"To get the baby out off the hook": a prospective, longitudinal, multicenter, observational study about decision making in vacuum-assisted operative vaginal delivery.

BACKGROUND: Since operative vaginal delivery may be risky for women and might cause neonatal complications, the aim of this study is to assess appropriateness of the procedure. This is a prospective, longitudinal, multicenter, observational study and it was conducted in three Italian Obstetric Units (Pisa, Massa Carrara and Prato). All term pregnant women, either nulliparous and multiparous, with singleton pregnancy and a cephalic fetus, with spontaneous or induced labour, requiring vacuum-assisted delivery were enrolled. Indications to operative vaginal delivery were grouped as alterations of fetal cardiotocography (CTG) patterns, delay/arrest of second stage of labour or elective shortening of second stage of labour. A board consisting of five among authors evaluated appropriateness of the procedure. RESULTS: Overall, 466 women undergoing operative vaginal deliveries were included. Cardiotocography, classified as ACOG category 2 or 3 was the indication for vacuum assisted delivery in 253 patients (54.29%). Among these, 66 women (26.1%) had an operative vaginal delivery which was then considered to be inappropriate, while in 114 cases (45.1%) CTG traces resulted to be unreadable. CONCLUSION: Decision making process, which leads clinicians to go for operative vaginal delivery, is often influenced by shortness of time and complexity of the situation. Therefore, clinicians tend to intervene performing vacuum delivery without adopting critical analysis and without adequately considering the clinical situation. Operative vaginal delivery might be a risky procedure and should be performed only when clinically indicated and after adequate critical analysis.

Comparison of perioperative outcomes and technical features using da Vinci Si and Xi robotic platforms for early stages of endometrial cancer.

We directly compared perioperative outcomes and technical features between previous da Vinci Si and the newer Xi robotic platform during total hysterectomy plus salpingo-oophorectomy with or without lymphadenectomy for early-stage endometrial cancer. We retrospectively analyzed147 patients with histological confirmation of endometrial carcinoma stage IA: grade 1-2, 3 and stage IB: grade 1-2 who underwent surgery with da Vinci Si or Xi system between January 2016 and December 2018. Perioperative data, technical features and postoperative complications were considered. 91 patients underwent surgery with the Si system and 56 with the Xi system. Docking time using the Xi system was significantly shorter (p < 0.002), while overall operating time was similar. There were no significant differences in the number of harvested lymph nodes, conversion rate, mean hospital stay, complications, and technical aspects between the two groups. Our study detected similar perioperative outcomes and the trend toward shorter docking and operating time for Xi over Si robot.

PCOS and pregnancy: a review of available therapies to improve the outcome of pregnancy in women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common cause of female infertility affecting multiple aspects of a women's health. AREAS COVERED: The aim of this review is to summarize the existing evidence on the treatment of PCOS patients and to examine the actual available therapies to overcome the problem of infertility and improve the outcome of pregnancy. We analyse different treatment strategies such as lifestyle modification, bariatric surgery, insulin sensitizing agents, inositol, clomiphene citrate (CC), aromatase inhibitors, gonadotrophins, laparoscopic ovarian drilling, and assisted reproductive techniques (ART). EXPERT COMMENTARY: Lifestyle modification is the best initial management for obese PCOS patients seeking pregnancy and insulin sensitizing agents seem to have an important role in treating insulin resistance. Up to now, CC maintains a central role in the induction of ovulation and it has been confirmed as the first-line treatment; the use of gonadotrophins is considered the second-line in CC resistant patients; laparoscopic ovarian drilling is an alternative to gonadotrophins in patients who need laparoscopy for another reason. However, in anovulatory patients, ART represents the only possible alternative to obtain pregnancy. Larger and well-designed studies are needed to clarify the best way to improve the outcome of pregnancy in PCOS women.

Assisted reproductive technique in women of advanced fertility age.

Over the past four decades, the postponement of childbearing has continued to increase, significantly impacting the age of first-time mothers. Female age is the most significant factor influencing clinical outcome in in-vitro fertilization. To overcome the limits of the age-related decline of fertility is a challenge for fertility experts. In the decrease of fertility in late reproductive age, a lot of factors related with advancing women's age and general health can be considered, however the dominant regulator of this age-dependent loss of fertility is the ovary. The key factors in the ovarian aging are oxidative stress, abnormalities of the meiotic spindle, decrease of function and number of oocyte mitochondria, alteration of sirtuins and androgen deficiency. The aim of this review was to assess the main biological factors involved in the female reproductive ageing according to the recent literature, focusing on oocyte-dependent ones, as well as the possible therapeutic strategies in assisted reproductive technique.

Estrogen treatment in infertile women with premature ovarian insufficiency in transitional phase: a retrospective analysis.

PURPOSE: During the transitional phase of premature ovarian insufficiency (POI), sporadic resumption of ovulation is possible because of fluctuation of hormonal levels but the chance of spontaneous pregnancy is low, and the main perspective of childbearing in these women is egg donation or adoption. The purpose of the study was to verify whether treatment with estrogens in POI patients in transitional phase could reduce FSH levels and to evaluate if this pre-treatment could improve reproductive outcomes of in vitro fertilization (IVF). METHODS: Study patients (26) were administered with valerate estradiol 2 mg daily adding dihydrogesterone 10 mg daily during luteal phase for 3 months before IVF. Control group (26 patients) did not receive any pre-treatment. Ovarian stimulation was conducted in both groups with the same short GnRH-antagonist protocol. Clinical and laboratory data of patients were retrospectively analyzed. RESULTS: In the study group, 4/26 POI patients became spontaneously pregnant during pre-treatment. In the remaining patients, the mean level of FSH after the pre-treatment was significantly reduced compared with baseline. Levels of circulating estradiol on the day of hCG administration were significantly higher in the study group. The total number of MII oocytes retrieved and fertilized oocytes was significantly higher in the study group, as well as the number of embryos transferred for pickup and clinical pregnancy rate. CONCLUSIONS: Treatment with estrogens in infertile POI patients in transitional phase reduces circulating FSH levels, hence causing potential spontaneous conception. Moreover, in these patients, estrogen pre-treatment seems to improve IVF outcomes in a GnRH-antagonist short protocol compared to no pre-treatment.

Ovarian response to controlled ovarian stimulation in women with different polycystic ovary syndrome phenotypes.

Controlled ovarian stimulation (COH) in PCOS is a challenge for fertility expert both ovarian hyperstimulation syndrome (OHSS) and oocytes immaturity are the two major complication. Ovarian response to COH vary widely among POCS patients and while some patients are more likely to show resistance to COH, other experienced an exaggerated response. The aim of our study is to investigate a possible correlation between PCOS phenotypes and the variety of ovarian response to COH and ART outcomes in patients with different PCOS phenotypes. We retrospectively analyzed a total of 71 cycles performed in 44 PCOS infertile patients attending ART at Centre of Infertility and Assisted Reproduction of Pisa University between January 2013 and January 2016. Patientsundergoing IVF with GnRH-antagonist protocol and 150-225 UI/days of recombinant FSH; triggering was carried out using 250 mg of recombinant hCG or a GnRH analogous on the basis of the risk to OHSS. We observed that Phenotype B had a tendency to have a greater doses of gonadotropins used respect to all phenotypes. Phenotype A group showed a greater serum estrogen levels compared to all phenotypes groups, a greater number of follicles of diameter between 8-12 mm found by ultrasound on the day of triggering and a greater mean number of freeze embryo. Additionally serum AMH and antral follicles count (AFC) follow the same trend in the different phenotypes ad they were significantly higher in phenotype A and in phenotype D. In conclusion this study shows that the features of PCOS phenotypes reflect the variety of ovarian response to COH as well as the risks to develop OHSS. Serum AMH and AFC are related to the degree of ovulatory dysfunction making these 'added values' in identifying the different PCOS phenotypes. Phenotype A seems to be the phenotype with the higher risk to develop OHSS and the use of GnRH as a trigger seems to improve oocyte quality. To classify PCOS phenotype at diagnosis might help clinicians to identify patients at greater risk of OHSS, customize therapy and subsequently plan the trigger agent.

The role of robotics in the management of endometriosis.

The advent of robot-assisted laparoscopy (RAL) is an important innovation which has provided new perspectives for the treatment of endometriosis, and particularly of deep infiltrating endometriosis (DIE). RAL offers several technical advantages in the treatment of this complex disease, such as 3D view, tremor filtration and better surgical ergonomics, thus improving surgical performances without no increase in surgical time, blood loss, and intra- or postoperative complications, while also reducing the rate of conversion to laparotomy. Additionally, thanks to its reduced learning curve compared to conventional laparoscopy (CL), it facilitates the training of less experienced surgeons. For these reasons, DIE might be one of the best indications for RAL in gynecologic surgery. However, very few retrospective studies and small cases series, and only one randomized clinical trial have been published in this regard. Further randomized control trials comparing CL to RAL for different stages of endometriosis and different procedures performed are warranted in order to be able to define potential benefits of RAL for endometriosis surgery.

Fertility-enhancing hysteroscopic surgery.

Anatomical uterine element and functional components play a fundamental role in the enhancing of fertility are the major actors. Uterine pathologies, including congenital or acquired lesions, have been reported in 21 to 47% of patients undergoing in vitro fertilization cycles. Hysteroscopy is an important procedure in the study of one of the most important element of fertility: the uterus, even if its use in the world of infertility is discussed. There are many studies on safety and feasibility of the procedure and on patient compliance, but there is no consensus on its systemic use. This study, thanks to the wide literature about the use of hysteroscopic surgery to enhance fertility in most of the congenital and acquired problems affecting women in fertility age, allows defining that diagnostic and operative hysteroscopy is a rapid and safety technology to improve fertility.

Antiangiogenic agents in gynecological cancer: State of art and perspectives of clinical research.

Vascular endothelial growth factor [VEGF] pathway, which plays a key role in angiogenesis, may be blocked by either extracellular interference with VEGF itself (bevacizumab [BEV] or aflibercept), or intracytoplasmic inhibition of VEGF receptor (pazopanib, nintedanib, cediranid, sunitinib and sorafenib). An alternative approach is represented by trebananib, a fusion protein that prevents the interaction of angiopoietin [Ang]-1 and Ang-2 with Tie2 receptor on vascular endothelium. The combination of antiangiogenic agents, especially BEV, and chemotherapy is a rational therapeutic option for primary or recurrent ovarian carcinoma. However, it will be difficult to accept that it represents the new standard treatment, until biological characterization of ovarian carcinoma has not identified subsets of tumors with different responsiveness to BEV. Anti-angiogenesis is an interesting target also for recurrent cervical or endometrial cancer, but nowadays the use of anti-angiogenic agents in these malignancies should be reserved to patients enrolled in clinical trials.

Squamous cell carcinoma of the vagina: natural history, treatment modalities and prognostic factors.

Squamous cell carcinoma of the vagina accounts for less than 2% of all gynecologic malignancies. Surgery has a role in selected cases only. The standard treatment is radiotherapy, external beam radiation and/or brachytherapy, depending on the extent, thickness, location and morphology of the lesion. The role of chemotherapy is still under evaluation. Radiotherapy obtained 5-year overall survival rates ranged from 35% to 78%, with severe late complication rates of 9.4-23.1%. Tumor stage is the strongest prognostic factor. Tumor size >4cm, tumor location outside the upper third of the vagina, and old age at presentation are additional predictors of poor survival in most papers, whereas the prognostic value of histological grade, prior hysterectomy, and hemoglobin levels is controversial. High-risk HPV DNA and low MIB-1 index are associated with better clinical outcome. Because of the rarity of this tumor, future multicenter studies would be strongly warranted.

Micro-RNAs and ovarian cancer: the state of art and perspectives of clinical research.

Dysregulation of microRNA (mi-RNA) expression plays a major role in the development and progression of most human malignancies. Members of the miR-200 family, miR-182, miR-214 and miR-221 are frequently up-regulated, whereas miR-100, let-7i, miR-199a, miR-125b, mir-145 and miR-335 are often down-regulated in ovarian cancer compared with normal ovarian tissue. Most mi-RNA signatures are overlapping in different tumor histotypes but some mi-RNAs seem to be histotype specific. For instance, the endometrioid type shares with the serous and clear cell types the up-regulation of miR-200 family members, but also presents over-expression of miR-21, miR-202 and miR-205. Clear cell carcinoma has a significantly higher expression of miR-30a and miR-30a*, whereas mucinous histotype has elevated levels of miR-192/194. In vitro and in vivo investigations have shown that several mi-RNAs can modulate the sensitivity of ovarian cancer to platinum and taxane, and clinical studies have suggested that mi-RNA profiling may predict the outcome of patients with this malignancy. Some mi-RNAs could be used as biomarkers to identify patients that might benefit from the addition of molecularly targeted agents (i.e. anti-angiogenic agents, MET inhibitors and poly(ADP-ribose) polymerase (PARP) inhibitors) to standard chemotherapy. Moreover, mi-RNAs could represent potential targets for the development of novel therapies.

Fertility outcome of breast cancer and Hodgkin's lymphoma female survivors: a growing clinical challenge for gynecologists and oncologists.

The issue of taking into consideration future fertility in young women with breast cancer and Hodgkin's lymphoma [HL] will become more and more common and represent a growing clinical challenge for gynecologists and oncologists. The present paper will review literature data on the attempts of preventing chemotherapy-induced ovarian damage in these women and on their fertility outcome. Gonadotropin-releasing hormone [Gn-RH] agonists have been widely investigated as agents able to prevent ovarian failure in animal models and in humans. The majority of the studies on women with breast cancer and HL have shown a protective effect of Gn-RH agonists. A recent meta-analysis of five randomized trials, including 528 premenopausal breast cancer patients, revealed that relative risk [RR] of developing premature ovarian failure within one year was 0.40 (95% confidence interval [CI] = 0.21-0.75) for the women who received Gn-RH agonists with chemotherapy compared to those who received chemotherapy alone. However, the concurrent administration of Gn-RH agonists during chemotherapy appeared to have no effect on spontaneous pregnancy rates. Limited information are available about pregnancies in breast cancer and HL survivors, but the current literature appears to show no apparent increase in pregnancy complications, spontaneous abortions, or congenital abnormalities compared to general obstetric population.

Antiangiogenic agents in advanced, persistent or recurrent endometrial cancer: a novel treatment option.

The limited efficacy of endocrine therapy and chemotherapy has stimulated several researches aimed to detect novel molecularly target therapies for advanced, persistent or recurrent endometrial cancer. Prior attempts to block vascular endothelial growth factor (VEGF) with sunitinib, sorafenib and thalidomide have obtained disappointing results. Bevacizumab has shown a promising activity in a phase II study. The percentages of patients with progression-free survival ≥6 months were similar for endometrioid (35%) and serous carcinoma (36%), but the number of cases was too small to assess the relevance of histological type for response to bevacizumab. In a phase II study, aflibercept was administered every 2 weeks to women with recurrent or persistent disease after chemotherapy. Forty-one percent of the patients were progression-free at 6 months, but 32% of the women had been removed from study because of toxicity. The detection of activating mutations of Fibroblast Growth Factor Receptor (FGFR)-2 in primary endometrial carcinoma has generated a new avenue for the development of molecularly target agents. Dovitinib, a tyrosine kinase inhibitor targeting both VEGF receptor (VEGFR) and FGFRs, is under clinical investigation in different malignancies including endometrial cancer.