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Alberto Revelli

Physiopathology of Reproduction and IVF Unit, Department of Gyn/Obst Sciences, University of Torino, S. Anna Hospital, Torino, Italy

Journal articles

Alberto Revelli, Simona Casano, Francesca Salvagno, Luisa Delle Piane (2011)  Milder is better? Advantages and disadvantages of "mild" ovarian stimulation for human in vitro fertilization.   Reprod Biol Endocrinol 9: 1. Feb  
Abstract: ABSTRACT: In the last decades, several steps have been made aiming at rendering human IVF more successful on one side, more tolerable on the other side. The "mild" ovarian stimulation approach, in which a lower-than-average dose of exogenous gonadotropins is given and gonadotropin treatment is started from day 2 to 7 of the cycle, represents a significant step toward a more patient's friendly IVF. However, a clear view of its virtues and defects is still lacking, because only a few prospective randomized trials comparing "mild" vs. conventional stimulation exist, and they do not consider some important aspects, such as, e.g., thawing cycles. This review gives a complete panorama of the "mild" stimulation philosophy, showing its advantages vs. conventional ovarian stimulation, but also discussing its disadvantages. Both patients with a normal ovarian responsiveness to exogenous gonadotropins and women with a poor ovarian reserve are considered. Overall, we conclude that the level of evidence supporting the use of "mild" stimulation protocols is still rather poor, and further, properly powered prospective studies about "mild" treatment regimens are required.
Erica Miraglia, Federico De Angelis, Elena Gazzano, Hossain Hassanpour, Angela Bertagna, Elisabetta Aldieri, Alberto Revelli, Dario Ghigo (2011)  Nitric oxide stimulates human sperm motility via activation of the cyclic GMP/protein kinase G signaling pathway.   Reproduction 141: 1. 47-54 Jan  
Abstract: Nitric oxide (NO), a modulator of several physiological processes, is involved in different human sperm functions. We have investigated whether NO may stimulate the motility of human spermatozoa via activation of the soluble guanylate cyclase (sGC)/cGMP pathway. Sperm samples obtained by masturbation from 70 normozoospermic patients were processed by the swim-up technique. The kinetic parameters of the motile sperm-rich fractions were assessed by computer-assisted sperm analysis. After a 30-90â min incubation, the NO donor S-nitrosoglutathione (GSNO) exerted a significant enhancing effect on progressive motility (77, 78, and 78% vs 66, 65, and 62% of the control at the corresponding time), straight linear velocity (44, 49, and 48âμm/s vs 34, 35, and 35.5âμm/s), curvilinear velocity (81, 83, and 84âμm/s vs 68âμm/s), and average path velocity (52, 57, and 54âμm/s vs 40, 42, and 42âμm/s) at 5âμM but not at lower concentrations, and in parallel increased the synthesis of cGMP. A similar effect was obtained with the NO donor spermine NONOate after 30 and 60â min. The GSNO-induced effects on sperm motility were abolished by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (a specific sGC inhibitor) and mimicked by 8-bromo-cGMP (8-Br-cGMP; a cell-permeating cGMP analog); the treatment with Rp-8-Br-cGMPS (an inhibitor of cGMP-dependent protein kinases) prevented both the GSNO- and the 8-Br-cGMP-induced responses. On the contrary, we did not observe any effect of the cGMP/PRKG1 (PKG) pathway modulators on the onset of hyperactivated sperm motility. Our results suggest that NO stimulates human sperm motility via the activation of sGC, the subsequent synthesis of cGMP, and the activation of cGMP-dependent protein kinases.
Teresa Lantieri, Alberto Revelli, Pietro Gaglioti, Guido Menato, Gianluca Gennarelli, Luisa Delle Piane, Marco Massobrio (2010)  Superfetation after ovulation induction and intrauterine insemination performed during an unknown ectopic pregnancy.   Reprod Biomed Online 20: 5. 664-666 May  
Abstract: This report describes the first case of superfetation after ovarian stimulation with gonadotrophins and intrauterine insemination (IUI) that were performed in the presence of an undiagnosed tubal pregnancy. A 32-year-old woman who underwent repeated attempts of ovarian stimulation and IUI was hospitalized for severe pelvic pain and submitted to laparoscopic salpingectomy because of ruptured salpynx containing a 6-week pregnancy. Transvaginal ultrasound examination showed a simultaneous intrauterine 2-week pregnancy that had been conceived by ovarian stimulation and IUI while the tubal pregnancy was already ongoing and still undiagnosed. The intrauterine pregnancy went on until term and ended with the spontaneous delivery of a healthy baby. This report demonstrates that human superfetation may occur after gonadotrophin treatment and IUI in the presence of an ongoing tubal pregnancy. It is recommended to perform a pregnancy test before starting ovulation induction even when an apparently normal blood discharge appeared.
Erica Miraglia, Cristina Lussiana, Daniele Viarisio, Cinzia Racca, Alessia Cipriani, Elena Gazzano, Amalia Bosia, Alberto Revelli, Dario Ghigo (2010)  The pentose phosphate pathway plays an essential role in supporting human sperm capacitation.   Fertil Steril 93: 7. 2437-2440 May  
Abstract: In swim-up-selected spermatozoa of 38 normozoospermic patients, capacitated spermatozoa exhibited enhanced pentose phosphate pathway (PPP) activity and increased expression of glucose-6-phosphate dehydrogenase (G6PD). The G6PD inhibitor DHEA and the inhibitors of NADPH oxidase apocynin and diphenylene iodonium (DPI) prevented both superoxide generation and capacitation in human spermatozoa, but whereas DPI and DHEA inhibited PPP, apocynin did not influence it, suggesting that PPP activation during capacitation is not a response to increased oxidative stress but exerts a role by supplying reducing equivalents to oxygen.
Emanuela Molinari, Alberto Revelli, Cinzia Racca, Luisa Delle Piane, Marco Massobrio (2010)  Slow-freezing-induced changes of birefringent structures in human oocytes are related to responsiveness to ovulation induction.   Reprod Biomed Online 20: 5. 619-624 May  
Abstract: The slow-freezing method is widely used to freeze human oocytes, both for fertility preservation and in routine IVF programmes. Slow freezing damages some of the cell's structures, including the meiotic spindle (MS) and the zona pellucida (ZP). Polarized light microscopy was used to study the variations induced by slow freezing on the MS and the ZP of human oocytes and to analyse the relationship between slow-freezing effects on the gamete and some clinical characteristics, such as age, body mass index and ovarian responsiveness to ovulation induction (expressed as total follicle-stimulating hormone dose/retrieved oocyte). Both the MS and the ZP (particularly its inner layer) underwent significant changes during slow-freezing procedure. The MS became thinner and structurally less organized (lower retardance) (P<0.001 and P<0.05, respectively), whereas the ZP became thicker and its inner layer lost structural organization (both P<0.05). These morphological changes were unrelated to the patient's age or body mass index, but ZP variations in thickness and retardance were significantly related to ovarian responsiveness (P=0.033 and P=0.026, respectively), suggesting that patients with a higher response to gonadotrophins produce oocytes better able to preserve their characteristics after freezing-thawing.
Elena Vasario, Valentina Borgarello, Carlotta Bossotti, Enrico Libanori, Marilisa Biolcati, Silvana Arduino, Rita Spinelli, Luisa Delle Piane, Alberto Revelli, Tullia Todros (2010)  IVF twins have similar obstetric and neonatal outcome as spontaneously conceived twins: a prospective follow-up study.   Reprod Biomed Online 21: 3. 422-428 Sep  
Abstract: Studies comparing the outcome of spontaneous versus IVF twin pregnancies report heterogeneous results. This may depend on differences in the studied populations and/or in the management approach to twin pregnancy. The aim of the present study was to compare both maternal and perinatal outcomes in dichorionic diamniotic twin pregnancies who where spontaneously conceived or originated by successful homologous IVF. In order to get homogeneous observations, monochorionic twin pregnancies and triplet pregnancies were excluded. Moreover, to avoid any possible bias deriving from differences in the obstetric management, all pregnancies were managed by the same team applying fixed obstetric protocols. The study included 223 twin pregnancies, 84 conceived by IVF and 139 spontaneously conceived. Overall, maternal and perinatal outcomes were similar in the two groups: no significant differences were observed as far as gestational age at delivery, birthweight, perinatal morbidity and mortality, and rate of malformations were concerned. The rate of Caesarean section was slightly, but not significantly, higher in IVF pregnancies. In conclusion, the outcome of IVF twin pregnancies is comparable to that of spontaneously conceived twin pregnancies, provided that the same management criteria are applied.
L Delle Piane, W Lin, X Liu, A Donjacour, P Minasi, A Revelli, E Maltepe, P F Rinaudo (2010)  Effect of the method of conception and embryo transfer procedure on mid-gestation placenta and fetal development in an IVF mouse model.   Hum Reprod 25: 8. 2039-2046 Aug  
Abstract: Abnormal placentation is a potential mechanism to explain the increased incidence of low birthweight observed after IVF. This study evaluates, in a mouse model, whether the method of conception and embryo transfer affect placentation and fetal development.
Valentina Rovei, Gianluca Gennarelli, Teresa Lantieri, Simona Casano, Alberto Revelli, Marco Massobrio (2010)  Family planning, fertility awareness and knowledge about Italian legislation on assisted reproduction among Italian academic students.   Reprod Biomed Online 20: 7. 873-879 Jun  
Abstract: Over the last century, most industrialized countries have experienced a progressive increase in maternal age at first pregnancy and a reduction of fertility rate, with important social and economic consequences. Moreover in Italy a very restrictive law on assisted reproductive technologies was introduced in 2004, limiting its effectiveness and causing a strong public debate that unfortunately focused more on the political and ethical implications of the law than on the medical and technical aspects of assisted reproduction. The present study performed an epidemiological investigation among the students of Turin University in the year 2006/07 in order to assess three aspects: the factors affecting the decision to become parents, their level of consciousness about human reproduction and their level of knowledge about the legal rules that regulate assisted reproduction in Italy. The study also wanted to clarify how the sex (male or female) and the type of education (sciences or humanities) could affect their opinions and knowledge in this area. It was observed that young people consider parenthood an important part of their life, but knowledge about human fertility and legal rules regulating assisted reproduction is rather poor, regardless of sex and type of education.
Federica Collino, Alberto Revelli, Marco Massobrio, Dionyssios Katsaros, Michel Schmitt-Ney, Giovanni Camussi, Benedetta Bussolati (2009)  Epithelial-mesenchymal transition of ovarian tumor cells induces an angiogenic monocyte cell population.   Exp Cell Res 315: 17. 2982-2994 Oct  
Abstract: Vasculogenesis, or recruitment of progenitors able to differentiate into endothelial-like cells, may provide an important contribution to neovessel formation in tumors. However, the factors involved in the vasculogenic process and in particular the role of the epithelial-mesenchymal transition of tumor cells have not yet been investigated. We found a CD14(+)/KDR(+) angiogenic monocyte population in undifferentiated ovarian tumors, significantly increased in the corresponding tumor metastasis. In vitro, monocyte differentiation into CD14(+)/KDR(+) cells was induced by conditioned media from the primary ovarian tumor cells expressing a mesenchymal phenotype. In contrast, the ovarian tumor cell line SKOV3 expressing an epithelial phenotype was unable to stimulate the differentiation of monocytes into CD14(+)/KDR(+) cells. When an epithelial-mesenchymal transition was induced in SKOV3, they acquired this differentiative ability. Moreover, after mesenchymal transition pleiotrophin expression by SKOV3 was increased and conversely its blockade significantly reduced monocyte differentiation. The obtained CD14(+)/KDR(+) cell population showed the expression of endothelial markers, increased the formation of capillary-like structures by endothelial cells and promoted the migration of ovarian tumor cells in vitro. In conclusion, we showed that the epithelial-mesenchymal transition of ovarian tumor cells induced differentiation of monocytes into the pro-angiogenic CD14(+)/KDR(+) population and thus it may provide a tumor microenvironment that favours vasculogenesis and metastatization of the ovarian cancer.
Alberto Revelli, Luisa Delle Piane, Simona Casano, Emanuela Molinari, Marco Massobrio, Paolo Rinaudo (2009)  Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics.   Reprod Biol Endocrinol 7: 05  
Abstract: The assessment of oocyte quality in human in vitro fertilization (IVF) is getting increasing attention from embryologists. Oocyte selection and the identification of the best oocytes, in fact, would help to limit embryo overproduction and to improve the results of oocyte cryostorage programs. Follicular fluid (FF) is easily available during oocyte pick-up and theorically represents an optimal source on non-invasive biochemical predictors of oocyte quality. Unfortunately, however, the studies aiming to find a good molecular predictor of oocyte quality in FF were not able to identify substances that could be used as reliable markers of oocyte competence to fertilization, embryo development and pregnancy. In the last years, a well definite trend toward passing from the research of single molecular markers to more complex techniques that study all metabolites of FF has been observed. The metabolomic approach is a powerful tool to study biochemical predictors of oocyte quality in FF, but its application in this area is still at the beginning. This review provides an overview of the current knowledge about the biochemical predictors of oocyte quality in FF, describing both the results coming from studies on single biochemical markers and those deriving from the most recent studies of metabolomics.
Carlo Alviggi, Roberto Clarizia, Gennaro Castaldo, Giuseppe Matarese, Camillo C Colucci, Salvatore Conforti, Tiziana Pagano, Alberto Revelli, Giuseppe De Placido (2009)  Leptin concentrations in the peritoneal fluid of women with ovarian endometriosis are different according to the presence of a 'deep' or 'superficial' ovarian disease.   Gynecol Endocrinol 25: 9. 610-615 Sep  
Abstract: Some studies have suggested a possible role of leptin, an active cytokine produced by adipocytes, in the pathogenesis of pelvic endometriosis. The present study was designed to assess leptin levels in the peritoneal fluid (PF) of women with the 'deep' or 'superficial' types of ovarian endometriosis. Twenty-seven women with a single ovarian endometrioma having a mean diameter between 3 and 5 cm were included in the study. Patients were divided into two groups according to the type of ovarian endometriosis: Group A (n = 11) consisted of women with 'superficial' endometriomas located at the ovarian surface; Group B (n = 16) included patients with 'deep' intra-ovarian endometriomas. Women undergoing laparoscopy for unexplained infertility and not affected by pelvic and/or ovarian endometriosis were considered as controls (Group C, n = 10). Patients with an ovarian endometrioma had significantly increased PF leptin concentrations than endometriosis-free controls (Groups A and B vs. Group C, p < 0.01). Patients with 'superficial' endometriomas had significantly higher PF leptin levels compared with patients with 'deep' endometriomas (Group A vs. B, p < 0.01). This difference remained significant after correction for the BMI; moreover, a positive correlation between PF leptin and BMI was observed in Groups B and C, but not in women with 'superficial' endometrioma (Group A). Our observations suggest that: (a) leptin could play an active role in promoting the development of 'superficial' ovarian endometriomas and (b) 'superficial' and 'deep' ovarian endometriomas could have a different pathogenesis.
Cristina Lussiana, Benedetta Guani, Gabriella Restagno, Valentina Rovei, Guido Menato, Alberto Revelli, Marco Massobrio (2009)  Ovarian hyper-stimulation syndrome after spontaneous conception.   Gynecol Endocrinol 25: 7. 455-459 Jul  
Abstract: Ovarian hyperstimulation syndrome (OHSS) is rather frequent (1-5%) in women submitted to superovulation with gonadotropins for in vitro fertilisation (IVF), whereas it is very rare in case of spontaneous ovulation. Spontaneous OHSS (sOHSS) was previously described to be associated to hydatiform mole, multiple conception, hypothyroidism in pregnancy. It may also depend on activating mutations of the FSH receptor (FSHR) gene that cause ovarian hyper-responsiveness to circulating FSH or even cross-responsiveness of FSHR to hormones having a structure similar to FSH, such as hCG or TSH. We report, herein, a case of sOHSS in a woman who conceived spontaneously. We checked the presence of all possible factors that could explain the onset of the syndrome, and we evidenced hypothyroidism and abnormally elevated hCG levels in the second trimester of pregnancy. The thorough molecular biology study of FSHR gene did not detect exonic mutations, but revealed the presence of intronic mutations whose role in the onset of sOHSS is still uncertain.
Marco Camanni, Luca Bonino, Elena Maria Delpiano, Paola Berchialla, Giuseppe Migliaretti, Alberto Revelli, Francesco Deltetto (2009)  Laparoscopic conservative management of ureteral endometriosis: a survey of eighty patients submitted to ureterolysis.   Reprod Biol Endocrinol 7: 10  
Abstract: this study aims to evaluate the effectiveness and safety of laparoscopic conservative management of ureteral endometriosis.
L Parmegiani, C Garello, F Granella, D Guidetti, S Bernardi, G E Cognigni, A Revelli, M Filicori (2009)  Long-term cryostorage does not adversely affect the outcome of oocyte thawing cycles.   Reprod Biomed Online 19: 3. 374-379 Sep  
Abstract: This multi-centre study evaluated systematically the influence of the duration of cryostorage on the outcome of thawing cycles when using slow-frozen oocytes. The thawing cycles were retrospectively divided into three main groups based on cryostorage duration: group A, 1-3 months; group B, 4-6 months; and group C, 7-48 months. Group C was subsequently divided into three subgroups: group C1, 7-9 months; group C2, 10-12 months; and group C3, 13-48 months. Main outcome measures observed were oocyte survival after thawing, fertilization, cleavage; embryo quality and development, implantation, and birth. No significant differences in main outcome measures were observed between all the groups studied. In conclusion, human oocytes can be safely cryostored for several years. This finding could encourage the wider use of oocyte cryopreservation as a clinical procedure in assisted reproduction.
Alberto Revelli, Simona Casano, Luisa Delle Piane, Giuseppina Grassi, Gianluca Gennarelli, Daniela Guidetti, Marco Massobrio (2009)  A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments.   Reprod Biol Endocrinol 7: 11  
Abstract: Anti-thyroid antibodies (ATA), even if not associated with thyroid dysfunction, are suspected to cause poorer outcome of in vitro fertilization (IVF).
Alberto Revelli, Elisabetta Dolfin, Gianluca Gennarelli, Teresa Lantieri, Marco Massobrio, Jan Gunnar Holte, Ilan Tur-Kaspa (2008)  Low-dose acetylsalicylic acid plus prednisolone as an adjuvant treatment in IVF: a prospective, randomized study.   Fertil Steril 90: 5. 1685-1691 Nov  
Abstract: To test whether adjuvant therapy with acetylsalicylic acid (ASA) and prednisolone (ASA+Pred) could improve the outcome of IVF in good-pregnancy prognosis patients.
Cristina Lussiana, Benedetta Guani, Caterina Mari, Gabriella Restagno, Marco Massobrio, Alberto Revelli (2008)  Mutations and polymorphisms of the FSH receptor (FSHR) gene: clinical implications in female fecundity and molecular biology of FSHR protein and gene.   Obstet Gynecol Surv 63: 12. 785-795 Dec  
Abstract: The portion of chromosome 2, including the gene codifying the receptor of FSH (FSHR gene), can display point mutations that cause variations in the amino acid sequence of the receptor protein (FSHR protein). Some of these structural changes affect the receptor functional properties that may be enhanced (activating mutations) or impaired (inactivating mutations). Activating mutations confer to FSHR a higher responsiveness to FSH, making it constitutively active even in the absence of the ligand, or render it able to nonspecifically respond to other tropic hormones (e.g., TSH). Inactivating mutations reduce the receptor's function up to a total block, altering either the formation of the receptor-ligand complex, or FSH signal transduction. FSHR inactivating mutations may cause primary or secondary amenorrhea, infertility, and premature ovarian failure (POF), whereas activating mutations can predispose to ovarian hyperstimulation syndrome (OHSS) as a consequence of exogenous FSH administration, or with a spontaneous onset. Beside point mutations, FSHR gene polymorphisms at specific sites (e.g., codons 307 and 680) may influence FSHR protein responsiveness to exogenous FSH, and finally affect the effectiveness of in vitro fertilization (IVF) treatment as well as the likelihood of developing a severe OHSS as a consequence of superovulation. This review summarizes the current knowledge about the FSHR gene mutations and polymorphisms, illustrating in the first part their clinical consequences for female reproductive function. In the second part, it describes the techniques to study the FSHR gene sequence, and gives more details about the molecular biology of FSHR protein, of FSHR gene and its mutations. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After reading this article, the reader should be able to list clinical disorders related to mutations in the follicle stimulating hormone receptor (FSHR) gene, explain the principles behind the study of FSHR mutations, and state possible future applications of knowledge of mutations in the FSHR gene in reproductive medicine.
J Holte, L Berglund, K Milton, C Garello, G Gennarelli, A Revelli, T Bergh (2007)  Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval.   Hum Reprod 22: 2. 548-557 Feb  
Abstract: Evidence-based morphological embryo scoring models for ranking of implantation potential are still scarce, and the need for a precise model increases when aiming for singleton pregnancies.
Federica Moffa, Chiara Perono Biacchiardi, Franca Fagioli, Eleonora Biasin, Alberto Revelli, Marco Massobrio, Enrico Madon (2007)  Ovarian tissue cryostorage and grafting: an option to preserve fertility in pediatric patients with malignancies.   Pediatr Hematol Oncol 24: 1. 29-44 Jan/Feb  
Abstract: Fertility preservation in childhood cancer has become an important area of investigation due to increasing survival rates after cancer therapy. For these patients with an increased risk of infertility and premature ovarian failure, cryopreservation of ovarian tissue is a promising tool to preserve at least part of the reproductive potential. In recent years significant improvements have been achieved in this area, and 2 live births after autografting of frozen-thawed ovarian tissue have been reported. However, further research is needed to assess the clinical effectiveness of ovarian cryopreservation, to optimize the technique, and to limit the risk of reintroducing cancer cells in the patient with the graft.
Erica Miraglia, Maria Luisa Rullo, Amalia Bosia, Marco Massobrio, Alberto Revelli, Dario Ghigo (2007)  Stimulation of the nitric oxide/cyclic guanosine monophosphate signaling pathway elicits human sperm chemotaxis in vitro.   Fertil Steril 87: 5. 1059-1063 May  
Abstract: To investigate whether nitric oxide (NO) may attract human spermatozoa via activation of the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway.
Alberto Revelli, Valentina Rovei, Cinzia Racca, Andrea Gianetti, Marco Massobrio (2007)  Impact of oncostatic treatments for childhood malignancies (radiotherapy and chemotherapy) on uterine competence to pregnancy.   Obstet Gynecol Surv 62: 12. 803-811 Dec  
Abstract: Fertility preservation in young girls affected by malignancies has got growing relevance in the last decade due to the improved survival chance of these patients after oncostatic treatments. Most studies have focused on preserving ovarian follicles and avoiding premature ovarian failure, whereas only a few have evaluated the effects exerted by radiotherapy and chemotherapy on the uterus. It is self-evident that fertility preservation after oncostatic therapies must include the maintenance of a functional uterus, and a certain degree of uterine damage must be considered when estimating reproductive prognosis in previously treated, childhood cancer survivors. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall the growing number of children who survive oncostatic treatments, explain the possible effects on future reproductive endeavors, and summarize the possible ways to preserve fertility.
Carlo Alviggi, Alberto Revelli, Paola Anserini, Antonio Ranieri, Luigi Fedele, Ida Strina, Marco Massobrio, Nicola Ragni, Giuseppe De Placido (2007)  A prospective, randomised, controlled clinical study on the assessment of tolerability and of clinical efficacy of Merional (hMG-IBSA) administered subcutaneously versus Merional administered intramuscularly in women undergoing multifollicular ovarian stimulation in an ART programme (IVF).   Reprod Biol Endocrinol 5: 12  
Abstract: Multifollicular ovarian stimulation (MOS) is widely used in IVF and the compliance to treatment is deeply influenced by the tolerability of the medication(s) used and by the ease of self-administration. This prospective, controlled, randomised, parallel group open label, multicenter, phase III, equivalence study has been aimed to compare the clinical effectiveness (in terms of oocytes obtained) and tolerability of subcutaneous (s.c.) self-administered versus classical intramuscular (i.m.) injections of Merional, a new highly-purified hMG preparation.
R Ciriminna, M L Papale, P G Artini, M Costa, L De Santis, L Gandini, L Parmegiani, G Ragni, A Revelli, L Rienzi, R Barbaro, V Cela, I Cino, D Colia, G D'Ambrogio, L Diotallevi, M Dusi, M Filicori, A R Genazzani, G Giuffrida, F Lombardo, A Paffoni, C Racca, E Greco (2007)  Impact of Italian legislation regulating assisted reproduction techniques on ICSI outcomes in severe male factor infertility: a multicentric survey.   Hum Reprod 22: 9. 2481-2487 Sep  
Abstract: In 2004, a law regulating assisted reproduction techniques (ART) was passed in Italy. The new rules allow for the formation and transfer of a maximum of three embryos at one time, whereas embryo selection and embryo storage are prohibited. The aim of this study is to evaluate the impact of these restrictions on ICSI outcome in couples affected by severe male factor infertility.
Alberto Revelli, Francesca Poso, Gianluca Gennarelli, Federica Moffa, Giuseppina Grassi, Marco Massobrio (2006)  Recombinant versus highly-purified, urinary follicle-stimulating hormone (r-FSH vs. HP-uFSH) in ovulation induction: a prospective, randomized study with cost-minimization analysis.   Reprod Biol Endocrinol 4: 07  
Abstract: Both recombinant FSH (r-FSH) and highly-purified, urinary FSH (HP-uFSH) are frequently used in ovulation induction associated with timed sexual intercourse. Their effectiveness is reported to be similar, and therefore the costs of treatment represent a major issue to be considered. Although several studies about costs in IVF have been published, data obtained in low-technology infertility treatments are still scarce.
P Cavalla, V Rovei, S Masera, M Vercellino, M Massobrio, R Mutani, A Revelli (2006)  Fertility in patients with multiple sclerosis: current knowledge and future perspectives.   Neurol Sci 27: 4. 231-239 Sep  
Abstract: The issue of fertility in patients with multiple sclerosis (MS) has not been exhaustively studied. Epidemiological data have suggested that spontaneous fecundity might be reduced; several endocrine and sexual disturbances potentially interfering with reproduction have been evidenced in MS patients of both sexes. Moreover, some medical treatments used in MS (e. g., mitoxantrone, cyclophosphamide) may exert detrimental effects on spermatozoa as well as on oocytes, leading to early impairment of fertility. This review illustrates the factors potentially interfering with fertility in MS and discusses the therapeutic tools that may be used to promote fertility in these patients. The safety of hormonal therapies in MS is also examined. The current applications of assisted reproductive technology (ART) are discussed, including in vitro fertilisation (IVF) techniques. Currently available methods to preserve fertility in patients that undergo cytotoxic treatments by means of sperm/oocyte cryostorage or by ovarian fragment cryopreservation and autografting are considered.
G Ambrosini, A Andrisani, E Porcu, E Rebellato, A Revelli, D Caserta, E Cosmi, R Marci, M Moscarini (2006)  Oocytes cryopreservation: state of art.   Reprod Toxicol 22: 2. 250-262 Aug  
Abstract: In the present review article we sought to analyze, on the basis of a systematic review, the indications, rationale of oocytes cryopreservation, as well as the techniques that improved the aforementioned procedure in order to higher the pregnancy rate in women undergoing that procedure. Moreover, we pointed out the importance of oocytes cryopreservation in the research field as oocyte banking may be of utmost importance to increase the availability of oocytes for research applications such as genetic engineering or embryo cloning. Oocyte freezing has 25 year of history alternating successes and setbacks. Human oocytes have a delicate architecture but are freezable. Clinical efficiency remains low, but healthy children have been born, indicating that chromosomally normal embryos can originate from frozen oocytes. Freezing protocols are not yet optimal and it is now desirable to combine empirical and theoretical knowledge.
G Gennarelli, V Rovei, R F Novi, J Holte, F Bongioanni, A Revelli, G Pacini, P Cavallo-Perin, M Massobrio (2005)  Preserved insulin sensitivity and {beta}-cell activity, but decreased glucose effectiveness in normal-weight women with the polycystic ovary syndrome.   J Clin Endocrinol Metab 90: 6. 3381-3386 Jun  
Abstract: Insulin resistance and hyperinsulinemia are often considered intrinsic features of the polycystic ovary syndrome (PCOS). Nevertheless, conflicting results of insulin sensitivity and secretion have been obtained in the subgroup of normal-weight women with PCOS. Differences in body composition, ethnicity, and diet composition and a family history of metabolic diseases may act as confounding variables in women with PCOS. In the present study, insulin sensitivity and secretion were estimated by an iv glucose tolerance test (IVGTT), analyzed by minimal models, in 20 normal-weight healthy women with PCOS and no family history of type 2 diabetes mellitus and in 20 normally ovulating women, matched for age and body mass index. Insulin sensitivity [mean (95% confidence intervals); PCOS 4.0 (2.8-5.1) vs. controls 4.5 (3.5-5.4) 10(-4) min(-1)/], and insulin secretion, expressed as the acute insulin response to glucose [PCOS 3.7 (3.3-4.2) vs. controls 3.7 (3.4-4.0) microU/ml] were similar in the two groups. The women with PCOS showed an increased proportion of total body fat (PCOS 29% vs. controls 27.2%; P < 0.01). They also showed decreased glucose effectiveness, i.e. the proportion of glucose uptake independent from insulin activity [PCOS 2.6 (2.1-3.0) vs. controls 3.8 (3.0-4.6) mg x 100 min(-1); P = 0.01]. The levels of insulin sensitivity and of glucose effectiveness did not correlate in either group. Whether the isolated finding of decreased glucose effectiveness could reflect an early stage in the development of the metabolic aberrations often associated with the syndrome remains to be clarified.
Alberto Revelli, Giovanni Battista La Sala, Gianluca Gennarelli, Laura Scatigna, Cinzia Racca, Marco Massobrio (2005)  Seasonality and human in vitro fertilization outcome.   Gynecol Endocrinol 21: 1. 12-17 Jul  
Abstract: Seasonal changes in spontaneous fecundity have been observed in several human populations, but it is not clear whether the same applies to human in vitro fertilization-embryo transfer (IVF) procedures. In the present study, 2067 patients undergoing their first IVF attempt between the years 1998 and 2003 were grouped into four 'seasons' (December-February, March-May, June-August, September-November) according to the day on which they were administered human chorionic gonadotropin. Several parameters known to affect IVF outcome (including ovarian response to gonadotropins, sperm and oocyte quality, fertilization rate, embryo quality, pregnancy and implantation rates) were considered and potential changes among the four seasonal periods were analyzed. Moreover, some confounding variables (sperm quality, age, duration of infertility, indications for IVF) were controlled for. Overall, pregnancy rate per oocyte pick-up and per embryo transfer of 32.5% and 35.8%, respectively, as well as implantation rate of 18.9%, were recorded. None of the observed IVF-related parameters showed any significant change clearly related to a specific seasonal period, their fluctuations throughout the year being randomly determined. Ovarian responsiveness to gonadotropins, quality of gametes and embryos, and fertilization and implantation processes were apparently not significantly affected by seasonality. It is concluded that the results of a good-quality IVF program in humans are not significantly affected by the season of the year in which the IVF attempt is accomplished; therefore, season is not a relevant factor to be considered when planning an IVF treatment.
Attila Jakab, Denny Sakkas, Elena Delpiano, Sevil Cayli, Ertug Kovanci, David Ward, Alberto Revelli, Alberto Ravelli, Gabor Huszar (2005)  Intracytoplasmic sperm injection: a novel selection method for sperm with normal frequency of chromosomal aneuploidies.   Fertil Steril 84: 6. 1665-1673 Dec  
Abstract: To test a newly invented intracytoplasmic sperm injection (ICSI) sperm selection method based on sperm hyaluronic acid (HA) binding.
Chiara Perono Biacchiardi, Alberto Revelli, Gianluca Gennarelli, Sergio Rustichelli, Federica Moffa, Marco Massobrio (2004)  Fallopian tube sperm perfusion versus intrauterine insemination in unexplained infertility: a randomized, prospective, cross-over trial.   Fertil Steril 81: 2. 448-451 Feb  
Abstract: To compare the results of fallopian tube sperm perfusion (FSP) versus standard intrauterine insemination (IUI) in patients with unexplained infertility undergoing controlled ovarian hyperstimulation (COH).
Roberta Favini, Elisabetta Aldieri, Alberto Revelli, Amalia Bosia, Marco Massobrio, Dario Ghigo (2003)  Nitric oxide synthesis in human nonpregnant myometrium and uterine myomas.   Fertil Steril 79 Suppl 1: 749-753 Mar  
Abstract: To clarify whether nitric oxide (NO) synthesis in myomas differs from that in parental human myometrium.
Federica Moffa, Francesca Comoglio, Lewis C Krey, James A Grifo, Alberto Revelli, Marco Massobrio, John Zhang (2002)  Germinal vesicle transfer between fresh and cryopreserved immature mouse oocytes.   Hum Reprod 17: 1. 178-183 Jan  
Abstract: We assessed the maturational competence and the chromosomal pattern of mouse oocytes reconstructed by germinal vesicle (GV) transfer technique using nuclear and/or cytoplasmic components from cryopreserved GV stage oocytes.
Alberto Revelli, Dario Ghigo, Federica Moffa, Marco Massobrio, Ilan Tur-Kaspa (2002)  Guanylate cyclase activity and sperm function.   Endocr Rev 23: 4. 484-494 Aug  
Abstract: In species with external fertilization, the guanylate cyclase family is responsible for the long-distance interaction between gametes, as its activation allows sperm chemotaxis toward egg-derived substances, gamete encounter, and fertilization. In species with internal fertilization, guanylate cyclase-activating substances, which are secreted by several tissues in the genital tracts of both sexes, deeply affect sperm motility, capacitation, and acrosomal reactivity, stimulating sperm metabolism and promoting the ability of the sperm to approach the oocyte, interact with it, and finally fertilize it. A complex system of intracellular pathways is activated by guanylate cyclase agonists in spermatozoa. Sperm motility appears to be affected mainly through an increase in intracellular cAMP, whereas the acrosome reaction depends more directly on cyclic GMP synthesis. Both cyclic nucleotides activate specific kinases and ion signals. A complex cross-talk between cAMP- and cyclic GMP-generating systems occurs, resulting in an upward shift in sperm function. Excessive amounts of certain guanylate cyclase activators might exert opposite, antireproductive effects, increasing the oxidative stress on sperm membranes. In view of the marked influence exerted by guanylate cyclase-activating substances on sperm function, it seems likely that guanylate cyclase activation or inhibition may represent a new approach for the diagnosis and treatment of male and/or female infertility.
P Tacconis, A Revelli, M Massobrio, G Battista La Sala, J Tesarik (2001)  Chemotactic responsiveness of human spermatozoa to follicular fluid is enhanced by capacitation but is impaired in dyspermic semen.   J Assist Reprod Genet 18: 1. 36-44 Jan  
Abstract: Our purpose was to study the chemotactic responsiveness of human spermatozoa from normal and pathological semen samples to follicular fluid (FF), as well as the effect exerted by capacitation on sperm chemotaxis.
A Revelli, C Costamagna, F Moffa, E Aldieri, S Ochetti, A Bosia, M Massobrio, B Lindblom, D Ghigo (2001)  Signaling pathway of nitric oxide-induced acrosome reaction in human spermatozoa.   Biol Reprod 64: 6. 1708-1712 Jun  
Abstract: Nitric oxide (NO) has been recently shown to modulate in vitro motility, viability, the acrosome reaction (AR), and metabolism of spermatozoa in various mammalian species, but the mechanism or mechanisms through which it influences sperm functions has not been clarified. In human capacitated spermatozoa, both the intracellular cGMP level and the percentage of AR-positive cells were significantly increased after 4 h of incubation with the NO donor, sodium nitroprusside (SNP). SNP-induced AR was significantly reduced in the presence of the soluble guanylate cyclase (sGC) inhibitors, LY83583 and ODQ; this block was bypassed by adding 8-bromo-cGMP, a cell-permeating cGMP analogue, to the incubation medium. Finally, Rp-8-Br-cGMPS and Rp-8-pCPT-cGMPS, two inhibitors of the cGMP-dependent protein kinases (PKGs), inhibited the SNP-induced AR. Furthermore, SNP-induced AR did not occur in Ca2+ -free medium or in the presence of the protein kinase C (PKC) inhibitor, calphostin C. This study suggests that the AR-inducing effect of exogenous NO on capacitated human spermatozoa is accomplished via stimulation of an NO-sensitive sGC, cGMP synthesis, and PKG activation. In this effect the activation of PKC is also involved, and the presence of extracellular Ca2+ is required.
A Revelli, L Bergandi, M Massobrio, B Lindblom, A Bosia, D Ghigo (2001)  The concentration of nitrite in seminal plasma does not correlate with sperm concentration, sperm motility, leukocytospermia, or sperm culture.   Fertil Steril 76: 3. 496-500 Sep  
Abstract: To correlate the concentration of nitrite (the stable metabolite of nitric oxide) in seminal plasma with sperm number and motility, leukocytospermia, and sperm culture.
P Rinaudo, T Niven-Fairchild, S Buradagunta, M Massobrio, A Revelli, D L Keefe (1999)  Microinjection of mitochondria into zygotes creates a model for studying the inheritance of mitochondrial DNA during preimplantation development.   Fertil Steril 71: 5. 912-918 May  
Abstract: To determine the effect of mutant mitochondria on preimplantation embryo development and of preimplantation embryo development on the survival of mutant mitochondrial DNA.
A Revelli, G Soldati, C Costamagna, O Pellerey, E Aldieri, M Massobrio, A Bosia, D Ghigo (1999)  Follicular fluid proteins stimulate nitric oxide (NO) synthesis in human sperm: a possible role for NO in acrosomal reaction.   J Cell Physiol 178: 1. 85-92 Jan  
Abstract: Nitric oxide (NO) is a free radical involved in the regulation of several functions of the male genitourinary system. It is produced by neurons and the endothelium and epithelia of reproductive system; it mediates penile erection and regulates sperm motility, viability, and metabolism. Here we show that human spermatozoa exhibit a detectable NO synthase (NOS) activity, measured both as ability of the intact sperm and cell lysate to convert L-[3H]arginine into L-[3H]citrulline and as 24 h accumulation of extracellular nitrite in intact sperm suspensions. NOS activity (identified as an endothelial isoform) was inhibited by L-canavanine and N(G)-monomethyl-L-arginine, and nitrite accumulation was inhibited by the NO scavenger hemoglobin; both enzyme activity and nitrite production were increased by a 24 h incubation of spermatozoa with protein-enriched extracts of human follicular fluid (PFF); a significant increase of citrulline synthesis was observed only after a 4 h incubation with 40% PFF, a time period during which acrosomal reactivity was significantly increased. PFF-induced acrosomal reaction was inhibited by L-canavanine and hemoglobin, and the NO donors sodium nitroprusside (SNP), S-nitroso-N-acetyl-penicillamine (SNAP), and DETA NONOate were able to increase the percentage of reacted spermatozoa. Our results suggest that NO synthesized by human sperm may play a role in follicular fluid-induced acrosomal reaction.
A Revelli, M Massobrio, J Tesarik (1998)  Nongenomic effects of 1alpha,25-dihydroxyvitamin D(3).   Trends Endocrinol Metab 9: 10. 419-427 Dec  
Abstract: The hormonally active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3), is the key molecule of the vitamin D endocrine system, which produces biological effects in about 30 target cell systems. Growing experimental evidence supports the hypothesis that these biological effects can be generated both by a signal transduction mechanism involving a nuclear receptor (nVDR) that modulates gene transcription, and via a nongenomic receptor located in the plasma membrane (mVDR), which modulates a complex signaling system involving the rapid opening of Ca(2+) channels. Some data reviewed herein also indicate that crosstalk between genomic and nongenomic pathways operates in several cell types, and suggest that the physiological role of the rapid, nongenomic actions might involve the regulation of hormone-mediated gene activation.
A Revelli, J Tesarik, M Massobrio (1998)  Nongenomic effects of neurosteroids.   Gynecol Endocrinol 12: 1. 61-67 Feb  
Abstract: This review summarizes the current knowledge about the synthesis, the mechanism of action, and the effects of neurosteroids in the central nervous system. Particular attention is paid to the nongenomic actions of neurosteroids, which are discussed in relation to their clinical relevance for physiological and pathological states.
G M Actis Dato, P Rinaudo, A Revelli, A Actis Dato, G Punta, P Centofanti, M Cavaglià, L Barbato, M Massobrio (1998)  Atrial septal defect and pregnancy: a retrospective analysis of obstetrical outcome before and after surgical correction.   Minerva Cardioangiol 46: 3. 63-68 Mar  
Abstract: To describe the obstetrical outcome and long-term cardiac follow-up of a group of patients who had surgery for atrial septal defect repair before pregnancy and a group who underwent pregnancy before surgical correction.
A Revelli, G B La Sala, A Miceli, M Balerna, M Massobrio (1997)  Preincubation in peritoneal fluid decreases the follicular fluid-induced acrosomal reactivity of human spermatozoa.   Andrologia 29: 1. 43-48 Jan/Feb  
Abstract: The aim of this study was to determine the effects of preincubation in peritoneal fluid on the follicular fluid-induced acrosomal reactivity of human spermatozoa in vitro. Thirty women participating in our IVF-ET program were given a GnRH-analogue, highly purified FSH and hCG in order to induce superovulation. Peritoneal and follicular fluids were aspirated during pick-up laparoscopy, centrifuged, filtered and frozen until use. An aliquot of swim-up suspension from normospermic semen specimens (n = 30) was incubated with peritoneal fluid or HAM-F10 for 30-180 min, and follicular fluid (in volumetric proportion approximately 50/50 with peritoneal fluid) was subsequently added. The percentage of acrosomally-reacted spermatozoa was assessed using the FITC-conjugated Pisum sativum lectin before and after incubation in peritoneal fluid or control medium, as well as after follicular fluid addition. Peritoneal fluid was not able to stimulate acrosomal reactivity; further, preincubation in peritoneal fluid decreased, but not abolished, the follicular fluid-induced acrosomal reactivity. A longer pre-incubation in peritoneal fluid was associated with a lower percentage of reacted spermatozoa in response to the addition of follicular fluid. In conclusion, our data suggest that peritoneal fluid acts maintaining spermatozoa in an unreacted status in the upper female genital tract. After mixing with follicular fluid, a phenomenon that is likely to occur at ovulation, peritoneal fluid reduces, but does not abolish, the stimulating effect of follicular fluid on acrosomal reactivity.
M G Catalano, A Comba, A Fazzari, E Benedusi-Pagliano, M Sberveglieri, A Revelli, M Massobrio, R Frairia, N Fortunati (1997)  Sex steroid binding protein receptor (SBP-R) is related to a reduced proliferation rate in human breast cancer.   Breast Cancer Res Treat 42: 3. 227-234 Feb  
Abstract: In the last years, an increasing amount of studies described a membrane receptor for the Sex Steroid Binding Protein (SBP) on several androgen-estrogen dependent tissues. One of the suggested biological roles of the interaction between SBP and its receptor seems to be a negative control of the E2 induced proliferation of human breast cancer cells through the cAMP pathway. In the present work, SBP membrane receptor was evaluated on human breast cancer specimens with a radio-binding assay. Each tissue sample was also evaluated for ER and PGR status. Cytosol Thymidine Kinase levels were measured in tissue samples in order to evaluate cell proliferation rate. SBP binding to membranes of ER +/PGR + samples was time and temperature dependent, specific and at high affinity. In addition, SBP recognized on breast cancer membranes two sites at different affinity, as previously described for other human tissues and cultured cells. Membrane SBP-R was detected in a significantly higher number of samples positive for both ER and PGR than in negative samples. SBP-R positive samples showed a significantly lower proliferation rate than SBP-R negative samples as demonstrated by TK activity. The present study contains evidences for the existence of a specific membrane receptor for SBP in breast cancer sample membranes and the presence of SBP-R seems to be strictly related to a lower proliferation rate of the sample.
A Revelli, D Pacchioni, P Cassoni, G Bussolati, M Massobrio (1996)  In situ hybridization study of messenger RNA for estrogen receptor and immunohistochemical detection of estrogen and progesterone receptors in the human ovary.   Gynecol Endocrinol 10: 3. 177-186 Jun  
Abstract: The expression of estrogen and progesterone receptors (ER and PR), as well as the presence of messenger RNA for estrogen receptor (ER-mRNA), were analyzed by immunohistochemistry and in situ hybridization, respectively, in the ovary of 25 healthy eumenorrheic women. Ovarian biopsies were taken in different phases of the menstrual cycle during laparotomy or operative laparoscopy performed for extraovarian benign diseases. A total of 126 follicles (105 primordial, 13 preantral and eight antral) and 50 corpora lutea (eight active and 42 atretic) was analyzed. Granulosa cells stained positively for ER, PR and ER-mRNA in 13.3, 9.5 and 17.1% of primordial follicles, respectively. The proportions of preantral and antral follicles with ER-positive granulosa cells were 23.1 and 37.5%, respectively; these follicles were positive for PR in 23.1 and 37.5% of cases, and for ER-mRNA in 30.7 and 37.5% of cases, respectively. For thecal cells, 38.5% of preantral and 37.5% of antral follicles were PR-positive, but no more than 25% stained positive for ER and ER-mRNA. Active corpora lutea stained positive for ER, PR and ER-mRNA in 50, 62.5 and 50% of cases, respectively. Corpora albicantes always stained negative. In all subjects the stroma surrounding both follicles and corpora lutea contained several fibroblast-like cells which stained positive for ER, PR and ER-mRNA. Oocytes and blood vessels stained negative in all cases. This study supports the hypothesis that estrogens and progesterone play a role in the intraovarian regulation of follicle growth from the first steps of follicle development, and participate in the regulation of corpus luteum.
A Revelli, G B La Sala, D Gallicchio, M Modotti, A Piffaretti-Yanez, M Massobrio, M Balerna (1995)  Effect of peritoneal fluid, follicular fluid, and their volumetric mixture on acrosomal reactivity in vitro.   Fertil Steril 63: 1. 200-203 Jan  
Abstract: To determine the effects of peritoneal and follicular fluids (PFs, FFs) on sperm acrosomal reaction (AR).
A Revelli, M Modotti, C Ansaldi, M Massobrio (1995)  Recurrent endometriosis: a review of biological and clinical aspects.   Obstet Gynecol Surv 50: 10. 747-754 Oct  
Abstract: The recurrence of pelvic endometriosis some time after the initial treatment is a common finding in clinical practice. When symptoms of endometriosis reappear several months after treatment, it is difficult to distinguish between recurrence and persistence of the disease. In this review, the current hypotheses about the biological basis of endometriosis recurrence/persistence are discussed. The results of several clinical trials estimating the recurrence rate of endometriosis after medical, surgical, and combined treatments are presented. In addition, a critical analysis of the tools available for the diagnosis of recurrent endometriosis is made, and some therapeutic options to treat recurrent endometriosis are discussed with recommendations for their use.
A Revelli, M Modotti, A Piffaretti-Yanez, M Massobrio, M Balerna (1994)  Steroid receptors in human spermatozoa.   Hum Reprod 9: 5. 760-766 May  
Abstract: The presence of steroid binding sites in (or on) human spermatozoa was first suggested in the late 1970s, by studies showing that some steroids were able to influence sperm function. Subsequently, several effects exerted on spermatozoa by biological fluids, such as follicular fluid, were found to be probably linked to the action of steroids, and among them progesterone. Since the effects of progesterone on spermatozoa were rapid, dose-dependent and not affected by progesterone conjugation with high molecular weight proteins unable to cross the plasma membrane, the existence of a novel class of non-genomic progesterone receptors was strongly suspected. This hypothesis was further supported by the observation that some of the effects of progesterone on human spermatozoa were not abolished by inhibitors of the classical progesterone nuclear receptors, nor mimicked by progesterone genomic receptor agonists. Recently, surface progesterone binding sites were directly identified on the membranes of human spermatozoa, and their mechanism of action partially characterized.
M Modotti, G Togni, G Medici, A Revelli, J Stamm, A Piffaretti-Yanez, M Massobrio, M Balerna (1994)  Effect of peritoneal fluid supplemented with exogenous progesterone on sperm motility in vitro.   Hum Reprod 9: 2. 303-309 Feb  
Abstract: Since progesterone has been claimed to induce acrosomal reaction and hyperactivated motility of human spermatozoa, the present study was undertaken to determine if its presence at concentrations similar to those of peri-ovulatory follicular fluid could influence the effect of peritoneal fluid on sperm motility in vitro. To this end, 11 sperm samples were incubated at 37 degrees C with five peritoneal fluids with/without exogenous progesterone, and sperm motility was assessed using a computer-assisted analyser at time (t) = 0, 2.5, 5 and 24 h. Overall there was no observable constant trend for enhancement or inhibition of sperm motility. Progesterone generally induced a negative effect on those sperm samples with high velocities in the native peritoneal fluids and a positive effect on those sperm samples demonstrating low motility in the native peritoneal fluids. The incorporation of progesterone into the incubation medium seemed to result in a 'tuning' of sperm velocity to around 30-50 micron/s. However, a given sperm sample reacted differently when incubated with various peritoneal fluids and, reciprocally, different semen samples incubated with the same peritoneal fluid showed very variable motility patterns. The greater variability of the effects exerted by progesterone on sperm motility could arise from the fact that each sperm sample may contain subpopulations of gametes with different sensitivity to progesterone.
M Massobrio, M Migliardi, P Cassoni, C Menzaghi, A Revelli, G Cenderelli (1994)  Steroid gradients across the cancerous breast: an index of altered steroid metabolism in breast cancer?   J Steroid Biochem Mol Biol 51: 3-4. 175-181 Nov  
Abstract: The concentrations of 17 beta-estradiol, estrone, testosterone (T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate, androstenedione (A), cortisol and prolactin (PRL) were determined in the peripheral venous blood and in the lateral thoracic vein of 14 premenopausal and 34 postmenopausal women who underwent surgery for a breast carcinoma. The difference between the two blood samples, defined as concentration gradient across the cancerous breast, was calculated for all hormones. A significant peripheral-local concentration gradient was found for DHEA and A both in pre- and postmenopausal patients, whereas for T it was observed only in postmenopausal subjects. Furthermore, DHEA and A gradients were correlated to the presence of estrogen receptors as determined by a radioligand binding assay. An inverse relationship between DHEA gradient and the expression of estrogen receptors was observed in premenopausal women, whereas in postmenopausal patients an opposite, although not significant, trend was found. These results suggest that in the cancerous breast: (1) DHEA, A and T (the latter only in postmenopause) could be taken up from plasma, and thus there could be a storage of these steroids inside the breast tissue and/or perhaps some alterations in their local metabolism; (2) androgens could play a different role in breast carcinogenesis in relation to the estrogen circulating levels and to the expression of estrogen receptors.
R Frairia, N Fortunati, A Revelli, D Guidetti, S Cavaglià, M Massobrio (1994)  Binding of sex steroid binding protein to plasma membranes of human testis.   J Steroid Biochem Mol Biol 51: 5-6. 319-322 Dec  
Abstract: The existence of a specific binding site for sex steroid binding protein (SBP or SHBG) was detected on plasma membranes prepared from the testis of a patient affected by a variant form of testicular feminization. A binding technique using [125I]SBP as a tracer allowed us to identify a single set of binding sites, characterized by a Kd of 1.917 x 10(-11) M. The maximum number of binding sites was 5.2 fmol/mg membrane protein. Membranes were also prepared from a sample of genital skin from the same patient, but no binding for [125I]SBP was detectable. The evidence of the SBP membrane receptor in the testis of a patient affected by Morris syndrome extends our knowledge about the tissue distribution of the SBP receptor and suggests the possible implication of SBP and its recognition system in a disorder related to peripheral androgen insensitivity.
F Guidi, A Revelli, G Soldati, J Stamm, M Massobrio, A Piffaretti-Yanez, M Balerna (1993)  Influence of peritoneal fluid from spontaneous and stimulated cycles on sperm motility in vitro.   Andrologia 25: 2. 71-76 Mar/Apr  
Abstract: Peritoneal fluids (PFs) from spontaneous (n = 14) and gonadotrophin-stimulated cycles (n = 20) were obtained during diagnostic laparoscopy and gamete intrafallopian transfer (GIFT) procedures, respectively. The effects of these fluids on the linear component of sperm motility and on the percentage of motile spermatozoa were studied in vitro by objective motility assessments and compared to a control medium (B2-Ménézo). Overall, the two types of PFs were found to have rather similar effects on the motility parameters studied. However, the fluids from hormonally-stimulated cycles sustained motility better (i.e., sperm velocity and percentage of motile sperm) and in a rather constant manner as a function of time (narrower range distributions of the motility measurements). Furthermore, it was observed that under identical experimental conditions motility measurements depended not only on the type of PF used but also on the sperm sample. These results suggest that assisted reproduction procedures in which PF is the medium where the gametes eventually meet and interact, such as direct peritoneal insemination (DIPI) or peritoneal oocyte and sperm transfer (POST), could have different success rates if performed in spontaneous rather than in stimulated cycles. At the same time, our results may help to explain why different pregnancy rates were reported in different studies using DIP or POST.
M Terzolo, A Revelli, D Guidetti, A Piovesan, P Cassoni, P Paccotti, A Angeli, M Massobrio (1993)  Evening administration of melatonin enhances the pulsatile secretion of prolactin but not of LH and TSH in normally cycling women.   Clin Endocrinol (Oxf) 39: 2. 185-191 Aug  
Abstract: The aim of the study was to evaluate the effects of exogenous melatonin on the spontaneous pulsatile release of PRL, TSH and LH in normal women.
A Revelli, G Soldati, J Stamm, M Massobrio, E Töpfer-Petersen, M Balerna (1992)  Effect of volumetric mixtures of peritoneal and follicular fluid from the same woman on sperm motility and acrosomal reactivity in vitro.   Fertil Steril 57: 3. 654-660 Mar  
Abstract: To study the effect of peritoneal (PF) and follicular fluids (FF from the same woman) as well as of given volumetric combinations thereof on sperm motility and acrosomal reactivity.
A Balsamo, A Revelli, I Borelli, A Amoroso, G Cenderelli, G De Sanso, G Mazzola, E S Curtoni, G Zoppetti, M Massobrio (1992)  Hormonal profiles in Italian late-onset adrenal hyperplasia correlate with HLA class III polymorphisms.   Gynecol Endocrinol 6: 2. 91-98 Jun  
Abstract: To investigate the genetic polymorphisms of the HLA region in late-onset adrenal hyperplasia, 13 Italian patients affected by the disease were analyzed for: (1) HLA-A and -B typing; (2) restriction fragment length polymorphism (RFLP) of DR beta, DQ beta, DQ alpha, 21-hydroxylase A and B genes; (3) fourth complement fraction loci A and B (C4A and C4B), second complement fraction (C2) and properdin B factor (Bf) complement typing; (4) hormonal characteristics associated with some HLA haplotypes. HLA alleles B14 and DR beta 1 were found to be significantly more frequent in patients with respect to controls (relative risk: 8.7 and 7.2, p less than 0.001 and p less than 0.0001, respectively). Also C4B*2, 1 duplication was more frequent in patients than in normal subjects (23% vs. 1.5%, p less than 0.0001). Moreover, patients carrying a duplicated C4B (as well as those having the B14 antigen) showed higher 17-hydroxyprogesterone levels after ACTH stimulation. RFLP analysis of 21-hydroxylase genes with a specific probe revealed a duplication of 21-hydroxylase A gene in 40% of patients. All these individuals carried the C4A*2 B*2,1 phenotype and 75% of them displayed a clearly recognizable duplication at the C4B locus. These data support the hypothesis that in late-onset adrenal hyperplasia the 21-hydroxylase A pseudogene, even if inactive, may play a negative role in the regulation of 21-hydroxylase biosynthesis. Furthermore, we suggest analyzing class III phenotypes to screen the enzymatic defect.
D Pacchioni, A Revelli, G Casetta, P Cassoni, P Piana, A Tizzani, G Bussolati, M Massobrio (1992)  Immunohistochemical detection of estrogen and progesterone receptors in the normal urinary bladder and in pseudomembranous trigonitis.   J Endocrinol Invest 15: 10. 719-725 Nov  
Abstract: According to recent studies showing the presence of estrogens receptors (ERs) in the human female lower urinary tract, we performed ER and progesterone receptor (PR) assays in fresh frozen and paraffin embedded biopsies taken from the urinary bladder. Fourteen females undergoing endoscopy during staging for gynecological cancer (endometrium, cervix, ovary) and 15 women complaining of recurrent abacterial cystitis (pseudomembranous trigonitis) were enrolled in the study as Group 1 and Group 2, respectively. After informed consent, they were submitted to cystoscopy, during which two biopsies were taken: one on the trigonum and the other on the bladder lateral wall. ERs were identified in both groups only in the trigonum (7/14 patients in Group 1 and 8/15 in Group 2), whereas the bladder lateral wall always stained negative. PRs were found at both sites in both groups (11/14 cases on the trigonum and 7/14 on the bladder lateral wall in Group 1; 11/15 and 2/15 respectively in Group 2). Morphological localization of PRs showed intense omogeneous staining in the nuclei of the stromal fibroblasts too. A clear correspondence between the presence of steroid receptors at the squamous metaplasia of the trigonum was observed. These data are discussed speculating about a possible endocrine pathogenesis of pseudomembranous trigonitis.
G Bussolati, A Tizzani, G Casetta, P Cassoni, D Pacchioni, P Piana, A Revelli, M Massobrio (1990)  Detection of estrogen receptors in the trigonum and urinary bladder with an immunohistochemical technique.   Gynecol Endocrinol 4: 3. 205-213 Sep  
Abstract: In order to detect estrogen receptors (ER) in the female bladder, 5 premenopausal and 10 postmenopausal women affected by gynecological diseases were submitted to cystoscopy, during which both the trigonum and the bladder lateral wall were biopsied. A new, simple, cost-effective immunohistochemical technique was employed to stain the estrogen specific binding sites. ER were found in the trigonum of 3 premenopausal and 4 postmenopausal subjects, while the bladder lateral wall was always ER-negative. A comparison with previously used ER detection methods and a discussion of further hypothetical applications of the immunohistochemical technique in the study of the lower female urogenital tract are reported.
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