Increased Vasoactive Intestinal Peptide (VIP) in polycystic ovary syndrome patients undergoing IVF.

Introduction: Polycystic ovary syndrome (PCOS) is a common multifactorial and polygenic disorder of the endocrine system, affecting up to 20% of women in reproductive age with a still unknown etiology. Follicular fluid (FF) represents an environment for the normal development of follicles rich in metabolites, hormones and neurotransmitters, but in some instances of PCOS the composition can be different. Vasoactive intestinal peptide (VIP) is an endogenous autonomic neuropeptide involved in follicular atresia, granulosa cell physiology and steroidogenesis. Methods: ELISA assays were performed to measure VIP and estradiol levels in human follicular fluids, while AMH, FSH, LH, estradiol and progesterone in the plasma were quantified by chemiluminescence. UHPLC/QTOF was used to perform the untargeted metabolomic analysis. Results: Our ELISA and metabolomic results show: i) an increased concentration of VIP in follicular fluid of PCOS patients (n=9) of about 30% with respect to control group (n=10) (132 ± 28 pg/ml versus 103 ± 26 pg/ml, p=0,03) in women undergoing in vitro fertilization (IVF), ii) a linear positive correlation (p=0.05, r=0.45) between VIP concentration and serum Anti-Müllerian Hormone (AMH) concentration and iii) a linear negative correlation between VIP and noradrenaline metabolism. No correlation between VIP and estradiol (E2) concentration in follicular fluid was found. A negative correlation was found between VIP and noradrenaline metabolite 3,4-dihydroxyphenylglycolaldehyde (DOPGAL) in follicular fluids. Conclusion: VIP concentration in follicular fluids was increased in PCOS patients and a correlation was found with noradrenaline metabolism indicating a possible dysregulation of the sympathetic reflex in the ovarian follicles. The functional role of VIP as noradrenergic modulator in ovarian physiology and PCOS pathophysiology was discussed.

Electro-Metabolic Coupling of Cumulus-Oocyte Complex.

Oocyte-cumulus cell interaction is essential for oocyte maturation and competence. The bidirectional crosstalk network mediated by gap junctions is fundamental for the metabolic cooperation between these cells. As cumulus cells exhibit a more glycolytic phenotype, they can provide metabolic substrates that the oocyte can use to produce ATP via oxidative phosphorylation. The impairment of mitochondrial activity plays a crucial role in ovarian aging and, thus, in fertility, determining the success or failure of assisted reproductive techniques. This review aims to deepen the knowledge about the electro-metabolic coupling of the cumulus-oocyte complex and to hypothesize a putative role of potassium channel modulators in order to improve fertility, promote intracellular Ca2+ influx, and increase the mitochondrial biogenesis and resulting ATP levels in cumulus cells.

Oxytocin augmentation and neurotransmitters in prolonged delivery: An experimental appraisal.

The uterus is a highly innervated organ, and during labor, this innervation is at its highest level. Oxytocinergic fibers play an important role in labor and delivery and, in particular, the Lower Uterine Segment, cervix, and fundus are all controlled by motor neurofibers. Oxytocin is a neurohormone that acts on receptors located on the membrane of the smooth cells of the myometrium. During the stages of labor and delivery, its binding causes myofibers to contract, which enables the fundus of the uterus to act as a mediator. The aim of this study was to investigate the presence of oxytocinergic fibers in prolonged and non-prolonged dystocic delivery in a cohort of 90 patients, evaluated during the first and second stages of labor. Myometrial tissue samples were collected and evaluated by electron microscopy, in order to quantify differences in neurofibers concentrations between the investigated and control cohorts of patients. The authors of this experiment showed that the concentration of oxytocinergic fibers differs between non-prolonged and prolonged dystocic delivery. In particular, in prolonged dystocic delivery, compared to non-prolonged dystocic delivery, there is a lower amount of oxytocin fiber. The increase in oxytocin appeared to be ineffective in patients who experienced prolonged dystocic delivery, since the dystocic labor ended as a result of the altered presence of oxytocinergic fibers detected in this group of patients.

European guidelines on perinatal care: corticosteroids for women at risk of preterm birth.

of recommendationsCorticosteroids should be administered to women at a gestational age between 24+0 and 33+6 weeks, when preterm birth is anticipated in the next seven days, as these have been consistently shown to reduce neonatal mortality and morbidity. (Strong-quality evidence; strong recommendation). In selected cases, extension of this period up to 34+6 weeks may be considered (Expert opinion). Optimal benefits are found in infants delivered within 7 days of corticosteroid administration. Even a single-dose administration should be given to women with imminent preterm birth, as this is likely to improve neurodevelopmental outcome (Moderate-quality evidence; conditional recommendation).Either betamethasone (12 mg administered intramuscularly twice, 24-hours apart) or dexamethasone (6 mg administered intramuscularly in four doses, 12-hours apart, or 12 mg administered intramuscularly twice, 24-hours apart), may be used (Moderate-quality evidence; Strong recommendation). Administration of two "all" doses is named a "course of corticosteroids".Administration between 22+0 and 23+6 weeks should be considered when preterm birth is anticipated in the next seven days and active newborn life-support is indicated, taking into account parental wishes. Clear survival benefit has been observed in these cases, but the impact on short-term neurological and respiratory function, as well as long-term neurodevelopmental outcome is still unclear (Low/moderate-quality evidence; Weak recommendation).Administration between 34 + 0 and 34 + 6 weeks should only be offered to a few selected cases (Expert opinion). Administration between 35+0 and 36+6 weeks should be restricted to prospective randomized trials. Current evidence suggests that although corticosteroids reduce the incidence of transient tachypnea of the newborn, they do not affect the incidence of respiratory distress syndrome, and they increase neonatal hypoglycemia. Long-term safety data are lacking (Moderate quality evidence; Conditional recommendation).Administration in pregnancies beyond 37+0 weeks is not indicated, even for scheduled cesarean delivery, as current evidence does not suggest benefit and the long-term effects remain unknown (Low-quality evidence; Conditional recommendation).Administration should be given in twin pregnancies, with the same indication and doses as for singletons. However, existing evidence suggests that it should be reserved for pregnancies at high-risk of delivering within a 7-day interval (Low-quality evidence; Conditional recommendation). Maternal diabetes mellitus is not a contraindication to the use of antenatal corticosteroids (Moderate quality evidence; Strong recommendation).A single repeat course of corticosteroids can be considered in pregnancies at less than 34+0 weeks gestation, if the previous course was completed more than seven days earlier, and there is a renewed risk of imminent delivery (Low-quality evidence; Conditional recommendation).

European Guidelines on Perinatal Care - Oxytocin for induction and augmentation of labor[Formula: see text].

OF RECOMMENDATIONS1. Oxytocin for induction or augmentation of labor should not be started when there is a previous scar on the body of the uterus (such as previous classical cesarean section, uterine perforation or myomectomy when uterine cavity is reached) or in any other condition where labor or vaginal delivery are contraindicated. (Moderate quality evidence +++-; Strong recommendation).2. Oxytocin should not be started before at least 1 h has elapsed since amniotomy, 6 h since the use of dinoprostone (30 min if vaginal insert) and 4 h since the use of misoprostol (Low quality evidence ++- -; Moderate recommendation).3. Cardiotocography (CTG) should be performed and a normal pattern without tachysystole should be documented for at least 30 min before oxytocin is used. Continuous CTG, with adequate monitoring of both fetal heart rate and uterine contractions, should be maintained for as long as oxytocin is used, and thereafter until delivery (Low ++- - to moderate +++- quality evidence; Strong recommendation).4. For labor induction, at least 1-h should be allowed after amniotomy before oxytocin infusion is started, to evaluate whether adequate uterine contractility has meanwhile ensued. For augmentation of labor, if the membranes are intact and there are conditions for a safe amniotomy, the latter should be considered before oxytocin is started (Very low quality evidence +- --; Weak recommendation).5. Oxytocin should be administered intravenously using the following regimen: 5 IU oxytocin diluted in 500 mL of 0.9% normal saline (NaCl) (each mL contains 10 mIU of oxytocin), in an infusion pump at increasing rates, as shown in Table 1, until a frequency of 3-4 contractions per 10 min is reached, a non-reassuring CTG pattern ensues, or maximum rates are reached (Low quality evidence ++ - -; Strong recommendation). If the frequency of contractions exceeds 5 in 10 min, the infusion rate should be reduced, even if a normal CTG pattern is present. With a non-reassuring CTG pattern, urgent clinical assessment by an obstetrician is indicated, and strong consideration should be given to reducing or stopping the oxytocin infusion. The minimal effective dose of oxytocin should always be used. (Low ++- - to Moderate +++- - quality evidence; Strong recommendation).[Table: see text]6. Use of oxytocin for induction and augmentation of labor should be regularly audited (Low quality evidence ++--; Strong recommendation).

European guidelines on perinatal care- Peripartum care Episiotomy.

OF RECOMMENDATIONS1. Episiotomy should be performed by indication only, and not routinely (Moderate quality evidence +++-; Strong recommendation). Accepted indications for episiotomy are to shorten the second stage of labor when there is suspected fetal hypoxia (Low quality evidence ++-; Weak recommendation); to prevent obstetric anal sphincter injury in vaginal operative deliveries, or when obstetric sphincter injury occurred in previous deliveries (Moderate quality evidence +++-; Strong recommendation)2. Mediolateral or lateral episiotomy technique should be used (Moderate quality evidence +++-; Strong recommendation). Labor ward staff should be offered regular training in correct episiotomy techniques (Moderate quality evidence +++-; Strong recommendation).3. Pain relief needs to be considered before episiotomy is performed, and epidural analgesia may be insufficient. The perineal skin needs to be tested for pain before an episiotomy is performed, even when an epidural is in place. Local anesthetics or pudendal block need to be considered as isolated or additional pain relief methods (Low quality evidence ++-; Strong recommendation).4. After childbirth the perineum should be carefully inspected, and the anal sphincter palpated to identify possible injury (Moderate quality evidence +++-; Strong recommendation). Primary suturing immediately after childbirth should be offered and a continuous suturing technique should be used when repairing an uncomplicated episiotomy (High quality evidence ++++; Strong recommendation).

Subspecialty training in Europe: a report by the European Network of Young Gynaecological Oncologists.

BACKGROUND: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. METHODOLOGY: National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. RESULTS: National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. CONCLUSION: Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.