Potential benefit of dehydroepiandrosterone supplementation for infertile but not poor responder patients in a IVF program.

AIM: The aim of this paper was to evaluate the hypothesis that pretreatment with dehydroepiandrosterone (DEHA) may improve the result on in vitro fertilization (IVF) and the pregnancy outcome among infertile women with normal ovarian reserve. METHODS: Double-blind, randomized, placebo-controlled study; 52 infertile patients received the long protocol IVF. Patients in Group 1, received 75 mg of DHEA once a day, 8 weeks before starting the IVF cycle and during treatment; control group (Group 2) received placebo. The primary endpoint was pregnancy, live birth and miscarriage rates, secondary endpoint was standard IVF parameters such us stimulation duration (hCG day), E2 on HCG-day, endometrial thickness, number of retrieved oocytes, metaphase II oocytes, embryos transferred and score of leading embryos transferred. RESULTS: Patients in the DHEA group had a significantly higher live birth rate compared with controls (P<0.05). Miscarriage rate was higher in control group (P<0.05). CONCLUSION: DHEA supplementation could have a beneficial effect on IVF outcome in infertile women with normal ovarian reserve.

Pivotal points in interstitial pregnancy: new insights in conservative medical treatment of non-ruptured interstitial pregnancy.

We report the efficacy of a minimally invasive approach of the multidose protocol with methotrexate (MTX) in the management of three cases of interstitial pregnancy (IP), with elevated serum ß-hCG in two cases. New considerations and management strategies are discussed. Successful termination of IP and in one case, a subsequent successful pregnancy, was achieved. The process led to the development of an enhanced understanding of diagnostic modalities and their limitations, with regard to the particular entities under discussion. We also focused attention on pivotal points and anatomical features in the management of this dangerous occurrence. Long-term results with careful follow-up were analysed by instrumental procedure. This hazardous type of ectopic pregnancy can be managed with systemic administration of MTX, also in patients with elevated ß-hCG values. The present report underlines that an integrated approach in early diagnosis, multidose treatment and close follow-up, are essential forms of medical management.

Abdominal fat accumulation, and not insulin resistance, is associated to oligomenorrhea in non-hyperandrogenic overweight/obese women.

BACKGROUND: There is a very high prevalence of obese women in the infertile population and many studies have highlighted the link between obesity and infertility. The aim of this study was to evaluate the prevalence of oligomenorrhea in uncomplicated obesity, and to examine whether this menstrual alteration is associated with anthropometric, hormonal, and metabolic parameters. PATIENTS AND METHODS: This is a cross-sectional study of 266 overweight and obese body mass index (BMI) > or =25.0 kg x m(-2)] women, all having apparent normal fertility. Measurements included BMI, central fat accumulation (evaluated by waist circumference), blood pressure levels, and fasting insulin, glucose, and lipid (triglycerides, total and HDL-cholesterol) serum concentrations, and insulin resistance [estimated by (homeostasis model assessment) HOMAIR] during the early follicular phase (days 2-5 of the menstrual cycle). RESULTS: One hundred and seventy-one (64.3%) of 266 women had normal menstrual cycles, 57 (21.4%) had oligomenorrhea, and 38 (14.3%) had hypermenorrhea and/or polimenorrhea. Women with oligomenorrhea had higher waist circumference, BMI, HOMAIR, and insulin levels than women with normal menstrual cycles. When association among oligomenorrhea and other variables (waist circumference, BMI, insulin and HOMAIR) was evaluated by logistic regression, and odds ratio was calculated per unit of SD increase, only waist circumference maintained a significant relationship with oligomenorrhea. CONCLUSIONS: This study shows that more than 20% of women with simple obesity have oligomenorrhea, and suggests that central fat accumulation seems to have a possible direct role in this menstrual alteration, independently of hyperinsulinemia and/or insulin resistance.

Endometriosis is characterized by an impaired localization of laminin-5 and alpha3beta1 integrin receptor.

Endometriosis is an estrogen-correlated benign disease characterized by a marked ability of endometrial-like cells to invade and proliferate outside uterine cavity, resembling for some invasive aspect the cancer growth. The molecular mechanisms regulating endometrial cell invasiveness are mostly unknown, although interactions between extracellular matrix (ECM) proteins and their transmembrane receptors, integrins, are likely to play a central role. In particular, laminin (Ln)-5 could be closely involved, as it is in cancer. We have investigated the expression of Ln-1, Ln-5, and collagen IV (Coll IV) ECM proteins and their receptors, alpha3beta1 and alpha6beta4 integrins, in atrophic, proliferative, and secretive endometrium and in endometriosis. The results show that Ln-5, but not Ln-I and Coll IV, is altered in secretive endometrium as well as in endometriosis tissues. No alterations are observed in atrophic or proliferative endometrium. Consistently, the polarization of both integrin subunits alpha3 and beta1, but not alpha6 and beta4, is altered in secretive endometrium and endometriosis tissues, but not in atrophic and proliferative endometrium. These results seem to suggest that Ln-5 and alpha3beta1 could be involved in the invasive mechanism of endometriosis. The altered expression of Ln-5, by upregulating matrix metalloproteases activity, suggest an invading process similar to that of many cancer processes.

Microfluidic channel fabrication in dry film resist for production and prototyping of hybrid chips.

Microfluidic networks are patterned in a dry film resist (Ordyl SY300/550) that is sandwiched in between two substrates. The technique enables fabrication of complex biochips with active elements both in the bottom and the top substrate (hybrid chips). The resist can be double bonded at relatively low temperatures without the use of extra adhesives. A postbake transfers the resist into a rigid structure. The resist is qualified in terms of resolution, biocompatibility and fluidic sealing. Fabrication in both a fully equipped cleanroom setting as well as a minimally equipped laboratory is described. The technique is applied for dielectrophoresis-based cell separation systems and a fuel cell reaction chamber with micropillars. The dry film resist can be considered a cheap and fast alternative to SU-8.

Evaluation of functional ovarian reserve in 60 patients.

Diminished ovarian reserve is a condition occurring in women at any adult age, although it is more frequent in women in their 30s and in couples with unexplained subfertility. Different tests are employed to diagnose the problem. The most common are basal tests for FSH, LH, oestradiol and inhibin B, or dynamic endocrine tests such as the clomiphene citrate challenge test and gonadotrophin analogue stimulating test. In recent years, great attention has been devoted to direct tests such as the antral follicle count and ovarian biopsy results. The basal FSH concentration is the most common test utilized for ovarian screening. An abnormal value is correlated with a decrease in pregnancy rate and an increase in cycle cancellation rate. Among other basal endocrine tests, inhibin concentrations appear promising, although more data are necessary before this can be included in clinical practice. The clomiphene citrate challenge test can unmask patients who might have not been detected by basal FSH screening alone, and appears to be more sensitive than day 3 FSH alone. A prospective study was performed on the simultaneous application of various markers of ovarian reserve (FSH, LH, oestradiol, inhibin B, antral follicle count) in the natural cycle preceding assisted reproductive therapy, in 60 women. The present study suggests that counting ovarian follicles by ultrasound appears, at the moment, the most reliable test of ovarian reserve, although it is influenced by subjective factors and more studies are needed in order to confirm its predictive value.

Free testosterone plasma levels are negatively associated with the intima-media thickness of the common carotid artery in overweight and obese glucose-tolerant young adult men.

OBJECTIVE: To evaluate the relation between free testosterone (FT) levels and the intima-media thickness of the common carotid artery (IMT-CCA) in overweight and obese glucose-tolerant (NGT) young adult men. DESIGN: Cross-sectional study of FT and IMT-CCA in obese men. SUBJECTS: A total of 127 overweight and obese NGT male individuals, aged 18-45 y. MEASUREMENTS: FT plasma levels; IMT-CCA, as measured by high-resolution B-mode ultrasound imaging; central fat accumulation, as evaluated by waist circumference; body composition, as measured by bioimpedance analysis; insulin resistance, as calculated by homeostatic model assessment (HOMA(IR)); systolic and diastolic blood pressure; and fasting concentrations of glucose, insulin, and lipids. RESULTS: IMT-CCA was positively correlated with age, body mass index (BMI), fat mass (FM), waist circumference, and fasting glucose concentrations, and inversely associated with FT levels. After multivariate analysis, IMT-CCA maintained an independent association with BMI, FM, and FT levels. This study indicates that IMT-CCA is negatively associated with FT levels, independent of age, total body fat, central fat accumulation, and fasting glucose concentrations in overweight and obese NGT patients. CONCLUSION: Hypotestosteronemia may accelerate the development of atherosclerosis and increase the risk for CHD in obese men.

Levitation and movement of human tumor cells using a printed circuit board device based on software-controlled dielectrophoresis.

In this study we describe an original, efficient, and innovative printed circuit board (PCB) device able to generate dielectrophoresis-based, software-controlled cages that can be moved to any place inside a microchamber. Depending on their dielectrophoretic properties, eukaryotic cells can be "entrapped" in cages and moved under software control. The main conclusion gathered from the experimental data reported is that the PCB device based on dielectrophoresis permits levitation and movement of different tumor cells at different dielectrophoresis conditions. The results presented herein are therefore the basis for experiments aimed at forced interactions or separation of eukaryotic cells using "lab-on-a-chip." In fact, because many cages can be controlled at the same time, and two or more cages can be forced to share the same or a different location, it is possible, in principle, either to bring in contact cells of a differing histotype or to separate them.

Model of counter-current transfer from vagina to urethra in postmenopausal women.

BACKGROUND: Low-dose vaginal oestrogens are effective in treating post-menopausal urogenital atrophy without inducing endometrial proliferation. We aimed to assess whether this dichotomic effect could be the result of a preferential vagina-to-urethra transfer via a counter-current transfer of oestrogens from vagina to the arterial blood supplying the urethra. Due to the impossibility of obtaining blood samples from urethral arteries, and since the nature of counter-current exchange of substances is similar to the transfer of heat, we investigated cold transfer throughout the anterior vaginal wall to the vesical trigone and urethra. METHODS: Plastic tubes filled with cold saline were inserted into the vagina of 30 menopausal women. Temperatures were recorded at the vesical trigone and at three different urethral sites. Comparisons were performed 2 and 4.5 min after starting of cooling, and 4.5 min after removal of tubes. RESULTS: The urethra cooled significantly more than the bladder. Urethral cooling was not homogeneous; distal sites of the urethra cooled significantly more than proximal site and bladder despite a larger distance to the vaginal cooling device. CONCLUSIONS: Distribution of cold from the vagina to the urethra is not the result of simple diffusion and mechanisms of preferential distribution may exist from the vagina to the middle and low part of the urethra.

The clivus-supraocciput angle: a useful measurement to evaluate the shape and size of the fetal posterior fossa and to diagnose Chiari II malformation.

OBJECTIVE: To obtain a nomogram of the clivus-supraocciput angle as a basis for the diagnosis of Chiari II malformation in fetuses with ventriculomegaly. METHODS: A cross-sectional study was undertaken on 310 normal pregnant women of 16-34 weeks' gestation. A mid-sagittal section of the fetal skull was obtained and the angle between the clivus and the supraocciput was measured. Forty-four fetuses with ventriculomegaly due to various causes (13 Chiari II malformation, 12 dysgenesis of the corpus callosum, 7 aqueductal stenosis, 6 borderline ventriculomegaly, 3 Dandy-Walker malformation, 2 porencephaly, 1 schizencephaly) were also included in the study and the values of the angle found in the pathological cases were compared with those found in the normal population. RESULTS: The clivus-supraocciput angle did not change during gestation and was almost constant with an average value of 79.3 +/- 6 degrees. All cases of Chiari II malformation showed a value below the 5th centile of our nomogram. CONCLUSIONS: The evaluation of the posterior fossa and particularly the measurement of the clivus-supraocciput angle is a useful parameter to differentiate the various causes of fetal ventriculomegaly and particularly to recognize Chiari II malformation.

Comparison of Diane 35 and Diane 35 plus finasteride in the treatment of hirsutism.

OBJECTIVE: To compare the clinical efficacy of an original combined therapy with cyproterone acetate, 2 mg, and ethinylestradiol, 35 microgram (Diane 35), plus finasteride (5 mg) for 2 weeks per month with that of Diane 35 alone in hirsute women. DESIGN: Prospective randomized, single-blinded study. SETTING: Outpatients in an academic research environment. PATIENT(S): Fifty women with idiopathic hirsutism (IH) or the polycystic ovary syndrome (PCOS). INTERVENTION(S): Group 1 (n = 25) received Diane 35 alone and group 2 (n = 25) received Diane 35 plus finasteride. The latter drug was administered using a new therapeutic scheme: 14 consecutive days for each therapeutic cycle. MAIN OUTCOME MEASURE(S): Hormonal evaluation was done before beginning treatment and after 3 and 6 months of therapy. Hirsutism was graded at 3-month intervals. RESULT(S): The combination of Diane 35 plus finasteride for 14 days significantly decreased the hirsutism score after 3 months of therapy, while Diane 35 alone induced this effect after 6 months. CONCLUSION(S): Finasteride in combination with Diane 35 for 14 days is effective, well accepted, and safe in hirsute patients, as the amount of antiandrogenic drugs administered is much lower than that in conventional treatment.

A randomised placebo-controlled trial of ursodeoxycholic acid and S-adenosylmethionine in the treatment of intrahepatic cholestasis of pregnancy.

A randomised placebo controlled study was performed in 32 women with intrahepatic cholestasis of pregnancy. The population was divided into four groups: for 20 days each group was treated only with ursodeoxycholic acid, or S-adenosylmethionine, or a combination of both drugs, or a placebo (vitamin). Itching, standard liver function tests and serum total bile acids were measured before, during, and after treatment. Itching improved in all the women as well as the biochemical abnormalities. No side-effects in the mother or in the infant were recorded during and after therapy. A combination of ursodeoxycholic acid and S-adenosylmethionine is more effective than placebo and than either drug alone.

Ursodeoxycholic acid therapy in pregnant women with cholestasis.

OBJECTIVE: To test the efficacy and safety of ursodeoxycholic acid (UDCA) in the treatment of intrahepatic cholestasis of pregnancy (ICP) by a randomized, double-blind, placebo-controlled trial. METHOD: Eight patients with pruritus and abnormal liver function tests received 600 mg/day of UDCA in two doses for 20 days, compared with a control group of eight patients who received placebo for 20 days. RESULTS: No adverse reactions were detected in any patient. During UDCA therapy a statistically significant improvement in pruritus, serum bile salt levels, serum glutamic pyruvic transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase and total and direct bilirubin was observed. Only two patients treated with UDCA underwent cesarean sections due to reasons unrelated to the therapeutic trial. All newborns had an Apgar score >7 and normal postnatal growth. CONCLUSION: Although the number of patients in this study was very small, we suggest that UDCA treatment has a role in improving clinical and biochemical results in ICP.

Development of melanoma throughout two close pregnancies. Case report.

Primary melanoma is the most malignant and the least frequent of all cutaneous tumors. Its incidence in pregnancy varies from 0.1 to 2.8/1000. Up to today, impact of pregnancy on melanoma's course is still a much debated question in the literature. Some earlier reports suggested a particularly serious prognosis for melanoma associated with pregnancy, while more recent studies show that pregnancy may influence relapses without significantly altering survival. This paper reports the case of a woman affected by melanoma, whose clinical conditions became more and more serious during her second pregnancy and the following puerperal period. The progressive impairment of her clinical condition has suggested a correlation between the two close pregnancies and the unfavourable course of her disease.

Long-term follow-up of women with amenorrhea-galactorrhea treated with bromocriptine.

The present study is aimed at investigating whether long-term use of bromocriptine on patients affected by amenorrhea and galactorrhea may improve the clinical picture after discontinuation of treatment. For this reason 26 patients with amenorrhea and galactorrhea have been studied. Sixteen had high PRL values and 10 were normoprolactinemic. The normoprolactinemic patients underwent a TRH test. All the patients underwent computed skull axial tomography (CT scan) and were treated with bromocriptine, at a daily dosage variable from 2.5 to 10 mg for an average period of 26 months. After discontinuation of treatment, follow-up was carried-out for 20 months. Eighty-seven percent of the patients affected by amenorrhea, galactorrhea and hyperprolactinemia had regular menses, in 75 of the patients galactorrhea completely disappeared. Of the ten patients with normoprolactinemic amenorrhea and galactorrhea, only those who positively responded to the TRH test had regular menstruation and showed disappearance of galactorrhea. Upon discontinuation of treatment amenorrhea recurred in 68% of the cases whereas galactorrhea recurred in 80%. CT scans revealed disappearance of 3 microadenomas and reduction in size of the macroadenoma. Long-term use of bromocriptine represents the first choice treatment for the syndrome of galactorrhea-amenorrhea. In case of relapse, treatment must be continued for an undefined period of time.

Induction of multifollicular growth in patients non responding to clomiphene citrate and gonadotropins or gonadotropins only.

OBJECTIVE: We aimed at inducing multifollicular recruitment in patients with chronic anovulation-resistant to Clomiphene Citrate (CC) and/or exogenous gonadotropins. DESIGN: At the II Department of Obstetrics and Gynecology we treated our patients with exogenous gonadotropins and concomitant endogenous gonadotropin suppression obtained by the use of a GnRH analog (Buserelin). PATIENTS: We studied 14 patients with chronic anovulation due to either hypothalamic dysfunction or polycystic ovarian syndrome. MEASUREMENTS: We monitored the follicular growth ultrasonographically from the eighth day of the menstrual cycle, and assessed E2 and LH daily dosage from the tenth day. RESULTS: With this protocol we obtained 2 or 3 mature follicles, and reached an ovulatory rate of 80.7% and a pregnancy rate of 71.4%. Premature luteinization never occurred, and progesterone increase took place only after human chorionic gonadotropins administration.

Neoplastic association of leiomyoma, bizarre leiomyoma and leiomyosarcoma uteri. Case report.

Leiomyoma uteri is the commonest mesenchymal neoplasia of this organ. Leiomyosarcoma uteri is the most frequent histologic variant of all sarcomatous forms. Among these there is bizarre leiomyoma, a borderline lesion with potential malignity, whose differential diagnosis is very difficult. This paper reports the case of a 44 year old woman who was simultaneously diagnosed with these anatomicoclinical lesions. The singularity of this case is represented by the coexistence in the same patient of three different lesions that, according to our data and those reported in the latest literature, do not seem to be correlated.

Relationship between some maternal haemato-clinical parameters and low neonatal weight. Preliminary study.

In a selected group of pregnant women we studied the influence of specific haematoclinical maternal factors (age, pre-pregnancy weight, pregnancy weight gain, blood pressure, haematocrit (HTC), haemoglobinaemia (Hb), platelets (PTL), uricaemia) on neonatal weight. The results show an association among pre-pregnancy low maternal weight, hypertension and low neonatal weight. The uricaemia behaviour and the role of PTL, Hb, HCT are uncertain.

Bari district birthweight study: comparison with the Bristol perinatal growth chart.

We studied the neonatal weight distribution of 15,298 newborns from the Bari District at various gestational ages by the 10th, 50th, and 90th percentiles. After analysis, we constructed a growth chart following the method of Dunn. By comparing our results with those of Dunn's Bristol Perinatal Growth Chart, we found a weight difference of +4.5% in our population. This difference may be related to ethnic as well as socioeconomic factors.

Hyperparathyroidism in a pregnant woman with previous thyroid carcinoma. Case report and review of the literature.

A 29 year old woman, primipara, at 26 weeks' gestation had been undergone, five years before, a total thyroidectomy owing to a mixed papillary-follicular carcinoma of thyroid. After thyroidectomy the patient was placed on suppressive thyroxine treatment. Since she was 22 years old she suffered from recurrent renal colics and cholelithiasis. For these reasons she underwent, at the age of 27, an operation to remove bilateral renal calculi and a cholecystectomy owing to gall-stones. During her pregnancy biochemical determinations revealed slight and persistent hypercalcemia, hypophosphatemia, elevated urine calcium besides elevated serum parathyroid hormone (PTH) levels. Thus a diagnosis of primary hyperparathyroidism was taken into consideration. It was considered, but temporarily delayed, the surgical exploration of the neck. A strict clinic overseeing of the patient, which allowed her to carry out the pregnancy happily, was undertaken. Any thyroid carcinoma repercussion on pregnancy was not noted. A left inferior parathyroid adenoma was removed five months after the woman's delivery. The child psychosomatic development, at one year of age, was absolutely normal. A review of the literature indicates that when a pregnancy is complicated by hyperparathyroidism its prognosis is improved by parathyroidectomy, if possible during the second trimester. In patients with asymptomatic hypercalcemia and/or in late pregnancy surgical treatment may be postponed until after delivery. It is also demonstrated that thyroid carcinoma is not aggravated by pregnancy and that the latter can develop without any worry for mother and fetus.