Papers by Natalia Lazzarin

American Journal of Reproductive Immunology, 2000
Thyroid abnormalities and recurrent spontaneous abortion: diagnostic and therapeutical approach. ... more Thyroid abnormalities and recurrent spontaneous abortion: diagnostic and therapeutical approach. AJRI 2000; 43:204-208 © Munksgaard, Copenhagen PROBLEM: The aim of this study is to evaluate the role of mild thyroid abnormalities in recurrent spontaneous abortion, and to assess the effects of two different therapeutical protocols. METHOD: A prospective study in the population of recurrent aborters with mild thyroid abnormalities, evaluating the obstetric outcome in 42 patients. Sixteen thyroid autoantibodies positive patients were treated with thyroid replacement therapy, while 11 patients received intravenous immunoglobulins (IVIG). Fifteen patients, characterized by negative antithyroid antibodies, and having underlying thyroid pathology, were treated with thyroid replacement therapy. RESULTS: Among patients with thyroid antibodies, 6 out of the 11 pregnancies (54.5%) treated with IVIG ended in live birth. In the thyroid supplementation group, 13 out of 16 pregnancies (81.2%) ended in live birth. Only one pregnancy loss occurred among patients with a mild underlying thyroid pathology treated with thyroid replacement therapy. CONCLUSIONS: Mild thyroid abnormalities are associated with an increased rate of miscarriage. This poor obstetrical prognosis seems to be related to an impaired thyroid adaptation to pregnancy. Thyroid replacement therapy appears to be more effective than IVIG in preventing a new miscarriage. * Our data, confirming that mild thyroid abnormalities are associated with increased risk of abortion, indicated that thyroid replacement therapy is more effective than IVIG in preventing new miscarriages in RSA patients with such pathologies.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2011
Pregnancy hypertension
in eclamptic women, whereas nonlethal intracranial hemorrhage is also frequently found. Such hemo... more in eclamptic women, whereas nonlethal intracranial hemorrhage is also frequently found. Such hemorrhage is more common in older women and perhaps secondary to longstanding hypertension-induced lipohyalinosis. Hemorrhage may also develop in areas of cerebral ischemia or infarction and is more common in young women with HELLP syndrome. Women with preeclampsia may experience subarachnoid hemorrhage as a result of rupture of cortical petechiae or pial veins over the surface of the brain. Only rarely is intracerebral hemorrhage in preeclampsia due to a ruptured aneurysm or arteriovenous malformation.

Ultrasound in Obstetrics and Gynecology, 2007
signs. This has proven to predict CA with a high degree of accuracy when compared to placental hi... more signs. This has proven to predict CA with a high degree of accuracy when compared to placental histology. We aimed to investigate whether scans in earlier pregnancy can be used to diagnose CA with similar reliability. Methods: This was a retrospective study of twin pregnancies over a three-year period. Women with viable twin pregnancies who underwent a transvaginal scan (TVS) between 7 and 9 weeks of gestation were included in the analysis, and CA documented. This was compared to the respective diagnoses of CA at the 11-14 week scan. CA at the 11-14 week scan was assumed to be diagnostic, given the previously reported high sensitivity and specificity. Results: 69 women with viable twin pregnancies between 7 and 9 weeks also attended for an 11-14 week scan at our hospital. In five women spontaneous single fetal demise occurred between scans and were excluded. Of the remaining twins, CA was documented in 58 cases at 7-9 weeks. Overall, there was agreement in CA between the two scans in 55 of these 58 (94.8%). Agreement was highest for dichorionic-diamniotic (DCDA) pregnancies at 7-9 weeks: 44/45 (97.8%) were confirmed as DCDA and 1 (2.2%) as monochorionic-diamniotic (MCDA) at the 11-14 week scan. Of the 11 MCDA pregnancies at 7-9 weeks, 10 (90.9%) were found to be MCDA and one (9.1%) DCDA. There were two monochorionic-monoamniotic (MCMA) pregnancies diagnosed at 7-9 weeks, of which one was subsequently found to be MCMA while the other was MCDA. Conclusions: TVS at 7-9 weeks will correctly diagnose CA in about 95% of twin pregnancies. Accuracy may be higher for DCDA twins than MCDA twins and this may relate to the gestation at which sonographic appearance of the amniotic sac occurs.

Hypertension in pregnancy and endothelial activation: An emerging risk factor for cardiovascular disease
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2012
There is emerging evidence suggesting that women who develop hypertensive disorders of pregnancy ... more There is emerging evidence suggesting that women who develop hypertensive disorders of pregnancy should be considered at risk for cardiovascular disease (CVD). Our objective was to determine whether persistent endothelial activation, which represents the earliest step in atherogenesis, is present after delivery in women with a history of hypertensive pregnancies compared to women with normal pregnancies. Two matched case-control studies were conducted. In the first study, endothelial activation was assessed by the measurement of soluble intercellular adhesion molecules, namely, intercellular adhesion molecules-1 (ICAM-1), vascular cellular adhesion molecules-1 (V-CAM-1), E-selectin and P-selectin in 25 women with hypertensive pregnancies and in a matched control group with an uncomplicated pregnancy one month and three months after delivery. In the second study, adhesion molecules were measured in 20 patients with a history of HELLP syndrome several years after pregnancy and in 20 matched controls. Increased levels of soluble adhesion molecules were found in women with hypertensive complications compared to women with uncomplicated pregnancies shortly after delivery. Significant differences were still present, several years after delivery comparing levels of adhesion molecules in women with a history of HELLP syndrome with those found in control patients. Patients with hypertensive pregnancies showed an abnormal activation of the endothelium which persists after pregnancy. This activation was particularly marked in patients experiencing HELLP syndrome. These observations may represent an explanation to the increased risk of CVD later in life in patients experiencing hypertensive pregnancies, especially in women with a history of HELLP syndrome.
The Journal of the American Association of Gynecologic Laparoscopists, 2004
To compare the reproductive outcome in women with recurrent spontaneous abortion (RSA) associated... more To compare the reproductive outcome in women with recurrent spontaneous abortion (RSA) associated with septate uterus after hysteroscopic metroplasty compared with patients who did not undergo surgery. Longitudinal evaluation (Canadian Task Force classification II-2). University of Rome, Tor Vergata-affiliated endoscopic unit. Forty-eight consecutive women with septate uterus and RSA were enrolled in the study. Hysteroscopic metroplasty. Reproductive outcome in terms of term pregnancy was significantly improved after hysteroscopic metroplasty compared with controls (76% vs. 20%). No differences were found in the prevalence of preterm delivery between groups (4% vs. 5%). Our data suggest that hysteroscopic septum incision can improve pregnancy outcome in patients with RSA associated with septate uterus.

International Journal of Endocrinology, 2012
It has been twenty years since the first paper reporting the association between thyroid antibodi... more It has been twenty years since the first paper reporting the association between thyroid antibodies (TAIs) and spontaneous miscarriage was published. Following this observation, several studies have clearly demonstrated an increased prevalence of TAI in patients with recurrent miscarriage (RM). However, the exact mechanism underlying this association remains a matter of debate. The aim of the present study was to evaluate the thyroid function, throughout a specific test, in patient with RM and TAI focusing on the hypothesis that TAI should be an indirect sign of a mild thyroid dysfunction. 46 patients with RM and TAI were included in the study. All patients underwent short TRH stimulation test showing an abnormal response in the vast majority of cases (65%). Normal FT4 and FT3 mean values were found whereas TSH values were in the upper normal range (2.64 ± 1.3 mUI/L). Our data support the hypothesis that in patients with RM the presence of TAI is an indirect sign of a subtle thyroid dysfunction detectable by a specific test. This test give the possibility to identify women with RM in which specific therapeutic approaches could effectively improve the possibility for a successful pregnancy.
Ultrasound in Obstetrics and Gynecology, 2008
were recorded upon infant discharge or death. An anomalous fetus was considered detected if an ab... more were recorded upon infant discharge or death. An anomalous fetus was considered detected if an abnormality of the relevant organ system was identified. BMI was based on weight at first prenatal visit and categorized as normal, overweight or class I-, II-, or IIIobesity using NIH criteria. Statistical analyses were performed using Mantel-Haenszel chi-square test. Results: There were 10,112 standard and 1023 targeted US examinations, and abnormalities were verified in 181 infants (1.6%). There was a significant decrease in the standard US detection of anomalous fetuses with increasing BMI, P = 0.03. When standard and targeted US were combined, a significant decrease in anomaly detection with increasing BMI was also observed, P = 0.04.

Ultrasound in Obstetrics and Gynecology, 2006
as maternal age, ovarian reserve, serum estradiol concentrations, follicular number and size are ... more as maternal age, ovarian reserve, serum estradiol concentrations, follicular number and size are being investigated as possible prognostic factors of success. In regard to the oocyte quality at the time of retrieval, a relationship between follicular vascularization and the IVF outcome has been established. Conventional pulsatility indices of intra-ovarian arteries are very difficult to use routinely. The aim of this study was to investigate the accuracy of power Doppler ultrasonography for assessment of follicular vascularization during IVF attempts, as well as a prognostic factor of IVF outcome. Methods: 35 patients undergoing IVF treatment were prospectively recruited. Using power Doppler ultrasound, we assessed individual follicular vascularization of about three follicules in each ovary, by a subjective graduation, at the time of oocyte collection. Using a validated system, follicles were determined to be at high or low grade on regard with the extension of vascularization. Subsequent follicular and oocyte quality parameters were collected: mean follicular diameter, presence and maturity of the corresponding oocyte, quality of zygotes and cleaved embryos whether transferred or not. Results: A total of 187 follicles were studied. The assessment of perifollicular vascularization, although highly subjective, was feasible in 92.51% of cases. Vascularization grade was not dependent on follicular size. There was no significant difference in any of the analysed follicular and oocyte quality parameters between high and low grade follicles. Conclusion: Power Doppler assessment of perifollicular vascularization does not seem to be a useful procedure to evaluate follicular and oocyte quality.
Ultrasound in Obstetrics and Gynecology, 2005
infertile couples the maximal chance of conception. As perifollicular vascularization is related ... more infertile couples the maximal chance of conception. As perifollicular vascularization is related to a better oocyte competence leading to the development of higher quality embryos, we used 3D power Doppler (pD) to relate perifollicular blood flow indexes to oocyte maturity, showing that increasing in perifollicular blood flow reflects into a better oocyte quality and embryo viability. 3D pD measurements of perifollicular blood flow changes reflect oocyte maturity and can be used as a useful tool to establish which oocytes to inject/fertilize to improve IVF outcome.

Ultrasound in Obstetrics and Gynecology, 2003
Background: Advances in MR contrast media pharmacokinetic studies of transit through tissues and ... more Background: Advances in MR contrast media pharmacokinetic studies of transit through tissues and dynamic MRI allow to characterize organs physiology in vivo. Placental function assessment has been disappointing to date and might be achieved using analysis of dynamic contrast enhanced MRI of tracers. This aim of this study was to build up a murine model of placenta functional assessment using dynamic MRI. Material and methods: Balb/c mice at sixteen days of gestation were injected either by a conventional contrast media (gadolinium-Dota/Dotarem = Group A) or by an experimental macromolecular contrast agent (P792/Vistarem = Group B) during a MR single slice, T1-weighted 2D Fast SPGR sequential acquisition. Imaging was refreshed every 1.1 second for a 15 minutes period. Signal intensities measurements in left ventricle (input function), placenta and fetus areas were performed for each time point and then converted into contrast media tissue concentrations. A compartmental model was build up to explore the kinetic parameters of placenta exchange functions using SAAM II (Software for kinetic analysis, Saam institute, University of Washington, USA). Results: A total of 50 mice were included and used to build up the animal model. Perfusion and permeability parameters were obtained using a compartmental analysis in 20 mice with (10 mice in each group). Differences in Dotarem and Vistarem placental distribution and permeability were highlighted. Conclusion: Perfusion and permeability assessment in mice placenta using dynamic MRI contrast media is feasible. Such technique allows to get near placental physiology and feto-maternal barrier. This could be of great interest to study drugs and infectious agents pathways through fetus.

Ultrasound in Obstetrics and Gynecology, 2008
Objectives: To evaluate the relationship between uterine arteries blood flow and endometrial and ... more Objectives: To evaluate the relationship between uterine arteries blood flow and endometrial and subendometrial volume and vascularity using three-dimensional (3D) power Doppler untrasonography in patients with recurrent miscarriage (RM). Methods: 40 women with unexplained RM were included in the study. All patients underwent an accurate screening in order to exclude all the etiological RM factors. Three-D ultrasound examination with power Doppler was performed in all cases in the midluteal phase of the cycle by Voluson 730 pro GE machine. Twenty patients showed increased resistance to uterine arteries blood flow whereas in 20 cases normal resistances were found. Endometrial and subendometrial volume, vascularization index (VI), flow index (VI) and vascularization flow index (VFI) were calculated using the VOCAL (Virtual Organ Computer-aided AnaLysis) software. Results: Endometrial and subendometrial volume and VI were found significantly lower in patients with increased resistance to uterine arteries blood flow. No statistically significant correlations between uterine arteries PI, endometrial and subendometrial FI and VFI were observed. Nonetheless, patients with increased resistances to uterine arteries blood flow showed lower 3D vascularization indices. Conclusions: 3D power Doppler ultrasonography study of uterine perfusion seems to reflect the actual blood flow to the subendometrium and endometrium. This technique represents a unique tool to examine the blood supply towards the endometrial and subendometrial regions providing the opportunity to identify women with RM in which appropriate therapeutic protocols may effectively improve the possibility for successfully pregnancy.
Effect of a competitive inhibitor of P450-aromatase on granulosa luteal cells from polycystic ovary
Journal of the Society for Gynecologic Investigation, 1998
47 Diagnostic evaluation of women experiencing repeated in vitro fertilization failure
Reproductive BioMedicine Online, 2011

Molecular and Cellular Endocrinology, 1994
The aim of this work is to evaluate the gonadotropin and growth factor effects in vitro on steroi... more The aim of this work is to evaluate the gonadotropin and growth factor effects in vitro on steroidal response in human granulosa luteal cells from polycystic ovaries compared with normal granulosa luteal cells in humans. The granulosa cells from polycystic (polycystic ovarian granulosa cells, PGGC) and normo-ovulating women (normal cells, NC) were collected in the preovulatory phase after oocyte retrieval during the GIFT program. The cells were cultured serum-free for 24, 48 and 96 h. Estradiol and progesterone production was determined with or without HCG (l-200 ng/ml), FSH (10-300 ng/ml), insulin (1-50pcg/ml) and IGF I (l-50 &ml) addition. All treatments significantly induced a 2-3 fold estradiol increase at the 48-h and 96-h time points in POGC. The progesterone production was unaffected by HCG, FSH, insulin and IGF I addition, respectively, in POGC, whereas the NC were responsive at the 48-h and 96-h time points. FSH did not stimulate progesterone production in granulosa cells either from polycystic or normovulating subjects. Our findings indicate that PGGC are hypersensitive to all substances in terms of estradiol production, whereas they show a reduced capacity of progesterone production with some treatments.

Molecular and Cellular Biochemistry, 2011
Involvement of genetic polymorphisms in arterial hypertension has already been reported, includin... more Involvement of genetic polymorphisms in arterial hypertension has already been reported, including GST genes, with contrasting results. The present research evaluates the possible association between GST gene polymorphisms and essential hypertension (EH) in an Italian population sample. 193 hypertensive subjects and 210 healthy controls were recruited. Buccal cells were collected from each subject using an oral swab and DNA was extracted using the phenol:chloroform:isoamilic alcohol method. GST SNPs were determined using the PCR-RFLP method, while GST null polymorphisms were determined using a Multiplex PCR. Among GST polymorphisms, only the frequency of the GSTT1 null phenotype was significantly higher in hypertensive patients than in normotensive participants. GSTT1 null individuals were significantly associated with increased risk of hypertension [P \ 0.001; adjusted OR 2.24 (1.43-3.50)]. In sex-based analysis, the risk was significantly higher in female hypertensives [P \ 0.001; adjusted OR 3.25 (1.78-5.95)] but not in male subjects. This study analyzed all GST gene that, in other research, have been studied in relation to arterial hypertension and the GSTO polymorphisms, showing an association only with GSTT1. The results for the GSTO genes represent the first analysis of this GST class in relation to blood pressure regulation. The association between the GSTT1 null phenotype and EH was confirmed in the overall population and in women, but not in men. These data suggest that GSTT1 could be a sexspecific candidate gene for EH.
Ultrasound in Obstetrics & Gynecology - ULTRASOUND OBSTET GYN, 2009
Ultrasound in Obstetrics & Gynecology, 2007
Oral poster abstracts distal end of the Fallopian tubes where fertilization normally takes place.
The Journal of the American Association of Gynecologic Laparoscopists, 2001
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Papers by Natalia Lazzarin