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1.
Eur Rev Med Pharmacol Sci ; 25(14): 4799-4809, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34337729

ABSTRACT

Polycystic ovary syndrome (PCOS) is an endo-crine disorder that occurs in 8-10% of women of reproduc-tive age. It is characterized by oligo or anovulation, hyperandrogenism and/or polycystic ovaries, but also by an increased insulin plasma level especially in overweight/obese women or in those with familial diabetes. In the last years, among the insulin sensitizers, the use of the two active isoforms of inositols (myo-inositol and d-chiro-inositol) has been spreading for the treatment of PCOS insulin resistance. Several studies have shown a positive role of inositols both on the metabolic profile of PCOS patients, but also on hormonal parameters. Hence, inositols can positively affect the infertility that characterizes many PCOS patients, acting both on ovarian function and spontaneous ovulation and during IVF procedures, in terms of oocyte quality and pregnancy rate.


Subject(s)
Inositol/pharmacology , Polycystic Ovary Syndrome/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , Female , Humans , Insulin Resistance , Polycystic Ovary Syndrome/metabolism
2.
Int J Endocrinol ; 2019: 8309405, 2019.
Article in English | MEDLINE | ID: mdl-31097963

ABSTRACT

[This corrects the article DOI: 10.1155/2017/5469409.].

3.
Hum Reprod ; 32(12): 2474-2484, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29087515

ABSTRACT

STUDY QUESTION: Is the phosphoinositol 1,3-kinase/protein kinase B (PI3K/AKT) pathway expression profile in cumulus cells (CCs) a potential marker of oocyte competence and predictive of pregnancy outcome? SUMMARY ANSWER: Eleven genes (AKT1, ARHGEF7, BCL2L1, CCND1, E2F1, HRAS, KCNH2, PIK3C2A, SHC1, SOS1 and SPP1) in the PI3K/AKT pathway were significantly down-regulated in CCs from oocytes that went on to produce a pregnancy compared to CCs associated with a negative outcome. WHAT IS KNOWN ALREADY: The PI3K/AKT pathway plays a pivotal role in the interdependence and continuous feedback between the oocyte and CCs. STUDY DESIGN SIZE, DURATION: The expression analysis of 92 transcripts in the PI3K/AKT pathway in CCs from patients with negative or positive pregnancy outcome, after single embryo transfer, was performed. Mouse CCs target gene expression was conducted to associate the expression profile of PI3K/AKT pathway to oocyte developmental profile. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fifty-five good prognosis IVF patients who had been referred to IVF or intracytoplasmic sperm injection treatment for male-factor infertility or tubal disease were enroled. CCs from single cumulus-oocyte complexes (COCs) from 16 patients who underwent a single embryo transfer were analyzed. Twenty-five CD-1 mice were used to assess gene expression in CCs associated with oocytes with different competence in relation to hCG priming. A total 220 human COCs were collected. The RNA extracted from CCs of 16 selected patients was used to analyze PI3K/AKT pathway gene expression employing a 96-well custom TaqMan Array. Expression data of CCs associated to positive IVF outcome were compared to data from negative outcome samples. Mice were sacrificed after 9, 12, 15, 21 and 24 h post-hCG administration to obtain CCs from MII oocytes with different developmental competence. Akt1, Bcl2l2 and Shc1 expression were tested in the collected mouse CCs. In addition, the expression of upstream regulator ESR1, the gene encoding for the oestrogen receptor ERß, and the downstream effectors of the pathway FOXO1, FOXO3 and FOXO4 was evaluated in human and mouse samples. MAIN RESULTS AND THE ROLE OF CHANCE: Transcripts involved in the PI3K Signaling Pathway were selectively modulated according to the IVF/ICSI outcome of the oocyte. Eleven transcripts in this pathway were significantly down-regulated in all samples of CCs from oocytes with positive when compared those with a negative outcome. These outcomes were confirmed in mouse CCs associated with oocytes at different maturation stages. Expression data revealed that the down-regulation of ESR1 could be related to oocyte competence and is likely to be the driver of expression changes highlighted in the PI3K/AKT pathway. LIMITATIONS REASONS FOR CAUTION: Small sample size and retrospective design. WIDER IMPLICATIONS OF THE FINDINGS: The CCs expression profile of PI3K/AKT signaling genes, disclosed a specific CCs gene signature related to oocyte competence. It could be speculated that CCs associated with competent oocytes have completed their role in sustaining oocyte development and are influencing their fate in response to metabolic and hormonal changes by de-activating anti-apoptotic signals. STUDY FUNDING/COMPETING INTEREST(S): Supported by Merck Serono an affiliate of Merck KGaA, Darmstadt, Germany (research grant for the laboratory session; Merck KGaA reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors). The authors declare no conflict of interest.


Subject(s)
Cumulus Cells/metabolism , Gene Expression Regulation, Developmental , Oocytes/cytology , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Adult , Animals , Cell Proliferation , Cell Survival , Down-Regulation , Female , Fertilization in Vitro , Gene Expression Profiling , Humans , Mice , Prognosis , Signal Transduction , Sperm Injections, Intracytoplasmic
4.
Int J Endocrinol ; 2017: 5469409, 2017.
Article in English | MEDLINE | ID: mdl-28348586

ABSTRACT

Recently, studies on inositol supplementation during in vitro fertilization program (IVF) have gained particular importance due to the effect of this molecule on reducing insulin resistance improving ovarian function, oocyte quality, and embryo and pregnancy rates and reducing gonadotropin amount during stimulation. Inositol and its isoforms, especially myoinositol (MYO), are often used as prestimulation therapy in infertile patients undergoing IVF cycle. Inositol supplementation started three months before ovarian stimulation, resulting in significant improvements in hormonal responses, reducing the amount of FSH necessary for optimal follicle development and serum levels of 17beta-estradiol measured the day of hCG injection. As shown by growing number of trials, MYO supplementation improves oocyte quality by reducing the number of degenerated and immature oocytes, in this way increasing the quality of embryos produced. Inositol can also improve the quality of sperm parameters in those patients affected by oligoasthenoteratozoospermia.

5.
Gynecol Endocrinol ; 33(2): 109-112, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27908215

ABSTRACT

It is a known fact that abnormal seminal liquid specimens contain abnormal amounts of oxygen free radicals and reactive oxygen species (ROS), and that the use of antioxidant molecules both in vivo and in vitro leads to improvement of semen quality in terms of motility, reduction in DNA damage, with obvious consequences on the fertilization potential. Myo-inositol has been observed to have anti-oxidant properties and be present in much greater concentrations specifically in seminal liquid than in the blood. Moreover, there seems to be a direct relationship between myo-inositol and mitochondrial membrane potential (MMP) and sperm motility. Studies performed in vivo have demonstrated that a dietary supplementation with myo-inositol in men undergoing assisted reproduction techniques may improve sperm quality and motility in oligoasthenospermia (OAT) patients. In the following study we utilized myo-inositol in vitro to verify its effect on semen quality in both normal and OAT patients undergoing in vitro fertilization (IVF) with respect to standard sperm medium. In vitro incubation of seminal liquid carried out using myo-inositol (Andrositol-Lab, Lo.Li. Pharma-Roma, Italy) at a concentration of 15 µl/ml improved progressive motility in both normospermia and OAT subjects. In our opinion, myo-inositol may prove to be a useful strategy to improve sperm preparation for clinical use in IVF.


Subject(s)
Asthenozoospermia/drug therapy , Fertilization in Vitro/methods , Inositol/pharmacology , Oligospermia/drug therapy , Sperm Motility/drug effects , Vitamin B Complex/pharmacology , Adult , Humans , Male
6.
Gynecol Endocrinol ; 29(4): 375-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23336594

ABSTRACT

OBJECTIVE: To evaluate the effects the administration of myo-inositol (MYO) on hormonal parameters in a group of polycystic ovary syndrome (PCOS) patients. DESIGN: Controlled clinical study. SETTING: PCOS patients in a clinical research environment. PATIENTS: 50 overweight PCOS patients were enrolled after informed consent. INTERVENTIONS: All patients underwent hormonal evaluations and an oral glucose tolerance test (OGTT) before and after 12 weeks of therapy (Group A (n»10): MYO 2 g plus folic acid 200 mg every day; Group B (n»10): folic acid 200 mg every day). Ultrasound examinations and Ferriman-Gallwey score were also performed. MAIN OUTCOME MEASURES: Plasma LH, FSH, PRL, E2, 17OHP, A, T, glucose, insulin, C peptide concentrations, BMI, HOMA index and glucose-to-insulin ratio. RESULTS: After 12 weeks of MYO administration plasma LH, PRL, T, insulin levels and LH/FSH resulted significantly reduced. Insulin sensitivity, expressed as glucose-to-insulin ratio and HOMA index resulted significantly improved after 12 weeks of treatment. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic subjects. No changes occurred in the patients treated with folic acid. CONCLUSIONS: MYO administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion.


Subject(s)
Folic Acid/therapeutic use , Inositol/therapeutic use , Polycystic Ovary Syndrome/drug therapy , Blood Glucose , Body Mass Index , C-Peptide/blood , Drug Therapy, Combination , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Glucose Tolerance Test , Humans , Insulin/blood , Insulin Resistance , Luteinizing Hormone/blood , Polycystic Ovary Syndrome/blood , Prolactin/blood , Testosterone/blood , Treatment Outcome
7.
Gynecol Endocrinol ; 29(1): 79-82, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22835042

ABSTRACT

INTRODUCTION: Laparoscopic myomectomy has recently gained wide acceptance but this procedure remains technically highly demanding and concerns have been raised about the increased blood loss and an higher risk of postoperative uterine rupture of the pregnant uterus. OBJECTIVE: The aim of the present study is to evaluate the fertility and endocrine outcome in women underwent robot-assisted laparoscopic myomectomy (RALM). METHODS: Data from 48 RALM performed in our department between the years 2007 and 2011 have been collected. Conception rate, abortion rate, incidence of feto-maternal morbidity or severe pregnancy and labor-related complications were reported; FSH and AMH levels and ultrasound valuation of AFC has been made before and 6 months after operation. Number of cesarean sections and vaginal deliveries were described. RESULTS: The average age of the patients was 35 years and median Body Mass Index was 23 kg/m(2) (range 18-35 kg/m(2)). Seven women (13%) became pregnant after RALM with eight pregnancies. One pregnancy is actually on going; there were six deliveries with caesarian section and one spontaneous delivery. No spontaneous abortions. No uterine ruptures occurred. No significant modification of ovarian function was found after myomectomy. CONCLUSION: RALM seems to have a favorable impact on the reproductive outcome of young patients with no impact on the ovarian function.


Subject(s)
Fertility/physiology , Leiomyoma/surgery , Postoperative Complications/epidemiology , Robotics , Uterine Myomectomy/methods , Uterine Neoplasms/surgery , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/prevention & control , Adult , Cesarean Section/statistics & numerical data , Endocrine System/physiology , Female , Humans , Incidence , Infertility, Female/epidemiology , Infertility, Female/prevention & control , Leiomyoma/epidemiology , Morbidity , Obstetric Labor Complications/epidemiology , Obstetric Labor Complications/prevention & control , Ovary/physiology , Postoperative Complications/prevention & control , Pregnancy , Pregnancy Rate , Uterine Myomectomy/adverse effects , Uterine Myomectomy/instrumentation , Uterine Neoplasms/epidemiology
8.
Gynecol Endocrinol ; 28(4): 241-4, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22420627

ABSTRACT

Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age. Features of PCOS are hyperandrogenism, chronic anovulation and polycystic ovaries on ultrasonography. Follicle development is a complex and carefully orchestrated phenomenon, involving gonadotropins and a rapidly expanding list of other intraovarian regulators, such as brain-derived neurotrophic factor (BDNF). The aim of this study is to evaluate BDNF in plasma and in follicular fluid in women affected by PCOS and in normal menstruating women. In PCOS patients the BDNF levels in plasma and in follicular fluid are higher than values obtained in healthy controls. Therefore we can hypothsize that high levels of luteinizing hormone, probably increase the secretion of BDNF in PCOS patients.


Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Follicular Fluid/metabolism , Polycystic Ovary Syndrome/metabolism , Adolescent , Adult , Brain-Derived Neurotrophic Factor/blood , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Polycystic Ovary Syndrome/blood , Progesterone/blood , Young Adult
9.
J Biol Regul Homeost Agents ; 24(1): 63-72, 2010.
Article in English | MEDLINE | ID: mdl-20385072

ABSTRACT

Reproductive dysfunction with ageing has been so far extensively characterized in terms of depletion of ovarian follicles and reduced ability to produce gametes competent for fertilization. Nevertheless, molecular mechanisms underlying this process are still poorly understood. In the present study we addressed the hypothesis that methylglyoxal (MG), a major precursor of Advanced Glycation Endproducts (AGE), may contribute to molecular damage occurring during ovarian ageing. Our results showed that the biochemical activity of glyoxalase 1, the main component of the MG scavenging system, is significantly decreased in ovaries from reproductively-aged mice in comparison with the young group. This effect was associated with decreased expression at protein and RNA level of this enzyme and increased intraovarian level of MG. MG-arginine adducts argpyrimidine as detected with a specific antibody was found to accumulate with ageing in specific ovarian compartments. Separation of ovarian proteins by 2D gels and Western blotting revealed an approximate 30-fold increase in the extent of protein glycation in aged ovaries along with the appearance of eight argpyrimidine modified proteins exclusive for the aged group. In conclusion, the present results show that impaired MG detoxification causing relevant damage to the ovarian proteome might be one of the mechanisms underlying reproductive ageing and/or ageing-like ovarian diseases.


Subject(s)
Aging/physiology , Glycation End Products, Advanced/biosynthesis , Ovary/physiopathology , Pyruvaldehyde/metabolism , Reproduction/physiology , Aging/genetics , Aging/metabolism , Animals , Base Sequence , DNA Primers/genetics , Female , Lactoylglutathione Lyase/genetics , Lactoylglutathione Lyase/metabolism , Mice , Models, Biological , Ovary/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reproduction/genetics
10.
Minerva Ginecol ; 62(1): 33-48, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20186113

ABSTRACT

The polycystic ovarian syndrome (PCOS) includes a wide spectrum of clinical symptoms and signs. Three different diagnostic classifications have been proposed to define this disease. The first one, published in 1990, known as the "NIH criteria" requires the simultaneous presence of hyperandrogenism and menstrual dysfunction in order to diagnose PCOS. Later on, in 2003, an expert panel met in Rotterdam and added to the previous criteria the presence of polycystic ovarian morphology detected by transvaginal ultrasonography. The later classification broadened the spectrum of PCOS and also included women with oligomenorrhea and PCO without hyperandrogenism or hyperandrogenism and PCO without menstrual dysfunction. Finally, the Androgen Excess Society, published in 2006 new diagnostic criteria which required the presence of clinical or biochemical hyperandrogenism, with either PCO or menstrual dysfunction to diagnose PCOS. This review focuses on the diagnostic techniques and methods of treatment for PCOS patients. Special attention is given to the role of insulin resistance and the potential utility of insulin sensitizers in management of the syndrome. The benefit and utmost importance of lifestyle modification for the long-term health of these women is stressed as well. It is hoped that some clarity in this regard will allow more women to not only be diagnosed and managed properly for their presenting symptoms (hirsutism, irregular menses, etc.), but also to be educated and managed for the continuing health risk of insulin resistance throughout their lives.


Subject(s)
Polycystic Ovary Syndrome/diagnosis , Polycystic Ovary Syndrome/drug therapy , Androgens/metabolism , Aromatase Inhibitors/therapeutic use , Clomiphene/therapeutic use , Contraceptives, Oral, Hormonal/therapeutic use , Diagnosis, Differential , Female , Follicle Stimulating Hormone/therapeutic use , Gonadotropin-Releasing Hormone/agonists , Gonadotropins, Pituitary/metabolism , Hirsutism/etiology , Hirsutism/therapy , Humans , Hyperandrogenism/etiology , Infertility, Female/drug therapy , Infertility, Female/etiology , Insulin Resistance , Menstruation Disturbances/drug therapy , Menstruation Disturbances/etiology , Metformin/therapeutic use , Obesity/complications , Ovarian Follicle/diagnostic imaging , Ovary/diagnostic imaging , Ovary/surgery , PPAR gamma/antagonists & inhibitors , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/physiopathology , Polycystic Ovary Syndrome/surgery , Reproductive Techniques, Assisted , Spironolactone/therapeutic use , Ultrasonography
11.
J Assist Reprod Genet ; 24(10): 477-80, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17721815

ABSTRACT

PURPOSE: The aim of the study was to measure circulating BDNF levels, a neurotrophin recently identified in the ovary, in parallel with estradiol, to verify if assessing this factor could add any predictive value to the outcome of in vitro fertilization. METHODS: Blood sampling for BDNF and estradiol was performed in 23 subjects undergoing IVF on day 1 (D1), day 8 (D8), day of HCG administration (DHCG) and day of oocyte retrieval.(DOR). RESULTS: There was a positive correlation between BDNF and estradiol throughout the stimulation cycle in all subjects. In both pregnant and nonpregnant patients, the values of BDNF grew significantly only between D8 and DHCG and remained constant until DOR. Between-group comparisons showed no statistically significant differences in both BDNF and estradiol values throughout the IVF cycle. CONCLUSION: Although BDNF plasma concentrations are not seemingly predictive of IVF outcome, this neurotrophin is highly correlated to estradiol levels and seems to be an important factor especially in the periovulatory period.


Subject(s)
Brain-Derived Neurotrophic Factor/blood , Fertilization in Vitro , Adult , Estradiol/blood , Female , Humans , Pregnancy , Pregnancy Outcome
12.
Hum Reprod ; 22(9): 2481-7, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17586834

ABSTRACT

BACKGROUND: 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. METHODS: Thirteen Italian ART Units were involved in this study. Data were collected on ICSI cycles performed during 2 years before (control group) and 2 years after (study group) the enforcement of the law. Only cases of obstructive azoospermia (OA), non-obstructive azoospermia (NOA) and severe oligoastenoteratozoospermia (OAT) (sperm count

Subject(s)
Azoospermia , Legislation, Medical , Pregnancy Rate/trends , Reproductive Techniques, Assisted/legislation & jurisprudence , Sperm Injections, Intracytoplasmic , Adult , Embryo Transfer , Female , Humans , Italy , Male , Pregnancy
13.
Ultrasound Obstet Gynecol ; 26(5): 546-51, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16184506

ABSTRACT

OBJECTIVE: To evaluate the effects of transdermal hormone replacement therapy (HRT) on plasma viscosity, serum levels of thromboxane B2 (TXB2) and vascular impedance in the uterine, bladder wall, internal carotid and ophthalmic arteries in normotensive and hypertensive postmenopausal patients. METHODS: Thirty postmenopausal patients underwent continuous estradiol transdermal supplementation at a dose of 50 microg/day and 12-day courses of medroxyprogesterone acetate 10 mg/day every 2 months. The women were divided into two groups according to their blood pressure: normotensive women (Group 1, n=14) and hypertensive subjects (Group 2, n=16). Before starting HRT and after 6 months of therapy, the patients underwent: transvaginal ultrasonographic examination of the pelvic organs; Doppler examination of the blood flow velocities in the uterine, bladder wall, internal carotid and ophthalmic arteries; and analysis of plasma viscosity and plasma TXB2. RESULTS: After 6 months of HRT plasma viscosity had decreased in both groups (mean reduction in Group 1, (14+/-1)%, P=0.005; mean reduction in Group 2, (10+/-1)%, P=0.005) as had the TXB2 levels (mean reduction in Group 1, (93+/-2)%, P<0.001; mean reduction in Group 2, (92+/-3)%, P<0.001). The mean percentage reduction in plasma viscosity was smaller in hypertensive women than in normotensive women (P<0.05). There was also a significant reduction in vascular impedance in the uterine artery (mean reduction in Group 1, (16+/-1)%, P=0.005; mean reduction in Group 2, (19+/-1)%, P=0.005), the bladder wall arteries (mean reduction in Group 1, (23+/-2)%, P=0.005; mean reduction in Group 2, (18+/-1)%, P=0.005), the internal carotid artery (mean reduction in Group 1, (25+/-1)%, P=0.005; mean reduction in Group 2, (26+/-1)%, P=0.005) and the ophthalmic artery (mean reduction in Group 1, (24+/-2)%, P=0.005; mean reduction in Group 2, (16+/-1)%, P=0.005). The percentage reduction in vascular impedance did not differ significantly between the two groups. CONCLUSIONS: Our results show that transdermal HRT is effective in reducing plasma viscosity, TXB2 levels and vascular impedance in the peripheral and central vessels both in normotensive and hypertensive postmenopausal patients.


Subject(s)
Estrogen Replacement Therapy , Hypertension/diagnostic imaging , Postmenopause/blood , Ultrasonography, Doppler , Administration, Cutaneous , Analysis of Variance , Arteries , Blood Viscosity/drug effects , Carotid Artery, Internal/physiopathology , Case-Control Studies , Estradiol/administration & dosage , Female , Humans , Hypertension/blood , Hypertension/drug therapy , Linear Models , Medroxyprogesterone Acetate/administration & dosage , Middle Aged , Ophthalmic Artery/physiopathology , Regional Blood Flow/drug effects , Thromboxane B2/blood , Urinary Bladder/blood supply , Uterus/blood supply , Vascular Resistance/drug effects
14.
Gynecol Endocrinol ; 21(1): 50-6, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16048802

ABSTRACT

OBJECTIVE: The soluble form of the vascular endothelial growth factor (VEGF) receptor, s-VEGFR-1, may negatively regulate the action of VEGF. Our purpose was to better understand the regulation of angiogenetic processes in ovarian cysts. METHODS: Seventy-three women, 36 with serous cystoadenoma, 30 with ovarian endometriosis and seven with cystoadenocarcinoma, were enrolled. We calculated both VEGF and s-VEGFR-1 levels in cystic fluid and a VEGF activity index by means of the ratio VEGF/s-VEGFR-1. Student's t test was used for the statistical analysis. RESULTS: We found higher VEGF concentration in both endometriotic and malignant lesions than in serous cystoadenoma (p=0.03 and 0.001, respectively). Also s-VEGFR-1 concentration was higher in endometrioma than in serous cysts (p=0.005); however, there was no statistically significant difference between cystoadenoma and the malignant lesions (p=0.15). VEGF activity index in cystoadenoma, endometriotic and malignant lesions was 0.61, 0.27 and 0.50, respectively. CONCLUSIONS: VEGF certainly has an important role in both ovarian endometriosis and for cancer progression; however, the activity index may be better to investigate the real role of VEGF in the pathology we have considered.


Subject(s)
Ovarian Diseases/metabolism , Ovarian Neoplasms/chemistry , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor Receptor-1/analysis , Cyst Fluid/chemistry , Cystadenocarcinoma/chemistry , Cystadenoma, Serous/chemistry , Endometriosis/metabolism , Female , Humans
15.
Gynecol Endocrinol ; 19(5): 274-81, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15726916

ABSTRACT

The aim of this study was to evaluate the effects of transdermal hormone replacement therapy on some biological cardiovascular risk factors, specifically the thromboxane B2 levels, plasma viscosity and the lipid profile. Furthermore, we investigated the Doppler flow modifications at the level of the uterine artery, the internal carotid, the ophthalmic and the bladder wall arteries, and we finally evaluated whether there were significant differences in the examined parameters between normal and overweight postmenopausal women. Forty-five postmenopausal women (mean age+/-standard deviation, 53.5+/-3.8 years) participated in the study and were divided into two groups (27 with a body mass index of < 25 kg/m2 and 18 with a body mass index of > 25 kg/m2). Patients were treated with a continous estradiol transdermal supplement and a 12-day course of medroxyprogesterone acetate every 2 months, and were studied at baseline and after 6 months (in the estrogen-only phase of the second cycle). Our results showed a beneficial effect of hormone substitution on plasma viscosity, thromboxane B2 levels and lipid profile after 6 months of therapy and significant improvements of Doppler flow parameters in the examined vessels. Furthermore, we observed a lower impact of the treatment in overweight women. In conclusion, obesity represents an additional cardiovascular risk condition and it can only partially be modified by the administration of hormone replacement therapy.


Subject(s)
Cardiovascular Diseases/diagnostic imaging , Estrogen Replacement Therapy/methods , Obesity/complications , Postmenopause , Administration, Cutaneous , Blood Viscosity , Body Mass Index , Cardiovascular Diseases/complications , Cardiovascular Diseases/prevention & control , Endometrium/diagnostic imaging , Estradiol/administration & dosage , Female , Humans , Lipids/blood , Medroxyprogesterone Acetate/administration & dosage , Middle Aged , Pulsatile Flow , Risk Factors , Thromboxane B2/blood , Triglycerides/blood , Ultrasonography, Doppler, Color , Urinary Bladder/diagnostic imaging , Vascular Resistance
17.
J Exp Clin Cancer Res ; 21(1): 37-43, 2002 Mar.
Article in English | MEDLINE | ID: mdl-12071527

ABSTRACT

The aim of this study was to indicate the patients treated with tamoxifen for breast cancer in which hysteroscopy with biopsy should be considered mandatory. 414 breast cancer patients who underwent hysteroscopy with bioptic evaluation were enrolled in the study. 334 subjects were treated with 20 mg of tamoxifen daily as adjuvant therapy for six up to a hundred months. Of the remaining 80 control patients, which had not received tamoxifen, 30 were in premenopause (Group IA) and 50, in postmenopause (Group IIA). The tamoxifen-treated patients were subdivided in premenopausal (Group IB = 72 patients) and in postmenopausal (Group IIB = 262 patients) groups. All patients were further classified in asymptomatic or symptomatic groups considering whether uterine bleeding was absent or present. The evaluation of the endometrial mucosa was performed by office hysteroscopy. In group IIB patients presenting uterine bleeding, malignant lesions were found in 7.8% of the cases. The incidence of premalignant and malignant lesions in IIB patients treated for longer than 3 years (11.7%) was higher than that observed in IIB patients treated for less than 3 years (1.3%). There was a significant difference in terms of endometrial pathology between Group IIB (32.8%) and Group IIA (8%) (p < 0.001); and between Group IIB (32.8%) and Group IB (13.9%) women (p = 0.003). Among IA and IIA patients there were no cases of endometrial hyperplasia or cancer; on the contrary, in IB and IIB women, 2 and 22 cases of atypical hyperplasia were observed, respectively. All cases of endometrial cancer were observed in Group IIB and had a diagnosis of poor prognosis. In conclusion the hysteroscopy with biopsy should be considered the first diagnostic procedure to perform in tamoxifen-treated postmenopausal patients presenting uterine bleeding and in postmenopausal women treated for longer than 3 years. In premenopause, hysteroscopy should be proposed to women with ultrasonographic abnormalities and/or with uterine bleeding to patients at high risk for endometrial cancer.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Endometrial Hyperplasia/diagnosis , Endometrial Neoplasms/diagnosis , Endometrium/drug effects , Hysteroscopy/methods , Tamoxifen/therapeutic use , Antineoplastic Agents, Hormonal/adverse effects , Biopsy , Endometrial Hyperplasia/chemically induced , Endometrial Neoplasms/chemically induced , Endometrium/pathology , Female , Follow-Up Studies , Humans , Incidence , Mass Screening , Middle Aged , Postmenopause , Premenopause , Risk Factors , Tamoxifen/adverse effects
18.
Eur J Obstet Gynecol Reprod Biol ; 101(2): 169-74, 2002 Mar 10.
Article in English | MEDLINE | ID: mdl-11858893

ABSTRACT

BACKGROUND: The pathogenesis of ovarian hyperstimulation syndrome (OHSS) is not completely understood. OBJECTIVE: To investigate the presence of VEGF, IL-6 and IL-2, in serum and follicular fluid, in patients developing severe OHSS. STUDY DESIGN: We enrolled 101 women undergoing in vitro fertilization. Eight patients developing severe OHSS were compared with 43 high risk patients and 50 controls. We analyzed VEGF and IL-6 in serum collected before hCG administration, and in both serum and follicular fluid on the day of oocyte retrieval. RESULTS: OHSS patients presented follicular fluid IL-6 levels higher than both the patients at risk and controls (P<0.05). On the day of the oocyte retrieval the patients developing OHSS showed serum and follicular VEGF values higher than the ones of the patients at risk (P<0.05). Serum and follicular fluid IL-2 levels showed no differences between the examined groups. IL-2, IL-6 and VEGF values were not correlated with each other. CONCLUSIONS: Angiogenesis and inflammation processes are both present in severe OHSS.


Subject(s)
Endothelial Growth Factors/metabolism , Follicular Fluid/metabolism , Interleukin-2/metabolism , Interleukin-6/metabolism , Lymphokines/metabolism , Ovarian Hyperstimulation Syndrome/metabolism , Adult , Case-Control Studies , Chorionic Gonadotropin/therapeutic use , Endothelial Growth Factors/blood , Female , Humans , Interleukin-2/blood , Interleukin-6/blood , Lymphokines/blood , Oocytes , Ovarian Hyperstimulation Syndrome/blood , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
19.
J Exp Clin Cancer Res ; 20(2): 239-46, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11484981

ABSTRACT

Proteolytic enzymes, like urokinase (uPA) and plasminogen activator inhibitor type-1 (PAI-1), are involved in remodelling tissues during invasion and metastasis of tumor cells. The purpose of the study is to evaluate the expression and the prognostic significance of these enzymes in endometrial hyperplasia and cancer. We used immunohistochemical staining to localize uPA and PAI-1 antigens and evaluate their expression, and the enzyme-linked immunosorbent assay (ELISA) to measure their levels during the progression of endometrial carcinoma. The results show that the levels of uPA and PAI-1 detection are systematically weak in simplex hyperplasia and are moderate in complex hyperplasia. In the endometrial carcinoma a very strong reaction was observed in the most aggressive variant of epithelial tumors. A positive signal for uPA was found only in the cytoplasm of normal and hyperplastic cells while, in tumors, uPA was present also in the cellular areas surrounding the neoplastic glands and at the apex of the malignant cells. The PAI-1 immunoreactivity was weak to moderate in 95.4% of carcinomas, with a diffuse signal mostly distributed in the cytoplasm of neoplastic cells and tumor stroma. UPA antigen concentrations were significantly higher in endometrial carcinoma than in endometrial hyperplasia (p<0.05) and in normal endometrium (p<0.001). PAI-1 antigen concentrations in carcinoma samples were significantly higher than in normal endometrium (p=0.002), but the difference was not statistically significant with respect to that in endometrial hyperplasia. We did not find any correlation between uPA and PAI-1 concentrations and the standard prognostic parameters for evaluating endometrial carcinoma. In conclusion, this study demonstrates that in hyperplastic endometria and in endometrial carcinoma there is a progressive increase in expression of uPA and PAI-1 than in normal endometrial tissue. In carcinoma tissues, the high expression of uPA is unregulated in the surrounding stroma tissue, particularly in the most aggressive histopathologic variants. UPA and PAI-1 may be factors associated with invasive behavior in endometrial carcinoma independent of other clinicopathological parameters.


Subject(s)
Adenocarcinoma/metabolism , Endometrial Hyperplasia/metabolism , Endometrial Neoplasms/metabolism , Plasminogen Activator Inhibitor 1/metabolism , Serine Proteinase Inhibitors/metabolism , Urokinase-Type Plasminogen Activator/metabolism , Adenocarcinoma/diagnosis , Adenocarcinoma/mortality , Adult , Aged , Disease Progression , Endometrial Hyperplasia/diagnosis , Endometrial Hyperplasia/mortality , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/mortality , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoenzyme Techniques , Middle Aged , Neoplasm Staging , Prognosis
20.
Fertil Steril ; 75(6): 1218-21, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11384653

ABSTRACT

OBJECTIVE: To determine the levels of the angiogenic factors vascular endothelial growth factor (VEGF) and interleukin (IL-8) in ovarian cysts. DESIGN: Prospective descriptive study. SETTING: University hospital. PATIENT(S): One hundred women, of whom 9 had ovarian carcinomas, 38 had ovarian endometriomata, 43 had serous ovarian cysts, and 10 had follicular ovarian cysts. INTERVENTION(S): Sampling of serum and ovarian cystic fluid before and during surgery. MAIN OUTCOME MEASURE: Levels of VEGF and IL-8 in cystic fluid and serum. RESULT(S): Levels of both VEGF and IL-8 were found to be significantly higher in the cystic fluid of ovarian carcinomas and endometriomata than in serous and follicular cysts. In endometriomata fluid, levels of VEGF and IL-8 were found to be directly correlated (r = 0.68; P=.0074). Serum levels of VEGF were significantly higher in women with ovarian carcinomas and endometriomata than in those with serous and follicular cysts. Ovarian cancers and endometriomata were similar in terms of cystic concentrations of VEGF and IL-8 and in serum levels of VEGF. CONCLUSION(S): An increase in angiogenic factors that differentiate ovarian carcinomas and endometriomata from other kinds of ovarian pathology is demonstrated.


Subject(s)
Carcinoma/metabolism , Endometriosis/metabolism , Endothelial Growth Factors/metabolism , Follicular Cyst/metabolism , Interleukin-8/metabolism , Lymphokines/metabolism , Ovarian Cysts/metabolism , Ovarian Diseases/metabolism , Ovarian Neoplasms/metabolism , Endothelial Growth Factors/blood , Female , Humans , Interleukin-8/blood , Lymphokines/blood , Osmolar Concentration , Prospective Studies , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
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