Retraction Note: Randomized, double blind placebo-controlled trial: effects of Myo-inositol on ovarian function and metabolic factors in women with PCOS.

The article "Randomized, double blind placebo-controlled trial: effects of Myo-inositol on ovarian function and metabolic factors in women with PCOS", by S. Gerli, E. Papaleo, A. Ferrari, G.C. Di Renzo, published in 2007; 11 (5): 347-354-PMID: 18074942 has been retracted by the Editor in Chief for the following reasons. The paper has been recently issued on PubPeer as multiple textual overlaps have been detected between this article and a previous article published by the same group of authors in 2003 (S. Gerli, M. Mignosa, G.C. Di Renzo. Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci 2003; 7 (6): 151-159. PMID-15206484). After having informed the Editor in Chief of a possible duplicate publication, the corresponding author was contacted to clarify this issue according to the policies of the journal. The corresponding author admitted that the 2007 paper had been written by an uncredited student, who adapted the 2003 paper and submitted it as novel work without the consent of the authors. Therefore, given the evidence, the Editor in Chief decided to withdraw the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/458.

From Myo-inositol to D-chiro-inositol molecular pathways.

OBJECTIVE: Inositol is a carbocyclic sugar polyalcohol. By epimerization of its hydroxyl groups, nine possible stereoisomers can be generated, two of major physiological and clinical relevance: myo-inositol and D-chiro-inositol. Myo-inositol and D-chiro-inositol are normally stored in kidney, brain and liver and are necessary for functions, such as signal transduction, metabolic flux, insulin signaling, regulation of ion-channel permeability, stress response and embryo development. In this narrative review, we summarize the mechanisms by which myo-inositol and D-chiro-inositol can be synthesized and absorbed and their possible role in the etiopathogenesis of neural tube defects. MATERIALS AND METHODS: We performed an online search in the PubMed database using the following keywords: "inositol", "D-chiro-inositol", "myo-inositol", "neural tube defects and inositol". RESULTS: Inositol requirements are partly met by dietary intake, while the rest is synthesized endogenously. Inositol deficiency may be involved in the pathogenesis of diseases, such as metabolic syndrome, spina bifida (a neural tube defect), polycystic ovary syndrome and diabetes. Supplementation of the two inositol stereoisomers, D-chiro-inositol and myo-inositol is important to prevent these conditions. CONCLUSIONS: Inositol is fundamental for signal transduction in the brain, kidneys, reproductive organs and other tissues in response to neurotransmitters, hormones and growth factors. Various genes are involved in inositol metabolism and associated pathways. Altered inositol concentrations are observed in several diseases. Analysis of the genes involved in inositol metabolism may provide important information for the clinical management of these conditions.

Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women.

PURPOSE: Fasting blood homocysteine is increased in PCOS women and is involved in several of its co-morbidities including cardiovascular disease and infertility. Corrective interventions based on the administration of supra-physiologic doses of folic acid work to a low extent. We aimed to test an alternative approach. METHODS: This was a prospective, randomized, parallel group, open label, controlled versus no treatment clinical study. PCOS women aged > 18, free from systemic diseases and from pharmacological treatments were randomized with a 2:1 ratio for treatment with activated micronutrients in support to the carbon cycle (Impryl, Parthenogen, Switzerland-n = 22) or no treatment (n = 10) and followed-up for 3 months. Fasting blood homocysteine, AMH, testosterone, SHBGs, and the resulting FTI were tested before and at the end of the follow-up. RESULTS: The mean baseline fasting blood homocysteine was above the normal limit of 12 µMol/L and inversely correlated with SHBG. AMH was also increased, whereas testosterone, SHBG, and FTI were within the normal limit. The treatment achieved a significant reduction of homocysteine, that did not change in the control group, independently of the starting value. The treatment also caused an increase of AMH and a decrease of SHBGs only in the subgroup with a normal homocysteine at baseline. CONCLUSIONS: In PCOS ladies, blood homocysteine is increased and inversely correlated with the SHBGs. Physiologic amounts of activated micronutrients in support to the carbon cycle achieve a reduction virtually in all exposed patients. Whether this is of clinical benefit remains to be established.

Dietary habits and semen parameters: a systematic narrative review.

Semen quality and male fertility are declining worldwide. As it was observed that physiologic and pathologic processes of spermatogenesis can be influenced by diet, the relation between dietary habits and semen parameters has been the focus of much interest. To review the human observational studies on this issue, we performed a systematic literature search, up to November 2016 (MEDLINE and EMBASE). We included all observational full-text papers reporting the relation between dietary habits and semen parameters. Article selection was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Twenty-three observational studies were included. Overall, 8477 healthy men and 1204 men presenting at Fertility Clinics were included in the selected studies. Even if some inconsistencies are present, possibly due to the different effect of nutrients in fertile and infertile men, results support the hypothesis that diets including fruit and vegetables, for their contents in vitamins, and fish or low-fat dairy products as the main source of proteins, are associated with better semen quality. Recommendations may be confidently provided because of the many beneficial effects of a healthy diet, although further studies are needed to clarify the currently inconsistent findings and to shed light on the underlying mechanisms.

Early ultrasonographic diagnosis of placental mesenchymal dysplasia.

Placental mesenchymal dysplasia (PMD) is a rare pathology characterized by vascular anomalies, placentomegaly and grapelike vesicles resembling partial molar pregnancy. PMD is often associated with fetal growth restriction or intrauterine fetal demise. We report a case of an early diagnosis of PMD at 10 weeks' gestation, with a regular intrauterine growth and a fetal demise occurring at 31 week's gestation. The placenta showed aneurysmally dilated and tortuous vessels with luminal thrombosis. Even in presence of a regular fetal growth, a fetal demise may always occur, suggesting the option of an early heparin administration to reduce the risk of thrombosis of chorionic vessels.

Endometrial carcinoma in women 40 year old or younger: a case report and literature review.

Endometrial cancer is the most frequent gynecologic cancer. Although it mainly occurs in menopausal women, it can hit younger patients as well. Only few cases of affected women under the age of 30 are reported. A case of a 23-year-old patient with endometrioid carcinoma grade II-III is presented. Hysterectomy is considered the standard treatment and it could represent a problem for those young women who desire to preserve fertility. A conservative management can be offered to these patients when the tumor is well differentiated and advanced stage is excluded. Several studies are available in literature about fertility sparing approach. Progestin treatment, combined or not with hysteroscopic ablation seem to be the most validated conservative management. Anyhow this treatment is not free risk, because it is not always effective and disease progression during or after treatment is possible. Then a strict evaluation and selection of patients before starting treatment is mandatory.

Prophylactic arterial catheterization in the management of high risk patients for obstetric haemorrhage.

OBJECTIVES: Post-partum haemorrhage still remains one of the major causes of maternal morbidity and mortality. In case of abnormal placentation it is possible to carry out preventive and therapeutic actions. To maintain fertility in reproductive-aged women and to avoid a more radical surgery, embolization has been introduced in patients at high risk for haemorrhage. To describe a new option in the management of patients with abnormal placentation by an elective, preventive arterial catheterization and selective embolization of pelvic arteries. PATIENTS AND METHODS: A retrospective study including thirty six patients with abnormal placental invasion. All patients were prepared in the angiographic room and preventive arterial catheterization was performed before elective caesarean delivery. Materials for interventional angiography were transferred to the operating room. During surgery, selective embolization of pelvic arteries was realized in case of uncontrolled bleeding. RESULTS: Thirty-six elective arterial catheterizations were performed: 4 cases (11.1%) required embolization, haemorrhage was stopped in 2 patients. Hysterectomy was performed in two cases (5.5%). No death was reported. Two humeral thrombosis (5.5%) were registered. CONCLUSIONS: Prophylactic arterial catheterization appears to be safe. The main advantage is the reduction of the interval between the onset of bleeding and the embolization. This new option of management may contribute to reduce the risk of hysterectomy and maternal death.

Establishing a combined stimulation protocol hFSH followed by rFSH might represent a breakthrough in the IVF practice.

INTRODUCTION: Controlled ovarian stimulation directly influences assisted reproductive technology (ART) outcomes. Indeed, several studies have shown that the total IU of gonadotropins used for ovarian stimulation inversely correlates with pregnancy rate. Nowadays, two main gonadotropins are used in ART protocols, human-derived and recombinant follicle-stimulating hormone (FSH). The difference between these two hormones is dramatic. Indeed, the human-derived FSH is an acidic isoform of the hormone while the recombinant is a less acid one. In particular, during a physiological menstrual cycle the acid isoform is produced during the follicular phase (probably it is more effective in recruiting follicles) while less acidic isoform is produced during the mid follicular phase (preovulatory). In the present study, we aim to evaluate the efficacy of a protocol that mimics the physiological shift form an acidic to a less acid FSH isoform during oocyte maturation. PATIENTS AND METHODS: A total of 308 infertile couples undergoing their first Intracytoplasmic Sperm Injection (ICSI) treatment were enrolled. All patients underwent a standard down-regulation protocol with GnRH analogue hormone. Patients were randomized in two groups: group 1, patients that received 225 IU of human-derived FSH (hFSH Fostimon, IBSA, Lodi, Italy) for 6 days from the second day of the cycle and then 225 IU of recombinant FSH (rFSH Gonal-F; Serono, Rome, Italy) from the 7th day of stimulation until hCG administration, and group 2, control group, patients that received 225 IU recombinant FSH alone from the second day of the cycle until hCG administration. RESULTS: The combined protocol (hFSH + rFSH) resulted in significantly less IU of FSH necessary for ovarian stimulation together with the stimulation days. Furthermore, oocyte and embryo quality was higher in the group of patients treated with the combined protocol. Noteworthy, a significantly higher implantation rate and pregnancy rate were observed in favour of group 1 compared to group 2. CONCLUSIONS: We demonstrated that establishing a stimulation protocol able to mimic the physiological differences in FSH isoforms, hFSH combined with rFSH positively impact on ART outcome.

Antisepsis regimen in the surgical treatment of HPV generated cervical lesions: polyhexamethylene biguanide vs chlorhexidine. A randomized, double blind study.

INTRODUCTION: To reduce the risk of local infections after surgical treatments for HPV infected cervical lesions, the post-operative regimen is generally based on the use of vaginal antimicrobial agents. AIM: The efficacy and safety of polyhexamethylene biguanide-based vaginal suppositories was compared to a similar chlorhexidine-based treatment, in the post recovery regimen after surgical treatment of cervical lesions. MATERIALS AND METHODS: 50 women who underwent to CO2 laser therapy for cervical lesions were randomly assigned to receive 10 days of antiseptic treatment with chlorhexidine digluconate vaginal suppositories, or polyhexamethylene biguanide vaginal suppositories (Monogin®/Biguanelle® ovuli, Lo.Li. Pharma, Italy). A weekly follow-up check was performed for 6 weeks. RESULTS: Polyhexamethylene biguanide-based treatment showed improved efficacy compared to chlorhexidine, in terms of healing process and prevention of bacterial infections. CONCLUSIONS: Due to its safety and effectiveness, the vaginal treatment with polyhexamethylene biguanide is preferred to chlorexidine, in accordance with previously reported in vitro evidences.

Postpartum hysterectomy: a regional multicentre analysis in Italy.

To estimate prevalence, indications, risk factors and complications associated with emergency postpartum hysterectomy and to compare different results in Teaching and District Hospitals we designed a retrospective analysis in 34 cases of postpartum hysterectomy performed from 1 January 2002 to 31 December 2006, in three different obstetrics and gynaecology units (one University Hospital and two Regional Hospitals). The prevalence of postpartum hysterectomies was 2.2 per 1,000 deliveries. District Hospitals revealed a significantly increased risk (OR: 2.28). Severe complications were few. No deaths were reported. Considering the totality of patients and cases of District Hospitals, placenta praevia was the main cause of hysterectomy (44.1% and 52.2%, respectively), but uterine atony had a major prevalence in the Teaching Hospital (45.4%). Operating time was significantly longer (p = 0.0001) and the blood loss was significantly more important (p = 0.041) in the Teaching Hospitals.

The importance of analyzing and standardizing surgical methods.

The outcome of operations performed in different institutions or by different surgeons can hardly be compared if the operative methods are not standardized. Six different vaginal hysterectomy methods were studied. The steps common in all of them were defined. These steps were analyzed for optimal performance and sequence during the operation. The resultant modified method was subjected to a prospective randomized study, which showed that the operation time and the need for pain drugs were reduced. This method was introduced to several departments in different countries. The optimization and standardization of surgical methods are expected not just to improve the postoperative outcome, but also to enable a comparison between different departments and surgeons.

The efficacy and safety of a single dose of polyhexamethylene biguanide gynaecologic solution versus a seven-dose regimen of vaginal clindamycin cream in patients with bacterial vaginosis.

OBJECTIVE: At the present the clinical treatment of choice of bacterial vaginosis (BV) is the use of systemic or local metronidazole or clindamycin. Aim of the study was to evaluate the efficacy and tolerability of a single dose of gynaecologic solution, Polyhexamethylene Biguanide (PHMB), Monogin, in the treatment of BV in comparison to a 7-days treatment with clindamycin vaginal cream. STUDY DESIGN: This multicenter, randomized, single-blind, parallel-group study enrolled 740 patients with BV infections. Treatment consisted of either a single intravaginal dose of PHMB or 7 daily doses of Clindamycin. Efficacy and safety were assessed 21-30 days after the start of treatment. The efficacy endpoints were Investigator Cure, Clinical Cure (a composite of all 4 Amsel's criteria and investigator Cure), Nugent Cure (Nugent score < 4), and therapeutic cure (a composite of clinical cure and Nugent Cure). Resolution of individual Amsel's criteria was also evaluated. Any adverse event of the treatment has been monitored throughout the study. RESULTS: No significant differences has been reported in cure rates between the PHMB and Clindamycin treatment groups in Investigator Cure (P = 0.702), Clinical Cure (P = 0.945), Nugent Cure (P = 0.788), or Therapeutic Cure (P = 0.572). Results were also similar for 3 of 4 and 2 of 4 Amsel's criteria and for each individual Amsel's criterion (all P-values > 0.200). Ninety-five percent confidence intervals for each endpoint were consistent with equivalence between the 2 products. There was no significant difference between the treatment groups in the incidence of treatment-emergent adverse events (P = 0.386). CONCLUSIONS: A single dose, of PHMB gynaecologic solution (Monogin) is equivalent in safety and efficacy to a 7-dose regimen of Clindamycin vaginal cream in the treatment of bacterial vaginosis. Futhermore the compliance as been reported to be higher for the single-dose treatment with PHMB than with 7-days treatment with Clindamycin.

Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS.

Oligomenorrhea and polycystic ovaries in women are one of the most important causes of the high incidence of ovulation failure. This is linked, perhaps, to insulin resistance and related metabolic features. A small number of reports show that myo-inositol improves ovarian function, but in these trials the quality of evidence supporting ovulation is suboptimal. Furthermore, few of them have been placebo-controlled. The aim of our study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. Of the 92 patients randomized, 47 received 400 mcg folic acid as placebo, and 45 received myo-inositol plus folic acid (4 g myo-inositol plus 400 mcg folic acid). The ovulation frequency assessed by the ratio of luteal phase weeks to observa-tion weeks was significantly (P < 0.01) higher in the treated group (25%) compared with the placebo (15%), and the time to first ovulation was significantly (P < 0.05) shorter [24.5 d; 95% confidence interval (CI), 18, 31; compared with 40.5 d; 95% CI, 27, 54]. The number of patients failing to ovulate during the placebo-treatment period was higher (P < 0.05) in the placebo group, and the majority of ovulations were characterized by normal progesterone concentrations in both groups. The effect of myo-inositol on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the myo-inositol group. A significant increase in circulating high-density lipoprotein was observed only in the myo-inositol-treated group. Metabolic risk factor benefits of myo-inositol treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). After 14-wk myo-inositol or placebo therapy, no change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded. There was an inverse relationship between body mass and treatment efficacy. In fact a significant weight loss (and leptin reduction) (P < 0.01) was recorded in the myo-inositol group, whereas the placebo group actually increased weight (P < 0.05). These data support a beneficial effect of myo-inositol in women with oligomenorrhea and polycystic ovaries in improving ovarian function.

[Treatment of uterine fibromyoma with bilateral uterine artery embolization: state of the art]. / Trattamento di fibromioma dell'utero mediante embolizzazione bilaterale dell'arteria uterina. Stato dell'arte.

Uterine fibroids are common tumors of the female pelvis. Uterine artery embolization (UAE) is a minimally invasive alternative procedure in appropriate candidates to conventional myomectomy and hysterectomy for symptomatic uterine leiomyoma, reducing or eliminating leiomyoma-related symptoms of bleeding, bulk, and/or pain. In order to completely block the arterial blood supply to the fibroid, UAE is typically performed in both uterine arteries. At 1 year follow-up, the uterus may shrink by up to 55%, however, a re-growth of the fibroid may occur. The rate of major complications and amenorrhea following this procedure is low, ranging in most series from 1% to 3.5% and 1% to 7%, respectively. Nevertheless, the rate of amenorrhea in women over 45 seems to be higher. Women who wish to become pregnant should be cautioned about potential complications during pregnancy. Despite the lack of controlled studies that compared UAE with conventional surgery, and despite limited extended outcome data, UAE has gained rapid acceptance, primarily because this procedure preserves the uterus, is less invasive, and has less short-term morbidity than most surgical options. This review focuses on recent publications evaluating UAE and concludes that it is a safe treatment option, providing substantial improvement in both health-related quality of life and symptom control for most patients, with a very low rate of major complications. Any centre that offers UAE should adhere to published clinical guidelines, maintain ongoing assessment of quality improvement measures, and observe strict criteria to obtain procedural privileges. The gynecologist is likely to be the primary initial consultant to patients who present with myomas symptoms. Therefore, they must be familiar with the indications, exclusions, outcome expectations, and complications of UAE. When hysterectomy is the only option, UAE should be seriously taken into consideration. At this particular moment in time, data are needed from randomized controlled trials comparing UAE with surgical procedures. Current efforts to provide prospective objective assessment of treatment outcomes and complications after UAE will help to optimize women options and clinical guidelines.

[Tocolysis: which are the benefits?]. / Qual é il reale beneficio dell'utilizzo dei tocolitici?

Spontaneous preterm labor is still a major problem in perinatal medicine and it is associated to overwhelming risks of neonatal morbidity and mortality. Delaying delivery for hours, days or sometimes weeks may greatly reduce the short- and long-term perinatal morbidity improving fetal maturity of several organs and systems. Inhibition of uterine contractions may in fact allow to take advantage of the prenatal administration of glucocorticosteroids, which have been shown to reduce the incidence and severity of newborn respiratory distress syndrome. Moreover, delaying delivery may allow the transfer in utero to a maternity attached to a neonatal intensive care unit, therefore guaranteeing the best care for the preterm newborn. Every day gained between 22 and 28 weeks gestation increases survival by 3%. However, since most of preterm deliveries happened to be after 29 weeks, newborn survival is a secondary issue while the main aim of delaying labor in these cases is to improve the function of fetal systems and to try to understand if it is the case of prolonging pregnancy balancing risks of a hostile intrauterine environment towards the possible complications of a premature extrauterine life.

The changing role of progesterone in preterm labour.

Progesterone is an essential hormone in the process of reproduction. It is involved in the menstrual cycle, implantation and is essential for pregnancy maintenance. Although the pharmacokinetics and pharmacodynamics of progesterone have been well studied, and since 1935 it has been synthesised and is now available commercially, its use in the pathophysiology of pregnancy remains controversial. One of these concerns is the way in which the hormone is administered, with parenteral use proving the best way to obtain optimal plasma levels. Another concern is the paucity of randomised controlled trials and the different dosages and populations studied. As a result, the therapeutic application of progesterone in pregnancy is restricted to the prevention and treatment of threatened miscarriage, recurrent miscarriage and preterm birth. Progesterone is efficacious when continuation of pregnancy is hampered by immunological factors, luteinic and neuroendocrine deficiencies and myometrial hypercontractility. This may explain the reduction in the incidence of preterm birth in high risk pregnant women using high-dosage prophylactic progesterone.