RNA from SARS-CoV-2 in endometrial biopsies from women with COVID-19: a preliminary study.
- Author
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de Miguel-Gómez L, Romeu M, Castells-Ballester J, Pellicer N, Faus A, Mullor JL, Pellicer A, and Cervelló I
- Subjects
- Biopsy, Endometrium, Female, Humans, RNA, Viral, COVID-19, SARS-CoV-2
- Published
- 2022
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39. The Use of Vaginal Lubricants and Ultrasound Gels Can have Deleterious Effects on Sperm Function.
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Soriano MJ, Botella IM, Sadeghi S, Rios AP, Balasch S, Luján S, Pellicer N, and Rubio JM
- Abstract
Context: Some vaginal lubricants and ultrasound gels are known to be detrimental to sperm function and therefore could negatively affect fertility., Aims: The aim of the current study was to develop a sperm motility index (SMI) to test the sperm toxicity of ultrasound gels and vaginal lubricants used in reproductive medicine., Settings and Design: Two ultrasound gels (Aquasonic
® and Kefus® ) and five vaginal lubricants (Vaginesil™, Velastisa® , K-Y Jelly® , Control® , and Durex® ) were studied. Three different concentrations (1%, 5%, and 10%) of each lubricant were tested., Subjects and Methods: SMI was calculated dividing the percentage of progressively motile sperm in each tested gel by that in the control at 0.5, 1, 2, and 24 h of incubation at 5% of CO2 and 37°C. SMI values <0.75 indicate sperm toxicity., Statistical Analysis Used: The main outcome measured was SMI for each concentration and time of incubation., Results: Only Durex® did not show any deleterious effect on sperm quality. The rest of lubricants presented different degrees of toxicity. Vaginesil™ resulted in toxic for all concentrations and incubation periods (SMI < 0.12). Control® and Velastisa® presented toxicity at 10% after 2 h, while K-Y Jelly® showed toxicity at 10% from 1 h of incubation. Regarding ultrasound gels, Aquasonic® showed toxic effects after only 0.5 h (SMI = 0.70 ± 0.15), while Kefus® showed slightly toxic effects after 2 h (SMI 0.69 ± 0.07)., Conclusions: SMI is an accurate tool to evaluate sperm toxicity. One of the main strengths of the article is the inclusion of representative semen samples and known products used worldwide. This study has a relevant clinical translation since it highlights the importance of evaluating the possible sperm toxicity of simple products used in reproductive medicine., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Human Reproductive Sciences.)- Published
- 2021
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40. Use of dopamine agonists to target angiogenesis in women with endometriosis.
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Pellicer N, Galliano D, Herraiz S, Bagger YZ, Arce JC, and Pellicer A
- Subjects
- Cabergoline, Dopamine Agonists therapeutic use, Endometrium, Female, Humans, Pregnancy, Vascular Endothelial Growth Factor A, Endometriosis drug therapy
- Abstract
Endometriosis requires medical management during a woman's reproductive years. Most treatments aim to create a hypoestrogenic milieu, but for patients wishing to conceive, drugs that allow normal ovarian function are needed. Targeting angiogenesis, a hallmark of the disease, using dopamine agonists (DAs) is a promising strategy for endometriosis treatment. Herein, we review experimental and clinical data that investigate this concept. In experimental models of endometriosis, DAs (bromocriptine, cabergoline, quinagolide) downregulate proangiogenic and upregulate antiangiogenic pathways in inflammatory, endothelial and endometrial cells, blocking cellular proliferation and reducing lesion size. Impaired secretion of vascular endothelial growth factor (VEGF) and inactivation of its receptor type-2 are key events. VEGF inhibition also reduces nerve fiber density in lesions. In humans, quinagolide shows similar effects on lesions, and DAs reduce pain and endometrioma size. Moreover, a 20-fold downregulation of Serpin-1, the gene that encodes for plasminogen activator inhibitor 1 (PAI-1), has been observed after DAs treatment. Pentoxifylline, a PAI-1, increases pregnancy rates in women with endometriosis. Thus, the data support the use of DAs in the medical management of endometriosis to reduce lesion size and pain while maintaining ovulation. A combined approach of DAs and pentoxifylline is perhaps a smart way of targeting the disease from a completely different angle than current medical treatments., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
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41. The differential diagnoses of uterine leiomyomas and leiomyosarcomas using DNA and RNA sequencing.
- Author
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Mas A, Alonso R, Garrido-Gómez T, Escorcia P, Montero B, Jiménez-Almazán J, Martín J, Pellicer N, Monleón J, and Simón C
- Subjects
- Adult, Aged, DNA Copy Number Variations, Diagnosis, Differential, Female, Gene Deletion, Gene Duplication, Gene Expression Profiling, Gene Fusion, Genomics, High-Throughput Nucleotide Sequencing, Humans, Leiomyoma genetics, Leiomyosarcoma genetics, Middle Aged, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Sequence Analysis, RNA, Uterine Neoplasms genetics, Leiomyoma diagnosis, Leiomyosarcoma diagnosis, Uterine Neoplasms diagnosis
- Abstract
Background: Although uterine leiomyomas and leiomyosarcomas are considered biologically unrelated tumors, they share morphologic and histologic characteristics that complicate their differential diagnosis. The long-term therapeutic option for leiomyoma is laparoscopic myomectomy with morcellation, particularly for patients who wish to preserve their fertility. However, because of the potential dissemination of undiagnosed or hidden leiomyosarcoma from morcellation, there is a need to develop a preoperative assessment of malignancy risk., Objective: Through an integrated comparative genomic and transcriptomic analysis, we aim to identify differential genetic targets in leiomyomas vs leiomyosarcomas using next-generation sequencing as the first step toward preoperative differential diagnosis., Study Design: Targeted sequencing of DNA and RNA coding regions for solid tumor-associated genes was performed on formalin-fixed paraffin-embedded samples from 13 leiomyomas and 13 leiomyosarcoma cases. DNA sequencing was used to identify copy number variations, single-nucleotide variants, and small insertions/deletions. RNA sequencing was used to identify gene fusions, splice variants, and/or differential gene expression profiles., Results: In leiomyosarcomas, tumor mutation burden was higher in terms of copy number variations, single nucleotide variants, small insertions/deletions, and gene fusions compared with leiomyomas. For copy number variations, 20 genes were affected by deletions in leiomyosarcomas, compared with 6 observed losses in leiomyomas. Gains (duplications) were identified in 19 genes in leiomyosarcomas, but only 3 genes in leiomyomas. The most common mutations (single-nucleotide variants and insertions/deletions) for leiomyosarcomas were identified in 105 genes of all analyzed leiomyosarcomas; 82 genes were affected in leiomyomas. Of note, 1 tumor previously diagnosed as leiomyosarcoma was established as inflammatory myofibroblastic tumor along this study with a novel ALK-TNS1 fusion. Finally, a differential transcriptomic profile was observed for 11 of 55 genes analyzed in leiomyosarcomas; 8.5% of initially diagnosed leiomyosarcomas showed high-confidence, novel gene fusions that were associated with these tumors., Conclusion: Through integrated comparative genomic and transcriptomic analyses, we identified novel differential genetic targets that potentially differentiate leiomyosarcomas and leiomyomas. This provides a new insight into the differential diagnosis of these myometrial tumors., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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42. Treatment potential of bone marrow-derived stem cells in women with diminished ovarian reserves and premature ovarian failure.
- Author
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Herraiz S, Pellicer N, Romeu M, and Pellicer A
- Subjects
- Adolescent, Adult, Animals, Apoptosis, Cell Proliferation, Female, Humans, Infertility, Female therapy, Oocytes physiology, Ovarian Follicle physiology, Pregnancy, Pregnancy Outcome, Reproductive Techniques, Assisted, Young Adult, Bone Marrow Cells cytology, Bone Marrow Transplantation, Ovarian Reserve, Primary Ovarian Insufficiency therapy, Stem Cells cytology
- Abstract
Purpose of Review: We review the techniques recently tested in both animal models and humans to provide a state-of-the-art on adult stem cell ovarian transplant to achieve ovarian rejuvenation in patients with diminished ovarian reserves., Recent Findings: As the firsts reports of spontaneous pregnancies achieved after bone marrow transplantation in oncologic women with primary ovarian insufficiency, increasing evidence supports the regenerative effects of stem cell-based therapies in the ovarian niche. Adult stem cells from several origins promote follicular development, increase ovarian local vascularization, increase follicle and stromal cell proliferation and reduce cell apoptosis and follicular atresia, although they do not modify embryo quality. Therefore, residual quiescent follicles of aged or damaged ovaries might produce competent oocytes in an adequate ovarian environment. Nevertheless, further research is needed to properly evaluate underlying mechanisms, identify best cell sources and design less invasive infusion techniques., Summary: Stem cells may be a relevant therapeutic alternative for ovary regeneration and follicular development in patients with impaired ovaries, such as poor ovarian responders or women diagnosed with primary ovarian insufficiency.
- Published
- 2019
- Full Text
- View/download PDF
43. Evaluation of PAI-1 in endometriosis using a homologous immunocompetent mouse model.
- Author
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Buigues A, Ferrero H, Martínez J, Pellicer N, Pellicer A, and Gómez R
- Subjects
- Animals, Cell Proliferation drug effects, Disease Models, Animal, Endometrium drug effects, Female, Indoleacetic Acids pharmacology, Mice, Serpin E2 antagonists & inhibitors, Endometriosis metabolism, Endometrium metabolism, Neovascularization, Pathologic metabolism, Serpin E2 metabolism
- Abstract
To analyze the role of PAI-1 (plasminogen activator inhibitor 1) in endometriotic lesion growth, we studied the effect of PAI-1 inhibition by PAI-039 using a homologous mouse model of endometriosis that allows noninvasive monitoring. Endometrial tissue from donor mice was collected, labeled with mCherry adenovirus, and implanted into a subcutaneous pocket on the ventral abdomen of recipient mice. Seven days after transplantation, mice were randomly allocated in two groups and treated once daily for 2 weeks with either vehicle (control group) or PAI-1 inhibitor (PAI-039 group). Endometriotic lesion size generated in recipient mice was monitored by mCherry signal. Animals were euthanized 21 days after endometrial tissue implantation and endometriotic lesions were harvested for fibrin deposit and vascularization analyses. Collagen content was also examined to determine the overall effects of proteolysis on extracellular matrix degradation. We demonstrated that endometriotic lesions generated in recipient mice from both groups presented characteristics typical of human endometriotic lesions. We observed a significant decrease in fluorescence signal in endometriotic lesions from the PAI-039 group at the beginning of the treatment correlated with a decrease in endometriotic lesion size. PAI-1 inhibition significantly decreased lesion cell proliferation. In addition, endometriotic lesions from the PAI-1 inhibition group showed a decreased percentage of neovascularization as well as fibrin deposits. However, the density and distribution of collagen were not affected by PAI-039. Our results suggest that in vivo inhibition of PAI-1 by PAI-039 may be a useful strategy to reduce endometriotic lesion size by blocking angiogenesis.
- Published
- 2018
- Full Text
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44. Autologous stem cell ovarian transplantation to increase reproductive potential in patients who are poor responders.
- Author
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Herraiz S, Romeu M, Buigues A, Martínez S, Díaz-García C, Gómez-Seguí I, Martínez J, Pellicer N, and Pellicer A
- Subjects
- Adult, Female, Fertilization in Vitro methods, Fertilization in Vitro trends, Humans, Infertility, Female diagnostic imaging, Ovary cytology, Pilot Projects, Prospective Studies, Stem Cell Transplantation trends, Transplantation, Autologous, Treatment Outcome, Infertility, Female therapy, Ovarian Reserve physiology, Ovary physiology, Ovary transplantation, Reproduction physiology, Stem Cell Transplantation methods
- Abstract
Objective: To evaluate effects of autologous stem cell ovarian transplant (ASCOT) on ovarian reserve and IVF outcomes of women who are poor responders with very poor prognosis., Design: Prospective observational pilot study., Setting: University hospital., Patient(s): Seventeen women who are poor responders., Intervention(s): Ovarian infusion of bone marrow-derived stem cells., Main Outcome Measure(s): Serum antimüllerian hormone levels and antral follicular count (AFC), punctured follicles, and oocytes retrieved after stimulation (controlled ovarian stimulation) were measred. Apheresis was analyzed for growth factor concentrations., Result(s): The ASCOT resulted in a significant improvement in AFC 2 weeks after treatment. With an increase in AFC of three or more follicles and/or two consecutive increases in antimüllerian hormone levels as success criteria, ovarian function improved in 81.3% of women. These positive effects were associated with the presence of fibroblast growth factor-2 and thrombospondin. During controlled ovarian stimulation, ASCOT increased the number of stimulable antral follicles and oocytes, but the embryo euploidy rate was low (16.1%). Five pregnancies were achieved: two after ET, three by natural conception., Conclusion(s): Our results suggest that ASCOT optimized the mobilization and growth of existing follicles, possibly related to fibroblast growth factor-2 and thrombospondin-1 within apheresis. The ASCOT improved follicle and oocyte quantity enabling pregnancy in women who are poor responders previously limited to oocyte donation., Clinical Trial Registration Number: NCT02240342., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
45. Lignocellulosic micro/nanofibers from wood sawdust applied to recycled fibers for the production of paper bags.
- Author
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Tarrés Q, Pellicer N, Balea A, Merayo N, Negro C, Blanco A, Delgado-Aguilar M, and Mutjé P
- Subjects
- Lignin chemistry, Nanofibers chemistry, Paper, Recycling, Wood chemistry
- Abstract
In the present work, lignocellulosic micro/nanofibers (LCMNF) were produced from pine sawdust. For that, pine sawdust was submitted to alkali treatment and subsequent bleaching stages, tailoring its chemical composition with the purpose of obtaining effective LCMNF. The obtained LCMNF were characterized and incorporated to recycled cardboard boxes with the purpose of producing recycled paper. The obtained results showed that it was possible to obtain LCMNF with the same reinforcing potential than those cellulose nanofibers (CNF) prepared by oxidative or other chemical methods In fact, the obtained papers increased the breaking length of recycled cardboard from 3338m to 5347m, being a value significantly higher than the requirements to produce paper bags. Overall, the studied strategies could allow a significant reduction of paper basis weight, with the consequent material saving and, thus, contribution to the environment., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
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46. Smart nanopaper based on cellulose nanofibers with hybrid PEDOT:PSS/polypyrrole for energy storage devices.
- Author
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Lay M, Pèlach MÀ, Pellicer N, Tarrés JA, Bun KN, and Vilaseca F
- Abstract
In the current work, flexible, lightweight, and strong conductive nanopapers based on cellulose nanofibers (CNFs) with poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and/or polypyrrole (PPy) were prepared by following a mixing and in situ chemical polymerization method. A successful homogeneous coating of PEDOT:PSS on cellulose nanofibers occurred by means hydrogen-bonding interactions between the hydroxyl functionalized CNF and the electronically charged PEDOT:PSS, as shown by FTIR spectra. The electrical conductivity and the specific capacitance of CNF-PEDOT:PSS nanopapers were 2.58Scm
-1 and 6.21Fg-1 , respectively. Further coating of PPy produced a substantial improvement on the electrical conductivity (10.55Scm-1 ) and the specific capacitance (315.5Fg-1 ) of the resulting CNF-PEDOT:PSS-PPy nanopaper. A synergistic phenomenon between both conductive polymers supported the high electrical conductivity and specific capacitance of the ternary formulation. Moreover, CNF-PEDOT:PSS-PPy nanopaper showed higher mechanical properties and it was more flexible than the nanopaper containing only polypyrrole conducting polymer (CNF-PPy). It is concluded that the good mechanical, electrical and electrochemical properties of the ternary formulation can apply for smart nanopaper in flexible electronics and energy storage devices., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2017
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47. Osmotic-shock produced by vitrification solutions improves immature human oocytes in vitro maturation.
- Author
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Molina I, Gómez J, Balasch S, Pellicer N, and Novella-Maestre E
- Subjects
- Adult, Calcium metabolism, Cell Survival, Culture Media, Embryonic Development, Female, Fertility Preservation, Humans, In Vitro Oocyte Maturation Techniques methods, Oocytes growth & development, Osmotic Pressure, Vitrification
- Abstract
Background: During cytoplasmic oocyte maturation, Ca(2+) currents are vital for regulating a broad range of physiological processes. Recent studies have demonstrated that DMSO and EG cause large transient increases in intracellular Ca(2+) in mouse oocytes. The CP used in vitrifying protocols also increases the intracellular calcium transient. The aim of this study is to evaluate the effects of vitrifying time (before and after IVM) and exposure to the vitrification solutions and ionomycin on oocyte quality and embryonic development., Methods: 221 GV-oocytes unsuitable for IVF-ICSI cycles were randomly distributed into one of the following three groups. G1 (control group): 41 GV-oocytes IVM until MII; G2: 43 oocytes vitrified at GV stage and IVM until MII stage; and G3: 53 GV-oocytes IVM until MII and then vitrified. In order to clarify the effect of vitrification solutions (VS) on human oocyte IVM through the intracellular Ca(2+) oscillation, the following two groups were also included. G4: 43 GV-oocytes exposed to VS and IVM until MII; and G5: 41 GV-oocytes exposed to ionomycin and IVM until MII. All GV-oocytes that reached MII-stage were parthenogenetically activated to assess oocyte viability. IVM was performed in IVF-medium (24-48 h). Chemical treatment (ionomycin) and osmotic treatment (vitrification solutions) were performed without liquid-N2 immersion. The following rates were evaluated: survival (SR), in-vitro maturation (IVMR), activation (AR), development to 2-cell (DRC), development to morula (DRCM) and development to blastocyst (DRB). Ratios between the different treatment groups were compared using contingency tables analysis (chi-square test)., Results: A high survival rate was obtained in G2 (95.5 %) and G4 (96.6 %). In-vitro maturation rate was significantly higher for G4 (86 %) and G2 (83.7 %) compared to G1 (63.4 %), G3 (56.6 %) and G5 (48.8 %). DRCM was significantly higher for G1 and G2 compared to G3 (G1: 15.8 %, G2: 20.7 % and G3: 0 %). DRB was only obtained for the oocytes vitrified before IVM (G2: 3.4 %). AR was also significantly higher for G2 and G4 compared to G5 (G2: 80.5 %, G4: 86.5 % and G5: 55 %). DRCM and DRB were only obtained in G2 and G4. DRCM was significantly higher for oocytes vitrified at GV stage (G2) and for oocytes exposed to the VS in G4 compared to the oocytes exposed to the ionomycin in G5 (G2: 20.7 %; G4: 37.5 % and G5: 0 %)., Conclusions: Vitrifying GV-oocytes improves their IVM. Further investigation could look to increase the oocyte pool and improve fertility preservation options.
- Published
- 2016
- Full Text
- View/download PDF
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