Ultrasound-guided embryo transfer: summary of the evidence and new perspectives. A systematic review and meta-analysis.

Despite the purported advantages of ultrasound guidance during embryo transfer, and the large number of clinical trials published on this topic, recommendations for the use of this technique in daily clinical practice are still under debate. We designed a meta-analysis based exclusively on evidence from published randomized controlled trials, with the aim of analysing the effect of trans-abdominal ultrasound guidance during embryo transfer versus clinical touch and of transvaginal ultrasound guidance (TV-US) versus the trans-abdominal approach on IVF outcomes. On the basis of 14 randomized trials, we found a moderate quality of evidence supporting the beneficial effects of transabdominal guidance during embryo transfer compared with conventional clinical touch in clinical pregnancy and ongoing or live birth rates. No significant differences were found in miscarriage and ectopic pregnancy rate, with low or very low quality of evidence, respectively. On the basis of three randomized trials, we found the quality of evidence supporting the equivalence of transvaginal versus transabdominal approach in clinical pregnancy and ongoing or live birth rates to be low. Finally, larger randomized controlled trials are necessary to explore the possible benefits of TV-US, three-dimensional ultrasound imaging modality, and uterine length measurement before transfer.

Oxidative Stress during Ovarian Torsion in Pediatric and Adolescent Patients: Changing The Perspective of The Disease.

Among the different causes of gynecological acute pelvic pain, ovarian torsion represents a surgical emergency. It is a rare case in the pediatric/adolescent aged group that must be included in the differential diagnosis of any girl with abdominal pain or pelvic/abdominal mass. Current recommendations suggest that laparoscopic detorsion should be performed in order to preserve the integrity of the ovaries and fertility, although oophoropexy may be considered in case of severe necrosis. Nevertheless, maintaining the circulation of the ovary after detorsion deteriorates the tissue injury and leads to a pathologic process called ischaemia/reperfusion (I/R) injury, which is characterized by oxidative stress. During the detorsion process, an excess amount of molecular oxygen is supplied to the tissues, and reactive species of oxygen (ROS) such as superoxide radical (O2 (-)), hydrogen peroxide (H2O2), hydroxyl radical (OH•), as well as reactive nitrogen species (RNS) are produced in excess. ROS, RNS and their toxic products cause DNA damage and lipid peroxidation in the cellular and mitochondrial membranes, leading to cell death. In spite of attention on this topic, currently there is no shared and clear evidence about the use of anti-inflammatory and antioxidant agents to prevent I/R damage after laparoscopic ovarian detorsion. Considering this element, future research should aim to develop shared protocols for the clinical use (route of application, dosage and time of application) of antioxidants after laparoscopic management of this condition.

Coexistence of adenomyosis and endometrioid endometrial cancer: Role in surgical guidance and prognosis estimation.

The aim of the current study was to diagnose the concomitant presence of adenomyosis (AM) in endometrioid endometrial cancer (EEC) in order to evaluate its value as an oncological prognostic marker. A retrospective analysis of 289 patients diagnosed with EEC who underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic-lymphadenectomy was conducted. The total cohort included 37 patients in Group A (those with concomitant AM and EEC) and 252 patients in Group B (those affected only by EEC). The following factors were evaluated: Presence or absence of AM, tumor grade, depth of myometrial invasion, tumor size, lymphovascular space involvement, lymph node status, peritoneal cytology, concomitant detection of endometrial atypical-hyperplasia or polypoid endometrial features and tumor stage according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Uterine examination of different sections of uterine cervix, corpus, myomas and cervical or endometrial polyps was performed. The diagnosis of AM was confirmed when the distance between the lower border of the endometrium and the foci of the endometrial glands and stroma was >2.5 mm. Parametric and nonparametric statistical tests were performed when possible; continuous variables were analyzed using a Student's t-test, and categorical variables were analyzed by the χ2 test or Fisher's exact test. The association between FIGO stage and group was determined to be significant: 83.8% of Group A patients were categorized as FIGO stage I, vs. 68.7% of Group B patients. In addition, Group A was associated with lower grades in FIGO stage, myometrial invasion, lymphovascular space involvement, lymph node involvement and tumor size. The findings suggest that the intraoperative evaluation of the presence of AM in patients with EEC may aid surgeons in estimating oncological risk and in selecting the most appropriate surgical treatment.

An Update on Maternal Hydration Strategies for Amniotic Fluid Improvement in Isolated Oligohydramnios and Normohydramnios: Evidence from a Systematic Review of Literature and Meta-Analysis.

OBJECTIVE: Several trials aimed at evaluating the efficacy of maternal hydration (MH) in increasing amniotic-fluid-volume (AFV) in pregnancies with isolated oligohydramnios or normohydramnos have been conducted. Unfortunately, no evidences support this intervention in routine-clinical-practice. The aim of this systematic-literature-review and meta-analysis was to collect all data regarding proposed strategies and their efficacy in relation to each clinical condition for which MH-therapy was performed with the aim of increasing amniotic-fluid (AF) and improving perinatal outcomes. MATERIALS AND METHODS: A systematic literature search was conducted in electronic-database MEDLINE, EMBASE, ScienceDirect and the Cochrane-Library in the time interval between 1991 and 2014. Following the identification of eligible trials, we estimated the methodological quality of each study (using QADAS-2) and clustered patients according to the following outcome measures: route of administration (oral versus intravenous versus combined), total daily dose of fluids administered (<2000 versus >2000), duration of hydration therapy: (1 day, >1 day but <1 week, >1 week), type of fluid administered (isotonic versus hypotonic versus combination). RESULTS: In isolated-oligohydramnios (IO), maternal oral hydration is more effective than intravenous hydration and hypotonic solutions superior to isotonic solutions. The improvement in AFV appears to be time-dependent rather than daily-dose dependent. Regarding normohydramnios pregnancies, all strategies seem equivalent though the administration of hypotonic-fluid appears to have a slightly greater effect than isotonic-fluid. Regarding perinatal outcomes, data is fragmentary and heterogeneous and does not allow us to define the real clinical utility of MH. CONCLUSIONS: Available data suggests that MH may be a safe, well-tolerated and useful strategy to improve AFV especially in cases of IO. In view of the numerous obstetric situations in which a reduced AFV may pose a threat, particularly to the fetus, the possibility of increasing AFV with a simple and inexpensive practice like MH-therapy may have potential clinical applications. Considering the various strategies of maternal hydration implemented in the treatment of IO, better results were observed when treatment was based on a combination of intravenous (for a period of 1 day) and oral (for a period of at least 14 days) hypotonic fluids (≥2000ml).

Quality of life in patients affected by endometrial cancer: comparison among laparotomy, laparoscopy and vaginal approach.

The aim of this study is to verify if the surgical approach (laparoscopy/laparotomy/vaginal) in stage-I endometrial cancer treatment, may have effects on intra- and post-operative outcomes and on the patient's quality of life. The study group consisted of patients with histological diagnosis of type-I endometrial adenocarcinoma, stage-I. They were divided into three groups according to surgical approach chosen (laparotomic/laparoscopic/vaginal). Every patient answered a telephone health survey (SF-36) at 30 and 180 days post-surgery. Surgical-operating times, hospitalization length and short/long-term complications after surgery were also compared. The SF-36 survey revealed a better performance status in patients who underwent laparoscopy as compared to those who received laparotomy or vaginal surgery. We found significantly better results considering General Health, Physical Functioning, Role-Physical and Bodily Pain in the laparoscopy group after 30 and 180 days. Patients who underwent laparoscopy had significantly shorter hospitalization and less post-operative complications even if laparoscopy required significantly longer surgical-operating times compared to vaginal surgery. Our data confirm the superiority of the laparoscopic approach respect to the laparotomic and vaginal ones both in term of hospitalization length and post-operative complications.

Female stress urinary incontinence: clinical efficacy and satisfaction after transobturator adjustable tape sling. An observational longitudinal cohort study.

We performed an observational longitudinal cohort study on patients affected by stress urinary incontinence (SUI) and surgically treated with a transobturator adjustable tape sling (TOA) in order to evaluate this surgical procedure in terms of efficacy, safety, quality of life (QoL) improvement, and patient satisfaction. For all patients, we recorded: general features, preoperative SUI risk factors, obstetrics history, preoperative urodynamic tests, intraoperative/postoperative complications, number of postoperative sling regulations, postmicturition residue, and hospital stay. All patients were asked to complete the validated short version of the Urogenital Distress Inventory (UDI-6) questionnaire 18 months after discharge to evaluate the efficacy of the TOA system. We added 2 adjunctive items to the UDI-6 in order to evaluate patient satisfaction and QoL. All 77 surgical procedures were performed under locoregional anesthesia without complications. Postoperative TOA regulations were performed in 46.8% of patients immediately after the procedure and in 14.3% during hospitalization. Before discharge, postmicturition residue was negative in 67 cases and less than 50 cc in 10 cases. Mean hospital stay was 2.18 days. From the questionnaire evaluation, we found that after the procedure, 90.9% of patients showed a complete regression of urinary symptoms, 1.3% obtained considerable relief from preoperative symptoms, and 6.6% reported poor or absent symptom improvements; 75.3% of patients were totally satisfied and 5.2% totally disappointed. The possibility of modulating postoperative sling tension and reusing the surgical materials in association with short hospitalization as well as high patient satisfaction render TOA a safe, effective, and low-cost technique for the treatment of female SUI.

Borderline ovarian tumors and diagnostic dilemma of intraoperative diagnosis: could preoperative He4 assay and ROMA score assessment increase the frozen section accuracy? A multicenter case-control study.

The aim of our study was to assess the value of a preoperative He4-serum-assay and ROMA-score assessment in improving the accuracy of frozen section histology in the diagnosis of borderline ovarian tumors (BOT). 113 women presenting with a unilateral ovarian mass diagnosed as serous/mucinous BOT at frozen-section-histology (FS) and/or confirmed on final pathology were recruited. Pathologists were informed of the results of preoperative clinical/instrumental assessment of all patients. For Group_A patients, additional information regarding He4, CA125, and ROMA score was available (in Group_B only CA125 was known). The comparison between Group A and Group B in terms of FS accuracy, demonstrated a consensual diagnosis in 62.8% versus 58.6% (P: n.s.), underdiagnosis in 25.6% versus 41.4% (P<0.05), and overdiagnosis in 11.6% versus 0% (P<0.01). Low FS diagnostic accuracy was associated with menopausal status (OR: 2.13), laparoscopic approach (OR: 2.18), mucinous histotype (OR: 2.23), low grading (OR: 1.30), and FIGO stage I (OR: 2.53). Ultrasound detection of papillae (OR: 0.29), septa (OR: 0.39), atypical vascularization (OR: 0.34), serum He4 assay (OR: 0.39), and ROMA score assessment (OR: 0.44) decreased the probability of underdiagnosis. A combined preoperative assessment through serum markers and ultrasonographic features may potentially reduce the risk of underdiagnosis of BOTs on FS while likely increasing the concomitant incidence of false-positive events.

Male and couple fertility impairment due to HPV-DNA sperm infection: update on molecular mechanism and clinical impact--systematic review.

Recent evidences identify Human Papillomavirus (HPV) sperm infection as a possible cause of male and couple infertility. It acts through different mechanisms at various steps of human conception and early gestational development. We performed a systematic review to assess the role of HPV semen infection on male and couple infertility. Analysis of available and eligible data does not permit us to fund clear evidences about clinical impact of HPV infection on fertility, although sperm parameters impairment is the most widely recognized effect. Regarding biomolecular implications, the available data are often conflicting. More studies are required to define the role of HPV sperm infection in clinical practice. The great majority of evidences are obtained by in vitro studies and this fact represents a limitation for the clinical management of HPVDNA sperm infection. Understanding the biological significance of HPV-DNA semen infection could permit us to explain most of the idiopathic male and couple infertility, leading to a better management of infertile men and a better timing for sperm banking storage before ART cycles.

Assessment of tumor size as a useful marker for the surgical staging of endometrial cancer.

Accumulating evidence suggests that the estimation of tumor size may improve endometrial cancer treatment. We conducted an observational study aimed at elucidating the association between tumor size and other universally accepted prognostic factors in order to identify suitable preoperative parameters which can guide surgery in a subgroup of early corpus endometrial cancer. We found that when tumor size increased, both stage and grading were significantly increased. Tumor size was correlated with CA 125 serum values, node metastasis and peritoneal cytology status. Patients who have grade 1 or 2 endometrioid corpus cancer, myometrial invasion < 50% and ≤ 3 cm largest tumor diameter can only be treated with hysterectomy. The tumor largest diameter should be evaluated as a preoperative parameter that indicates patients who do not require lymphadenectomy.

Twin pregnancy after kidney transplantation: what's on? A case report and review of literature.

OBJECTIVE: To describe the maternal and neonatal outcome of a twin pregnancy in a renal transplant recipient patient and reviewe the current literature on this theme. METHODS: A case of 27 years old woman with a twin pregnancy arisen spontaneously in a renal transplant recipient from living donor characterized by an episode of slight anemia, mild hypertension, and a subsequent optimal maternal/neonatal outcome. During admission, the patient was treated with iron therapy, nifedipine, and methyldopa due to anemia and hypertension episodes. Strict monitoring of patient's blood and urinary parameters, ultrasound fetues evaluation, and fetal lung maturity induction was performed. RESULTS: Both anemia and hypertension were controlled through pharmacological intervention. During the second admission, the serum creatinine was 185 µmol/L and urine examination showed a proteinuria of 0.3 g/L. Ultrasound evaluation showed fetal wellness for both twin. Patient underwent caesarean section and gave birth to two healthy babies. CONCLUSIONS: It is necessary to define more strict criteria for the management of women with twin pregnancy and a history of renal transplantation to ensure the better maternal and neonatal outcome.

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.

Impact of Highly Active Antiretroviral Therapy on the Natural History of Cervical Precancerous Lesions: A 17-Year Institutional Longitudinal Cohort Study.

We performed an observational cohort study in order to assess the correlation between precancerous cervical lesions (cervical intraepithelial neoplasia [CIN]) and immunological state in human immunodeficiency virus (HIV)-positive women treated by highly active antiretroviral therapy (HAART). We analyzed 194 HIV-infected women referred to the Parma-Universitary Hospital for early detection of human papilloma virus-induced CINs. We analyzed cytology, colposcopy, and CIN degree according to HAART: group A untreated and group B treated. We compared the CD4+ count and viral load at the time of CIN onset and the time interval between diagnosis of HIV and the onset of CIN. Group A and group B showed homogeneous results for general features, CD4+ count, viral load, and Papanicolaou test features. Differences were not found in terms of histology and CD4+ value, viral load count, pharmacological treatment, years since the diagnosis of HIV, age, smoking, sexual promiscuity, previous intravenous narcotics abuse, prostitution, sexually transmitted diseases, ethnicity, and age at diagnosis. Histology and the clinical stage of HIV showed significant concordances between the high degree of cervical dysplasia and advanced stage of HIV disease.

High-risk human papillomavirus DNA test: could it be useful in low-grade cervical lesion triage? Five-year follow-up.

We conducted a retrospective, observational study in order to evaluate the role of high-risk human papillomavirus (hrHPV)-DNA test in patients with first diagnosis of low-grade squamous intraepithelial lesions (L-SILs).Patients were divided into group A, annual Papanicolaou test and hrHPV-DNA tests (167 patients) and group B, immediate colposcopy, followed by annual papanicolaou test and hrHPV-DNA tests (164 patients). We assessed sensitivity, specificity, negative predictive value (NPV), positive predictive value, positive-negative likelihood ratio of hrHPV-DNA test, and 5-year relative risk of cervical intraepithelial neoplasia grade 2 in hrHPV-DNA+. Colposcopy is still considered the best choice for women with L-SIL and hrHPV-DNA+ test. High sensitivity and NPV of hrHPV-DNA test permit to use it in the follow-up of L-SIL with a HPV-negative status, without necessity of referring to colposcopy.

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.

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.

Risk of preterm delivery associated with prior treatment of cervical precancerous lesion according to the depth of the cone.

The aim of this study was to evaluate the impact of the surgical excisional procedures for cervical intraepithelial neoplasia (CIN) treatment both on subsequent fertility (cervical factor) and pregnancy complication (risk of spontaneous preterm delivery). We retrospectively analyzed 236 fertile women who underwent conization for CIN. We included in the study 47 patients who carried on pregnancy and delivered a viable fetus. Patients were asked about postconization pregnancies, obstetrical outcomes, and a possible diagnosis of secondary infertility caused by cervical stenosis. We evaluated the depth of surgical excision, the timing between cervical conization and subsequent pregnancies, surgical technique, and maternal age at delivery. We recorded 47 deliveries, 10 cases of preterm delivery; 8 of them were spontaneous. The depth of surgical excision showed a statistically significant inverse correlation with gestational age at birth. The risk of spontaneous preterm delivery increased when conization depth exceeded a cut-off value of 1.5 cm. Our data do not demonstrated a relation between conization and infertility due to cervical stenosis.

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.