UPA and LNG in emergency contraception: the information by EMA and the scientific evidences indicate a prevalent anti-implantation effect.

RATIONALE AND OBJECTIVES: Emergency contraceptives pills (ECPs) are described as drugs that work by either inhibiting or delaying ovulation without affecting implantation. In our opinion, as we aim at demonstrating, both EMA documents and the experimental papers indicate that they prevalently inhibit embryo-implantation. LNG-ECPs: literature: LNG-ECPs never prevent ovulation when are taken in the most fertile days (EMA-EPAR on ellaOne® p. 9, first table). Conversely, they prevent the formation of an adequate corpus luteum. When they are taken pre-ovulatory ovulations occur regularly, but pregnancies do not appear. Taken after ovulation, they seem ineffective in preventing pregnancies. UPA-ECPs: literature: EllaOne® prevents ovulation only when is taken in the first fertile day. Thereafter, its anti-ovulatory effect drops sharply and becomes insignificant (8%) 36 h before ovulation, in the most fertile days (Brache); its decreasing anti-ovulatory effect cannot explain a consistently high effectiveness in preventing pregnancies (≥80%) that does not decrease depending on which of the 5 d it is taken after unprotected intercourse. Besides, ovulation occurs regularly in 91.7% of women taking ellaOne® weekly, for eight consecutive weeks (EMA-CHMP-Assessment Report 'EMA/73099/2015': study HRA2914-554, p. 7). Lastly, Lira-Albarrán administered ellaOne® to women in the most fertile pre-ovulatory days: they had normal ovulation, but their endometrium, evaluated through samples obtained in the implantation window, became inhospitable: the expression of 1183 genes was exactly the opposite of that observed in the receptive pro-gestational endometrium. This agrees with information by EMA-CHMP-Assessment Report 'EMEA/261787/2009' (p. 8): after UPA administration 'the proteins necessary to begin and maintain pregnancy are not synthesized'. CONCLUSIONS: Emergency Contraceptives work prevalently by preventing embryo-implantation. People shall receive correct information.

Uterine fibroid size modifications during pregnancy and puerperium: evidence from the first systematic review of literature.

PURPOSE: The influence of pregnancy on uterine fibroid size still remains an unsolved dilemma. Basing on current knowledge, physicians are not able to inform patients about the likelihood of uterine fibroids to modify their size during pregnancy. Study aim was to summarize available evidence concerning the size modifications of uterine fibroids during each trimester of pregnancy and during puerperium. METHODS: The review was reported following the PRISMA guidelines and registered in PROSPERO (registration number: CRD42017071117). A literature search was conducted in electronic database (PubMed, Embase, Sciencedirect, the Cochrane library and Clinicaltrials.gov) until July 2017. All studies evaluating fibroids' changes during pregnancy and puerperium by ultrasound or magnetic-resonance-imaging were included. Descriptive characteristics of studies and patients were collected. The modifications of uterine fibroid diameter and volume were the outcome measures. RESULTS: Concerning the first trimester of pregnancy, all authors reported a significant growth of uterine fibroids. Contradictory evidence was found about uterine fibroid modifications during the second and third trimesters, mainly supporting a slowdown during mid pregnancy and a subsequent size reduction during late pregnancy. Concerning the overall modifications during pregnancy and puerperium, poor evidence quality suggests that uterine fibroids do not modify their volume/slightly enlarge during pregnancy and subsequently reduce in size during puerperium. CONCLUSIONS: Uterine fibroids seem to be subject to a non-linear trend of modifications during pregnancy and puerperium, which may vary from myoma to myoma. Adequate evidence supports uterine fibroid systematic enlargement during the first trimester of pregnancy, while inconsistent evidence is available about the changes of uterine fibroids during second and third trimesters. In addition, the overall modifications of myomas during pregnancy and puerperium remain unclear.

Dysregulation of gene expression in human fetal endothelial cells from gestational diabetes in response to TGF-ß1.

Enhanced biosynthesis of several cytokines, such as, transforming growth factor-ß1 (TGF-ß1), is detected in gestational diabetes mellitus (GDM). In this study, we addressed the question of whether the exposure to the abnormal milieu of GDM in vivo affects gene expression pattern of human umbilical vein endothelial cells (HUVEC) in response to TGF-ß1. We found that HUVEC isolated from GDM (dHUVEC) had reduced migratory capacity versus those of healthy women (nHUVEC) and this quiescent phenotype was associated with higher expression levels of the TGF-ßtype I receptor ALK5 and a slight increase in the endogenous production of TGF-ß1 (mainly in its latent form). Moreover, we performed transcriptome analysis, using microarray technology, of dHUVEC versus nHUVEC, after 3h treatment with exogenous TGF-ß1 (10 ng/ml). The treatment of dHUVEC with TGF-ß1 caused downregulation of the transcription of multiple genes involved in development, cell movement and migration of cells versus TGF-ß1-treated nHUVEC. These changes in transcriptome profile might contribute to GDM-dependent alterations in cardiac morphogenesis and placental development.

Could molecular assessment of calcium metabolism be a useful tool to early screen patients at risk for pre-eclampsia complicated pregnancy? Proposal and rationale.

One of the most frequent causes of maternal and perinatal morbidity is represented by hypertensive disorders during pregnancy. Women at high risk must be subjected to a more intensive antenatal surveillance and prophylactic treatments. Many genetic risk factors, clinical features and biomarkers have been proposed but none of these seems able to prevent pre-eclampsia onset. English literature review of manuscripts focused on calcium intake and hypertensive disorders during pregnancy was performed. We performed a critical analysis of evidences about maternal calcium metabolism pattern in pregnancy analyzing all possible bias affecting studies. Calcium supplementation seems to give beneficial effects on women with low calcium intake. Some evidence reported that calcium supplementation may drastically reduce the percentage of pre-eclampsia onset consequently improving the neonatal outcome. Starting from this evidence, it is intuitive that investigations on maternal calcium metabolism pattern in first trimester of pregnancy could represent a low cost, large scale tool to screen pregnant women and to identify those at increased risk of pre-eclampsia onset. We propose a biochemical screening of maternal calcium metabolism pattern in first trimester of pregnancy to discriminate patients who potentially may benefit from calcium supplementation. In a second step we propose to randomly allocate the sub-cohort of patients with calcium metabolism disorders in a treatment group (calcium supplementation) or in a control group (placebo) to define if calcium supplementation may represent a dietary mean to reduce pre-eclampsia onset and to improve pregnancy outcome.

Could HPV-DNA test solve the dilemma about sentinel node frozen section accuracy in early stage cervical cancer? Hypothesis and rationale.

In order to reduce the surgical invasiveness in early-stage cervical-cancer treatment, the sentinel lymph-node (SLN) technique could be considered as a possible intraoperative-guidance to lymphadenectomy decision making. Unfortunately its accuracy ranges between 33.3% and 100% in different studies. Recent manuscripts suggest that HPV-DNA presence in pelvic-lymph-nodes may represent a molecular marker of micrometastases. According to this hypothesis, the rationale in proposing the HPV-DNA-test when negative frozen-section occurs is due to the expected improvement of its diagnostic-accuracy. HPV-DNA test may represent a marker able to discriminate at frozen section the false-negative from the truth-negative tests filling the gap between optimal and real frozen-section accuracy.

Which luteal phase support is better for each IVF stimulation protocol to achieve the highest pregnancy rate? A superiority randomized clinical trial.

In vitro fertilization (IVF) cycles generate abnormalities in luteal-phase sex steroid concentrations and this represent an important limiting factor to achieve a good pregnancy rate. Although there are evidences about the usefulness of luteal phase support (LPS) after IVF cycles, no consensus exist about the best dose and way of progesterone (PG) administration, the advantages of estradiol (E2) supplementation and which IVF protocol could benefit from one more than other LPS scheme. Aim of the study was to assess the best LPS (low-dose PG, high-dose PG, high-dose PG and E2 supplementation) to achieve the highest clinical/ongoing pregnancy rate according to stimulation protocol, E2 at ovulation induction, endometrial thickness at pick-up and women's age. We conducted a randomized trial on 360 women undergoing IVF (180 treated by long-GnRH agonist, 90 by short-GnRH agonist and 90 by short-GnRH antagonist protocol) and stimulated by recombinant follicle-stimulating hormone alone. Our data demonstrated that high-dose PG is better than low-dose to increase both clinical and ongoing pregnancy rate. E2 supplementation are mandatory in case of short-GnRH antagonist protocol and strongly suggested in all protocols when E2max <5 nmol/l and endometrial thickness <10 mm. In long-GnRH agonist protocols, as well as in patients >35 years, the real advantages of E2 supplementation remain debatable and require further confirmation.

Pharmacological anti-thrombotic prophylaxis after elective caesarean delivery in thrombophilia unscreened women: should maternal age have a role in decision making?

In obstetrical practice, the best prevention strategy for pregnant women aged >35 years without known thrombosis risk factors who underwent elective caesarean delivery (CD) is controversial. We performed an observational-longitudinal cohort study on pregnant women aged >35 years who delivered at term by elective caesarean section after a physiological single pregnancy to evaluate the role of maternal age in the decision-making process of whether or not to perform low-molecular-weight heparin (LMWH) prophylaxis during the post-partum period after elective CD in healthy women with unknown inherited thrombophilia status. During the 6 post-partum weeks, we followed two groups: GROUP-A (349 women treated for 7 days with low-molecular-weight heparin) and GROUP-B (180 women not treated with LMWH treatment). The outcomes were as follows: onset of thromboembolic events during the post-partum period; non-obstetrical-linked maternal haemorrhage; blood transfusion; re-laparotomy; detection of a surgical site haematoma; length of hospitalisation; and treatment suspension because of decreased platelet count. Except for the parity number, the two groups were homogeneous with regard to general features. In both the groups, we reported no cases of thromboembolic events during the follow-up period. Maternal haemorrhage requiring transfusion occurred in 16 women in GROUP-A and none in GROUP-B. Among the GROUP-A women, 11 demonstrated a surgical site haematoma and 4 required re-laparotomy. No cases of treatment suspension were reported. Pneumatic compression stockings represent a better, low cost and safe way to prevent post-partum venous thromboembolic episodes after elective caesarean section in an unscreened population. Pharmacological prophylaxis after elective caesarean section should be performed only in case of clear and known adjunctive risk factors, independent of maternal age.

Could empirical low-dose-aspirin administration during IVF cycle affect both the oocytes and embryos quality via COX 1-2 activity inhibition?

PURPOSE: To compare qualitative and quantitative ovarian response in idiopathic infertile women treated with low-dose-aspirin (LDA) during in-vitro-fertilization (IVF) cycles (pl) versus untreated ones. METHODS: We conducted an observational-cohort-study on normo-responders patients aged between 25 and 45,years referred to Assisted-Reproductive Unit --University of Padua--in order to evaluate the ovarian response effects (both qualitative and quantitative) after LDA administration. In detail we aim to assess if LDA administration could improve ovarian response, reducing the gonadotropin administration, and if its administration could increase the amount of follicles greater than 16 mm at pick-up, the amount and quality of oocytes retrieved, the amount and quality of embryos, the chance to achieve a pregnancy and to carry it on. RESULTS: One hundred six LDA-treated patients (Group-A) and 100 not-treated ones (Group-B) were homogeneous for age and BMI. The Group-A, compared to Group-B, showed higher gonadotropin request, higher number of ovarian follicles at pick-up, more follicles bigger than 16 mm in diameter and more retrieved oocytes (despite higher number of immature and at germinal vesicle stage oocytes) but lower quality of obtained embryos. The comparison between two Groups in term of retrieved oocytes /number of follicles, mature oocytes/retrieved oocytes, fertilized oocytes/mature oocytes and good embryos quality/mature oocytes showed a strongly advantageous ratio for Group-B. For each considered outcome, we found a dose-related effect. CONCLUSIONS: It is mandatory to define which patients could benefit from LDA administration and the adequate timing to administer it since the empirical administration could negatively affect both oocyte and embryo quality during IVF cycles.

Update on best available options in obstetrics anaesthesia: perinatal outcomes, side effects and maternal satisfaction. Fifteen years systematic literature review.

PURPOSE: In modern obstetrics, different pharmacological and non-pharmacological options allow to obtain pain relief during labour, one of the most important goals in women satisfaction about medical care. The aim of this review is to compare all the analgesia administration schemes in terms of effectiveness in pain relief, length of labour, mode of delivery, side effects and neonatal outcomes. METHODS: A systematic literature search was conducted in electronic databases in the interval time between January 1999 and March 2013. Key search terms included: "labour analgesia", "epidural anaesthesia during labour" (excluding anaesthesia for Caesarean section), "epidural analgesia and labour outcome" and "intra-thecal analgesia". RESULTS: 10,331 patients were analysed: 5,578 patients underwent Epidural-Analgesia, 259 patients spinal analgesia, 2,724 combined spinal epidural analgesia, 322 continuous epidural infusion (CEI), 168 intermittent epidural bolus, 684 patient-controlled infusion epidural analgesia and 152 intra-venous patient-controlled epidural analgesia. We also considered 341 women who underwent patient-controlled infusion epidural analgesia in association with CEI and 103 patients who underwent patient-controlled infusion epidural analgesia in association with automatic mandatory bolus. CONCLUSION: No significant differences occurred among all the available administration schemes of neuraxial analgesia. In absence of obstetrical contraindication, neuraxial analgesia has to be considered as the gold standard in obtaining maternal pain relief during labour. The options available in the administration of analgesia should be known and evaluated together by both gynaecologists and anaesthesiologists to choose the best personalized scheme and obtain the best women satisfaction. Since it is difficult to identify comparable circumstances during labour, it is complicate to standardize drugs schemes and their combinations.

Cervicoisthmic pregnancy near cesarean scar after oocyte donation in premature ovarian failure: literature review starting from a single case.

OBJECTIVE: This study aimed to identify the best management options in decision making in cases of cervicoisthmic and cesarean scar pregnancies and rare forms of ectopic pregnancies with high rates of pregnancy-related morbidity in the first trimester, more commonly associated with assisted reproductive medicine. MATERIALS AND METHODS: We performed a literature review of the description of a case report of a cervicoisthmic pregnancy near a cesarean scar in a premature ovarian failure woman. She obtained pregnancy after ovum donation, hormonal therapy, and in vitro fertilization. The researchers focused on the MEDLINE/PubMed database articles on ectopic pregnancies, particularly on cesarean scar pregnancies, cervical pregnancies, and ectopic pregnancies after in vitro fertilization in English-language journals published from January 1996 to December 2011. RESULTS: The conservative or nonconservative options for medical or surgical treatments are disposables. Moreover, in literature, no consensus was found about the best treatment method. CONCLUSIONS: Obstetricians should pay great attention to a possible cesarean scar pregnancy in patients with risk factors in their medical history. Until now, the rarity of these findings does not allow the definition of a commonly accepted management, so the best personalized approach may be guided by early recognition, close surveillance, and appropriate counseling. Further investigations are necessary to recognize high-risk factors for all ectopic pregnancies and those unique to cesarean scar ectopic pregnancies.

Secondary amenorrhea in severe Asherman's syndrome: step by step fertility retrieval by Bettocchi's hysteroscope: some considerations.

The aim of this report was to define the best diagnostic and therapeutic approach when secondary amenorrhea is related to undiagnosed Asherman syndrome. We present a single case of secondary amenorrhea with a previous diagnosis of alterated hypothalamic-hypophysary regulation, with a component of ovarian function in probable reduction, which was evaluated in our department and resulted affected by Asherman's syndrome IV stage. We describe step by step the diagnosis and treatment of a previously misdiagnosed case of severe Asherman's syndrome. An appropriate diagnosis and adequate treatment are mandatory to allow menses and fertility to be restored when severe Asherman's syndrome occurs.

Female sterilization: update on clinical efficacy, side effects and contraindications.

PURPOSE: The aim of this review is to compare studies concerning female sterilization in order to define the most suitable approach and device for each patient considering timing, safety, cost-effectiveness, failure rate, complication rate and patient satisfaction. METHODS: A systematic literature search was conducted in electronic databases MEDLINE-EMBASE-Sciencedirect and Cochrane Library between 2000 and 2012. All original descriptions, case reports, retrospective and review articles on tubal sterilization methods have been considered. Outcome measures were effectiveness, tolerability, procedure complications and female satisfaction. RESULTS: The ideal female sterilization system should be a simple, safe, highly efficient, easily learned, inexpensive, one-time procedure without negative side-effects. Nowadays, the trans-cervical approach is associated with minimal postoperative pain, allowing short hospitalization and fast resumption of daily activities. Laparoscopic and laparotomic approaches are considered second choices, since, particularly in developing countries, the transcervical hysteroscopic methods will increasingly spread within gynaecological clinical practice. CONCLUSIONS: Safety issues, hospital stay, costs and surgeons' experience are important factors in decision-making of the method for female sterilization. Hysteroscopic devices should be preferred when possible. The counselling time remains a fundamental step in choice. The decision concerning method depends on the setting, the surgeon's experience, the country's economical development and the woman's preference.

Cyclic variations of bone resorption mediators and markers in the different phases of the menstrual cycle.

Female hormones are very important in regulating bone homeostasis; the drop of estrogen levels occurring at menopause is linked to a dramatic prevalence of bone resorption on formation. Only a small number of studies investigated the relationship between changes in circulating female sex hormones and the markers and mediators of bone homeostasis and they showed conflicting results. To explore such relationships we studied 20 young fertile healthy women, aged between 19 and 32 years. None had received hormone treatment for at least 6 months. We assayed luteinizing hormone, follicle-stimulating hormone, progesterone and 17ß-estradiol, as well as the levels of osteoprotegerin (OPG), C-terminal telopeptide of collagen type I (CTx) and RANKL (receptor activator of nuclear factor-B ligand) in samples drawn from every subject at four different times during the menstrual cycle when estrogens are lowest, at the start of the cycle: T 0 (2-4th day); when estrogens are highest, in the pre-ovulatory period: T 14 (12-14th day); when progesterone activity is highest, in the advanced luteal phase: T 26 (24-26th day); and again at the start of the next cycle: T 01 (2-4th day). We observed that CTx levels are highest at the start of the cycle, decreased significantly from T 0 to T 26 (pfwe = 0.0455) and then increased from T 26 to T 01 (pfwe = 0.0415); OPG, on the other hand, which was also highest at the start of the cycle, decreased significantly from T 0 to T 14 (pfwe = 0.02) and then increased, though not significantly, from T 14 to T 01; no variation was observed in RANKL values at any time. We observed inverse correlations between estradiol and OPG levels, which became highly significant at T 01 between estradiol nadir and OPG peak levels (pfw = 0.0095). Furthermore, the increase of estradiol from T 0 to T 14 was negatively correlated with the concomitant decrease of OPG (pfwe = 0.0277), as was the fall of estradiol from T 26 to T 01 with the OPG peak levels, both at T 01 (pfw = 0.0045) and at T 0 (pfwe = 0.0381). We also observed direct correlations between the OPG levels and the variations of progesterone in the preceding intervals, but they never attained statistical significance. We conclude that OPG and CTx fluctuation during the menstrual cycle are likely due to the physiological variations of sex steroids levels.

A preliminary investigation on placenta protein profile reveals only modest changes in well controlled gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is associated with a wide range of tissue-specific changes depending on the quality of glycemic control of the mothers. Here we tested the hypothesis that GDM is associated with alterations in the human term placenta proteome. For this aim, two different approacheswere employed. The placenta homogenates from 20 healthy subjects and those from 20 GDM pregnant women were pooled. The two samples thus obtained were analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and the proteins detected were tentatively identified by comparison of their molecular weight with the Human Protein Reference Database, restricting the search to the species expressed in the placenta tissue. However this approach led to misleading results: in fact, an in deep analysis of the spectra and tandem mass spectrometry (MS/MS) measurements of the digestion products from the protein detected, unequivocally proved that the species observed are maternal and fetal globins. Consequently, the two pools were analyzed by 1D sodium dodecyl sulphate polyacrylamide gel electrophoresis; the different bands obtained were digested by trypsin and the digestion products were analyzed by MALDI-MS; the protein identification was carried out by comparison of the peptide mass fingerprint with databases. Only modest quantitative differences were observed between the placenta protein profiles of healthy and GDM subjects, indicating that GDM, if well controlled, induces only minor changes in the placental proteome. One example of differently expressed proteins in the placenta homogenate pool from GDM and the controls was the SRRM1 protein, a member of the serine-arginine protein kinase family; for GDM samples, the MALDI spectrum of its digestion products showed the presence of molecular species attributable to glycation and glyco-oxidation processes.

LigaSure vessel sealing system in vaginal hysterectomy: safety, efficacy and limitations.

PURPOSE: The aim of this study is to compare vaginal hysterectomy performed with standard technique versus the one performed with LigaSure. METHODS: Observational-longitudinal-cohort study on 42 women candidates to vaginal hysterectomy because of benign uterine pathology. Outcome variables, methods of analysis, inclusion and exclusion criteria were determined prospectively. Eligible patients were subdivided in Group-A (LigaSure-21 patients), or in Group-B (classical-21 patients). Group-A was divided into Subgroup-A1 (10 patients) and Subgroup-A2 (11 patients), depending on the point where the stump of the uterosacral-ligament was transfixed: Subgroup-A1 at cervical portion, Subgroup-A2 at intermediate portion. For all patients were reported: pre-post surgery haemoglobin and hematocrit, number of sutures, duration of intervention and blood loss, NRS-score on first/third post-operative days. All patients underwent gynaecological examination 30 and 180 days after surgery. RESULTS: General characteristics did not show significant differences between the two groups. Statistically significant differences emerged from the comparison between Group-A versus Group-B in terms of: intraoperative bleeding, post-operative value of haemoglobin, Δ-Hb, number of sutures, surgical time, pain at first and third post-operative day. The 180 days follow-up demonstrated four cases of vaginal vault prolapse, only in the Subgroup-A1 related to thermal damage of the uterosacral ligament. CONCLUSION: LigaSure vessel sealing system is a safe alternative for securing pedicles in vaginal hysterectomy with significant improvement in patients outcome. Following vaginal vault prolapse, we determined the optimal fixation-site to perform the colposuspension in the intermediate portion of the uterosacral-ligament, especially if the cervical portion received a thermal damage, as occurs during the LigaSure use.

An update on diabetic women obstetrical outcomes linked to preconception and pregnancy glycemic profile: a systematic literature review.

Women with type 2 diabetes were less likely to have diabetes related complications than women with type 1. Women with type 1 diabetes had a high prepregnancy care and showed a worse glycemic control than women with type 2 both in the preconception period and during pregnancy. Obstetrical outcomes showed that preeclampsia and stillbirth rate is almost doubled in type 1 patients while perinatal deaths and SGA importantly increased in type 2 diabetes. In modern obstetrical care it is mandatory to maintain glucose levels as close to normal as possible particularly in diabetic population. HbA1C no higher than 6% before pregnancy and during the first trimester seems to decrease the risk of adverse obstetrical outcomes. Both the preconceptional counseling and glycemic profile optimization represent a fundamental step to improve pregnancy outcomes in women with preexisting diabetes. A systematic approach to family planning and the availability of preconception care for all diabetic women who desire pregnancy could be an essential step for diabetic management program.

Nowadays which emergency contraception? Comparison between past and present: latest news in terms of clinical efficacy, side effects and contraindications.

Despite many highly effective methods of contraception are available nowadays, many pregnancies are unintended. Emergency contraception (EC) is the use of drug or device after unprotected intercourse to prevent an unwanted pregnancy. It is a woman's last chance to prevent unintended pregnancy. Nevertheless the confusion about mechanisms of action, side effects, clinical efficacy and controindications makes the intervention underused in every setting investigated. So far levonorgestrel (LNG) has been considered the gold standard for oral EC. Today, a new type of second generation progesterone receptor modulator, ulipristal acetate (UPA) has been proposed as a more effective drug than LNG in prevention of unwanted pregnancies by delaying or inhibiting ovulation; even if many other devices are disposable in commerce. We revised the literature to concern most of the data available on the role of EC and moreover clarifying the available methods, the action windows of the accessible devices, the adverse events and the controindications.

Placental mesenchymal dysplasia: can early diagnosis ensure a good materno-foetal outcome? A case report.

Placental mesenchymal dysplasia is a rare disorder characterized by an increased size placenta with cystic villi and ectasic vessels. The correct diagnosis is very important, because placental mesenchymal dysplasia is usually compatible with a normal foetal morphology and a good materno-foetal outcome. An accurate ultrasound evaluation can help in the identification of characteristic patterns associated to this trophoblastic disease, particularly to distinguish it from its main differential diagnosis, i.e. hydatidiform mole. We report an early second-trimester ultrasound diagnosis of placental mesenchymal dysplasia complicated by foetal growth restriction, but with normal female karyotype and good healthy baby.

Cervical Mullerian adenosarcoma with heterologous sarcomatous overgrowth: a fourth case and review of literature.

BACKGROUND: Uterine sarcomas are relatively rare tumors that account for approximately 1-3% of female genital tract malignancies and between 4-9% of uterine cancers. Less than 8% of all cases are Mullerian adenosarcoma, a distinctive uterine neoplasm characterized by a benign, but occasionally atypical, epithelial and a malignant, usually low-grade, stromal component, both of which should be integral and neoplastic constituents of the tumor. Mullerian adenosarcoma with sarcomatous overgrowth (MASO) is a very aggressive variant, associated with post-operative recurrence, metastases, even when diagnosed in early stage. CASE PRESENTATION: We present a fourth MASO case derived from uterine cervix in a 72-year-old woman with metrorrhagia and a polypoid mass protruding through the cervical ostium. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, systematic pelvic lymph node dissection, omental biopsy and appendectomy were performed. Surgery treatment was associated with adjuvant whole-pelvis radiation (45 Gy) and adjuvant chemotherapy (cisplatin/ifosfamide). After nine months of follow up, the patient was free of tumor. CONCLUSIONS: The rarity of MASO of the cervix involves a management difficult. Most authors recommend total abdominal hysterectomy, usually accompanied by bilateral salpingo-oophorectomy. There is no common agreement on staging by lymphadenectomy during primary surgery and adjuvant chemo-radio therapy.

Effects of octreotide exposure during pregnancy in acromegaly.

BACKGROUND: Only six women who were treated with somatostatin analogues (SSAs) throughout their pregnancies have been described so far. The influence of SSAs on the course of pregnancy and newborn outcomes remains largely unknown. Many aspects of SSAs pharmacokinetics in mother and foetus have not yet been defined. METHODS AND FINDINGS: We report a case study on the effects of octreotide on uterine artery blood flow, octreotide concentrations in biological fluids of mother and newborn, and somatostatin (SST) receptor expression and binding at the level of the maternal-foetal barrier tissues in an acromegalic woman treated with short-acting octreotide throughout her pregnancy. An acute decrease in uterine artery blood flow was observed after octreotide injections, without affecting the pregnancy course, delivery, or foetal development. Octreotide concentrations were high in maternal serum and colostrum and lower in umbilical cord serum, amniotic fluid, and newborn serum. All SST receptor subtypes can be expressed in placental tissue but their binding profile was weak both in the placenta and umbilical cord. The child was healthy and developed normally up to age 6 from an anthropometric, metabolic, and endocrine point of view. We reviewed all published reports on pregnancy SSA exposure and outcomes were compared to a time-matched group of acromegalic women not exposed to SSA. No significant effect on the mother or foetus was observed. CONCLUSIONS: Short-acting octreotide appears not to affect the function of the maternal-foetal barrier or foetal development, except for the occurrence of acute, reversible, and clinically irrelevant haemodynamic changes. These data support the feasibility and safety of treatment with short-acting octreotide in acromegalic women during pregnancy and excludes major matters of concern about the effects of this medication on pregnancy itself and its outcome.