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1. Effectiveness of recombinant human follicle-stimulating hormone (r-hFSH):recombinant human luteinizing hormone versus r-hFSH alone in assisted reproductive technology treatment cycles among women aged 35–40 years: a German database study

Author

Bielfeld, A.P., primary, Schwarze, J.E., additional, Verpillat, P., additional, Lispi, M., additional, Fischer, R., additional, Hayward, B., additional, Chuderland, D., additional, D'Hooghe, T., additional, and Krussel, J.S., additional

Published
2023
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2. Withdrawal notice to: ‘Effectiveness of recombinant human follicle-stimulating hormone (r-hFSH): recombinant human luteinizing hormone versus r-hFSH alone in assisted reproductive technology treatment cycles among women aged 35–40 years: A German database study’ [YBEOG 89C (2023) 102350]

Author

Bielfeld, A.P., primary, Schwarze, J.E., additional, Verpillat, P., additional, Lispi, M., additional, Fischer, R., additional, Hayward, B., additional, Chuderland, D., additional, D'Hooghe, T., additional, and Krussel, J.S., additional

Published
2023
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3. Treatment algorithms for high responders: What we can learn from randomized controlled trials, real-world data and models

Author

Drakopoulos, P, Khalaf, Y, Esteves, SC, Polyzos, NP, Sunkara, SK, Shapiro, D, Rizk, B, Ye, H, Costello, M ; https://orcid.org/0000-0001-7340-1356, Koloda, Y, Salle, B, Lispi, M, D'Hooghe, T, La Marca, A, Drakopoulos, P, Khalaf, Y, Esteves, SC, Polyzos, NP, Sunkara, SK, Shapiro, D, Rizk, B, Ye, H, Costello, M ; https://orcid.org/0000-0001-7340-1356, Koloda, Y, Salle, B, Lispi, M, D'Hooghe, T, and La Marca, A

Abstract

A high ovarian response to conventional ovarian stimulation (OS) is characterized by an increased number of follicles and/or oocytes compared with a normal response (10–15 oocytes retrieved). According to current definitions, a high response can be diagnosed before oocyte pick-up when >18–20 follicles ≥11–12 mm are observed on the day of ovulation triggering; high response can be diagnosed after oocyte pick-up when >18–20 oocytes have been retrieved. Women with a high response are also at high risk of early ovarian hyper-stimulation syndrome (OHSS)/or late OHSS after fresh embryo transfers. Women at risk of high response can be diagnosed before stimulation based on several indices, including ovarian reserve markers (anti-Müllerian hormone [AMH] and antral follicle count [AFC], with cutoff values indicative of a high response in patients with PCOS of >3.4 ng/mL for AMH and >24 for AFC). Owing to the high proportion of high responders who are at the risk of developing OHSS (up to 30%), this educational article provides a framework for the identification and management of patients who fall into this category. The risk of high response can be greatly reduced through appropriate management, such as individualized choice of the gonadotropin starting dose, dose adjustment based on hormonal and ultrasound monitoring during OS, the choice of down-regulation protocol and ovulation trigger, and the choice between fresh or elective frozen embryo transfer. Appropriate management strategies still need to be defined for women who are predicted to have a high response and those who have an unexpected high response after starting treatment.

Published
2023

5. Effect of Rehabilitation Treatments on Disability in Persons With Disorders of Consciousness: A Propensity Score Study

Author

Sattin D., Leonardi M., Nelli B., Bramanti P., Marino S., Ferro S., Basaglia N., Guido D., Dolce G., Lucca L. F, Cortese M. D., Ermio C., Dattilo T. L., Capomolla S., Di Iasi G., Estraneo A., De Tanti A., Maradini N., Piperno R., Ferri A., Basaglia N, Bergonzoni A., Chiavaroli F., Di Marco F., Carli S., Biasutti E., Marin D., Formisano R., Rizza F., Pisarri F. M., Vichi R., D'Urso A., Grillo G., Leto A., Guerrasio M., Taliento C., Napolitano F., Castelli E., Lispi M. L., Diverio M., Barbieri C., Bini P. P., Angelino G., Dada O., Orlandi A., Pistarini C., Pisoni C., Manera M., Compostini A., Aiachini B., Pessina A., Musio A., Colombetti E., Taraschi S., Aluas M., Croci M., Negri M., Zucchella M. A., Guizzetti G. B., Salamone E., De Valle G., Caroppi S. M., Ramorino E., Salina D., Spannocchi G., Strazzer S., Villa F., Guarnerio C., Chiambretto P., Dartizio R., Feller S., Franzoni L., Giunco F., Massironi L., Azimonti R., Marcolli S. S., Meinecke C., Buse G., Marchesi V, Molteni F., Gramigna C., Lanfranchi M., Pisani L., Sozzi M., Borri G., Cannata A. P., Grillo A., Roca S., Locati D., Arenare F., Magnoni A., Perin C., Sussele M., Quintana T. Y., Camici M. E., Magistrelli F., Samueli T., San Felici L., Manganelli F., Vignati M., Bellanova L., Cattaneo N., Ferraro F., Olgiati E., Brizioli E., Vallasciani M., Gironelli L., Calderisi E., Novelli A., Scaramuzzo R., Perino C., Forno R., Zamponi E., Corna S., Ferrario S., Lamberti G., Rosso S., Colonna F., Navarro J., Trabacca A., Gennaro L., Bertolini A., Addante L., Amenduni M. T., Fiore P., Amoruso M. T., Colella D., Angelillo M. T., Melis G., Desogus G., Baglieri A., Galardi G., Sant'Angelo A., Posteraro F., Forte F., Logi F., Potenza F., Lino M., Zaccara G., Ragazzoni A., Chiaramonti R., March A., Grober G., Kaczor M., Zelger P, Mazzini N., Monti A., Zampolini M., Scarponi F., Avesani R., Salvi L., Tonin P., Cosentino E., Furlanetto N., Bordin M., Martinuzzi A., Buffoni M., Boldrini P., Semerjian M., Sattin, D, Leonardi, M, Nelli, B, Bramanti, P, Marino, S, Ferro, S, Basaglia, N, Guido, D, Dolce, G, Lucca, L, Cortese, M, Ermio, C, Dattilo, T, Capomolla, S, Di Iasi, G, Estraneo, A, De Tanti, A, Maradini, N, Piperno, R, Ferri, A, Bergonzoni, A, Chiavaroli, F, Di Marco, F, Carli, S, Biasutti, E, Marin, D, Formisano, R, Rizza, F, Pisarri, F, Vichi, R, D'Urso, A, Grillo, G, Leto, A, Guerrasio, M, Taliento, C, Napolitano, F, Castelli, E, Lispi, M, Diverio, M, Barbieri, C, Bini, P, Angelino, G, Dada, O, Orlandi, A, Pistarini, C, Pisoni, C, Manera, M, Compostini, A, Aiachini, B, Pessina, A, Musio, A, Colombetti, E, Taraschi, S, Aluas, M, Croci, M, Negri, M, Zucchella, M, Guizzetti, G, Salamone, E, De Valle, G, Caroppi, S, Ramorino, E, Salina, D, Spannocchi, G, Strazzer, S, Villa, F, Guarnerio, C, Chiambretto, P, Dartizio, R, Feller, S, Franzoni, L, Giunco, F, Massironi, L, Azimonti, R, Marcolli, S, Meinecke, C, Buse, G, Marchesi, V, Molteni, F, Gramigna, C, Lanfranchi, M, Pisani, L, Sozzi, M, Borri, G, Cannata, A, Grillo, A, Roca, S, Locati, D, Arenare, F, Magnoni, A, Perin, C, Sussele, M, Quintana, T, Camici, M, Magistrelli, F, Samueli, T, San Felici, L, Manganelli, F, Vignati, M, Bellanova, L, Cattaneo, N, Ferraro, F, Olgiati, E, Brizioli, E, Vallasciani, M, Gironelli, L, Calderisi, E, Novelli, A, Scaramuzzo, R, Perino, C, Forno, R, Zamponi, E, Corna, S, Ferrario, S, Lamberti, G, Rosso, S, Colonna, F, Navarro, J, Trabacca, A, Gennaro, L, Bertolini, A, Addante, L, Amenduni, M, Fiore, P, Amoruso, M, Colella, D, Angelillo, M, Melis, G, Desogus, G, Baglieri, A, Galardi, G, Sant'Angelo, A, Posteraro, F, Forte, F, Logi, F, Potenza, F, Lino, M, Zaccara, G, Ragazzoni, A, Chiaramonti, R, March, A, Grober, G, Kaczor, M, Zelger, P, Mazzini, N, Monti, A, Zampolini, M, Scarponi, F, Avesani, R, Salvi, L, Tonin, P, Cosentino, E, Furlanetto, N, Bordin, M, Martinuzzi, A, Buffoni, M, Boldrini, P, and Semerjian, M

Subjects
Adult, Male, 030506 rehabilitation, medicine.medical_specialty, Propensity score, medicine.medical_treatment, Physical Therapy, Sports Therapy and Rehabilitation, Disorders of consciousness, Severity of Illness Index, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Clinical Protocols, Severity of illness, medicine, Humans, Longitudinal Studies, Aged, Vegetative state, Rehabilitation, business.industry, Minimally conscious state, Recovery of Function, Disability Rating Scale, Middle Aged, medicine.disease, Treatment Outcome, Italy, Propensity score matching, Physical therapy, Consciousness Disorders, Female, Observational study, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract

To evaluate the effects of rehabilitation (physical and cognitive) treatments on the diagnosis severity and Disability Rating Scale (DRS) scores, adjusted for a number of potential confounders measured at baseline, in a large cohort of patients with disorders of consciousness across time.An observational, longitudinal (2 evaluations), multicenter project was made in 90 Italian centers.Patients (N=364) with a diagnosis of disorders of consciousness.Primary outcome was the severity of diagnosis, expressed on an ordinal scale (OtherMCSVSdeath). In the Other group were included patients who emerged from an MCS and recovered consciousness. The secondary outcome was the DRS score (range of 0-30 with 30 being the worst value). The DRS is a tool used to define the level of residual disability, commonly used to classify the level of functional impairment in patients with acquired brain injury. Both outcomes were measured for each wave.A total of 364 subjects having a complete set of demographic, clinical, and pharmacologic data were included in the propensity score (PS) analysis. Results showed that the rehabilitation treatments (physical and cognitive) reduced the clinical worsening over time in both severity diagnosis and DRS (around 6.5 points) in patients with disorders of consciousness across different propensity score strategies (ie, PS matching, PS adjustment, and PS-weighted procedures). In addition, cognitive protocols seem to be limited to patients with a median value of DRS=23.Our propensity score analysis suggests that rehabilitation treatment protocols seem effective and should be applied to a broader spectrum of patients with disorders of consciousness.

Published
2020
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9. Effect of Rehabilitation Treatments on Disability in Persons With Disorders of Consciousness: A Propensity Score Study

Author

Sattin, D, Leonardi, M, Nelli, B, Bramanti, P, Marino, S, Ferro, S, Basaglia, N, Guido, D, Dolce, G, Lucca, L, Cortese, M, Ermio, C, Dattilo, T, Capomolla, S, Di Iasi, G, Estraneo, A, De Tanti, A, Maradini, N, Piperno, R, Ferri, A, Bergonzoni, A, Chiavaroli, F, Di Marco, F, Carli, S, Biasutti, E, Marin, D, Formisano, R, Rizza, F, Pisarri, F, Vichi, R, D'Urso, A, Grillo, G, Leto, A, Guerrasio, M, Taliento, C, Napolitano, F, Castelli, E, Lispi, M, Diverio, M, Barbieri, C, Bini, P, Angelino, G, Dada, O, Orlandi, A, Pistarini, C, Pisoni, C, Manera, M, Compostini, A, Aiachini, B, Pessina, A, Musio, A, Colombetti, E, Taraschi, S, Aluas, M, Croci, M, Negri, M, Zucchella, M, Guizzetti, G, Salamone, E, De Valle, G, Caroppi, S, Ramorino, E, Salina, D, Spannocchi, G, Strazzer, S, Villa, F, Guarnerio, C, Chiambretto, P, Dartizio, R, Feller, S, Franzoni, L, Giunco, F, Massironi, L, Azimonti, R, Marcolli, S, Meinecke, C, Buse, G, Marchesi, V, Molteni, F, Gramigna, C, Lanfranchi, M, Pisani, L, Sozzi, M, Borri, G, Cannata, A, Grillo, A, Roca, S, Locati, D, Arenare, F, Magnoni, A, Perin, C, Sussele, M, Quintana, T, Camici, M, Magistrelli, F, Samueli, T, San Felici, L, Manganelli, F, Vignati, M, Bellanova, L, Cattaneo, N, Ferraro, F, Olgiati, E, Brizioli, E, Vallasciani, M, Gironelli, L, Calderisi, E, Novelli, A, Scaramuzzo, R, Perino, C, Forno, R, Zamponi, E, Corna, S, Ferrario, S, Lamberti, G, Rosso, S, Colonna, F, Navarro, J, Trabacca, A, Gennaro, L, Bertolini, A, Addante, L, Amenduni, M, Fiore, P, Amoruso, M, Colella, D, Angelillo, M, Melis, G, Desogus, G, Baglieri, A, Galardi, G, Sant'Angelo, A, Posteraro, F, Forte, F, Logi, F, Potenza, F, Lino, M, Zaccara, G, Ragazzoni, A, Chiaramonti, R, March, A, Grober, G, Kaczor, M, Zelger, P, Mazzini, N, Monti, A, Zampolini, M, Scarponi, F, Avesani, R, Salvi, L, Tonin, P, Cosentino, E, Furlanetto, N, Bordin, M, Martinuzzi, A, Buffoni, M, Boldrini, P, Semerjian, M, Sattin D., Leonardi M., Nelli B., Bramanti P., Marino S., Ferro S., Basaglia N., Guido D., Dolce G., Lucca L. F, Cortese M. D., Ermio C., Dattilo T. L., Capomolla S., Di Iasi G., Estraneo A., De Tanti A., Maradini N., Piperno R., Ferri A., Basaglia N, Bergonzoni A., Chiavaroli F., Di Marco F., Carli S., Biasutti E., Marin D., Formisano R., Rizza F., Pisarri F. M., Vichi R., D'Urso A., Grillo G., Leto A., Guerrasio M., Taliento C., Napolitano F., Castelli E., Lispi M. L., Diverio M., Barbieri C., Bini P. P., Angelino G., Dada O., Orlandi A., Pistarini C., Pisoni C., Manera M., Compostini A., Aiachini B., Pessina A., Musio A., Colombetti E., Taraschi S., Aluas M., Croci M., Negri M., Zucchella M. A., Guizzetti G. B., Salamone E., De Valle G., Caroppi S. M., Ramorino E., Salina D., Spannocchi G., Strazzer S., Villa F., Guarnerio C., Chiambretto P., Dartizio R., Feller S., Franzoni L., Giunco F., Massironi L., Azimonti R., Marcolli S. S., Meinecke C., Buse G., Marchesi V, Molteni F., Gramigna C., Lanfranchi M., Pisani L., Sozzi M., Borri G., Cannata A. P., Grillo A., Roca S., Locati D., Arenare F., Magnoni A., Perin C., Sussele M., Quintana T. Y., Camici M. E., Magistrelli F., Samueli T., San Felici L., Manganelli F., Vignati M., Bellanova L., Cattaneo N., Ferraro F., Olgiati E., Brizioli E., Vallasciani M., Gironelli L., Calderisi E., Novelli A., Scaramuzzo R., Perino C., Forno R., Zamponi E., Corna S., Ferrario S., Lamberti G., Rosso S., Colonna F., Navarro J., Trabacca A., Gennaro L., Bertolini A., Addante L., Amenduni M. T., Fiore P., Amoruso M. T., Colella D., Angelillo M. T., Melis G., Desogus G., Baglieri A., Galardi G., Sant'Angelo A., Posteraro F., Forte F., Logi F., Potenza F., Lino M., Zaccara G., Ragazzoni A., Chiaramonti R., March A., Grober G., Kaczor M., Zelger P, Mazzini N., Monti A., Zampolini M., Scarponi F., Avesani R., Salvi L., Tonin P., Cosentino E., Furlanetto N., Bordin M., Martinuzzi A., Buffoni M., Boldrini P., Semerjian M., Sattin, D, Leonardi, M, Nelli, B, Bramanti, P, Marino, S, Ferro, S, Basaglia, N, Guido, D, Dolce, G, Lucca, L, Cortese, M, Ermio, C, Dattilo, T, Capomolla, S, Di Iasi, G, Estraneo, A, De Tanti, A, Maradini, N, Piperno, R, Ferri, A, Bergonzoni, A, Chiavaroli, F, Di Marco, F, Carli, S, Biasutti, E, Marin, D, Formisano, R, Rizza, F, Pisarri, F, Vichi, R, D'Urso, A, Grillo, G, Leto, A, Guerrasio, M, Taliento, C, Napolitano, F, Castelli, E, Lispi, M, Diverio, M, Barbieri, C, Bini, P, Angelino, G, Dada, O, Orlandi, A, Pistarini, C, Pisoni, C, Manera, M, Compostini, A, Aiachini, B, Pessina, A, Musio, A, Colombetti, E, Taraschi, S, Aluas, M, Croci, M, Negri, M, Zucchella, M, Guizzetti, G, Salamone, E, De Valle, G, Caroppi, S, Ramorino, E, Salina, D, Spannocchi, G, Strazzer, S, Villa, F, Guarnerio, C, Chiambretto, P, Dartizio, R, Feller, S, Franzoni, L, Giunco, F, Massironi, L, Azimonti, R, Marcolli, S, Meinecke, C, Buse, G, Marchesi, V, Molteni, F, Gramigna, C, Lanfranchi, M, Pisani, L, Sozzi, M, Borri, G, Cannata, A, Grillo, A, Roca, S, Locati, D, Arenare, F, Magnoni, A, Perin, C, Sussele, M, Quintana, T, Camici, M, Magistrelli, F, Samueli, T, San Felici, L, Manganelli, F, Vignati, M, Bellanova, L, Cattaneo, N, Ferraro, F, Olgiati, E, Brizioli, E, Vallasciani, M, Gironelli, L, Calderisi, E, Novelli, A, Scaramuzzo, R, Perino, C, Forno, R, Zamponi, E, Corna, S, Ferrario, S, Lamberti, G, Rosso, S, Colonna, F, Navarro, J, Trabacca, A, Gennaro, L, Bertolini, A, Addante, L, Amenduni, M, Fiore, P, Amoruso, M, Colella, D, Angelillo, M, Melis, G, Desogus, G, Baglieri, A, Galardi, G, Sant'Angelo, A, Posteraro, F, Forte, F, Logi, F, Potenza, F, Lino, M, Zaccara, G, Ragazzoni, A, Chiaramonti, R, March, A, Grober, G, Kaczor, M, Zelger, P, Mazzini, N, Monti, A, Zampolini, M, Scarponi, F, Avesani, R, Salvi, L, Tonin, P, Cosentino, E, Furlanetto, N, Bordin, M, Martinuzzi, A, Buffoni, M, Boldrini, P, Semerjian, M, Sattin D., Leonardi M., Nelli B., Bramanti P., Marino S., Ferro S., Basaglia N., Guido D., Dolce G., Lucca L. F, Cortese M. D., Ermio C., Dattilo T. L., Capomolla S., Di Iasi G., Estraneo A., De Tanti A., Maradini N., Piperno R., Ferri A., Basaglia N, Bergonzoni A., Chiavaroli F., Di Marco F., Carli S., Biasutti E., Marin D., Formisano R., Rizza F., Pisarri F. M., Vichi R., D'Urso A., Grillo G., Leto A., Guerrasio M., Taliento C., Napolitano F., Castelli E., Lispi M. L., Diverio M., Barbieri C., Bini P. P., Angelino G., Dada O., Orlandi A., Pistarini C., Pisoni C., Manera M., Compostini A., Aiachini B., Pessina A., Musio A., Colombetti E., Taraschi S., Aluas M., Croci M., Negri M., Zucchella M. A., Guizzetti G. B., Salamone E., De Valle G., Caroppi S. M., Ramorino E., Salina D., Spannocchi G., Strazzer S., Villa F., Guarnerio C., Chiambretto P., Dartizio R., Feller S., Franzoni L., Giunco F., Massironi L., Azimonti R., Marcolli S. S., Meinecke C., Buse G., Marchesi V, Molteni F., Gramigna C., Lanfranchi M., Pisani L., Sozzi M., Borri G., Cannata A. P., Grillo A., Roca S., Locati D., Arenare F., Magnoni A., Perin C., Sussele M., Quintana T. Y., Camici M. E., Magistrelli F., Samueli T., San Felici L., Manganelli F., Vignati M., Bellanova L., Cattaneo N., Ferraro F., Olgiati E., Brizioli E., Vallasciani M., Gironelli L., Calderisi E., Novelli A., Scaramuzzo R., Perino C., Forno R., Zamponi E., Corna S., Ferrario S., Lamberti G., Rosso S., Colonna F., Navarro J., Trabacca A., Gennaro L., Bertolini A., Addante L., Amenduni M. T., Fiore P., Amoruso M. T., Colella D., Angelillo M. T., Melis G., Desogus G., Baglieri A., Galardi G., Sant'Angelo A., Posteraro F., Forte F., Logi F., Potenza F., Lino M., Zaccara G., Ragazzoni A., Chiaramonti R., March A., Grober G., Kaczor M., Zelger P, Mazzini N., Monti A., Zampolini M., Scarponi F., Avesani R., Salvi L., Tonin P., Cosentino E., Furlanetto N., Bordin M., Martinuzzi A., Buffoni M., Boldrini P., and Semerjian M.

Abstract

Objective: To evaluate the effects of rehabilitation (physical and cognitive) treatments on the diagnosis severity and Disability Rating Scale (DRS) scores, adjusted for a number of potential confounders measured at baseline, in a large cohort of patients with disorders of consciousness across time. Design and Setting: An observational, longitudinal (2 evaluations), multicenter project was made in 90 Italian centers. Participants: Patients (N=364) with a diagnosis of disorders of consciousness. Main Outcome Measures: Primary outcome was the severity of diagnosis, expressed on an ordinal scale (Other

Published
2020

15. Membrane Estrogen Receptor (GPER) and Follicle-Stimulating Hormone Receptor (FSHR) Heteromeric Complexes Promote Human Ovarian Follicle Survival

Author

Casarini, L, Lazzaretti, C, Paradiso, E, Limoncella, S, Riccetti, L, Sperduti, S, Melli, B, Marcozzi, S, Anzivino, C, Sayers, Ns, Czapinski, J, Brigante, G, Poti, F, La Marca, A, De Pascali, F, Reiter, E, Falbo, A, Daolio, J, Villani, Mt, Lispi, M, Orlando, G, Klinger, Fg, Fanelli, F, Rivero-Muller, A, Hanyaloglu, Ac, Simoni, M, Biotechnology and Biological Sciences Research Council (BBSRC), Genesis Research Trust, Università degli Studi di Modena e Reggio Emilia (UNIMORE), University of Rome 'Tor Vergeta', Imperial College London, Medical University of Lublin, University of Parma = Università degli studi di Parma [Parme, Italie], Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Dynamiques de populations multi-échelles pour des systèmes physiologiques (MUSCA), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Merck Research Laboratories, Università degli Studi di Roma Tor Vergata [Roma], Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Università degli studi di Parma = University of Parma (UNIPR), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE)

Subjects
endocrine system, Settore BIO/17, Endocrine Regulation, Female Reproductive Endocrinology, [SDV]Life Sciences [q-bio], lcsh:Q, Molecular Biology, lcsh:Science, Article
Abstract

Summary Classically, follicle-stimulating hormone receptor (FSHR)-driven cAMP-mediated signaling boosts human ovarian follicle growth and oocyte maturation. However, contradicting in vitro data suggest a different view on physiological significance of FSHR-mediated cAMP signaling. We found that the G-protein-coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with preferential Gαs protein/cAMP-pathway coupling and FSH responsiveness of patients undergoing controlled ovarian stimulation. In contrast, FSHR/GPER heteromers triggered anti-apoptotic/proliferative FSH signaling delivered via the Gβγ dimer, whereas impairment of heteromer formation or GPER knockdown enhanced the FSH-dependent cell death and steroidogenesis. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation., Graphical Abstract, Highlights • G-protein-coupled estrogen receptor (GPER) interacts with FSH receptor (FSHR) • FSHR/GPER heteromers reprogram FSH-induced death signals to proliferative stimuli • Anti-apoptotic signaling of heteromers is via a GPER-Gαs inhibitory complex and Gβγ • Heteromer formation impacts follicle maturation and FSH responses of IVF patients, Molecular Biology; Female Reproductive Endocrinology; Endocrine Regulation

Published
2020
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17. APOPTOSIS RATE IN CUMULUS CELLS AS POSSIBLE MOLECULAR BIOMARKER FOR OOCYTE COMPETENCE

Author

Bosco, L., Roccheri, M., Martino, C., Chiarelli, R., Lispi, M., Ruvolo, G., Bosco, L, Roccheri, MC, Martino, C, Chiarelli, R, Lispi, M, and Ruvolo, G.

Subjects
Oocyte competence, Granulosa cells, DNA fragmentation, Hormonal treatment, Poor responder, Settore BIO/06 - Anatomia Comparata E Citologia
Abstract

Several lines of evidence showed that apoptosis rate of cumulus cells in oocytes derived by assisted reproductive technologies could be used as an indicator of fertilizing gamete quality. Aim of the study was to investigate the effects of three different ovarian stimulation protocols on the biological and clinical outcome in hyporesponder patients. Collected data showed a higher significant rate of DNA fragmentation index (DFI) in U group (patients treated with Highly Purified human Menopausal Gonadotrophin) than in P group (treated with recombinant human Follicle Stimulating Hormone (r-hFSH) combined with recombinant human Luteinizing Hormone (r-hLH)). Both groups R (treated with r-hFSH alone) and P showed a significant increase in collected and fertilized oocytes number, embryo quality number. This study showed that combined r-hFSH/r-hLH therapy could represent the best pharmacological strategy for controlled ovarian stimulation and suggests to use DFI as a biomarker of ovarian function in hyporesponder patients.

Published
2017

18. Apoptosis and pAKT levels in cumulus cells of patients undergoing in vitro fertilization program with specific polymorphisms of gonadotropins and their receptors: a case-control study

Author

Bosco, L., Roccheri, M., Paffoni, A., Piomboni, P., Valerio, D., Sarcina, E., Lispi, M., Ruvolo, G., Bosco, L, Roccheri, MC, Paffoni, A, Piomboni, P, Valerio, D, Sarcina, E, Lispi, M, and Ruvolo, G.

Subjects
Apoptosis, polymorphism, oocytes, Settore BIO/06 - Anatomia Comparata E Citologia
Abstract

Study question Is there a difference in oocyte competence among patients with different gonadotrophin polymorphisms, after ovarian stimulation with r-FSH? Summary Answer Higher DNA Fragmentation Index and cleaved caspase-3 related to lower level of pAKT has been observed in patients with specific gonadotrophin polymorphism (FSHR and LHB). What is known already • In our experience, the DFI, the percentage of cleaved caspase-3 and the pAKT on cumulus cells can be used as molecular markers of oocyte competence; • The polymorphic variant of LHB is characterized by an extra glycosylation signal into the β subunit. This molecular variation influences the pharmacokinetic properties of v-betaLH, showing an elevated bioactivity in vitro, but a significantly shorter half-life in circulation if compared with the wild type LH. These patients show sub-optimal ovarian response after pharmacological ovarian stimulation with r-FSH; We know that FSH receptor (FSHR) variants, Thr307/Asn680 and Ala307/Ser680, are involved in the response to ovarian stimulation. Study design, size, duration The aim of the study was to determine the apoptosis levels (in terms of percentage of DNA fragmentation and percentage of cleaved caspase-3) and the pAKT levels as potential markers of oocyte competence in the cumulus cells of individual patients with specific FSHR and LHB polymorphisms. It was a retrospective study. It was included 36 patients. The duration of the study was 12 months. Participants/materials, setting, methods Patients were normo-responder patients with a normal basic level of FSH (

Published
2016

25. Male and female fertility preservation

Author

Berthelot-ricou, A., primary, Perrin, J., additional, Roustan, A., additional, Di Giorgio, C., additional, De Meo, M., additional, Botta, A., additional, Orsiere, T., additional, Courbiere, B., additional, Martinez, J. G., additional, Botella, I. M., additional, Casas, I. P., additional, Novella-Maestre, E., additional, Colom, P. J. F., additional, Rubio, J., additional, Martinez, A. P., additional, Rodriguez-Wallberg, K. A., additional, de Mena, S. A., additional, Malm, E., additional, Larsson, A., additional, Kuiper, R., additional, Hassan, M., additional, Herraiz, S., additional, Rodriguez-Iglesias, B., additional, Diaz-Garcia, C., additional, Mirabet, V., additional, Pellicer, A., additional, Aljaser, F. S., additional, Medrano, J. H., additional, Rhodes, S., additional, Tomlinson, M. J., additional, Campbell, B. K., additional, Dong, F., additional, Shi, S., additional, Dai, S., additional, Liu, X., additional, Su, Y., additional, Guo, Y., additional, Wang, F., additional, Xin, Z., additional, Song, W., additional, Jin, H., additional, Sun, Y., additional, Ortega-Hrepich, C., additional, Stoop, D., additional, Guzman, L., additional, Van Landuyt, L., additional, Tournaye, H., additional, Smitz, J., additional, De Vos, M., additional, Diaz, C., additional, Vera, F., additional, Youm, H., additional, Lee, J., additional, Lee, J. r., additional, Lee, J. y., additional, Jee, B. c., additional, Suh, C. s., additional, Kim, S. h., additional, Lotz, L., additional, Hoffmann, I., additional, Muller, A., additional, Hackl, J., additional, Schulz, C., additional, Reissmann, C., additional, Cupisti, S., additional, Oppelt, P. G., additional, Heusinger, K., additional, Hildebrandt, T., additional, Beckmann, M. W., additional, Dittrich, R., additional, Klinger, F., additional, Rossi, V., additional, Lispi, M., additional, Longobardi, S., additional, De Felici, M., additional, Fabbri, R., additional, Vicenti, R., additional, Martino, N. A., additional, Parazza, I., additional, Macciocca, M., additional, Magnani, V., additional, Pasquinelli, G., additional, Dell'Aquila, M. E., additional, Venturoli, S., additional, Fisch, B., additional, Orvieto, R., additional, Fisher, N., additional, Ben-Haroush, A., additional, Stein, A., additional, Abir, R., additional, Al-Samerria, S., additional, McFarlane, J., additional, Almahbobi, G., additional, Klocke, S., additional, Tappehorn, C., additional, and Griesinger, G., additional

Published
2013
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26. Andrology

Author

Carchenilla, M. S. C., primary, Agudo, D., additional, Rubio, S., additional, Becerra, D., additional, Bronet, F., additional, Garcia-Velasco, J. A., additional, Pacheco, A., additional, Lardone, M., additional, Piottante, A., additional, Parada-Bustamante, A., additional, Argandona, F., additional, Florez, M., additional, Espinoza, A., additional, Ebensperger, M., additional, Castro, A., additional, Cohen-Bacrie, M., additional, Belloc, S., additional, Dalleac, A., additional, Amar, E., additional, Izard, V., additional, Hazout, A., additional, Cohen-Bacrie, P., additional, de Mouzon, J., additional, Muzzonigro, F., additional, Crivello, A. M., additional, Stanghellini, I., additional, Bernardini, L., additional, Ferraretti, A. P., additional, Magli, C., additional, Gianaroli, L., additional, Martin, P. S., additional, Duvison, M. H., additional, Silva, M. D., additional, Gosalvez, J., additional, Martin, F. S., additional, Pomante, A., additional, Colombo, F., additional, Mattioli, M., additional, Barboni, B., additional, Magli, M. C., additional, Hacifazlioglu, O., additional, Findikli, N., additional, Goktolga, U., additional, Bahceci, M., additional, Jakab, A., additional, Mokanszki, A., additional, Varga, A., additional, Benyo, M., additional, Kassai, Z., additional, Olah, E., additional, Molnar, Z., additional, Gundogan, G. I., additional, Bozkurt, H. H., additional, Irez, T., additional, Domingo, A., additional, Anarte, C., additional, Presilla, N., additional, Calvo, I., additional, Aguirre, O., additional, Oroquieta, A., additional, Agirregoikoa, J. A., additional, De Pablo, J. L., additional, Barrenetxea, G., additional, Moragues, I., additional, Medrano, M. L., additional, Montoya, A., additional, Ramos, B., additional, Torres, M. J. G., additional, Aizpurua, J., additional, Ibala, S. R., additional, Ghedir, H., additional, Mehri, A., additional, Zidi, I., additional, Brahem, S., additional, Mehdi, M., additional, Ajina, M., additional, Saad, A., additional, Gomez-Torres, M. J., additional, Cavaco, J. E., additional, Rato, L., additional, Alves, M. G., additional, Dias, T. R., additional, Lopes, G., additional, Socorro, S., additional, Oliveira, P. F., additional, Lobascio, A. M., additional, Minasi, M. G., additional, Greco, E., additional, Bungum, M., additional, Bungum, A., additional, Silver, N., additional, Zahiri, M., additional, Movahedin, M., additional, Mowla, S. J., additional, Noruzinia, M., additional, Huleihel, M., additional, Abarbanel, Y., additional, Haber, E. P., additional, Azab, M., additional, Lan, D., additional, Lunenfeld, E., additional, Smith, M. J., additional, Neri, Q. V., additional, Harvey, L., additional, Rosenwaks, Z., additional, Palermo, G. D., additional, Alhalabi, M., additional, Samawi, S., additional, Droubi, H., additional, Khalaf, M., additional, Taha, A., additional, Khatib, R., additional, Bednarowska-flisiak, A., additional, Wcislo, M., additional, Liss, J., additional, Swider, A., additional, Szczyglinska, J., additional, Grzymkowska, M., additional, Bruszczynska, A., additional, Glowacka, J., additional, Kitowska-Marszalkowska, K., additional, Krapchev, M., additional, Mirecka, A., additional, Wisniewska, K., additional, Lukaszuk, K., additional, Natali, I., additional, Tamburrino, L., additional, Cambi, M., additional, Marchiani, S., additional, Noci, I., additional, Maggi, M., additional, Forti, G., additional, Baldi, E., additional, Muratori, M., additional, Ferraretto, X., additional, Pasquet, B., additional, Damond, F., additional, Matheron, S., additional, Epelboin, S., additional, Yahi, S., additional, Demailly, P., additional, Rougier, N., additional, Yazbeck, C., additional, Delaroche, L., additional, Longuet, P., additional, Llabador, M., additional, Estellat, C., additional, Patrat, C., additional, Askarijahromi, M., additional, Amanlu, M., additional, Mowla, S. j., additional, Mazaheri, Z., additional, Christensen, P., additional, Sills, E. S., additional, Fischer, R., additional, Naether, O. G. J., additional, Walsh, D., additional, Rudolf, K., additional, Coull, G., additional, Baukloh, V., additional, Labouriau, R., additional, Birck, A., additional, Parisi, F., additional, Parrilla, B., additional, Oneta, M., additional, Savasi, V., additional, Veleva, L., additional, Milachich, T., additional, Bochev, I., additional, Antonova, I., additional, Shterev, A., additional, Vlaisavljevic, V., additional, Breznik, B. P., additional, Kovacic, B., additional, Serrano, M., additional, Gonzalvo, M. C., additional, Clavero, A., additional, Fernandez, M. F., additional, Mozas, J., additional, Martinez, L., additional, Fontes, J., additional, Carrillo, S., additional, Lopez-Regalado, M. L., additional, Lopez-Leria, B., additional, Orozco, I., additional, Mantilla, A., additional, Castilla, J. A., additional, Mskhalaya, G., additional, Zakharova, E., additional, Zaletova, V., additional, Kasatonova, E., additional, Melnik, Y., additional, Efremov, E., additional, Schiewe, M. C., additional, Verheyen, G., additional, Tournaye, H., additional, Phletincx, I., additional, Sims, C. A., additional, Rothman, C., additional, Borges, E., additional, Setti, A. S., additional, Braga, D. P. A. F., additional, Vingris, L., additional, Iaconelli, A., additional, Dupont, C., additional, Faure, C., additional, Sermondade, N., additional, Gautier, B., additional, Herbemont, C., additional, Aknin, I., additional, Klein, J. P., additional, Cedrin-Durnerin, I., additional, Wolf, J. P., additional, Czernichow, S., additional, Levy, R., additional, Rondanino, C., additional, Chauffour, C., additional, Ouchchane, L., additional, Artonne, C., additional, Janny, L., additional, Lobaccaro, J. M., additional, Volle, D. H., additional, Brugnon, F., additional, Colacurci, N., additional, Piomboni, P., additional, Ruvolo, G., additional, Lombardo, F., additional, Verde, E. L., additional, De Leo, V., additional, Lispi, M., additional, Papaleo, E., additional, De Palo, R., additional, Gandini, L., additional, Longobardi, S., additional, Yokota, Y., additional, Yokota, M., additional, Yokota, H., additional, Araki, Y., additional, Alshahrani, S., additional, Durairajanayagam, D., additional, Sharma, R., additional, Sabanegh, E., additional, Agarwal, A., additional, Hattori, H., additional, Nakajo, Y., additional, Ikeno, T., additional, Sato, Y., additional, Kyoya, T., additional, Kyono, K., additional, Li, B., additional, Li, J. B., additional, Xiao, X. F., additional, Ma, Y. F., additional, Wang, J., additional, Liang, X. X., additional, Zhao, H. X., additional, Jiang, F., additional, Yao, Y. Q., additional, Wang, X. H., additional, Roan, N. R., additional, Liu, H., additional, Muller, J., additional, Avila-Herrera, A., additional, Pollard, K. S., additional, Lishko, P., additional, Kirchhoff, F., additional, Munch, J., additional, Witkowska, H. E., additional, Greene, W. C., additional, Mangiarini, A., additional, Paffoni, A., additional, Restelli, L., additional, Guarneri, C., additional, Somigliana, E., additional, Ragni, G., additional, Bou, R., additional, Aleman, M., additional, Guardiola, F., additional, Camargo, C., additional, Oliveira, J. B. A., additional, Petersen, C. G., additional, Mauri, A. L., additional, Massaro, F. C., additional, Nicoletti, A., additional, Nascimento, A. M., additional, Vagnini, L. D., additional, Martins, A. M. V. C., additional, Cavagna, M., additional, Baruffi, R. L. R., additional, and Franco, J. G., additional

Published
2013
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27. POSTER VIEWING SESSION - FEMALE (IN) FERTILITY

Author

Engman, M., primary, Bystrom, B., additional, Varghese, S., additional, Lalitkumar, P. G. L., additional, Gemzell-Danielsson, K., additional, Romeu, C., additional, Urries, A., additional, Lierta, M., additional, Sanchez Rubio, J., additional, Sanz, B., additional, Perez, I., additional, Casis, L., additional, Salerno, A., additional, Nazzaro, A., additional, Di Iorio, L., additional, Bonassisa, P., additional, Van Os, L., additional, Vink-Ranti, C. Q. J., additional, de Haan-Cramer, J. H., additional, Rijnders, P. M., additional, Jansen, C. A. M., additional, Marino, S., additional, Granato, C., additional, Pastore, E., additional, Brandes, M., additional, Hamilton, C. J. C. M., additional, de Bruin, J. P., additional, Bots, R. S. G. M., additional, Nelen, W. L. D. M., additional, Kremer, J. A. M., additional, Szkodziak, P., additional, Wozniak, S., additional, Czuczwar, P., additional, Paszkowski, T., additional, Agirregoitia, N., additional, Peralta, L., additional, Mendoza, R., additional, Exposito, A., additional, Matorras, R., additional, Agirregoitia, E., additional, Chuderland, D., additional, Ben-Ami, I., additional, Kaplan-Kraicer, R., additional, Grossman, H., additional, Satchi- Fainaro, R., additional, Eldar-Boock, A., additional, Ron-El, R., additional, Shalgi, R., additional, Custers, I. M., additional, Scholten, I., additional, Moolenaar, L. M., additional, Flierman, P. A., additional, Dessel, T. J. H. M., additional, Gerards, M. H., additional, Cox, T., additional, Janssen, C. A. H., additional, van der Veen, F., additional, Mol, B. W. J., additional, Wathlet, S., additional, Adriaenssens, T., additional, Verheyen, G., additional, Coucke, W., additional, Smitz, J., additional, Feliciani, E., additional, Ferraretti, A. P., additional, Paesano, C., additional, Pellizzaro, E., additional, Magli, M. C., additional, Gianaroli, L., additional, Hernandez, J., additional, Rodriguez-Fuentes, A., additional, Garcia-Guzman, R., additional, Palumbo, A., additional, Radunovic, N., additional, Tosic, T., additional, Djukic, S., additional, Lockwood, J. C., additional, Van Landuyt, L., additional, Karayalcin, R., additional, Ozcan, S. A. R. P., additional, Ozyer, S., additional, Gurlek, B., additional, Kale, I., additional, Moraloglu, O., additional, Batioglu, S., additional, Chaudhury, K., additional, Narendra Babu, K., additional, Mamata Joshi, V., additional, Srivastava, S., additional, Chakravarty, B. N., additional, Viardot-Foucault, V., additional, Prasath, E. B., additional, Tai, B. C., additional, Chan, J. K. Y., additional, Loh, S. F., additional, Cordeiro, I., additional, Leal, F., additional, Soares, A. P., additional, Nunes, J., additional, Sousa, S., additional, Aguiar, A., additional, Carvalho, M., additional, Calhaz-Jorge, C., additional, Karkanaki, A., additional, Piouk, A., additional, Katsikis, I., additional, Mousatat, T., additional, Koiou, E., additional, Daskalopoulos, G. N., additional, Panidis, D., additional, Tolikas, A., additional, Tsakos, E., additional, Gerou, S., additional, Prapas, Y., additional, Loufopoulos, A., additional, Abanto, E., additional, Barrenetxea, G., additional, Agirregoikoa, J., additional, Anarte, C., additional, De Pablo, J. L., additional, Burgos, J., additional, Komarovsky, D., additional, Friedler, S., additional, Gidoni, Y., additional, Ben-ami, I., additional, Strassburger, D., additional, Bern, O., additional, Kasterstein E, E., additional, Komsky, A., additional, Maslansky, B., additional, Raziel, A., additional, Fuentes, A., additional, Argandona, F., additional, Gabler, F., additional, Galleguillos, A., additional, Torres, A., additional, Palomino, W. A., additional, Gonzalez-Fernandez, R., additional, Pena, O., additional, Avila, J., additional, Talebi Chahvar, S., additional, Biondini, V., additional, Battistoni, S., additional, Giannubilo, S., additional, Tranquilli, A. L., additional, Stensen, M. H., additional, Tanbo, T., additional, Storeng, R., additional, Abyholm, T., additional, Fedorcsak, P., additional, Johnson, S. R., additional, Foster, L., additional, Ellis, J., additional, Choi, J. R., additional, Joo, J. K., additional, Son, J. B., additional, Lee, K. S., additional, Helmgaard, L., additional, Klein, B. M., additional, Arce, J. C., additional, Sanhueza, P., additional, Donoso, P., additional, Salinas, R., additional, Enriquez, R., additional, Saez, V., additional, Carrasco, I., additional, Rios, M., additional, Gonzalez, P., additional, Macklon, N., additional, Guo, M., additional, Richardson, M., additional, Wilson, P., additional, Chian, R. C., additional, Eapen, A., additional, Hrehorcak, M., additional, Campbell, S., additional, Nargund, G., additional, Oron, G., additional, Fisch, B., additional, Ao, A., additional, Freidman, O., additional, Zhang, X. Y., additional, Ben-Haroush, A., additional, Abir, R., additional, Hantisteanu, S., additional, Ellenbogen, A., additional, Hallak, M., additional, Michaeli, M., additional, Fainaru, O., additional, Maman, E., additional, Yong, G., additional, Kedem, A., additional, Yeruahlmi, G., additional, Konopnicki, S., additional, Cohen, B., additional, Dor, J., additional, Hourvitz, A., additional, Moshin, V., additional, Croitor, M., additional, Hotineanu, A., additional, Ciorap, Z., additional, Rasohin, E., additional, Aleyasin, A., additional, Agha Hosseini, M., additional, Mahdavi, A., additional, Safdarian, L., additional, Fallahi, P., additional, Mohajeri, M. R., additional, Abbasi, M., additional, Esfahani, F., additional, Elnashar, A., additional, Badawy, A., additional, Totongy, M., additional, Mohamed, H., additional, Mustafa, F., additional, Seidman, D. S., additional, Tadir, Y., additional, Goldchmit, C., additional, Gilboa, Y., additional, Siton, A., additional, Mashiach, R., additional, Rabinovici, J., additional, Yerushalmi, G. M., additional, Inoue, O., additional, Kuji, N., additional, Fukunaga, T., additional, Ogawa, S., additional, Sugawara, K., additional, Yamada, M., additional, Hamatani, T., additional, Hanabusa, H., additional, Yoshimura, Y., additional, Kato, S., additional, Casarini, L., additional, La Marca, A., additional, Lispi, M., additional, Longobardi, S., additional, Pignatti, E., additional, Simoni, M., additional, Halpern, G., additional, Braga, D. P. A. F., additional, Figueira, R. C. S., additional, Setti, A. S., additional, Iaconelli Jr., A., additional, Borges Jr., E., additional, Vingris, L., additional, Pasqualotto, F. F., additional, Collado-Fernandez, E., additional, Harris, S. E., additional, Cotterill, M., additional, Elder, K., additional, Picton, H. M., additional, Serra, V., additional, Garrido, N., additional, Casanova, C., additional, Lara, C., additional, Remohi, J., additional, Bellver, J., additional, Steiner, H. P., additional, Kim, C. H., additional, You, R. M., additional, Nah, H. Y., additional, Kang, H. J., additional, Kim, S., additional, Chae, H. D., additional, Kang, B. M., additional, Reig Viader, R., additional, Brieno Enriquez, M. A., additional, Toran, N., additional, Cabero, L., additional, Giulotto, E., additional, Garcia Caldes, M., additional, Ruiz-Herrera, A., additional, Brieno-Enriquez, M., additional, Reig-Viader, R., additional, Martinez, F., additional, Garcia-Caldes, M., additional, Velthut, A., additional, Zilmer, M., additional, Zilmer, K., additional, Haller T. Kaart, E., additional, Karro, H., additional, Salumets, A., additional, Bromfield, J. J., additional, Sheldon, I. M., additional, Rezacova, J., additional, Madar, J., additional, Cuchalova, L., additional, Fiserova, A., additional, Shao, R., additional, and Billig, H., additional

Published
2011
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29. Clinical and molecular findings in patients with giant axonal neuropathy (GAN)

Author

Bruno, C., primary, Bertini, E., additional, Federico, A., additional, Tonoli, E., additional, Lispi, M. L., additional, Cassandrini, D., additional, Pedemonte, M., additional, Santorelli, F. M., additional, Filocamo, M., additional, Dotti, M. T., additional, Schenone, A., additional, Malandrini, A., additional, and Minetti, C., additional

Published
2004
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30. Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy

Author

Nabbout, R., primary, Gennaro, E., additional, Dalla Bernardina, B., additional, Dulac, O., additional, Madia, F., additional, Bertini, E., additional, Capovilla, G., additional, Chiron, C., additional, Cristofori, G., additional, Elia, M., additional, Fontana, E., additional, Gaggero, R., additional, Granata, T., additional, Guerrini, R., additional, Loi, M., additional, La Selva, L., additional, Lispi, M. L., additional, Matricardi, A., additional, Romeo, A., additional, Tzolas, V., additional, Valseriati, D., additional, Veggiotti, P., additional, Vigevano, F., additional, Vallée, L., additional, Dagna Bricarelli, F., additional, Bianchi, A., additional, and Zara, F., additional

Published
2003
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31. Effectiveness of recombinant human follicle-stimulating hormone (r-hFSH):recombinant human luteinizing hormone versus r-hFSH alone in assisted reproductive technology treatment cycles among women aged 35–40 years: A German database study

Author

Bielfeld, A.P., Schwarze, J.E., Verpillat, P., Lispi, M., Fischer, R., Hayward, B., Chuderland, D., D’Hooghe, T., and Krussel, J.S.

Abstract

This non-interventional study compared the effectiveness of recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) (2:1 ratio) versus r-hFSH alone for ovarian stimulation during assisted reproduction technology treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register (D·I·R). Numerically higher clinical pregnancy (29.8% [95% CI 28.2, 31.6] vs. 27.8% [26.5, 29.2]) and live birth (20.3% [18.7, 21.8] vs. 18.0% [16.6, 19.4]) rates were observed with r-hFSH:r-hLH versus r-hFSH alone. The treatment effect was consistently higher for r-hFSH:r-hLH compared with r-hFSH alone in terms of clinical pregnancy (RR 1.16 [1.05, 1.26]) and live birth (relative risk [RR] 1.16 [1.02, 1.31]) in a post-hoc analysis of women with 5–14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of r-hFSH:r-hLH for OS in women aged 35–40 years with normal ovarian reserve.

Published
2023
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36. Ketogenic diet in pharmacoresistant epilepsies

Author

Cusmai, R., Dionisi, C., Rizzo, C., Elia, M., Lispi, M. L., Coppohr, G., Distintcr, I., Scisciîr, N., Pascotur, A., Veggiotli, P., Resi, C., Cardinal, S., Bertoli, S., ANNA TAGLIABUE, Trentani, C., Lanzola, E., and Lanzi, G.

37. Testosterone Serum Levels Are Related to Sperm DNA Fragmentation Index Reduction after FSH Administration in Males with Idiopathic Infertility

Author

Monica Lispi, Panagiotis Drakopoulos, Giorgia Spaggiari, Francesca Caprio, Nicola Colacurci, Manuela Simoni, Daniele Santi, Lispi, M., Drakopoulos, P., Spaggiari, G., Caprio, F., Colacurci, N., Simoni, M., Santi, D., Clinical sciences, Surgical clinical sciences, and Centre for Reproductive Medicine - Gynaecology

Subjects
FSH, sperm DNA fragmentation index, idiopathic male infertility, testosterone, Medicine (miscellaneous), General Biochemistry, Genetics and Molecular Biology, reproductive medicine
Abstract

Purpose: Although a robust physiological rationale supports follicle stimulating hormone (FSH) use in male idiopathic infertility, useful biomarkers to evaluate its efficacy are not available. Thus, the primary aim of the study was to evaluate if testosterone serum levels are related to sperm DNA fragmentation (sDF) index change after FSH administration. The secondary aim was to confirm sDF index validity as a biomarker of FSH administration effectiveness in male idiopathic infertility. Methods: A retrospective, post-hoc re-analysis was performed on prospectively collected raw data of clinical trials in which idiopathic infertile men were treated with FSH and both testosterone serum levels and sDF were reported. Results: Three trials were included, accounting for 251 patients. The comprehensive analysis confirmed FSH’s beneficial effect on spermatogenesis detected in each trial. Indeed, an overall significant sDF decrease (p < 0.001) of 20.2% of baseline value was detected. Although sDF resulted to be unrelated to testosterone serum levels at baseline, a significant correlation was highlighted after three months of FSH treatment (p = 0.002). Moreover, testosterone serum levels and patients’ age significantly correlated with sDF (p = 0.006). Dividing the cohort into responders/not responders to FSH treatment according to sDF change, the FSH effectiveness in terms of sDF improvement was related to testosterone and male age (p = 0.003). Conclusion: Exogenous FSH administration in male idiopathic infertility is efficient in reducing sDF basal levels by about 20%. In terms of sDF reduction, 59.2% of the patients treated were FSH-responders. After three months of FSH administration, a significant inverse correlation between sDF and testosterone was detected, suggesting an association between the FSH-administration-related sDF improvement and testosterone serum levels increase. These observations lead to the hypothesis that FSH may promote communications or interactions between Sertoli cells and Leydig cells.

Published
2022

38. Exploring the human chorionic gonadotropin induced steroid secretion profile of mouse Leydig tumor cell line 1 by a 20 steroid LC-MS/MS panel

Author

Flaminia Fanelli, Matteo Magagnoli, Marco Mezzullo, Monica Lispi, Silvia Limoncella, Alessia Tommasini, Carla Pelusi, Daniele Santi, Manuela Simoni, Uberto Pagotto, Livio Casarini, Fanelli F., Magagnoli M., Mezzullo M., Lispi M., Limoncella S., Tommasini A., Pelusi C., Santi D., Simoni M., Pagotto U., and Casarini L.

Subjects
History, Androgen, Backdoor pathway, Leydig cells, Liquid chromatography – tandem mass spectrometry, Progesterone, Polymers and Plastics, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Cell Biology, Biochemistry, Industrial and Manufacturing Engineering, Leydig cell, Endocrinology, Molecular Medicine, Business and International Management, Molecular Biology
Abstract

The canonical androgen synthesis in Leydig cells involves Delta 5 and Delta 4 steroids. Besides, the backdoor pathway, eompassing 5 alpha and 5 alpha,3 alpha steroids, is gaining interest in fetal and adult pathophysiology. Moreover, the role of androgen epimers and progesterone metabolites is still unknown. We developed a liquid chromatographytandem mass spectrometry (LC-MS/MS) method for measuring 20 steroids and used it to investigate the steroid secretion induced by human chorionic gonadotropin (hCG) in the mouse Leydig tumor cell line 1 (mLTC1). Steroids were extracted from 500 mu L supernatants from unstimulated or 100 pM hCG-exposed mLTC1 cells, separated on a Luna C8 100 x 3 mm, 3 mu m column, with 100 mu M NH4F and methanol as mobile phases, and analyzed by positive electrospray ionization and multiple reaction monitoring. Sensitivity ranged within 0.012-38.0 nmol/L. Intra-assay and inter-assay imprecision were < 9.1% and 10.0%, respectively. Trueness, recovery and matrix factor were within 93.4-122.0, 55.6-104.1 and 76.4-106.3%, respectively. Levels of 16OH-progesterone, 11-deoxycortisol, androstenedione, 11-deoxycorticosterone, testosterone, 17OH-progesterone, androstenedione, epitestosterone, dihydrotestosterone, progesterone, androsterone and 17OH-allopregnanolone were effectively measured. Traces of 17OH-dihydroprogesterone, androstanediol and dihydroprogesterone were found, whereas androstenediol, 17OH-pregnenolone, dehydroepiandrosterone, pregnenolone and allopregnanolone showed no peak. hCG induced an increase of 80.2-102.5 folds in 16OH-progesterone, androstenedione and testosterone, 16.6 in dihydrotestosterone, 12.2-27.5 in epitestosterone, progesterone and metabolites, 8.1 in 17OH-allopregnanolone and

Published
2023
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39. Gene Expression and Apoptosis Levels in Cumulus Cells of Patients with Polymorphisms of FSHR and LHB Undergoing in Vitro Fertilization Program

Author

Monica Lispi, Maria Carmela Roccheri, Elena Sarcina, Claudio Luparello, Domenico Valerio, Stefania Ferrari, Liana Bosco, Daniele Santi, Giovanni Ruvolo, Paola Piomboni, Bosco, L., Ruvolo, G., Luparello, C., Ferrari, S., Valerio, D., Santi, D., Piomboni, P., Sarcina, E., Lispi, M., and Roccheri, M.

Subjects
0301 basic medicine, Apoptosis, Cumulus cells, FSHR, Gene expression, LH, Polymorphism, Physiology, lcsh:Physiology, Gonadotropin-Releasing Hormone, 0302 clinical medicine, Gene Frequency, lcsh:QD415-436, Settore BIO/06 - Anatomia Comparata E Citologia, Cells, Cultured, In Situ Hybridization, Fluorescence, 030219 obstetrics & reproductive medicine, lcsh:QP1-981, Caspase 3, medicine.anatomical_structure, Cumulus cell, Receptors, FSH, DNA fragmentation, Female, Signal Transduction, Adult, Heterozygote, medicine.medical_specialty, endocrine system, Genotype, Granulosa cell, DNA Fragmentation, Fertilization in Vitro, Biology, Real-Time Polymerase Chain Reaction, Buserelin, Polymorphism, Single Nucleotide, lcsh:Biochemistry, 03 medical and health sciences, Follicle, Internal medicine, medicine, Humans, Apoptosi, Heterozygote advantage, Luteinizing Hormone, beta Subunit, Oocyte, 030104 developmental biology, Endocrinology, Haplotypes, Multivariate Analysis, Oocytes, Follicle-stimulating hormone receptor, Proto-Oncogene Proteins c-akt
Abstract

Background/Aims: FSH receptor (FSHR) Ala307Thr and Asn680Ser and LHβ chain (LHB) Trp28Arg and Ile35Thr polymorphisms affect the response to pharmacological ovarian stimulation with r-FSH in women undergoing assisted reproductive treatment (ART). Here, we evaluated the expression level of selected genes involved in follicle maturation and the possible onset of apoptosis in cumulus cells of patients with single and double FSHR and LHB polymorphisms, as potential markers of oocyte competence. Methods: Cumulus cells from 36 stimulated patients were collected and SNP genotyping performed by PCR. Gene expression was evaluated through real-time PCR, and apoptosis estimated via TUNEL assay, and cleaved caspase-3 and pAKT immunostaining. Results: The cumulative data show significant correlations indicating that the genetic alteration of FSHR and/or LHB genes may lead to perturbations of the signaling network programmed to granulosa cell survival and follicle development. Notably, when double heterozygotes were compared to the rest of the patients, a higher level of apoptosis in terms of both DNA fragmentation index and amount of active caspase-3 was observed in cumulus cells. Conclusions: These results may help to define personalized stimulation protocols in ART programs, to increase the success rate of ICSI procedures in accordance with the polymorphic condition of the individual patient.

Published
2017

40. Expert opinion on refined and extended key performance indicators for individualized ovarian stimulation for assisted reproductive technology.

Author

Sunkara SK, Schwarze JE, Orvieto R, Fischer R, Dahan MH, Esteves SC, Lispi M, D'Hooghe T, and Alviggi C

Abstract

Objective: To assess the adequate ovarian follicular development and oocyte recovery between ovarian potential (antral follicle count [AFC]) before the start of ovarian stimulation (OS) and oocyte quantity and quality at oocyte retrieval. A holistic overview of the current key performance indicators (KPIs) was applied to identify the complementary strengths and identify where the current repertoire can be expanded., Design: Expert opinion., Setting: Not applicable., Patient(s): Not applicable., Intervention(s): None., Main Outcome Measure(s): To formulate a proposal for a refined and expanded repertoire of KPIs for individualized OS for assisted reproductive technology., Result(s): The performance and outcomes of OS on ovarian follicular development can be evaluated through the application of defined KPIs. Current KPIs for OS are the ovarian sensitivity index, follicular output rate (FORT), oocyte retrieval rate, and follicle-to-oocyte index (FOI). Notably, there are no specific KPIs dedicated to the assessment of follicular development (i.e., recruitment, selection, growth, and dominance). In light of this, we recommend expanding the current KPIs for OS to include "early FORT" (accounting for the number of follicles measuring ≥10 to 11 mm on day 5/6 of OS relative to AFC) and "modified FORT" (the ratio between the number of follicles measuring ≥12 mm at the time of oocyte maturation triggering and AFC); the extension of oocyte retrieval rate to include two discrete categories at oocyte retrieval-follicles measuring ≥12 mm and ≥16 mm-to ensure that all responsive follicles are accounted for; and FOI to be measured at oocyte maturation triggering and oocyte retrieval ("advanced FOI")., Conclusion(s): Once validated and adopted in clinical practice, we envisage that the proposed expanded KPIs measuring the effect of OS on follicular development (recruitment, selection, growth, and dominance) will increase the understanding of the relationship between ovarian reserve, measured by AFC, and oocyte quantity and quality at oocyte retrieval. This understanding will enable physicians to better evaluate the direct effect of different gonadotropins and doses on ovarian response, leading to a more personalized approach to OS in the context of assisted reproductive technology treatment., Competing Interests: Declaration of Interests S.K.S. reports receipt of payment or honoraria for nonpromotional educational lectures from Merck, Ferring, and MSD. J.-E.S. is an employee of Merck Healthcare KGaA, Darmstadt, Germany. R.O. reports receipt of consulting fees from Merck and Ferring and payment or honoraria for lectures from Merck and Ferring. RF has received honoraria for lectures from Merck Healthcare KGaA, Medea and Event Planet. M.H.D. has nothing to disclose. S.C.E. has received unrestricted research grants from Merck KGaA and consulting fees from Merck, Medea, and Event Planet; payment or honoraria for lecture fees from Merck, Sanitanova, Medea, and Event Planet; has a patent on the ART calculator; and is an advisory board member for Nature Reviews Urology (unpaid), Head of the Andrology Committee of the Brazilian Society of Human Reproduction (unpaid), and Co-chair of the Male Infertility Group, WHO Infertility Guidelines (unpaid). M.L. is an employee of Merck Healthcare KGaA, Darmstadt, Germany. T.D. is an employee of Merck Healthcare KGaA, Darmstadt, Germany. C.A. declares receipt of personal fees from Merck, Medea, Event Planet, IBSA, Ely Lilly, and Biogen and payment or honoraria from Merck, Medea, Event Planet, IBSA, and Ferring., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2024
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41. Analytical Investigation of the Profile of Human Chorionic Gonadotropin in Highly Purified Human Menopausal Gonadotrophin Preparations.

Author

Capolupo A, Petrocchi S, Melchiorre M, Jonas K, D'Hooghe T, Hanyaloglu A, Sunkara S, Palmese A, Ozgumus B, Amoresano A, Angiuoni G, Montenegro S, Simone P, and Lispi M

Subjects
Female, Humans, Chromatography, Liquid methods, Follicle Stimulating Hormone urine, Follicle Stimulating Hormone analysis, Glycopeptides analysis, Glycopeptides chemistry, Glycopeptides urine, Glycosylation, Luteinizing Hormone urine, Luteinizing Hormone analysis, Oxidation-Reduction, Polysaccharides analysis, Polysaccharides chemistry, Polysaccharides urine, Tandem Mass Spectrometry methods, Menopause, Postmenopause, Chorionic Gonadotropin analysis, Chorionic Gonadotropin isolation & purification, Chorionic Gonadotropin urine, Menotropins urine, Menotropins analysis
Abstract

Highly purified human menopausal gonadotropin (HP-hMG [Menopur ® , Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur ® and two of Menogon ® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid ® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel ® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid ® ) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20-30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9-1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18-47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20-30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG.

Published
2024
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42. Effectiveness of recombinant human FSH: recombinant human LH combination treatment versus recombinant human FSH alone for assisted reproductive technology in women aged 35-40 years.

Author

Bielfeld AP, Schwarze JE, Verpillat P, Lispi M, Fischer R, Hayward B, Chuderland D, D'Hooghe T, and Krussel JS

Subjects
Humans, Female, Pregnancy, Adult, Pregnancy Rate, Reproductive Techniques, Assisted, Drug Therapy, Combination, Treatment Outcome, Live Birth, Recombinant Proteins therapeutic use, Recombinant Proteins administration & dosage, Ovulation Induction methods, Follicle Stimulating Hormone, Human administration & dosage, Follicle Stimulating Hormone, Human therapeutic use, Luteinizing Hormone administration & dosage, Luteinizing Hormone therapeutic use
Abstract

Research Question: According to real-world data, is recombinant human FSH (r-hFSH) combined with recombinant human LH (r-hLH) or r-hFSH alone more effective for women of advanced maternal age (AMA) in terms of live birth?, Design: Non-interventional study comparing the effectiveness of r-hFSH and recombinant r-hLH (2:1 ratio) versus r-hFSH alone for ovarian stimulation during ART treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register., Results: Overall clinical pregnancy (29.8%, 95% CI 28.2 to 31.6 versus 27.8%, 95% CI 26.5 to 29.2) and live birth (20.3%, 95% CI 18.7 to 21.8 versus 18.0%, 95% CI 16.6 to 19.4) rates were not significantly different between the combined r-hFSH and r-hLH group and the r-hFSH alone group (P = 0.269 and P = 0.092, respectively). Treatment effect was significantly higher for combined r-hFSH and r-hLH compared with r-hFSH alone for clinical pregnancy (33.1%, 95% CI 31.0 to 35.0 versus 28.5%, 95% CI 26.6 to 30.4; P = 0.001, not adjusted for multiplicity) and live birth (22.5%, 95% CI 20.5 to 24.2 versus 19.4%, 95% CI 17.6 to 20.9; P = 0.014, not adjusted for multiplicity) in a post-hoc analysis of women with five to 14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of combined r-hFSH and r-hLH for ovarian stimulation in women aged 35-40 years with normal ovarian reserve., Conclusions: Women of AMA with normal ovarian response benefit from treatment with combined r-hFSH and r-hLH in a 2:1 ratio versus r-hFSH alone in terms of live birth rate. The effectiveness of treatments is best assessed by RCTs; however, real-world data are valuable for examining the effectiveness of fertility treatment, especially among patient groups that are not well represented in clinical trials., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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43. Dose accuracy of the follitropin alfa pen injector 2.0, the follitropin alfa:lutropin alfa 2:1 combination pen injector 2.0 and the choriogonadotropin alfa pen injector 1.0 used for fertility treatment.

Author

Cottell E, Michalet D, Lispi M, Araujo TD, Gleixner R, Longobardi S, and D'Hooghe T

Subjects
Follicle Stimulating Hormone, Human, Injections, Recombinant Proteins, Chorionic Gonadotropin, Luteinizing Hormone therapeutic use
Abstract

Background: This study aimed to confirm that the incremental dose/clicks system dispenses accurate doses for the Merck family of fertility pen injectors., Research Design and Methods: Set doses (V set ) for three dose dial settings (minimum dose [V min ], midpoint dose [V mid ] and maximum dose [V max ] for the follitropin alfa, choriogonadotropin alfa [D2 classification: single use/variable dose], and follitropin alfa:lutropin-alfa 2:1 combination pen injectors) or a single V set for the choriogonadotropin alfa (D1 classification: single use/single dose) were assessed. Last dose administered by the multi-dose device was assessed for the 900 IU, 450 IU, 300 IU and 150 IU follitropin alfa, and the 900:450 IU, 450:225 IU and 300:150 IU follitropin alfa:lutropin-alfa 2:1 combination pen presentations., Results: Dose accuracy tests for V min , V mid and V max for the follitropin alfa and the follitropin alfa:lutropin-alfa 2:1 combination pen injectors, and last dose administered, were within acceptable limits according to ISO 11,608-1:2012/2014. Dose accuracy tests for the single use/single dose device classification and the single use/variable dose device classification of the choriogonadotropin alfa pen injector were also within the acceptable limits, according to ISO 11608-1:2000/2014., Conclusions: The Merck family of fertility pen injectors functions reliably and the incremental dose/clicks system dispenses accurate doses.

Published
2024
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44. Response to: Randomized, assessor-blinded trial comparing highly purified human menotropin and recombinant follicle-stimulating hormone in high responders undergoing intracytoplasmic sperm injection.

Author

Batista AR, Schwarze JE, and Lispi M

Subjects
Humans, Male, Fertilization in Vitro, Follicle Stimulating Hormone, Ovulation Induction, Recombinant Proteins, Semen, Randomized Controlled Trials as Topic, Menotropins, Sperm Injections, Intracytoplasmic
Abstract

Competing Interests: Declaration of interests AR.B., J.E.S. and M.L. are employees of Merck Healthcare, Darmstadt, Germany.

Published
2024
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45. Letter to the editor in response to 'A real-world study of ART in France (REOLA) comparing a biosimilar rFSH against the originator according to rFSH starting dose' by P. Barrière, S. Hamamah, E. Arbo, C. Avril, B. Salle, J.-L. Pouly, et al. (J Gynecol Obstet Hum Reprod. 2023;52(1):102510).

Author

Montenegro S, Helwig C, Schwarze JE, Castello-Bridoux C, Marque S, Lispi M, and D'Hooghe T

Subjects
Humans, Follicle Stimulating Hormone, Follicle Stimulating Hormone, Human, France, Biosimilar Pharmaceuticals therapeutic use
Abstract

Competing Interests: Declaration of Competing Interest Juan-Enrique Schwarze, Claire Castello-Bridoux, Christoph Helwig, Thomas D'Hooghe, Susana Montenegro, Monica Lispi are employees of Merck Healthcare KGaA, Darmstadt, Germany or affiliate. Sebastien Marque is a full-time employee of Horiana company, Bordeaux, France.

Published
2023
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47. Follicle-Stimulating Hormone Biological Products: Does Potency Predict Clinical Efficacy?

Author

Lispi M, Humaidan P, Bousfield GR, D'Hooghe T, and Ulloa-Aguirre A

Subjects
Female, Humans, Follicle Stimulating Hormone pharmacology, Follicle Stimulating Hormone, Human pharmacology, Chorionic Gonadotropin pharmacology, Treatment Outcome, Biological Products, Infertility
Abstract

Follicle-stimulating hormone (FSH), together with luteinizing hormone (LH) and human chorionic gonadotropin (hCG), plays a fundamental role in human reproduction. The discovery of FSH and other gonadotropins was a defining moment in our understanding of reproduction and led to the development of many treatments for infertility. In this regard, exogenous FSH has been used to treat infertility in women for decades. Today, several recombinant and highly purified urinary forms of FSH are used in medically assisted reproduction (MAR). However, differences in the macro- and micro-heterogeneity of FSH result in a variety of FSH glycoforms, with glycoform composition determining the bioactivity (or potency), pharmacokinetic/pharmacodynamic (PK/PD) profiles, and clinical efficacy of the different forms of FSH. This review illustrates how the structural heterogeneity of FSH glycoforms affects the biological activity of human FSH products, and why potency does not predict effects in humans in terms of PK, PD, and clinical response.

Published
2023
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48. Biological Assay to Determine Gonadotropin Potency: From In Vivo to In Vitro Sustainable Method.

Author

Nevelli F, Palmese A, Gleixner R, Peroglio F, D'Acunto CW, Dadone A, D'Hooghe T, and Lispi M

Subjects
Biological Assay methods, In Vitro Techniques, Follicle Stimulating Hormone, Human, Follicle Stimulating Hormone
Abstract

Various preparations of follicle-stimulating hormone (FSH) are commercially available; however, they differ in glycoforms composition and purity owing to their respective sources. Additional chemical/physical changes can also be introduced during manufacturing and can impact their biological activity (biopotency), which is routinely assessed using an in vivo bioassay (Steelman-Pohley). This study aimed to determine whether an in vitro bioassay could assess biopotency by distinguishing between r-hFSH chemical/physical variants with similar ability to the in vivo bioassay. The specific activity (units of biological activity per mg of product) of variants of r-hFSH generated through enrichment (acidic/basic), stress (oxidative/acidic pH) and enzymatic treatment (desialylation and desialylation/degalactosylation) was compared using the in vivo and in vitro bioassays. The in vitro bioassay reliably detected potential chemical/physical modifications in r-hFSH variants that may impact biopotency. Overall, the methods demonstrated a comparable ability to detect changes in specific activities due to chemical/physical differences in r-hFSH variants. These data indicate that the in vitro bioassay is suitable to replace the in vivo bioassay.

Published
2023
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49. Treatment algorithms for high responders: What we can learn from randomized controlled trials, real-world data and models.

Author

Drakopoulos P, Khalaf Y, Esteves SC, Polyzos NP, Sunkara SK, Shapiro D, Rizk B, Ye H, Costello M, Koloda Y, Salle B, Lispi M, D'Hooghe T, and La Marca A

Subjects
Female, Humans, Randomized Controlled Trials as Topic, Ovary physiology, Ovulation Induction methods, Algorithms, Anti-Mullerian Hormone, Fertilization in Vitro methods, Follicle Stimulating Hormone
Abstract

A high ovarian response to conventional ovarian stimulation (OS) is characterized by an increased number of follicles and/or oocytes compared with a normal response (10-15 oocytes retrieved). According to current definitions, a high response can be diagnosed before oocyte pick-up when >18-20 follicles ≥11-12 mm are observed on the day of ovulation triggering; high response can be diagnosed after oocyte pick-up when >18-20 oocytes have been retrieved. Women with a high response are also at high risk of early ovarian hyper-stimulation syndrome (OHSS)/or late OHSS after fresh embryo transfers. Women at risk of high response can be diagnosed before stimulation based on several indices, including ovarian reserve markers (anti-Müllerian hormone [AMH] and antral follicle count [AFC], with cutoff values indicative of a high response in patients with PCOS of >3.4 ng/mL for AMH and >24 for AFC). Owing to the high proportion of high responders who are at the risk of developing OHSS (up to 30%), this educational article provides a framework for the identification and management of patients who fall into this category. The risk of high response can be greatly reduced through appropriate management, such as individualized choice of the gonadotropin starting dose, dose adjustment based on hormonal and ultrasound monitoring during OS, the choice of down-regulation protocol and ovulation trigger, and the choice between fresh or elective frozen embryo transfer. Appropriate management strategies still need to be defined for women who are predicted to have a high response and those who have an unexpected high response after starting treatment., Competing Interests: Declaration of competing interest PD declares research grants and honoraria from Merck KGaA, Darmstadt, Germany, MSD, Ferring Pharmaceuticals; and paid consultancy work from Merck KGaA, Darmstadt, Germany. YaK received lecture fees/honoraria/grants from MSD; Merck KGaA, Darmstadt, Germany; Besins Healthcare; Gedeon Richter; Abbott; Bayer; ISBA; LD Collins; Ferring and Sun Pharma. SCE declares the receipt of unrestricted research grants from Merck and lecture fees from Merck, Event Planet, and Med.E.A. NP declares research grants and honoraria from Merck KGaA, Darmstadt, Germany; MSD; Organon; Ferring Pharmaceuticals; Besins International; Roche Diagnostics; IBSA; Theramex; Gedeon Richter. SKS has received speaker fees for non-promotional educational symposia by Merck KGaA, Darmstadt, Germany; MSD; Ferring; Pharmasure. DS has participated in Speaker's bureaus for both Merck KGaA, Darmstadt, Germany and Organon. BR has no conflicts of interest to declare. HY has no conflicts of interest to declare. MC has declared past sponsorship from Merck KGaA, Darmstadt, Germany, for scientific conference presentations. YuK received speaker fees/honoraria/grants from MSD, Merck KGaA, Darmstadt, Germany; Besins Healthcare; Gedeon Richter; Abbott; Bayer; and Sun Pharma. BS received research grants and honoraria from Merck KGaA, Darmstadt, Germany and Gedeon Richter. ML and TDH are employees of Merck Healthcare KGaA, Darmstadt, Germany. ALM declares research grants and honoraria from Merck KGaA, Darmstadt, Germany; MSD; Ferring Pharmaceuticals; Gedeon Richter; ISBA; Theramex; Organon; Roche; Beckman Coulter., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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50. LH increases the response to FSH in granulosa-lutein cells from sub/poor-responder patients in vitro.

Author

Sperduti S, Paradiso E, Anzivino C, Lazzaretti C, Limoncella S, D'Alessandro S, Roy N, Reggianini F, Ferrari T, Melli B, La Sala GB, Nicoli A, Daolio J, Villani MT, Tagliavini S, Trenti T, Potì F, Sandhowe R, Centonze C, Lispi M, Simoni M, and Casarini L

Subjects
Humans, Female, Progesterone, Gonadotropins, Reproduction, Ovulation Induction methods, Fertilization in Vitro methods, Follicle Stimulating Hormone therapeutic use, Luteal Cells metabolism
Abstract

Study Question: Does LH addition to FSH in vitro recover the human primary granulosa lutein cell (hGLC) sub/poor-response?, Summary Answer: A picomolar concentration of LH may recover the FSH-induced cAMP and progesterone production of hGLC from sub/poor-responder women., What Is Known Already: Clinical studies suggested that FSH and LH co-treatment may be beneficial for the ovarian response of sub/poor-responders undergoing ovarian stimulation during ART., Study Design, Size, Duration: hGLC samples from 286 anonymous women undergoing oocyte retrieval for ART were collected from October 2017 to February 2021., Participants/materials, Setting, Methods: hGLCs from women undergoing ovarian stimulation during ART were blindly purified, cultured, genotyped and treated in vitro by increasing concentrations of FSH (nM) ±0.5 nM LH. cAMP and progesterone levels produced after 3 and 24 h, respectively, were measured. In vitro data were stratified a posteriori, according to the donors' ovarian response, into normo-, sub- and poor-responder groups and statistically compared. The effects of LH addition to FSH were compared with those obtained by FSH alone in all the groups as well., Main Results and the Role of Chance: hGLCs from normo-responders were shown to have higher sensitivity to FSH treatment than sub-/poor-responders in vitro. Equimolar FSH concentrations induced higher cAMP (about 2.5- to 4.2-fold), and progesterone plateau levels (1.2- to 2.1-fold), in cells from normo-responder women than those from sub-/poor-responders (ANOVA; P < 0.05). The addition of LH to the cell treatment significantly increased overall FSH efficacy, indicated by cAMP and progesterone levels, within all groups (P > 0.05). Interestingly, these in vitro endpoints, collected from the normo-responder group treated with FSH alone, were similar to those obtained in the sub-/poor-responder group under FSH + LH treatment. No different allele frequencies and FSH receptor (FSHR) gene expression levels between groups were found, excluding genetics of gonadotropin and their receptors as a factor linked to the normo-, sub- and poor-response. In conclusion, FSH elicits phenotype-specific ovarian lutein cell response. Most importantly, LH addition may fill the gap between cAMP and steroid production patterns between normo- and sub/poor-responders., Limitations, Reasons for Caution: Although the number of experimental replicates is overall high for an in vitro study, clinical trials are required to demonstrate if the endpoints evaluated herein reflect parameters of successful ART. hGLC retrieved after ovarian stimulation may not fully reproduce the response to hormones of granulosa cells from the antral follicular stage., Wider Implications of the Findings: This in vitro assay may describe the individual response to personalize ART stimulation protocol, according to the normo-, sub- and poor-responder status. Moreover, this in vitro study supports the need to conduct optimally designed, randomized clinical trials exploring the personalized use of LH in assisted reproduction., Study Funding/competing Interest(s): This study was supported by Merck KGaA. M.L. and C.C. are employees of Merck KGaA or of the affiliate Merck Serono SpA. Other authors have no competing interests to declare., Trial Registration Number: N/A., (© The Author(s) 2022. 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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