'Primary gingival and later primary vulval carcinomas arising in lichen planus: report of a case and clinical suggestions for diagnosis of a neglected disease'.

Lichen planus (LP) is a chronic immune-mediated dermatosis mainly affecting skin, oral, and genital mucosa. The heterogeneous clinical presentation, spectrum of symptoms depending on subtype and overlap with other vulval and cutaneous disorders can lead to challenging in diagnosis. We report an unusual case of vulval SCC arising within a patient with initial oral mucosal lichen planus who later developed lichen planus of the vulva. Discussion of this case is important as it typifies the difficulties in diagnosis of vulvo-vaginal disorders and potential complications. Evidence is available that lichen planus may be potentially precancerous condition and is associated with SCC development. This case may confirm an inherent oncologic potential of the disease. All efforts must be made by specialists involved in the management of this disease to obtain an early diagnosis, ensure proper treatment and adequate follow up. This highlights the need to perform vulval examination in patients with symptoms or with a history muco-cutaneous LP and if necessary consider referral to specialist center for biopsy and management.

Milking of the Umbilical Cord in Term and Late Preterm Infants.

INTRODUCTION: Umbilical cord milking is a procedure in which clamped or unclamped umbilical cord is grasped, and blood is pushed ("stripped") two to four times towards the newborn, in a rapid time frame, usually within 20 seconds. The target of umbilical cord milking is to provide infants with their whole potential blood volume-of which they are deprived when early cord clamping is carried out-completing placental transfusion in a shorter time than delayed cord clamping. The aim of this narrative review is to analyse the literature regarding umbilical cord milking in term and late-preterm infants and to assess all possible benefits and limits of this procedure in clinical practice, especially in comparison to immediate and delayed cord clamping. METHODS: We analysed literature data concerning maternal, as well as neonatal, outcomes for term and late-preterm (gestational age ≥ 34 weeks) newborns who received umbilical cord milking. RESULTS: Most studies show comparable benefits for both umbilical cord milking and delayed cord clamping, especially in terms of haematological parameters when compared to immediate cord clamping. Umbilical cord milking may be a feasible procedure also for newborns requiring resuscitation. CONCLUSIONS: Literature data concerning positive effects of umbilical cord milking are encouraging and suggest that umbilical cord milking may be a quick and effective method to provide placental transfusions to depressed infants. However, the lack of standardised procedures and the variation in evaluated outcomes as well as the limited number of patients enrolled in trials, along with the retrospective nature of some of them, prevent recommending umbilical cord milking as a routine procedure.

Fertility Preservation: Current and Future Perspectives for Oncologic Patients at Risk for Iatrogenic Premature Ovarian Insufficiency.

Progress in recent years in the efficacy of oncologic treatment and early diagnosis of cancer has determined an increase in life expectance in cancer patients. About 10% of all cancer cases affect women younger than 45 years; therefore nowadays approximately 5-6% of the population in childbearing age consists in cancer survivors. A crucial issue is the high risk of premature ovarian insufficiency due to possible gonadotoxic effects of oncologic treatments. Considering combined chemotherapy, radiation therapy, and bone marrow transplantation, this risk can reach 92-100%, depending on the age and ovarian reserve of the patient, as well as the schedule and type of therapy. International guidelines recommend addressing all the patients diagnosed with a neoplasia treatable with potentially gonadotoxic therapies to fertility preservation. Moreover, fertility preservation also seems to reserve fascinating implications for women who want to delay childbearing for social reasons or women affected with endometriosis, who could receive unexpected opportunities. At present, the most widespread techniques to preserve fertility in adult women are embryo or oocyte cryopreservation, depending on the presence of a partner or according to legislative issues, but these procedures require time for ovarian stimulation. In prepubertal patients or when there is no possibility of delaying chemotherapy, ovarian tissue cryopreservation and subsequent transplantation represent the main strategy.

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.

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.

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.

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.

Is there a critical endometrioma size associated with reduced ovarian responsiveness in assisted reproduction techniques?

This study investigated the relationships between ovarian endometrioma size, ovarian responsiveness and the number of retrieved oocytes following ovarian stimulation. A prospective study was conducted in a public clinical assisted reproduction centre. A total of 64 infertile women with monolateral endometriomas undergoing IVF or intracytoplasmic sperm injection were included in the study. The total number of follicles, number of follicles ≥ 16 mm and number of oocytes retrieved of ovaries containing endometrioma and normal ovaries were compared. Multivariate linear regression was used to assess whether number of follicles and collected oocytes varied by endometrioma size, age, basal FSH concentration. Significantly lower numbers of follicles ≥ 16 mm (P = 0.024) and oocytes retrieved (P = 0.001) in the ovaries containing endometrioma were observed. In patients with endometriomas ≥ 30 mm, endometrioma size was the most influential contributor to the total number of follicles and oocytes retrieved. Ovarian endometriomas result in reduced response to ovarian stimulation, compared with the response of the contralateral normal ovary in the same individual. In case of endometriomas <30 mm, basal FSH concentration remains the most important prognostic factor for oocyte retrieval.

Conventional IVF as a laboratory strategy to rescue fertility potential in severe poor responder patients: the impact of reproductive aging.

OBJECTIVE: To investigate whether laboratory strategies can improve in vitro fertilization (IVF) outcome in poor responder patients. We compared the effectiveness of conventional IVF and intra cytoplasmic sperm injection (ICSI) in assisted reproductive technologies cycles in which only one or two oocytes were retrieved at ovarian pick up, in the absence of male infertility. DESIGN: Retrospective analysis of 425 cycles in 386 poor responder patients. INTERVENTION(S): Standard stimulation protocol with gonadotropins and gonadotropin releasing hormone (GnRH) antagonist. MAIN OUTCOME MEASURE(S): Fertilization rate, cleavage rate, good-quality embryo rate, implantation rate, clinical pregnancy rate (PR) and miscarriage rate. RESULTS: IVF was found to be more advantageous for implantation and PR, especially in patients under 35 years and in women aged between 35 and 38 years. No differences were noted in the other parameter evaluated. Patients aged over 38 years showed no difference using the two techniques. CONCLUSION: The employment of ICSI in the absence of a male factor can reduce reproductive outcome in poor responder. Probably because of aging-related defects overcoming the advantage of sperm selection, the choice of IVF technique is not relevant to reproductive success when oocyte quality is compromised by reproductive aging. Although further randomized trials are needed to confirm our results, we propose that, in absence of male infertility, conventional IVF might be the technique of choice in young patients, especially in those aged below 35 years.

Management of sexual dysfunction due to vulvar lichen sclerosus in postmenopausal women.

Lichen sclerosus is a chronic skin disease, probably immune-mediated, with a strong genetic component. It shows a predilection for external genitalia. It is most common in postmenopausal women, although it has been documented at all ages and in both sexes. The exact prevalence of lichen sclerosus is unknown. However, in recent years much progress has been made in defining its etiology and epidemiology, and we now know that it is far more frequent than previously thought. The purpose of this review is to focus more attention on the relationship between LS and sexual dysfunction, and on a few important aspects of managing perimenopausal patients diagnosed with LS. Lichen sclerosus is a chronic, debilitating condition that may progress to cause significant physical and psychological complications. The disease calls for lifetime follow-up.

DHEA supplementation improves follicular microenviroment in poor responder patients.

OBJECTIVE: To analyze the effect of dehydroepiandrosterone (DHEA) supplementation on follicular microenvironment and on in vitro fertilization (IVF) outcomes among poor responder patients. STUDY DESIGN: We enrolled 24 patients diagnosed as poor responders based on ESHRE consensus criteria. One group received 25 mg/die three times daily of DHEA supplementation for 3 months previous to IVF cycle, while the other did not receive any treatment. COH was performed with rFSH and hMG, and a GnRH antagonist was administered according to a flexible protocol. We evaluated perifollicular vascularization of recruited follicles through power Doppler blood flow analysis and follicles were graded as described by Chui et al. Follicular fluids (FF) from F3-F4 follicles were collected, and FF levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor1 (HIF1) were measured. RESULTS: FF levels of HIF1 were statistically significant lower in women treated with DHEA (14.76 ± 51.13 vs. 270.03 ± 262.18 pg/ml; p = 0.002). On the contrary, VEGF levels did not differ between the two groups. Concerning COH, in the DHEA-group the mean duration of treatment was significantly shorter (9.83 ± 1.85 vs. 12.09 ± 2.81; p = 0.023). Total numbers of oocytes retrieved, fertilized oocytes, good quality embryos, number of transferred embryos and clinical pregnancies tended to be higher in study group, but the results were not significant. On the other hand, considering the oocytes retrieved in selected F3-F4 follicles, there was a relation between HIF1 levels and oocytes quality. In fact, mature oocytes retrieved in selected follicles were significantly more numerous in DHEA-group (0.50 ± 0.52 vs. 0.08 ± 0.29; p = 0.018). CONCLUSIONS: The improvement of reproductive parameters after DHEA supplementation in poor responders may be explained through the effect that this pro-hormone exerts on follicular microenvironment.