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1. P-179 Euploid blastocysts rate in pre-implantation genetic testing (PGT) cycles with high levels of sperm DNA fragmentation does not improve after Magnetic Activated Cell Sorting (MACS)

Author

Filardi, P, primary, Chiarello Sosa, J M, additional, Verdura, R, additional, Pomeraantz, C, additional, Perez Olgiati, M, additional, Papayannis, M, additional, De Martino, E, additional, Magri, L, additional, Figueroa, C, additional, Lombardi, C, additional, Kopcow, L, additional, Horton, M, additional, De Zuñiga, I, additional, and Bisioli, C, additional

Published
2023
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2. P-223 Women aged 40 or older and non-male factor have the same reproductive outcome using intracytoplasmic sperm injection (ICSI) or conventional in vitro fertilization (cIVF)

Author

Filardi, P, primary, De Martino, E, additional, Chiarello Sosa, J.M, additional, Gomez Peña, M, additional, Papayannis, M, additional, Figueroa, C, additional, Magri, L, additional, Oubiña, A, additional, Horton, M, additional, De Zuñiga, I, additional, Kopcow, L, additional, Sobral, F, additional, and Bisioli, C, additional

Published
2022
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3. O-077 The chromosomal constitution of embryos developing from 0PN zygotes

Author

Gomez Peña, M, primary, Papayannis, M, additional, De Martino, E, additional, Filardi, P, additional, Magri, L, additional, Chiarello, J M, additional, Figueroa, C, additional, De Zuñiga, I, additional, Kopcow, L, additional, Horton, M, additional, Sobral, F, additional, Oubiña, A, additional, and Bisioli, C, additional

Published
2022
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4. Multicenter prospective study of concordance between embryo cell-free DNA and trophectoderm biopsies from 1,301 human blastocysts

Author

Rubio C, Navarro-Sanchez L, Garcia-Pascual C, Ocali O, Cimadomo D, Venier W, Barroso G, Kopcow L, Bahceci M, Roos Kulmann M, Lopez L, De la Fuente E, Navarro R, Valbuena D, Sakkas D, Rienzi L, and Simon C

Subjects
embryonic structures
Abstract

BACKGROUND: The recent identification of embryo cell-free DNA in the spent blastocyst media opened a new era of possibilities for non-invasive embryo aneuploidy testing in assisted reproductive technologies. Yet, previous studies assessing limited numbers of embryos reported variable concordance between embryo cell-free DNA and trophectoderm biopsies, thus questioning the validity of this approach.; OBJECTIVE(S): 1) To evaluate the concordance and reproducibility of testing embryo cell-free DNA versus trophectoderm DNA obtained from the same embryo in a large sample of human blastocysts. 2) To assess the contribution of the inner cell mass and/or trophectoderm to the embryo cell-free DNA released to the culture media.; STUDY DESIGN: This is the interim analysis of a prospective, observational study among eight in vitro fertilization centers, on four continents, to assess consistency between non-invasive embryo aneuploidy testing of embryo cell-free DNA and conventional trophectoderm biopsy. Analysis included 1,301 day-6/7 blastocysts obtained in 406 IVF cycles from 371 patients aged 20-44 years undergoing preimplantation genetic testing for aneuploidy. Fresh oocytes underwent intracytoplasmic sperm injection or in vitro fertilization. No previous assisted hatching or vitrification was allowed before media collection. Individual spent blastocyst medium was collected from embryos cultured at least 40 hours from day 4. After media collection, conventional PGT-A analysis was performed, comprising of trophectoderm biopsy and blastocyst vitrification. Embryo cell-free DNA was analyzed blindly after embryo transfer. Inner cell mass and trophectoderm biopsies were also performed in a subset of 81 aneuploid blastocysts donated for research.; RESULTS: Embryo cell-free DNA analyses were 78.2% (866/1,108) concordant with the corresponding trophectoderm biopsies. No significant differences were detected among centers ranging from 72.5% to 86.3%. Indeed, concordance rates exceeded 86% when all defined steps in the culture laboratory were controlled to minimize the impact of maternal and operator contamination. Sensitivity per center ranged from 76.5% to 91.3%, and specificity from 64.7% to 93.3%. The false-negative rate was 8.3% (92/1,108), and false-positive rate was 12.4% (137/1,108). Interestingly, the two fertilization techniques provided similar sensitivity (80.9% vs. 87.9%) and specificity (78.6% vs. 69.9%). Multivariate analysis did not reveal any bias from patient clinical background, ovarian stimulation protocols, culture conditions, or embryo quality on testing accuracy of concordance. Moreover, concordances of embryo cell-free DNA with trophectoderm and inner cell mass suggest that the embryo cell-free DNA originates from both compartments of the embryo.; CONCLUSION(S): Non-invasive analysis of embryo cell-free DNA analyzed in spent blastocyst culture media demonstrates high concordance with trophectoderm biopsy results in this large multicenter series. A non-invasive approach for prioritizing embryo euploidy offers important advantages such as avoiding invasive embryo biopsy and decreased cost, potentially increasing accessibility for a wider patient population. Copyright © 2020 Elsevier Inc. All rights reserved.

Published
2020

9. Posters * Endometriosis, Endometrium and Implantation

Author

Jiang, Y., primary, Zhao, J., additional, Hua, M., additional, Zhen, X., additional, Yan, G., additional, Hu, Y., additional, Sun, H., additional, Selvaggi, L., additional, Zannoni, G. F., additional, Tagliaferri, V., additional, De Cicco, S., additional, Vellone, V. G., additional, Romualdi, D., additional, Lanzone, A., additional, Guido, M., additional, Fassbender, A., additional, Vodolazkaia, A. V., additional, Bossuyt, X. B., additional, Kyama, M. K., additional, Meuleman, C. M., additional, Peeraer, K. P., additional, Tomassetti, C. T., additional, D'Hooghe, T. M., additional, Lumini, A., additional, Nanni, L., additional, Manna, C., additional, Pappalardo, S., additional, Melin, A., additional, Lundholm, C., additional, Malki, N., additional, Swahn, M. L., additional, Sparen, P., additional, Bergqvist, A., additional, Crescenzi, F., additional, Farrag, A., additional, Sallam, H. N., additional, Zou, L., additional, Ding, G., additional, Zhang, R., additional, Sheng, J., additional, Huang, H., additional, von Kleinsorgen, C., additional, Wilson, T., additional, Thiel-Moder, U., additional, Ebert, A. D., additional, Reinfandt, M., additional, Papadopolous, T., additional, Melo, A. S., additional, Rodrigues, J. K., additional, Dib, L. A., additional, Andrade, A. Z., additional, Donabela, F. C., additional, Ferriani, R. A., additional, Navarro, P. A., additional, Tocci, A., additional, Royo, P., additional, Lucchini, C., additional, Ramos, P., additional, Alcazar, J. L., additional, Habara, T., additional, Terada, S., additional, Yoshioka, N., additional, Hayashi, N., additional, Haouzi, D., additional, Assou, S., additional, Monzo, C., additional, Anahory, T., additional, Dechaud, H., additional, De Vos, J., additional, Hamamah, S., additional, Gonzalez-Ramos, R., additional, Rojas, C., additional, Rocco, J., additional, Poch, A., additional, Sovino, H., additional, Kohen, P., additional, Munoz, A., additional, Devoto, L., additional, Aygen, M. A., additional, Atakul, T., additional, Oner, G., additional, Ozgun, M. T., additional, Sahin, Y., additional, Ozturk, F., additional, Li, R., additional, Qiao, J., additional, Zhylkova, I., additional, Feskov, A., additional, Feskova, I., additional, Somova, O., additional, Chumakova, N., additional, Bontekoe, S., additional, Blake, D., additional, Heineman, M. J., additional, Williams, E. C., additional, Johnson, N. P., additional, Motta, A., additional, Colaci, D., additional, Horton, M., additional, Faut, M., additional, Bisioli, C., additional, Kopcow, L., additional, de Zuniga, I., additional, Wiener-Megnazi, Z., additional, Khaytov, M., additional, Lahav - Baratz, S., additional, Shiloh, H., additional, Koifman, M., additional, Oslander, R., additional, Dirnfeld, M., additional, Sundqvist, J., additional, Andersson, K. L., additional, Scarselli, G., additional, Gemzell-Danielsson, K., additional, Lalitkumar, P. G. L., additional, Tokushige, N., additional, Markham, R., additional, Crossett, B., additional, Ahn, S., additional, Nelaturi, V., additional, Khan, A., additional, Fraser, I. S., additional, Van Vaerenbergh, I., additional, Fatemi, H. M., additional, Blockeel, C., additional, Van Lommel, L., additional, In't Veld, P., additional, Schuit, F., additional, Kolibianakis, E. M., additional, Devroey, P., additional, Bourgain, C., additional, Sugino, N., additional, Tamura, I., additional, Lee, R., additional, Maekawa, R., additional, Gelbaya, T., additional, Gordts, S., additional, D'Hooghe, T. N., additional, Gergolet, M., additional, Nardo, L. G., additional, Yu, H., additional, Wang, H., additional, Lee, C., additional, Soong, Y., additional, Kremenska, Y., additional, Masliy, Y., additional, Goncharova, Y., additional, Kremenskoy, M., additional, Veselovskyy, V., additional, Zukin, V., additional, Sudoma, I., additional, Delgado-Rosas, F., additional, Gomez, R., additional, Tamarit, S., additional, Abad, A., additional, Simon, C., additional, Pellicer, A., additional, Racicot, M., additional, Dean, N. L., additional, Antaki, R., additional, Menard, S., additional, Kadoch, I. J., additional, Garcia-Guzman, R., additional, Cabrera Romero, L., additional, Hernandez, J., additional, Palumbo, A., additional, Marshall, E., additional, Lowry, J., additional, Maybin, J. A., additional, Collins, F., additional, Critchley, H. O. D., additional, Saunders, P. T. K., additional, Chaudhury, K., additional, Jana, S. K., additional, Banerjee, P., additional, Mukherjee, S., additional, Chakravarty, B. N., additional, Allegra, A., additional, Marino, A., additional, Lama, A., additional, Santoro, A., additional, Agueli, C., additional, Mazzola, S., additional, Volpes, A., additional, Delvoux, B., additional, de Graaff, A. A., additional, Kyama, C. M., additional, Dunselman, G. A. J., additional, Romano, A., additional, Caccavo, D., additional, Pellegrino, N. M., additional, Totaro, I., additional, Panzarino, M., additional, Nardelli, C., additional, Depalo, R., additional, Flores, R., additional, Montanana, V., additional, Monzo, A., additional, Polo, P., additional, Garcia-Gimeno, T., additional, Cabo, A., additional, Rubio, J. M., additional, Beets, G. L., additional, van Lankveld, J. J., additional, Kim, H. Y., additional, Lee, B. S., additional, Cho, S. H., additional, Choi, Y. S., additional, Seo, S. K., additional, Lee, K. E., additional, Yang, H. I., additional, Abubakirov, A., additional, Vacheyshvili, T., additional, Krechetova, L., additional, Ziganshina, M., additional, Demura, T., additional, Nazarenko, T., additional, Fulop, I., additional, Rucz, A., additional, Herczegh, S. Z., additional, Ujvari, A., additional, Takacs, S. Z., additional, Szakonyi, T., additional, Lopez - Muniz, A., additional, Zamora, L., additional, Serra, O., additional, Guix, C., additional, Lopez-Teijon, M., additional, Benadiva, C., additional, Alvarez, J. G., additional, Goudakou, M., additional, Karkanaki, A., additional, Kalogeraki, A., additional, Mataliotakis, I., additional, Kalogiannidis, I., additional, Prapas, I., additional, Hosie, M., additional, Thomson, K. J., additional, Penny, C. B., additional, Penny, C., additional, Hosie, M. J., additional, McKinnon, B., additional, Klaeser, B., additional, Bersinger, N., additional, Mueller, M. D., additional, Horcajadas, J. A., additional, Martinez-Conejero, J. A., additional, Montesinos, M., additional, Morgan, M., additional, Fortuno, S., additional, Yi, K. W., additional, Shin, J. H., additional, Park, H. T., additional, Kim, T., additional, Kim, S. H., additional, Hur, J. Y., additional, Chan, R. W. S., additional, Chan, Y. Y., additional, Ng, E. H. Y., additional, Yeung, W. S. B., additional, Santulli, P., additional, Borghese, B., additional, Chopin, N., additional, Marcellin, L., additional, de Ziegler, D., additional, Chapron, C., additional, Elnashar, A., additional, Badawy, A., additional, Mosbah, A., additional, Tzioras, S., additional, Polyzos, N. P., additional, Messini, C. I., additional, Papanikolaou, E. G., additional, Valachis, A., additional, Patavoukas, E., additional, Mauri, D., additional, Messinis, I. E., additional, Acar, N., additional, Hirota, Y., additional, Tranguch, S., additional, Daikoku, T., additional, Burnum, K. E., additional, Xie, H., additional, Kodama, A., additional, Osuga, Y., additional, Ustunel, I., additional, Friedman, D. B., additional, Caprioli, R. M., additional, Dey, S. K., additional, Mitra, A., additional, Sahu, R., additional, Pal, M., additional, Bhattachrayya, A. K., additional, Bhattachrya, J., additional, Ferrero, S., additional, Remorgida, V., additional, Rollandi, G. A., additional, Biscaldi, E., additional, Cho, S., additional, Arena, E., additional, Morando, A., additional, Tomazevic, T., additional, Ban-Frangez, H., additional, Virant-Klun, I., additional, Verdenik, I., additional, Pozlep, B., additional, Vrtacnik-Bokal, E., additional, Valenzano Menada, M., additional, Morotti, M., additional, Venturini, P. L., additional, Dimitriadis, E., additional, Salamonsen, L. A., additional, Hannan, N., additional, O'Connor, O., additional, Rombauts, L., additional, Stoikos, C., additional, Mahmoudi, M., additional, Shaikh, A., additional, Mousavifar, N., additional, Rastin, M., additional, Baharara, J., additional, Tabasi, N., additional, Takemura, Y., additional, Fujimoto, A., additional, Tsutsumi, R., additional, Ooi, N., additional, Yano, T., additional, Taketani, Y., additional, Panagiotidis, I., additional, Prapas, Y., additional, Zhang, D., additional, Lv, P. P., additional, Ding, G. L., additional, Zhang, R. J., additional, Zou, L. B., additional, Xu, G. F., additional, Gao, H. J., additional, Zhu, Y. M., additional, Sheng, J. Z., additional, Huang, H. F., additional, Labarta, E., additional, Alama, P., additional, and Bosch, E., additional

Published
2010
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14. Reproductive biology. Relationship of ovarian stimulation response with vascular endothelial growth factor and degree of granulosa cell apoptosis

Author

Quintana, R., Kopcow, L., Marconi, G., Sueldo, C., Speranza, G., and Barañao, R.I.

Abstract

BACKGROUND: The aim of this study was to evaluate the concentration of vascular endothelial growth factor (VEGF) in follicular fluid and in granulosa cell cultures in relation to the degree of apoptosis in granulosa cells from patients with different types of ovarian response to controlled ovarian hyperstimulation. METHODS: We studied 30 women who underwent controlled ovarian hyperstimulation and oocyte retrieval. Group A comprised patients with 1–4 follicles (n = 10), group B patients with 5–14 follicles (n = 10) and group C patients with >15 follicles (n = 10). RESULTS: Mean (±SD) VEGF concentrations in follicular fluid were 1232 ± 209, 813 ± 198 and 396 ± 103 pg/ml for groups A, B and C respectively (P > 0.01). Concentrations of VEGF in granulosa cell supernatant were 684 ± 316, 1101 ± 295 and 1596 ± 227 pg/ml respectively (P < 0.05). Percentages of apoptotic cells in granulosa cells culture was 55.02 ± 7.5, 23.98 ± 4.4 and 14.2 ± 2.3% respectively (A versus B, P < 0.01, A versus C, P < 0.006, B versus C, NS). CONCLUSIONS: Our findings showed that in patients with decreased ovarian response to controlled ovarian hyperstimulation, follicular fluid VEGF concentration is elevated, the concentration from granulosa cells culture supernatant is decreased and the percentage of apoptotic granulosa cells is increased, while opposite findings occurred in patients with normal or hyper-responses.

Published
2001

15. The impact of implementing a non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) embryo culture protocol on embryo viability and clinical outcomes.

Author

Sakkas D, Navarro-Sánchez L, Ardestani G, Barroso G, Bisioli C, Boynukalin K, Cimadomo D, Frantz N, Kopcow L, Andrade GM, Ozturk B, Rienzi L, Weiser A, Valbuena D, Simón C, and Rubio C

Subjects
Adult, Female, Humans, Pregnancy, Cell-Free Nucleic Acids, Embryo Transfer methods, Embryonic Development, Fertilization in Vitro methods, Pregnancy Outcome, Pregnancy Rate, Aneuploidy, Blastocyst, Embryo Culture Techniques methods, Genetic Testing methods, Preimplantation Diagnosis methods
Abstract

Study Question: Are modifications in the embryo culture protocol needed to perform non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) affecting clinical reproductive outcomes, including blastocyst development and pregnancy outcomes?, Summary Answer: The implementation of an embryo culture protocol to accommodate niPGT-A has no impact on blastocyst viability or pregnancy outcomes., What Is Known Already: The recent identification of embryo cell-free (cf) DNA in spent blastocyst media has created the possibility of simplifying PGT-A. Concerns, however, have arisen at two levels. First, the representativeness of that cfDNA to the real ploidy status of the embryo. Second, the logistical changes that need to be implemented by the IVF laboratory when performing niPGT-A and their effect on reproductive outcomes. Concordance rates of niPGT-A to invasive PGT-A have gradually improved; however, the impact of culture protocol changes is not as well understood., Study Design, Size, Duration: As part of a trial examining concordance rates of niPGT-A versus invasive PGT-A, the IVF clinics implemented a specific niPGT-A embryo culture protocol. Briefly, this involved initial culture of fertilized oocytes following each laboratory standard routine up to Day 4. On Day 4, embryos were washed and cultured individually in 10 μl of fresh media. On Day 6 or 7, blastocysts were then biopsied, vitrified, and media collected for the niPGT-A analysis. Six IVF clinics from the previously mentioned trial were enrolled in this analysis. In the concordance trial, Clinic A cultured all embryos (97 cycles and 355 embryos) up to Day 6 or 7, whereas in the remaining clinics (B-F) (379 cycles), nearly a quarter of all the blastocysts (231/985: 23.5%) were biopsied on Day 5, with the remaining blastocysts following the niPGT-A protocol (754/985: 76.5%). During the same period (April 2018-December 2020), the IVF clinics also performed standard invasive PGT-A, which involved culture of embryos up to Days 5, 6, or 7 when blastocysts were biopsied and vitrified., Participants/materials, Setting, Methods: In total, 428 (476 cycles) patients were in the niPGT-A study group. Embryos from 1392 patients underwent the standard PGT-A culture protocol and formed the control group. Clinical information was obtained and analyzed from all the patients. Statistical comparisons were performed between the study and the control groups according to the day of biopsy., Main Results and the Role of Chance: The mean age, number of oocytes, fertilization rates, and number of blastocysts biopsied were not significantly different for the study and the control group. Regarding the overall pregnancy outcomes, no significant effect was observed on clinical pregnancy rate, miscarriage rate, or ongoing pregnancy rate (≥12 weeks) in the study group compared to the control group when stratified by day of biopsy., Limitations, Reasons for Caution: The limitations are intrinsic to the retrospective nature of the study, and to the fact that the study was conducted in invasive PGT-A patients and not specifically using niPGT-A cases., Wider Implications of the Findings: This study shows that modifying current IVF laboratory protocols to adopt niPGT-A has no impact on the number of blastocysts available for transfer and overall clinical outcomes of transferred embryos. Whether removal of the invasive biopsy step leads to further improvements in pregnancy rates awaits further studies., Study Funding/competing Interest(s): This study was funded by Igenomix. C.R., L.N.-S., and D.V. are employees of Igenomix. D.S. was on the Scientific Advisory Board of Igenomix during the study., Trial Registration Number: ClinicalTrials.gov (NCT03520933)., (© The Author(s) 2024. 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
2024
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16. Involvement of the ANGPTs/Tie-2 system in ovarian hyperstimulation syndrome (OHSS).

Author

Scotti L, Abramovich D, Pascuali N, de Zúñiga I, Oubiña A, Kopcow L, Lange S, Owen G, Tesone M, and Parborell F

Subjects
Adult, Angiopoietin-1 antagonists & inhibitors, Animals, Antibodies pharmacology, Case-Control Studies, Cell Movement, Cells, Cultured, Female, Humans, Luteal Cells metabolism, Ovary metabolism, Ovary pathology, Proto-Oncogene Proteins c-sis metabolism, Rats, Rats, Sprague-Dawley, Receptor, Platelet-Derived Growth Factor beta metabolism, Angiopoietin-1 metabolism, Angiopoietin-2 metabolism, Follicular Fluid metabolism, Ovarian Hyperstimulation Syndrome metabolism, Receptor, TIE-2 metabolism
Abstract

Ovarian hyperstimulation syndrome (OHSS) is a disorder associated with ovarian stimulation. OHSS features are ovarian enlargement with fluid shifting to the third space. Disturbances in the vasculature are considered the main changes that lead to OHSS. Our aim was to analyze the levels of angiopoietins 1 and 2 (ANGPT1 and 2) and their soluble and membrane receptors (s/mTie-2) in follicular fluid (FF) and in granulosa-lutein cells culture (GLCs) from women at risk of developing OHSS. We also evaluated the effect of ANGPT1 on endothelial cell migration. In ovaries from an OHSS rat model, we analyzed the protein concentration of ANGPTs, their mTie-2 receptor, and platelet-derived growth factor PDGF-B, -D and PDGFR-β. ANGPT1 levels were increased in both FF and GLCs from women at risk of OHSS. Incubation of these FF with an ANGPT1 neutralizing antibody decreased endothelial cell migration. In the ovaries of OHSS rat model, mTie-2 protein levels increased and PDGF-B and -D decreased. In summary, these results suggest that ANGPT1 could be another mediator in the development of OHSS., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Published
2013
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17. Inhibition of cyclooxygenase-2 (COX-2) by meloxicam decreases the incidence of ovarian hyperstimulation syndrome in a rat model.

Author

Quintana R, Kopcow L, Marconi G, Young E, Yovanovich C, and Paz DA

Subjects
Animals, Cyclooxygenase 2 genetics, Female, Gene Expression drug effects, Humans, Incidence, Meloxicam, Organ Size, Ovarian Hyperstimulation Syndrome drug therapy, Ovarian Hyperstimulation Syndrome epidemiology, Ovarian Hyperstimulation Syndrome metabolism, Ovary drug effects, Ovary metabolism, Rats, Rats, Wistar, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Cyclooxygenase 2 metabolism, Cyclooxygenase 2 Inhibitors therapeutic use, Down-Regulation, Ovarian Hyperstimulation Syndrome prevention & control, Thiazines pharmacology, Thiazoles pharmacology
Abstract

Objective: To investigate the effects of selective cyclooxygenase-2 (COX-2) inhibition on the ovarian hyperstimulation syndrome (OHSS) in an experimental model., Design: Controlled laboratory study., Setting: University-affiliated fertility center., Animal(s): Female Wistar rats., Intervention(s): Female Wistar rats (22 days old) were divided into four groups: group 1 (control group; n = 10) received 0.1 mL of intraperitoneal (IP) saline from days 22-26; group 2 (mild-stimulated group; n = 10) received 10 IU of pregnant mare serum gonadotropin (PMSG) on day 24 and 10 IU of hCG 48 hours later (day 26); group 3 (OHSS group; n = 10) was given 10 IU of PMSG for 4 consecutive days from day 22 and 30 IU hCG on the fifth day to induce OHSS; group 4 was treated the same as group 3, but received 2 muL (15 mg/mL) of meloxicam 2 hours before the PMSG injection for 4 consecutive days, and 2 hours before the hCG injection on the fifth day. All groups were killed on day 26., Main Outcome Measure(s): Number of antral and luteinized follicles, ovarian weight, semiquantitative vascular endothelial growth factor (VEGF) and COX-2 immunohistochemistry., Result(s): There were no differences in the ovarian weight between groups 1 and 2. Group 3 showed significantly increased ovarian weight that was suppressed, in group 4, by meloxicam. There was no difference in the number of antral follicles among the four groups. In the mild-stimulated and OHSS groups, the granulosa cells (GC) of preovulatory follicles and the stromal cells showed intense VEGF immunoreactivity. The ovaries from the meloxicam-treated group showed less immunoreactivity than the OHSS group, indicating diminished VEGF expression associated with meloxicam treatment. Group 3 (OHSS group) showed increased COX-2 immunoreactivity that was diminished in the meloxicam-treated group. Meloxicam treatment did not affect the hormone-induced increase in serum E(2) levels seen in OHSS rats., Conclusion(s): Our results in a rat model suggest that meloxicam has a beneficial effect on OHSS by reducing the increases in ovarian weight and VEGF expression associated with OHSS. These effects may be mediated by the COX-2 inhibitory capacity of meloxicam.

Published
2008
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18. Significance of ovarian macrophages in the follicular aspirates from ART patients.

Author

Barañao RI, Quintana R, Martín A, Kopcow L, Marconi G, and Sueldo C

Subjects
Adult, Apoptosis, Cytokines metabolism, Estradiol blood, Female, Follicle Stimulating Hormone blood, Humans, Interleukin-1 analysis, Interleukin-6 analysis, Oocytes, Ovarian Follicle pathology, Vascular Endothelial Growth Factor A analysis, Granulosa Cells pathology, Macrophages pathology, Ovary pathology, Reproductive Techniques, Assisted
Abstract

Purpose: To evaluate the percentages of macrophages present in granulosa cells (GC) cultures from patients with different responses to the hyperstimulation, in relation to the percentages of apoptotic cells (ApC), as well as to the release of cytokines., Methods: We studied 42 patients: 12 Hyporesponders, (with < or =4 follicles), 15 Normoresponders, (5-14 follicles), and 15 Hyperresponders, (> or =15 follicles). In GC cultures percentages of macrophages and ApC were counted and, in the conditioned media, cytokines were measured., Results: Percentages of macrophages were significantly higher in GC cultures from Hyporesponders compared with Hyperresponders patients. Also, the percentages of ApC cells were the highest in Hyporesponders. On the contrary, cytokines concentrations were the lowest in this group., Conclusions: The low ovarian response is probably due to the decreased angiogenesis, which in turn produces increased apoptosis and decreased production of cytokines. The increased percentage of macrophages could be related to increased frequency of apoptotic cells.

Published
2007
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19. Direct injection of vascular endothelial growth factor into the ovary of mice promotes follicular development.

Author

Quintana R, Kopcow L, Sueldo C, Marconi G, Rueda NG, and Barañao RI

Subjects
Animals, Apoptosis drug effects, Chorionic Gonadotropin pharmacology, Female, Gonadotropins, Equine pharmacology, Humans, Mice, Mice, Inbred BALB C, Neovascularization, Physiologic drug effects, Ovarian Follicle blood supply, Ovary cytology, Ovary metabolism, Ovulation Induction, Proto-Oncogene Proteins c-bcl-2 metabolism, Recombinant Proteins administration & dosage, Recombinant Proteins pharmacology, Vascular Endothelial Growth Factor A pharmacology, Ovarian Follicle drug effects, Ovarian Follicle physiology, Ovary drug effects, Vascular Endothelial Growth Factor A administration & dosage
Abstract

Objective: To investigate the effects of an ovarian injection of vascular endothelial growth factor (VEGF) on antral follicle development, neoangiogenesis, and apoptosis., Design: Controlled laboratory study., Setting: University-affiliated fertility center., Animal(s): Balb/c female mice (n = 32) were studied., Intervention(s): Mice were divided into four groups: control group (C) n = 6, no treatment; hyperstimulated group (HS), n = 8, ovaries were stimulated with 7.5 IU pregnant mare serum gonadotropin (PMSG) and 10 IU of hCG; VEGF group (V), n = 8, injected with 0.1 mL of VEGF (0.2 microg) in each ovary; V+HS, n = 8 injected with VEGF and 2 weeks later hyperstimulated., Main Outcome Measure(s): Number of antral and luteinized follicles, number of vessels, and percentage of Bcl-2-positive cells., Result(s): The number of antral follicles with VEGF was higher than in the C and HS groups (16.0 +/- 2.5 vs. 6.0 +/- 0.9 and 11.3 +/- 0.6, respectively, p<0.005). All treatments significantly increased the number of vessels (C: 5.0 +/- 0.5 vs. V: 20.0 +/- 4.8, p<0.005 and V+HS: 22.2 +/- 1.2, p<0.01), as well as increased Bcl-2-positive cells compared to controls (C: 0; V: 11.8 +/- 3.5, p<0.005; V+HS: 12.5 +/- 3.7, p<0.005)., Conclusion(s): Our findings demonstrated that a direct injection of VEGF into the mouse ovary results in the development of an enhanced vascular network promoting follicular development and diminishing apoptosis.

Published
2004
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