Marco Noventa

Update on Raloxifene: Mechanism of Action, Clinical Efficacy, Adverse Effects, and Contraindications

Raloxifene is the only selective estrogen receptor modulator approved for long-term treatment in the prevention of osteoporotic fractures and for the reduction of invasive breast cancer risk in postmenopausal women. The demonstrated beneficial effects on bone and mammalian tissue led clinical and molecular research to focus mainly on these organs, giving less attention to all other systemic effects. The aim of this review was to evaluate all described systemic effects of raloxifene, investigating its molecular and tissutal mechanism of action. A literature research was carried out in electronic databases MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library in interval time between 2000 and 2012. Outcomes were considered in relation to positive/adverse effects concerning bone metabolism, lipid metabolism, coagulation pattern, menopausal symptoms, breast cancer onset, and endometrial cancer onset. Raloxifene acts as an estrogen agonist or antagonist depending on the tissue. This feature is related to specific actions on at least 2 distinct estrogen receptors, whose proportions vary according to tissue type. Raloxifene is a drug for the treatment of osteoporosis and for the prevention of estrogen receptor–positive breast cancer because it guarantees a safety profile on the endometrium. Raloxifene is furthermore an effective therapy in women with increased levels of plasma cholesterol. Raloxifene treatment shifts the coagulation pattern toward prothrombosis, and the patients should be exhaustively informed about the risks associated with therapy. Raloxifene does not show to affect memory and cognition. Finally, it is noteworthy that quality-of-life studies demonstrated some favorable effects of raloxifene. Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to identify the mechanism of action of raloxifene, treat the adverse effects of raloxifene, prescribe raloxifene for patients with osteoporosis, to prevent estrogen receptor–positive breast cancer, as effective therapy in women with osteoporosis and concomitant increased levels of plasma cholesterol, and select the appropriate patients for raloxifene treatment using the patient’s medical history and risk of thromboembolism.

Magnetic Resonance-Guided Focused Ultrasound Myomectomy: Safety, Efficacy, Subsequent Fertility and Quality-of-Life Improvements, A Systematic Review.

We performed a systematic review about studies reporting data of myomectomy performed by magnetic resonance-guided focused ultrasound (MRgFUS) technique in order to define its safety, feasibility, indications, complications, and impact on uterine fibroid symptom and health-related quality of life (UFS-QOL) and fertility. Outcomes were considered according to fibroids shrinkage, nonperfused volume (NPV), NPV ratio, and uterine fibroid symptoms assessed with UFS-QOL questionnaire (baseline 3, 4, 6, and 12 months). We analyzed 38 eligible studies reporting outcomes about 2500 patients (mean age 43.67 years). The MRgFUS results a safe, efficient, and cost-effective minimal invasive technique for treatment of uterine fibroids. Increasing experience, device improvements, and availability for a larger number of patients are enhancing the outcomes, while the obstetrical ones should be more extensively explored. The MRgFUS could be considered as a minimal invasive alternative to traditional surgical or radiological procedures for the treatment of symptomatic uterine myomas improving both QOL and subsequent fertility.

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

PurposeIn 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.MethodsA 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”.Results10,331 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.ConclusionNo 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.

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.

Radical trachelectomy: The first step of fertility preservation in young women with cervical cancer (Review)

Radical trachelectomy (RT) can be performed vaginally or abdominally (laparotomic, laparoscopic or robotic). The aim of this systematic review was to compare all techniques in terms of surgical complications, disease recurrence and subsequent fertility/pregnancy outcomes. A total of 1293 RTs were analyzed (FIGO-stage: IA1–IIA). The most frequent surgical complications do not differ from the ones of radical hysterectomy. The recurrence risk is approximately 3% (range 0–16.8%). The majority of women conceive spontaneously: 284 pregnancies with 173 live births. The most frequent pregnancy complication was miscarriage and chorioamnionitis. RT appears to be a safe option for eligible women who intend to maintain their future pregnancy desire.

Fertility rate and subsequent pregnancy outcomes after conservative surgical techniques in postpartum hemorrhage: 15 years of literature

OBJECTIVE To investigate the most appropriate surgical technique for optimizing hemostasis and preservation of subsequent fertility after postpartum hemorrhage (PPH). DESIGN Systematic review of the literature. SETTING Not applicable. PATIENT(S) None. INTERVENTION(S) Review of MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library. MAIN OUTCOME MEASURE(S) Comparison of the effectiveness of conservative surgical techniques, separately or together, with respect to success rate (ability to stop bleeding and preserve the uterus), fertility rate (subsequent pregnancies or the return of regular menstrual cycles), complication rate of the procedure, and the outcomes of subsequent pregnancies in terms of type of delivery and eventual delivery complications. RESULT(S) Compressive sutures and vessel embolization may be considered life-saving procedures by achieving the best hemostatic efficacy. Data on restoration of menses and pregnancy rates after these procedures are limited by short-term follow-up and by the paucity of studies, especially for vascular ligation. CONCLUSION(S) Pelvic vessel embolization and compressive sutures are associated with high rates of restoration of regular menses and successive pregnancies, even if the former is burdened by an increased rate of placental disorders and fetal growth restriction and the latter by an increased risk of cesarean deliveries and PPH recurrence. Randomized trials would be desirable to define the best management of PPH.

Levonorgestrel Intrauterine System in Adjuvant Tamoxifen Treatment Balance of Breast Risks and Endometrial Benefits—Systematic Review of Literature

Levonorgestrel intrauterine system (LNG-IUS) is used in patients with breast patients taking tamoxifen (TAM) to prevent endometrial proliferation. The benefits (on endometrium), the side effects (on breast), and the patients suitable for this treatment are not still clear. Aim of this systematic review is to define the breast risks and endometrial benefits in TAM-treated women using Mirena and to define which patients could benefit from LNG-IUS use. In all, 3 studies on LNG-IUS effects on endometrium in TAM-treated women and 4 studies on breast cancer recurrence were selected for the study. All studies described a reduction in benign endometrial pathologies among Mirena users, but controversial data showed malignant disease and breast cancer recurrence. So it is mandatory to define hormonal status before TAM treatment. In selected patients Mirena was proven to protect endometrium. Perspective clinical trials on Mirena pharmacological features are necessary to establish whether systemic levels of progesterone could increase breast cancer recurrence in such patients.

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

Abstract 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. Chinese abstract 在体外受精（IVF）周期中黄体期的性激素浓度会产生异常，这是获得高妊娠率的一个重要的限制因素。尽管证据表明IVF周期后的黄体支持（LPS）是有益的，但在给予孕酮（PG）的最佳剂量和给药方式，补充雌二醇（E2）的优点，以及哪种IVF方案会比其它LPS方案获得更多益处等方面，尚未达成一致意见。本研究旨在依据促排卵方案、诱发排卵时的E2浓度、取卵时的子宫内膜厚度以及患者年龄，评估可获得最高临床/继续妊娠率的最佳LPS（低剂量PG，高剂量PG，高剂量PG加补充E2）。我们对360名正在进行IVF的女性（180名进行长GnRH激动剂方案，90名给予短GnRH激动剂方案，90名给予短GnRH拮抗剂方案）实施了随机试验，仅用重组卵泡刺激素促排卵。数据显示，高剂量PG比低剂量PG更能提高临床妊娠率和继续妊娠率。短GnRH拮抗剂方案必须补充E2，在所有方案中当E2max＜5nmol/l和子宫内膜厚度＜10mm时强烈建议补充E2。对于长GnRH激动剂方案以及年龄＞35岁的患者，补充E2是否真正有益仍有争议，且需要进一步证实。

HPV-DNA sperm infection and infertility: from a systematic literature review to a possible clinical management proposal.

The objectives of this study were to investigate the implications of human papillomavirus (HPV) sperm infection on male fertility, impairment of sperm parameters, and possible alteration of sperm nuclear status and to identify a possible effective management of infertile men with HPV sperm infection. We employed a systematic review and clinical management proposal at the Centers for Reproductive and Health care for treating infertile male patients with HPV infection. Literature search was carried out in electronic databases in the last two decades. We focused our attention on: (i) HPV sperm prevalence (ii) HPV‐related alteration of sperm parameters; (iii) molecular mechanisms of HPV semen infection and infertility. The main outcome measures were HPV prevalence in infertile male patients and semen parameters. The prevalence of HPV sperm infection ranges between 2 and 31% in men from general population and between 10 and 35.7% in men affected by unexplained infertility. The presence of HPV in semen is associated with an impairment of sperm motility and the presence of anti‐sperm antibodies. The molecular mechanisms underlying impairment of sperm motility apparatus need further evaluations. A greater attention should be applied to assess HPV sperm infection, particularly in men undergoing assisted reproduction techniques cycle for male infertility or sperm banking. It would be useful to perform HPV test and fluorescent in situ hybridization analysis for HPV in semen from these patients both at first admission, to define the possible presence and localization of semen infection, and after 6 months, to assess the possible virus clearance retrieval on normal sperm parameters.

Women's choice of positions during labour: return to the past or a modern way to give birth? A cohort study in Italy.

Background. Childbirth medicalization has reduced the parturients opportunity to labour and deliver in a spontaneous position, constricting her to assume the recumbent one. The aim of the study was to compare recumbent and alternative positions in terms of labour process, type of delivery, neonatal wellbeing, and intrapartum fetal head rotation. Methods. We conducted an observational cohort study on women at pregnancy term. Primiparous women with physiological pregnancies and single cephalic fetuses were eligible for the study. We considered data about maternal-general characteristics, labour process, type of delivery, and neonatal wellbeing at birth. Patients were divided into two groups: Group-A if they spent more than 50% of labour in a recumbent position and Group-B when in alternative ones. Results. 225 women were recruited (69 in Group-A and 156 in Group-B). We found significant differences between the groups in terms of labour length, Numeric Rating Scale score and analgesia request rate, type of delivery, need of episiotomy, and fetal occiput rotation. No differences were found in terms of neonatal outcomes. Conclusion. Alternative maternal positioning may positively influence labour process reducing maternal pain, operative vaginal delivery, caesarean section, and episiotomy rate. Women should be encouraged to move and deliver in the most comfortable position.