Macroscopic and microscopic findings of the placenta in women with polycystic ovary syndrome.

STUDY QUESTION: Do patients with polycystic ovary syndrome (PCOS) have macroscopic and/or microscopic placental alterations? SUMMARY ANSWER: The placental structure in patients with PCOS, even in those with uncomplicated pregnancy, is altered. WHAT IS KNOWN ALREADY: The spectrum of pregnancy complications seems to have a common denominator: a defective trophoblast invasion and placentation. In women with PCOS, alterations in endovascular trophoblast invasion related to insulin resistance and hyperandrogenism have been observed. STUDY DESIGN, SIZE, DURATION: For this prospective case-control study, 30 pregnant patients with PCOS (cases) and 60 healthy pregnant women without PCOS features (controls) were enrolled and studied until delivery. Clinical, biochemical, ultrasonographic and obstetric data were recorded. The baseline clinical and biochemical data for screening for PCOS and for inclusion/exclusion were obtained before the seventh week of gestation. At delivery, placentas were collected and detailed macroscopic and microscopic analyses were performed. PARTICIPANTS, SETTING, METHODS: Cases and controls were matched for age and BMI (all <30 kg/m(2)). The matching procedure was one-to-two. Only subjects with spontaneous conception and uncomplicated pregnancies were included in the final analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Placental weight (P = 0.04), thickness (P = 0.02), density (P = 0.02) and volume (P = 0.01) were significantly inferior in women with, compared with those without PCOS. The placentas from patients with PCOS more frequently had an irregular shape (P = 0.03) and a higher cord coiling index (P = 0.02). Differences between cases and controls also concerned the extent of villous (P = 0.04) and intervillous (P = 0.01) spaces, the extent of fibrosis (P = 0.03), endovascular trophoblast (depth, extension and morphometry) (P < 0.05) and mitotic activity (P = 0.01). The percentage of patients with lesions [22/30 (73.3%) versus 25/60 (41.7%), respectively; P = 0.01] and the mean number of placental lesions (3.5 ± 2.1 versus 1.4 ± 1.1, respectively; P = 0.02) were higher in the PCOS than the control group. The odds ratio for placental alterations, adjusted for weight gain, was 2.8 (95% confidence interval 1.3-9.9). LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study was the selection of a specific PCOS sample, which is probably not representative of the PCOS phenotype as a whole. In fact, we excluded patients with PCOS who were obese and who achieved a pregnancy following the use of ovulation inductors or assisted reproduction techniques. WIDER IMPLICATIONS OF THE FINDINGS: The present study is the first to demonstrate that the morphology and microscopic structure of placenta in patients with PCOS with an uncomplicated pregnancy are altered. Further studies are needed to assess a correlation of these changes with the increased risk of obstetric complications observed in some pregnancies of women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no conflict of interest and no financial support for the research. TRIAL REGISTRATION NUMBER: N/A.

Six weeks of structured exercise training and hypocaloric diet increases the probability of ovulation after clomiphene citrate in overweight and obese patients with polycystic ovary syndrome: a randomized controlled trial.

BACKGROUND: Clomiphene citrate (CC) is the first-line therapy for the induction of ovulation in infertile women with polycystic ovary syndrome (PCOS), but ∼20% of patients are unresponsive. The aim of the current study was to test the hypothesis that a 6-week intervention that consisted of structured exercise training (SET) and hypocaloric diet increases the probability of ovulation after CC in overweight and obese CC-resistant PCOS patients. METHODS: A cohort of 96 overweight and obese CC-resistant PCOS patients was enrolled consecutively in a three-arm randomized, parallel, controlled, assessor-blinded clinical trial. The three interventions were: SET plus hypocaloric diet for 6 weeks (Group A); 2 weeks of observation followed by one cycle of CC therapy (Group B); and SET plus hypocaloric diet for 6 weeks, with one cycle of CC after the first 2 weeks (Group C). The primary end-point was the ovulation rate. Other reproductive data, as well as anthropometric, hormonal and metabolic data, were also collected and considered as secondary end points. RESULTS: After 6 weeks of SET plus hypocaloric diet, the ovulation rate was significantly (P =0.008) higher in Group C [12/32 (37.5%)] than in Groups A [4/32 (12.5%)] and B [3/32 (9.4%)] with relative risks of 3.9 [95% confidence interval (CI) 1.1-8.3; P = 0.035] and 4.0 (95% CI 1.2-12.8; P = 0.020) compared with Groups A and B, respectively. Compared with baseline, in Groups A and C, a significant improvement in clinical and biochemical androgen and insulin sensitivity indexes was observed. In the same two groups, the insulin sensitivity index was significantly (P < 0.05) better than that in Group B. CONCLUSIONS: In overweight and obese CC-resistant PCOS patients, a 6-week intervention of SET and a hypocaloric diet was effective in increasing the probability of ovulation under CC treatment. The study was registered at Clinicaltrials.gov:NCT0100468.

Uterine blood flow in pregnant patients with polycystic ovary syndrome: relationships with clinical outcomes.

OBJECTIVE: To study the impedance to blood flow through the uterine artery in pregnant women with polycystic ovary syndrome (PCOS), and to evaluate its predictive value for adverse pregnancy and perinatal outcomes in this population. DESIGN: Prospective case-control study. SETTING: Academic Departments of Obstetrics and Gynaecology in Italy. POPULATION: Seventy-three pregnant women with ovulatory PCOS (PCOS group) and 73 age- and body mass index-matched healthy pregnant controls (control group). METHODS: Serial Doppler velocimetry measurements of the uterine artery. MAIN OUTCOME MEASURES: Blood flow impedance indices and pregnancy/perinatal outcomes. RESULTS: A significantly (P < 0.05) higher rate of subjects with abnormal velocimetry findings was observed in the PCOS group than in the control group. In the PCOS group, the pulsatility index (PI) at first (P = 0.042) and mid-second (P = 0.039) trimesters of pregnancy, and bilateral notch at first (P = 0.025) and mid-second (P = 0.007) trimesters of pregnancy, were the strongest independent predictors of adverse outcomes. Conversely, in the control group, PI at the first trimester of pregnancy was a predictor of adverse outcomes only when combined with bilateral notch (P = 0.042), whereas at mid-second trimester of pregnancy PI (P = 0.033) and bilateral notch (P = 0.048) were independent predictors of adverse outcomes. CONCLUSIONS: Uterine artery Doppler indices are more commonly altered in pregnant patients with PCOS than in controls, showing a high predictive value for abnormal pregnancy/perinatal outcomes.

Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study.

BACKGROUND: Lifestyle modifications are successfully employed to treat obese and overweight women with polycystic ovary syndrome (PCOS). The aims of the current pilot study were (i) to compare the efficacy on reproductive functions of a structured exercise training (SET) programme with a diet programme in obese PCOS patients and (ii) to study their clinical, hormonal and metabolic effects to elucidate potentially different mechanisms of action. METHODS: Forty obese PCOS patients with anovulatory infertility underwent a SET programme (SET group, n = 20) and a hypocaloric hyperproteic diet (diet group, n = 20). Clinical, hormonal and metabolic data were assessed at baseline, and at 12- and 24-week follow-ups. Primary endpoint was cumulative pregnancy rate. RESULTS: The two groups had similar demographic, anthropometric and biochemical parameters. After intervention, a significant improvement in menstrual cycles and fertility was noted in both groups, with no differences between groups. The frequency of menses and the ovulation rate were significantly (P < 0.05) higher in the SET group than in diet group but the increased cumulative pregnancy rate was not significant. Body weight, body mass index, waist circumference, insulin resistance indexes and serum levels of sex hormone-binding globulin, androstenedione and dehydroepiandrosterone sulphate changed significantly (P < 0.05) from baseline and were significantly different (P < 0.05) between the two groups. CONCLUSIONS: Both SET and diet interventions improve fertility in obese PCOS patients with anovulatory infertility. We hypothesize that in both interventions an improvement in insulin sensitivity is the pivotal factor involved in the restoration of ovarian function but potentially acting through different mechanisms.

Endometrial metastasis of a primitive neuroendocrine ovarian carcinoma: management and treatment of a case.

BACKGROUND: Neuroendocrine tumours are a heterogeneous group of separate clinico-pathological entities which have a common characteristic, i.e., expression of potential endocrine differentiation. In the ovary, the term "neuroendocrine" relates mainly to widely known carcinoids, but it may also be applied to rare neuroendocrine carcinomas as non-small cell type and small cell carcinomas of pulmonary type. In the literature only 11 cases of primary ovarian non-small cell neurendocrine carcinomas have been described and ten of these were associated with a surface epithelial ovarian tumour. Small cell neuroendocrine carcinoma of the ovary is a rare malignant tumour of the ovary. Advanced small cell carcinoma of the ovary is a very aggressive tumour with an overall poor prognosis and unfavourable outcome. CASE REPORT: The case reported is unique in the literature because the authors describe a rare case of endometrial metastasis of a primary ovarian non-small cell neurendocrine carcinoma without any surface epithelial ovarian tumour association. The tumour invaded up to less than half of the myometrium. The first symptoms were related to endometrial metastasis as metrorrhagia and pelvic pain while the asymptomatic presence of primary ovarian carcinoma was not acknowledged with physical examination, routine biochemistry, tumour markers, blood count and traditional transvaginal greyscale ultrasound. CONCLUSION: Magnetic resonance and three-dimensional (3D) ultrasonography with power Doppler are a great help in the diagnosis of ovarian localisation but only immunohistochemistry on histological material can provide a correct diagnosis. Immunohistochemistry expression of Ki67 is a useful marker of malignancy. Due to the rarity of this neoplasm, a general consensus for optimal treatment has yet to emerge. The reported biological aggressiveness of these tumours prompts combined treatment with radical surgery and adjuvant polychemotherapy.

Evaluation of ovarian functionality after a dietary treatment in obese women with polycystic ovary syndrome.

In women with polycystic ovary syndrome (PCOS) weight loss is associated with an improvement in insulin sensitivity and a reduction of the insulin concentration in the plasma. It is clear, then, that the first therapeutic approach that can be considered in obese PCOS patients for restoration of the menstrual cycle should be a diet. The aim of our study was to examine the effect of long-term caloric restriction on the clinical and biochemical abnormalities in obese PCOS women. The results obtained make it clear that caloric restriction for 4 weeks causes an increase in SHBG and decreases of free testosterone and insulin, with consequent improvement of the clinical picture.

The role of D-aspartic acid and N-methyl-D-aspartic acid in the regulation of prolactin release.

In this study, using an enzymatic HPLC method in combination with D-aspartate oxidase, we show that N-methyl-D-aspartate (NMDA) is present at nanomolar levels in rat nervous system and endocrine glands as a natural compound, and it is biosynthesized in vivo and in vitro. D-aspartate (D-Asp) is its natural precursor and also occurs as an endogenous compound. Among the endocrine glands, the highest quantities of D-Asp (78 +/- 12 nmol/g) and NMDA (8.4 +/- 1.2 nmol/g) occur in the adenohypophysis, whereas the hypothalamus represents the area of the nervous system where these amino acids are most abundant (55 +/- 9 and 5.6 +/- 1.1 nmol/g for D-Asp and NMDA, respectively). When D-Asp is administered to rats by ip injection, there is a significant uptake of D-Asp into the adenohypophysis and a significant increase in the concentration of NMDA in the adenohypophysis, hypothalamus and hippocampus, suggesting that D-Asp is an endogenous precursor for NMDA biosynthesis. Experiments conducted on tissue homogenates confirm that D-Asp is the precursor of the NMDA and that the enzyme catalyzing this reaction is a methyltransferase. S-adenosyl-L-methionine (SAM) is the methyl group donor. In vivo experiments consisting of ip injections of sodium D-aspartate show that this amino acid induced a significant serum PRL elevation and this effect is dose and time dependent. In vitro experiments conducted on isolated adenohypophysis or adenohypophysis coincubated with the hypothalamus, showed that the release of PRL is caused by a direct action of D-Asp on the pituitary gland and also mediated by the indirect action of NMDA on the hypothalamus. Then, the latter induces the release of a putative factor that in turn stimulates the adenohypophysis reinforcing the PRL release. In conclusion, our data suggest that D-Asp and NMDA are present endogenously in the rat and are involved in the modulation of PRL release.

Finasteride in the treatment of hirsutism: new therapeutic perspectives.

OBJECTIVE: To determine of the clinical and hormonal effects of finasteride (Proscar; Merck, Sharp, and Dohme, Rahway, NJ) in the treatment of idiopathic hirsutism and hirsutism in patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Istitute of Obstetrics and Gynecology, University of Naples "Federico II." PATIENTS: Ten women affected by idiopathic hirsutism and 15 women with PCOS. INTERVENTIONS: Finasteride was administered orally at a daily dose of 5 mg for a period of 6 months. MAIN OUTCOME MEASURES: Rating of hirsutism with the Ferriman-Gallwey method; serum androgen assays. RESULTS: Finasteride produced a reduction in the average hirsutism scores ( > 50% in all patients), whereas no change was observed in serum T, androstenedione, and DHEAS levels. A significant reduction was measured in serum dihydrotestosterone and 3 alpha, 17 beta-androstenediol glucuronide levels. CONCLUSIONS: This study demonstrates that symptomatic hirsutism has to be considered as a skin disease associated with the increased activity of the 5 alpha-reductase. It also indicates that the selective 5 alpha-reductase inhibitor, finasteride, is very effective and well tolerated in the treatment of both idiopathic hirsutism and of hirsutism in patients with PCOS.

Prognostic value of desmoplastic reaction and lymphocytic infiltration in the management of breast cancer.

OBJECTIVE: To ascertain whether the prognostic value of desmoplastic reaction and lymphocytic infiltration are a good prognostic index to estimate survival in breast cancer patients. METHODS: From 1987 to 1994, the authors have evaluated the prognostic value of desmoplastic reaction and lymphocytic infiltration related to rode state in 34 patients with breast cancer. For statistical analysis and comparison of means the "t"-test was used. The significance level was 0.01. RESULTS: The group of patients with abundant desmoplastic reaction shows an overall survival rate lower than the group with poor desmoplastic reaction (p < 0.01) and the survival of the group with abundant desmoplastic reaction was related to lymphnodal status. CONCLUSIONS: Many prognostic factors have been shown during these years, some connected to patient, some connected to neoplasm and others connected to the treatment. Recently many other prognostic factors have been recognized, among which the possible prognostic role of desmoplasia has been carefully valued. Certainly, today the prognostic value of desmoplastic reaction and lymphocytic infiltration cannot take the place of usual prognostic factors in the evaluation of breast cancer patient yet the desmoplastic reaction is a good prognostic index to estimate the survival in these patients.

Fetal fibronectin as a screening test for premature delivery in multiple pregnancies.

OBJECTIVE: To evaluate fetal fibronectin as a screening test for premature delivery in asymptomatic women with multiple pregnancies. METHODS: In the mid-second trimester, the concentrations of fetal fibronectin in the cervical and vaginal secretions of 68 patients with multiple gestations were sampled weekly by monoclonal antibody immunoassay in order to predict preterm labor. RESULTS: The results for the prediction of preterm labor differ according to whether we consider a single positive result (fetal fibronectin > 50 ng/ml) as predictive of preterm labor or whether we only consider at least two consecutive positive results as predictive of perterm labor. The fetal fibronectin test had a sensitivity for preterm birth before 37 weeks of 90.9% and 86.6%, respectively, with a specificity of 68.5% vs. 78.9% and a positive and negative values of 73.1% vs. 76.4% and 88.8% vs. 88.2%, respectively. Similar results were obtained for perterm birth before 34 weeks. CONCLUSIONS: In a condition such as multiple pregnancy which is already at risk for premature delivery the possibility of raising the specificity of the test with virtually no decrease in sensitivity guarantees better recognition of patients likely to develop premature labor. This possibility can be achieved simply by considering two positive consecutive samples as predictive of preterm labor.

Tamoxifen, megestrol acetate, and beta interferon in endometrial cancer.

22 patients with endometrial cancer were studied. Twelve (54.5%) between 45 and 66 years were treated for six days before surgery with 160 mg per os of Megestrol acetate administered twice daily plus Beta interferon 3,000,000 IU- on alternate days for a week, plus Tamoxifen--two cp of 10 mg daily for six days. Before and after surgery and associated medical therapies the steroid receptor values (ER and PgR) were checked. After treatment an average increase was observed of the ER (19 fmol/mg) and PgR (17 fmol/mg). Of the twelve patients one died of a stroke during the study (8.33%); five (41.67%) showed complete remission (CR); four (33.34%) a partial remission (PR) and two (16.67%) were not responders (NR).

[Determination of squamous cell carcinoma antigen in the blood of patients with cancer of the uterine cervix]. / Dossaggio dell'antigene "Carcinoma squamocellulare" (SCC) nel siero di pazienti affette da cancro del collo dell'utero.

The RIA method has been used to assay the squamous cell carcinoma antigen in the serum of twenty-four patients suffering from cervical cancer. The results obtained showed expressive differences between the levels in women with metastatic relapse and in those in remission, but the SCC antigen is particularly useful in the therapeutic monitoring, since it can assess of the current treatment.

[The role of prolactin in endometrial lesions]. / Ruolo della prolattina nelle lesioni endometriali.

The Authors examine serum levels of HPRL in basal conditions and after TRH and sulpiride test in 15 patients with endometrial lesions (hyperplasia) and in 15 patients with endometrial adenocarcinoma included in a age range between 44 and 62 years, in which 7 patients present obesity, 10 patients present hypertension and 2 patients are hyperglycemic. The same examination is carried out in a control group of 30 healthy patients. Then the 15 patients with adenocarcinoma and 3 patients with adenomatosa hyperplasia are subjected to surgery and they estimate HPRL levels in endometrium. The results prove that there is no correlation between HPRL plasma levels and endometrium lesions and between endometrium HPRL. The Authors conclude that HPRL does not play a significant role in the pathogenesis of endometrial lesions; use of HPRL plasma levels as a marker of endometrial lesions is not possible.

[Endometrial carcinoma with simultaneous endometrioid carcinoma of the ovary. Report of two clinical cases]. / Carcinoma dell'endometrio e simultaneo carcinoma endometrioide dell'ovaio. Presentazione di due casi clinici.

The paper reports two cases of simultaneous endometrial carcinoma and endometrioid carcinoma of the ovary. The clinical and pathological characteristics are examined. Both patients underwent radical surgery with an intraoperative examination for metastatic involvement of the lumbo-aortic, iliac and infundibulo-ovarian lymphonodes. Surgery was followed by antiblastic (cisplatin, adriamycin, cyclophosphamide), hormonal (progestogens) and immuno-modulating (thymostimulin treatment). The two patients (respectively approximately 10 and 7 years after the operation) both enjoy good health.

[Carcinoma of the vulva. Report of a case originating from Bartholin's gland]. / Carcinoma della vulva. Considerazioni su di un caso a partenza dalla ghiandola del Bartholin.

A case of vulvar carcinoma arising from Bartholin's gland is described. At admission the patient showed a large suppurated swelling of the left labium maior. The neoformation reached the groin of the same side. Malignant cells were detected in biopsy specimens of both the vulvar swelling and the lymphonodes. The histological test showed a vulvar carcinoma arising from Bartholin's gland. The vulvar swelling and the ulcerated lesion were removed and the patient was treated with radiotherapy, chemotherapy (bleomicina) and immunomodulant therapy (Timostimoline). Pulmonary methastases were detected eighteen months after the operation and the patient died two years later.

[Reliability of ultrasound examination confirmed at autopsy in foetuses suffering from Dandy-Walker Syndrome]. / Attendibilità dell'esame ecografico confermata all'esame autoptico in feti affetti da Sindrome di Dandy-Walker.

BACKGROUND: The Dandy-Walker Syndrome (DWS) is a congenital malformation of the structures of the posterior cranial fossa with failure of the Luschka and Magendie foramina, which connect the ventricular system to the subarachnoid space, to open. In this syndrome, the cerebellar vermis may be absent or hypoplastic, the hemispheres small, the encephalic trunk and cervical spinal bone marrow flattened, complete or partial absence of cerebellar vermis, cystic dilatation of IV ventricle and frequently hydrocephalus. METHODS: We evaluated 56 cases of fetal malformations of the central nervous system from January 1998 to May 2001. Of these 56, 11 regarded the Dandy-Walker Syndrome. Ultrasound examinations were carried out at the 9(th) and 10(th) weeks, at the 21(st)-23(rd) weeks and at the 31(st) to 34(th) weeks of gestation so as to assess foetal anatomy and morphology. RESULTS: The results of the 11 pregnancies with Dandy-Walker Syndrome were as follows: 3 spontaneous miscarriages (at the 15(th), 18(th) and 20(th) weeks of gestation), 5 therapeutic abortions, 3 term pregnancies. Of the 3 newborns we were only able to follow the clinical course of two of them; both newborns underwent an intervention for ventriculo-peritoneal fluid derivation. At the moment both babies, aged respectively 30 and 25 months, are in good physical, intellectual and behavioural condition. CONCLUSIONS: Bearing in mind the notable clinical and socioeconomic importance of this malformation, we consider foetal morphological ultrasound to be a valid instrument for the correct management of pregnancy. Identification of lesions makes use of the comparison of ultrasound data with the results of histopathological examinations.

[Atelectasis following cesarean section. Personal experience]. / Atelettasia secondari a taglio cesareo. Nostra esperienza.

Purpose of this paper is to evaluate the risk of ateletasis in patients that underwent surgery of the abdomen (cesarean section), since the reflex of cough in these patients is notably altered for the limitation of the diaphragmatic excursions, due to analgesic contracture. The inhibition of cough's reflex causes retention of secretions with consequent bronchial obstruction and atelectasis. Personal experience in 6 cases of atelectasis following cesarean section is reported.

Hysterosalpingography and laparoscopy in the study of infertile women.

The Authors confront the data obtained from HSG and laparoscopy carried out in women with sterility problems to evaluate the diagnostic validity of each one of these investigations. There is agreement between the results of both methods in 74.19% of the patients. They think that, for a conclusive evaluation of the tubal factor in infertility, laparoscopy is most useful.

Ultrasound placental study and fetal lung maturity.

This study was undertaken to ascertain the usefulness of placental development ultrasound study in prediction of RDS. We examined 96 women near term of pregnancy; the accuracy of placental maturity grades in predicting fetal lung maturity was compared with lecithin/sphingomyelin ratio and with clinical development of RDS in the infants. We observed good correlation among ultrasound placental grades and fetal maturity.

The relationship between metoclopramide and milk secretion in puerperium.

The Authors administered Metoclopramide to women in puerperium with poor lactation. An increased lactation and high serum prolactin levels were noted. The administration of this medicine did not provoke any variations in serum T3, T4 and TSh levels. thyroid screening of the treated mothers' babies resulted negative.