GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET).

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in "in Vitro" Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

Carcinosarcoma of the ovary: analysis of 13 cases and review of the literature.

OBJECTIVES: The aim of this study was to evaluate our experience with patients affected by ovarian carcinosarcoma. PATIENTS AND METHODS: During a 16-year period, data on 13 patients with ovarian carcinosarcoma were collected. They were obtained from hospital charts and follow-up visits. Survival curves were estimated by the Kaplan-Meier method and compared using the log-rank test. All tests were two-tailed with p values < 0.05 considered significant. RESULTS: Our study was conducted on 13 patients with ovarian carcinosarcoma referred to our unit, during an observation time of about 16 years (March 1994 to October 2010). An improved survival was observed in patients treated with optimal cytoreductive surgery with residual tumors <2 cm (30 vs. 5 months; p = 0.042). All patients underwent adjuvant chemotherapy based on the combination of cisplatin, epirubicin and ifosfamide (PEI) and taxol and carboplatin (TAX-CBDCA) regimen. Overall survival of the patient population was 17 months. CONCLUSIONS: Similarly to data published in the literature, we observed that malignant mixed mullerian ovarian tumors are very aggressive and are usually diagnosed at an advanced age and at an advanced stage of disease. Therefore, due to the rarity of the tumor we would like to add our series to those already published in the literature, although our treatment recommendations are actually based upon retrospective studies with a small patient population.

Central nervous system metastases from epithelial ovarian cancer: prognostic factors and outcomes.

OBJECTIVES: To analyze the clinicopathological characteristics and prognostic factors associated with survival in patients with central nervous system (CNS) metastases from epithelial ovarian cancer. METHODS: Twenty patients with CNS involvement from ovarian carcinoma were evaluated in this retrospective study; their features and survivals were analyzed using Kaplan-Meier and log-rank test methods. RESULTS: The incidence of CNS metastases was 5%, among 400 patients with ovarian cancer treated in our single institution. The median age at diagnosis of the ovarian cancer was 55 years. The median interval to the brain involvement and the median survival were 33 and 18 months, respectively. Prognostic factors associated with survival were the International Federation of Gynecology and Obstetrics stage, the surgical resection, the multimodal treatment, and the response after the therapy of the brain metastases. CONCLUSIONS: Brain involvement from ovarian cancer is uncommon but is increasing in incidence. Although the prognosis is usually poor, a multimodal approach can result in a long-term remission of the metastases and in an improvement of the overall survival.

Characterization of endometrial growth in proliferative and early luteal phase in IVF cycles.

Human endometrium has a definite role in implantation, although knowledge about its modifications in the course of IVF cycles is still limited. This study was performed to characterize endometrial growth throughout stimulation treatment in women undergoing IVF cycles, regardless of clinical outcomes. Endometrial growth was longitudinally evaluated by ultrasonography in the first induced ovarian stimulation cycle (717 patients). Acceleration and length of significant growth were used to assess the slope of the growth curve mathematically. Endometrial growth showed a parabolic trend and final thickness was significantly affected by age (P < 0.01). Endometria that tended to overgrowth had a more rapid and longer growth during the whole phase. A similar stimulation treatment was repeated within 6 months of the first one and a second evaluation was carried out to verify whether similar growth occurred. Similar growth was observed in 76% of the patients, with an absolute difference between the two cycles of <4 mm in 84% of cases. The endometrium seems to have an individual intrinsic potential that can be expressed regardless of the stimulation protocol. This supports the hypothesis that individual factors (intrinsic properties of the endometrium) significantly affect endometrial growth.

Increased inositol phosphoglycan P-type in the second trimester in pregnant women with type 2 and gestational diabetes mellitus.

A progressive insulin resistant state develops throughout human pregnancy. Inositol phosphoglycan P-type (P-IPG), a second messenger of insulin, was reported to negatively correlate with the degree of insulin resistance in non-pregnant diabetic subjects. Urinary levels of P-IPG were assessed in insulin resistant states during pregnancy such as gestational diabetes mellitus (GDM, n=44) and type 2 diabetes mellitus (type 2 DM, n=25) and in 69 normal pregnant women. Urinary levels of P-IPG were higher in GDM than controls with a positive trend of release throughout normal pregnancy (P<0.01). P-IPG excretion was higher in diabetic (GDM and type 2 DM) than in healthy women in the second trimester (P<0.05). A higher P-IPG urinary excretion occurs during the second trimester in pregnant women with clinically evident insulin resistance with a positive association with poor glycemic control.

Estimation of birth weight by two-dimensional ultrasonography: a critical appraisal of its accuracy.

OBJECTIVE: To assess the accuracy and characterize two-dimensional ultrasonographic formulas for the estimation of birth weight according to the type of fetal biometric parameters these formulas rely on to make fetal weight predictions. METHODS: A prospective recruitment of 589 pregnant women was carried out for this cross-sectional study. Different biometric parameters were taken ultrasonographically to estimate birth weight using 35 different formulas. Only those patients who delivered within 48 hours were considered for the analysis (n=441). Differences between the estimated and actual birth weight were assessed by percentage error, accuracy in predictions within +/-10% and +/-15% of error, and use of the Bland-Altman method. All formulas were assessed individually and clustered on the basis of the type of fetal biometric information that they incorporate. RESULTS: Twenty-nine formulas provided an overall mean absolute percentage error less than or equal to 10%, with overall predictions within +/-10% and +/-15% of the actual birth weight (69.2% and 86.5%, respectively). Twenty formulas showed a good accuracy (bias 0.50 or less) and low variability (mean standard deviation 1.2). Among the categorized algorithms, formulas based on head-abdomen-femur measurements showed the lowest mean absolute percentage error. Upon stratification for birth weight, the group of formulas that rely on abdomen and femur measurements performed best for fetuses weighing more than 3,500 g (P<.01). CONCLUSION: Our findings show that most formulas are relatively accurate at predicting birth weight up to 3,500 g, and all algorithms tend to underestimate large fetuses. LEVEL OF EVIDENCE: III.

Inositol phosphoglycan P-type in healthy and preeclamptic pregnancies.

An association between inositol phosphoglycan P-type (P-IPG) and preeclampsia has been demonstrated over recent years. This molecule can mediate many of the metabolic and growth promoting effects of insulin. Dysregulation of the mediator family is associated with insulin resistance. An increased concentration of P-IPG has been reported in preeclamptic placenta, although its precursor (GPI) was undetectable in those placental samples. Insulin administration, that induces P-IPG release in normal human placenta, was shown not to cause production/release of the mediator from preeclamptic placental tissue as a consequence of a disturbed insulin signalling. Amniotic fluid is enriched of this mediator, with further increase during preeclampsia. We have found that the fetus released increasing amounts of P-IPG in the urine between 13 and 18 weeks of gestation, reaching a plateau beyond 20 weeks. Cord blood of infants of preeclamptic mothers showed an increased content of soluble P-IPG compared to controls and to the mother.

Insulin resistance in human preeclamptic placenta is mediated by serine phosphorylation of insulin receptor substrate-1 and -2.

CONTEXT: Preeclampsia is a severe complication of human pregnancy often associated with maternal risk factors. Insulin resistance represents a major risk for developing preeclampsia during pregnancy. OBJECTIVE: A putative second messenger of insulin, inositol phosphoglycan P type (P-IPG), was previously shown to be highly increased during active preeclampsia. Its association with insulin resistance was investigated. DESIGN AND SETTING: A cross-sectional study was carried out in a referral center. PATIENTS: Nine preeclamptic (PE) and 18 healthy women were recruited and matched for maternal age, body mass index, parity, and ethnicity in a 1:2 ratio. Placental specimens were collected immediately after delivery. INTERVENTION: Placental tissue was incubated with insulin and P-IPG production assessed. Insulin signaling proteins were subsequently studied by immunoblotting. RESULTS: P-IPG extracted from human term placentas upon incubation with insulin was found to be far lower in those with preeclampsia than controls (P < 0.001). Immunoblotting studies revealed serine phosphorylation of insulin receptor substrate-1 and -2 in PE placentas (P < 0.001) with downstream impairment of insulin signaling. The activation of the p85 regulatory subunit of phosphatidylinositol 3- kinase was markedly decreased in PE samples (P < 0.001). CONCLUSIONS: These findings highlight the importance of P-IPG in active preeclampsia and demonstrate a substantially different response to the insulin stimulus of human PE placentas. Acquired alterations in activation of proteins involved in insulin signaling may play a role in the complex pathogenesis of preeclampsia, probably as a consequence of the immunological dysfunction that occurs in this syndrome. These results seem to confirm an insulin-resistant state in PE placenta and shed a different light on its role in the pathogenesis of this disease with potential therapeutic implications.

Inositol phosphoglycan putative insulin mediator in human amniotic fluid.

BACKGROUND: Many hormones such as insulin, insulin-like growth factors, and the glucocorticoids are involved in regulating fetal growth. Inositol phosphoglycans (IPGs), a family of putative second messengers of insulin, are reported to exert several of insulin's metabolic effects. METHODS: A prospective cross-sectional study was carried out to investigate IPG P-type (P-IPG) in human amniotic fluid and in adult urine under physiological conditions. An amniotic fluid sample was taken from 78 women undergoing early amniocentesis and a mid-stream urine specimen was collected from 109 healthy pregnant and 66 non-pregnant women. All samples were assessed using a polyclonal antibody-based ELISA. RESULTS: The P-IPG content was a thousand times higher in the amniotic fluid than in the urine (p < 0.0001). Urinary specimens showed a four-fold higher P-IPG content during pregnancy than in healthy non-pregnant women (p < 0.001). CONCLUSIONS: Under physiological conditions, human amniotic fluid was found to be enriched in P-IPG compared with maternal urine, suggesting a possible fetal origin. Therefore, IPGs may play a role in insulin sensitivity and fetal growth and, perhaps, be involved in some of its abnormalities such as macrosomia and intrauterine growth restriction.

Changes in the management and outcome of central nervous system involvement from ovarian cancer since 1994.

OBJECTIVE: To identify differences in the management and outcome of patients with central nervous system metastases from epithelial ovarian cancer. METHODS: The clinical and pathologic characteristics, treatment, and outcome of 23 patients with brain metastases from epithelial ovarian cancer who were treated during 1982-1994 were compared with those of 20 patients treated during 1995-2010 at the same center. RESULTS: No differences were found in terms of primary tumor characteristics, time interval from ovarian cancer diagnosis to brain involvement diagnosis, sites of metastasis, and presence of extracranial disease. The main difference between the 2 groups was the therapeutic approach. During 1982-1994, most patients received radiotherapy only, whereas most patients during 1995-2010 underwent surgical resection followed by radiotherapy and/or chemotherapy. The duration of survival during 1982-1994 was 5 months, which was significantly shorter than the duration of survival (18 months) during 1995-2010. CONCLUSION: An aggressive multimodal treatment approach might prolong the survival of patients with brain involvement from ovarian cancer.

Is there a link between insulin resistance and inflammatory activation in preeclampsia?

Preeclampsia is a severe complication of human pregnancy and an insulin resistant state has been demonstrated in this multisystem disorder, although its bases remain unclear. Inositol phosphoglycans P-type belongs to a family of putative insulin mediators and was described to exert many insulin-like effects on lipid and glucose metabolism. A definite association between this molecule and preeclampsia was reported. The systemic inflammatory activation that occurs in preeclampsia as a consequence of the immunological dysfunction can exacerbate placental insulin resistance leading to an over-expression of P-IPG as a counterregulatory mechanism to insulin resistance. Besides, the lipidic form of P-IPG was reported to be similar to endotoxins, and may represent the link between insulin resistance, systemic inflammation and increased angiogenic factors. In this article we propose a new working theory on insulin resistance and preeclampsia.

Are active labour and mode of delivery still a challenge for extremely low birth weight infants? Experience at a tertiary care hospital.

OBJECTIVE: This study was to evaluate the impact of mode of delivery and timing of caesarean section in extremely preterm births, below 28 weeks of gestation, on long-term survival and psychomotor outcomes. STUDY DESIGN: This was a single-centre retrospective cohort study of 84 cases of extremely low birth weight infants with complete maternal, obstetrical and neonatological information. Mortality and survival with neurological disabilities at 18 months of life were considered outcome measures. RESULTS: Forty percent of deliveries were at or less than 25 weeks of gestation and birth weight was

Fibrotic tissue in the endometrioma capsule: surgical and physiopathologic considerations from histologic findings.

Ovarian tissue inadvertently excised along with endometriomas was associated with the presence of pericystic fibrosis and serum levels of CA-125, representing the only clinical parameter for predicting follicle loss before surgery. A consecutive series of 91 ovarian endometriotic cysts were studied, and an inverse relationship between serum CA-125 and the thickness of the fibrotic tissue of the endometrioma capsule was demonstrated.

Parabolic trend in endometrial thickness at embryo transfer in in vitro fertilization/intracytoplasmic sperm injection cases with clinical pregnancy evidence.

Sonographic measurement of endometrial thickness at embryo transfer is thought to be a good predictor of the success of in vitro fertilization/intracytoplasmic sperm injection cycles because the clinical pregnancy rate increases as the endometrium thickens. Nevertheless, a retrospective analysis of a study population of 606 patients showed a decrease of clinical pregnancy rates in the setting of extreme endometrial thicknesses.

Prenatal diagnosis of Freeman-Sheldon syndrome and usefulness of an ultrasound fetal lip width normogram.

OBJECTIVES: Freeman-Sheldon syndrome (FSS) is a rare genetic condition with facial and joint abnormalities. Here we report the first case of prenatal diagnosis in a fetus with negative familial history for this syndrome. A chart of the fetal mouth length was generated and its usefulness verified. METHODS: A cross-sectional study was carried out to derive standard charts for fetal lip lengths. The study population was made up of 371 fetuses between 15 and 38 weeks of gestation examined only once for this purpose. A statistical analysis previously recommended to derive normal ranges in fetal growth charts was employed. RESULTS: A 34-year-old woman was referred at 28 weeks of gestation for polyhydramnios and clubfeet. A detailed scan confirmed those findings and showed joint contractures of hands, a severe microstomia with a 'whistling' mouth, and an H-shaped mark over the chin. FSS was suspected, though there was no family history for this genetic syndrome. After emergency delivery at 32 weeks, the syndrome was confirmed. The infant died two months later from pneumonia. Upon construction of a standard mouth length chart, it was found that the fetal lip width in this case of FSS was well below the 5th centile. CONCLUSION: Here we present a standard chart for fetal lip width. We demonstrated its usefulness in cases with fetal face anomalies. Specific charts are fundamental for an objective assessment of the fetal parameters.