New Findings in the Multidisciplinary Management of a Fetal Intrapericardial Teratoma: A Case Report.

INTRODUCTION: Fetal intrapericardial teratoma is a rare tumor that can be diagnosed by antenatal ultrasonography early in pregnancy. CASE PRESENTATION: A fetal intrapericardial teratoma was detected on routine ultrasonography in the second trimester of pregnancy. At 31 weeks gestation, a marked increase in tumor size, fetal ascites, and pericardial effusion were observed, indicating that preterm delivery would be inevitable. Corticosteroid prophylaxis (24 mg of betamethasone in two doses of 12 mg 24 h apart) initiated for prophylaxis of respiratory distress syndrome led to a reduction in fetal ascites and pericardial effusion. Betamethasone therapy (4 mg/per day) was continued with the aim to postpone the expected date of delivery. Gestation was extended for more than 2 weeks. At 33 weeks and 5 days gestation, the neonate was delivered by elective cesarean section with ex utero intrapartum treatment and immediately submitted to fetal cardiac surgery. The infant was discharged from the hospital in good health about 4 months later. CONCLUSION: The present report draws attention to improvement in fetal status and extension of gestation achieved with maternal low-dose corticosteroid therapy on antenatal ultrasound finding of fetal ascites and pericardial effusion due to intrapericardial teratoma.

Innovative Strategies for Fertility Preservation in Female Cancer Survivors: New Hope from Artificial Ovary Construction and Stem Cell-Derived Neo-Folliculogenesis.

Recent advances in anticancer treatment have significantly improved the survival rate of young females; unfortunately, in about one third of cancer survivors the risk of ovarian insufficiency and infertility is still quite relevant. As the possibility of becoming a mother after recovery from a juvenile cancer is an important part of the quality of life, several procedures to preserve fertility have been developed: ovarian surgical transposition, induction of ovarian quiescence by gonadotropin-releasing hormone agonists (GnRH-a) treatment, and oocyte and/or ovarian cortical tissue cryopreservation. Ovarian tissue cryostorage and allografting is a valuable technique that applies even to prepubertal girls; however, some patients cannot benefit from it due to the high risk of reintroducing cancer cells during allograft in cases of ovary-metastasizing neoplasias, such as leukemias or NH lymphomas. Innovative techniques are now under investigation, as in the construction of an artificial ovary made of isolated follicles inserted into an artificial matrix scaffold, and the use of stem cells, including ovarian stem cells (OSCs), to obtain neo-folliculogenesis and the development of fertilizable oocytes from the exhausted ovarian tissue. This review synthesizes and discusses these innovative techniques, which potentially represent interesting strategies in oncofertility programs and a new hope for young female cancer survivors.

Hormone Receptors and Epithelial Ovarian Cancer: Recent Advances in Biology and Treatment Options.

Epithelial ovarian cancer (EOC) is a significant cause of cancer-related mortality in women. Despite advances in diagnosis and treatment, EOC remains a challenging disease to manage, and the 5-year survival rate is still poor. The role of hormone receptors (HRs) in EOC carcinogenesis and prognosis has been actively explored; however, the role of hormone therapy (HT) in the treatment of these tumors is not well established. Most available data on HT mainly come from retrospective series and small early clinical trials. Several of these studies suggest that HT may have a role in adjuvant, maintenance therapy, or in the case of recurrent disease, especially for some subtypes of EOC (e.g., low-grade serous EOC). Furthermore, HT has recently been combined with targeted therapies, but most studies evaluating these combinations are still ongoing. The main aim of this review is to provide an overview of the progress made in the last decade to characterize the biological and prognostic role of HRs for EOC and the developments in their therapeutic targeting through HT.

Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells.

Endometrial mesenchymal stromal cells (E-MSCs) extensively contribute to the establishment and progression of endometrial ectopic lesions through formation of the stromal vascular tissue, and support to its growth and vascularization. As E-MSCs lack oestrogen receptors, endometriosis eradication cannot be achieved by hormone-based pharmacological approaches. Quinagolide is a non-ergot-derived dopamine receptor 2 agonist reported to display therapeutic effects in in vivo models of endometriosis. In the present study, we isolated E-MSCs from eutopic endometrial tissue and from ovarian and peritoneal endometriotic lesions, and we tested the effect of quinagolide on their proliferation and matrix invasion ability. Moreover, the effect of quinagolide on E-MSC endothelial differentiation was assessed in an endothelial co-culture model of angiogenesis. E-MSC lines expressed dopamine receptor 2, with higher expression in ectopic than eutopic ones. Quinagolide inhibited the invasive properties of E-MSCs, but not their proliferation, and limited their endothelial differentiation. The abrogation of the observed effects by spiperone, a dopamine receptor antagonist, confirmed specific dopamine receptor activation. At variance, no involvement of VEGFR2 inhibition was observed. Moreover, dopamine receptor 2 activation led to downregulation of AKT and its phosphorylation. Of interest, several effects were more prominent on ectopic E-MSCs with respect to eutopic lines. Together with the reported effects on endometrial and endothelial cells, the observed inhibition of E-MSCs may increase the rationale for quinagolide in endometriosis treatment.

A Novel Xeno-Free Method to Isolate Human Endometrial Mesenchymal Stromal Cells (E-MSCs) in Good Manufacturing Practice (GMP) Conditions.

The cyclic regeneration of human endometrium is guaranteed by the proliferative capacity of endometrial mesenchymal stromal cells (E-MSCs). Due to this, the autologous infusion of E-MSCs has been proposed to support endometrial growth in a wide range of gynecological diseases. We aimed to compare two different endometrial sampling methods, surgical curettage and vacuum aspiration biopsy random assay (VABRA), and to validate a novel xeno-free method to culture human E-MSCs. Six E-MSCs cell samples were isolated after mechanical tissue homogenization and cultured using human platelet lysate. E-MSCs were characterized for the colony formation capacity, proliferative potential, and multilineage differentiation. The expression of mesenchymal and stemness markers were tested by FACS analysis and real-time PCR, respectively. Chromosomal alterations were evaluated by karyotype analysis, whereas tumorigenic capacity and invasiveness were tested by soft agar assay. Both endometrial sampling techniques allowed efficient isolation and expansion of E-MSCs using a xeno-free method, preserving their mesenchymal and stemness phenotype, proliferative potential, and limited multi-lineage differentiation ability during the culture. No chromosomal alterations and invasive/tumorigenic capacity were observed. Herein, we report the first evidence of efficient E-MSCs isolation and culture in Good Manufacturing Practice compliance conditions, suggesting VABRA endometrial sampling as alternative to surgical curettage.

Does Ovarian Endometriosis Increase Oocyte Sensitivity to ICSI-Induced Mechanical Damage?

Some studies have shown that ICSI obtains poorer results than conventional IVF in women with ovarian endometriosis, suggesting that oocytes could be sensitive to ICSI-induced mechanical damage. The aims of this study were to clarify (a) whether ovarian endometriosis could induce peculiar fragility in the oocyte, so that ICSI would finally result harmful, and (b) whether endometrioma removal before IVF could be advisable in order to avoid any hypothetical detrimental effect. We retrospectively studied 368 women, 203 with in situ endometrioma (128 of which underwent ICSI, 75 conventional IVF) and 164 who received laparoscopic stripping of endometrioma before ICSI. For women with in situ endometrioma, cIVF and ICSI outcome was comparable for all parameters studied, including the clinical pregnancy rate per embryo transfer (PR/ET: 31.8% vs. 39.5% in the cIVF and ICSI groups) and cumulative live birth rate per ovum pick-up (CLBR/OPU: 24.4% vs. 27.7%). ICSI outcome was similar comparing women with in situ endometrioma and women previously submitted to laparoscopic stripping of cysts (CLPR/OPU 27.7% vs. 25.3%). Our findings suggest that (a) in women with in situ endometrioma ICSI may be performed, when needed, without harming oocytes and compromising the outcome and (b) that there is no advantage in removing endometrioma before ICSI.

Gut Microbiota and Gynecological Cancers: A Summary of Pathogenetic Mechanisms and Future Directions.

Over the past 20 years, important relationships between the microbiota and human health have emerged. A link between alterations of microbiota composition (dysbiosis) and cancer development has been recently demonstrated. In particular, the composition and the oncogenic role of intestinal bacterial flora has been extensively investigated in preclinical and clinical studies focusing on gastrointestinal tumors. Overall, the development of gastrointestinal tumors is favored by dysbiosis as it leads to depletion of antitumor substances (e.g., short-chain fatty acids) produced by healthy microbiota. Moreover, dysbiosis leads to alterations of the gut barrier, promotes a chronic inflammatory status through activation of toll-like receptors, and causes metabolic and hormonal dysregulations. However, the effects of these imbalances are not limited to the gastrointestinal tract and they can influence gynecological tumor carcinogenesis as well. The purpose of this Review is to provide a synthetic update about the mechanisms of interaction between gut microbiota and the female reproductive tract favoring the development of neoplasms. Furthermore, novel therapeutic approaches based on the modulation of microbiota and their role in gynecological oncology are discussed.

Is HPV the Novel Target in Male Idiopathic Infertility? A Systematic Review of the Literature.

Infertility is an important health problem that affects up to 16% of couples worldwide. Male infertility is responsible for about 50% of the cases, and the various causes of male infertility may be classified in pre-testicular (for example hypothalamic diseases), testicular, and post-testicular (for example obstructive pathologies of seminal ducts) causes. Sexually transmitted infections (STI) are increasingly widely accepted by researchers and clinicians as etiological factors of male infertility. In particular, several recent reports have documented the presence of HPV in seminal fluid and observed that sperm infection can also be present in sexually active asymptomatic male and infertile patients. In this review, we aimed to perform a systematic review of the whole body of literature exploring the impact of HPV infection in natural and assisted fertility outcomes, from both an experimental and a clinical point of view. Starting from in-vitro studies in animals up to in-vivo studies in humans, we aimed to study and evaluate the weight of this infection as a possible cause of idiopathic infertility in males with any known cause of conception failure.

Hyaluronidase-based swim-up for semen selection in patients with human papillomavirus semen infection.

Infection by human papillomavirus (HPV) represents one of the most common sexually transmitted diseases in both men and women worldwide. Recently, the detection of HPV virions in the semen of a large percentage of sexually active men has been associated with detrimental effects on both sperm parameters and on assisted reproductive technologies (ART) treatment outcomes. Conventional semen washing procedure used in ART have proved to be ineffective in removing HPV bound to sperm, requiring the identification of more effective and specific methods. In the present study, we assessed the possible use of hyaluronidase for the detachment of HPV from sperm cell surface. Semen samples from five normozoospermic control subjects (CTRL) were incubated with HPV virus-like particles (HPV-VLP) and treated with hyaluronidase by both a modified swim-up procedure (M-SU) and single-cell approach (SCA). The treatment with hyaluronidase was associated with the complete loss of HPV-VLP signal on sperms by both M-SU and SCA. In addition, semen samples from 12 HPV-positive infertile patients were treated with hyaluronidase 80 IU/mL by M-SU, resulting in the complete loss of HPV-DNA signal from sperm surface. Finally, the possible impact of hyaluronidase treatment on sperm parameters was assessed on both sperms from the five CTRL subjects and on further five oligo-astheno-terato-zoospermic (OAT) patients, both HPV negative. The treatment with hyaluronidase was equally associated with a slight reduction of sperm viability and progressive motility in both CTRL and OAT. In conclusion, the treatment with hyaluronidase removed efficiently and safely HPV virions bound to spermatozoa.

A Fascial Reinterpretation of the Classical Female Pelvic Surgical Anatomy: Seeing Things from a Different Angle.

STUDY OBJECTIVE: The classical surgical anatomy of the female pelvis was born with radical hysterectomy [1] and focused on the pivotal role of the lateral parametrium, a conceptually complex structure, an artifact of surgical anatomy [2] without which the whole classical model would collapse. Here, using natural planes, we tried to simplify the puzzle of the virtual spaces surrounding this structure [3,4]. With the aim of better conceptualizing the classical model of the female pelvic surgical anatomy, we broadened its perspective, which had been narrowly focused on the historic gynecologic setting, by developing a comprehensive model of pelvic retroperitoneal compartmentalization. This dissection was based on the invariable anatomic (fasciae) rather than the surgical-anatomic (parametrium) structures and aimed at providing a holistic, more user-friendly approach intended for surgical and educational purposes [5]. Because each compartment has its own surgical function (hence the name), the excavation of a single compartment may be used as a rational guide to tailor surgery to the site of the pathologic condition to be treated or the type of procedure required, whereas the compartments' sequential development may be useful in planning surgical strategies. Redefining the classical model according to the anatomic fascial planes of dissection potentially allows for an intrinsic surgical reproducibility, minimizing dissective bias. A reinterpretation of the known anatomy is required to enhance education. The breaking down of such a complex system (the pelvis) into smaller parts (compartments) will hopefully provide a useful guide for conceptualization and navigation; surgical navigation requires a holistic mental map and a few invariable anatomic reference points or landmarks. DESIGN: A step-by-step laparoscopic demonstration of the fascial model, developed on a fresh frozen female pelvis, and its correlation with the classical female retroperitoneal surgical anatomy. SETTING: Cadaver Laboratory, Department of Legal Medicine, University of Turin. INTERVENTIONS: The first part of the video shows the progressive development of the 3 hemicompartments in the right hemipelvis and of the fourth median compartment after the identification of 3 invariable anatomic reference points: the obliterated umbilical artery, the ureter, and the sacrouterine ligament as superficial landmarks of 3 deeper fascial-ligamentous structures: the umbilicovesical fascia, the urogenital-hypogastric fascia, and the sacropubic ligament, respectively (Figure 1). The areas delimited by the aforementioned deep fascial ligamentous structures have been designated as compartments: • the right parietal hemicompartment, so called because it is bordered by the sidewall of the pelvis, lateral to the umbilicovesical fascia • the right vascular hemicompartment, so called because of the presence of the internal iliac vessel's visceral branches between the umbilicovesical fascia and the urogenital-hypogastric fascia • the visceral compartment, so called because it contains the pelvic organs between the sacropubic ligaments • the right neural hemicompartment, so called because of the presence of the organ-specific vegetative bundles, medial to the urogenital-hypogastric fascia. The second part of the video describes the retrorectal, presacral, and retropubic connection areas between the neural, vascular, and parietal hemicompartments of each hemipelvis, justifying their overall crescent shape. Finally, the spaces of classical surgical anatomy included in each hemicompartment are listed not only according to their anatomic criterion, but also according to their functional criterion. In fact, the parietal compartment should be developed for the evaluation of the pelvic lymph node status or during exenterative and urogynecologic procedures. The vascular compartment must be prepared when sectioning of the vascular visceral pedicles at their origin is required. Development of the neural compartment is required whenever visceral neural components are to be spared. The visceral compartment has to be developed for complete organ mobilization and exposure. CONCLUSION: Taken as a whole, our 4-compartment model of pelvic anatomic surgery is intended for use in planning and optimizing surgical strategies. Moreover, it is potentially able to simplify surgical teaching and training, allowing the fitting together of puzzle-like pieces of disjointed organ-specific retroperitoneal spaces according to their function (Figure 2). The correlation of this approach to clinical outcomes is still being determined.

Affected Ovary Relative Volume: A Novel Sonographic Predictor of Ovarian Reserve in Patients with Unilateral Endometrioma-A Pilot Study.

BACKGROUND: The assessment of ovarian reserve in the case of endometrioma is of pivotal importance for planning a tailored management. However, both the antral follicle count (AFC) and the antimüllerian hormone (AMH) dosage are subject to a fair degree of variability in ovarian endometriosis. This study aimed to identify a sonographic parameter of ovarian reserve that could implement current available markers in patients with unilateral endometrioma. METHODS: Patients with unilateral endometrioma admitted to our Endometriosis Center between March 2018 and April 2019 were enrolled. Transvaginal ultrasonography for the evaluation of eight sonographic indicators and AMH level determination were performed. The relationship between AMH level and each indicator was assessed. RESULTS: Thirty-four women were included. There was a positive significant correlation between AMH level and the healthy ovary AFC (HO-AFC) (r = 0.36 p = 0.034). A stronger, negative correlation between AMH level and the ratio between the volume of the affected and the healthy ovary (affected ovary relative volume, AORV) (r = -0.47; p = 0.005) was evidenced. AORV had a satisfactory accuracy (AUC 0.73; CI 0.61-0.90; p = 0.0008), and the cut-off value of 5.96 had the best balance of sensitivity/specificity in distinguishing between patients with a good ovarian reserve (AMH ≥ 2 ng/mL) and those at risk of ovarian reserve depletion after excisional surgery. CONCLUSION: AORV may be a useful tool to assess ovarian reserve in patients with unilateral endometrioma without previous surgery and to guide physicians in clinical management.

Is There a Place for Immune Checkpoint Inhibitors in Vulvar Neoplasms? A State of the Art Review.

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.

Brain Metastases from Ovarian Cancer: Current Evidence in Diagnosis, Treatment, and Prognosis.

With this review, we provide the state of the art concerning brain metastases (BMs) from ovarian cancer (OC), a rare condition. Clinical, pathological, and molecular features, treatment options, and future perspectives are comprehensively discussed. Overall, a diagnosis of high-grade serous OC and an advanced disease stage are common features among patients who develop brain metastases. BRCA1 and BRCA2 gene mutations, as well as the expression of androgen receptors in the primary tumor, are emerging risk and prognostic factors which could allow one to identify categories of patients at greater risk of BMs, who could benefit from a tailored follow-up. Based on present data, a multidisciplinary approach combining surgery, radiotherapy, and chemotherapy seem to be the best approach for patients with good performance status, although the median overall survival (<1 year) remains largely disappointing. Hopefully, novel therapeutic avenues are being explored, like PARP inhibitors and immunotherapy, based on our improved knowledge regarding tumor biology, but further investigation is warranted.

Controlled ovarian stimulation and progesterone supplementation affect vaginal and endometrial microbiota in IVF cycles: a pilot study.

PURPOSE: Does controlled ovarian stimulation (COS) and progesterone (P) luteal supplementation modify the vaginal and endometrial microbiota of women undergoing in vitro fertilization? METHODS: Fifteen women underwent microbiota analysis at two time points: during a mock transfer performed in the luteal phase of the cycle preceding COS, and at the time of fresh embryo transfer (ET). A vaginal swab and the distal extremity of the ET catheter tip were analyzed using next-generation 16SrRNA gene sequencing. Heterogeneity of the bacterial microbiota was assessed according to both the Bray-Curtis similarity index and the Shannon diversity index. RESULTS: Lactobacillus was the most prevalent genus in the vaginal samples, although its relative proportion was reduced by COS plus P supplementation (71.5 ± 40.6% vs. 61.1 ± 44.2%). In the vagina, an increase in pathogenic species was observed, involving Prevotella (3.5 ± 8.9% vs. 12.0 ± 19.4%), and Escherichia coli-Shigella spp. (1.4 ± 5.6% vs. 2.0 ± 7.8%). In the endometrium, the proportion of Lactobacilli slightly decreased (27.4 ± 34.5% vs. 25.0 ± 29.9%); differently, both Prevotella and Atopobium increased (3.4 ± 9.5% vs. 4.7 ± 7.4% and 0.7 ± 1.5% vs. 5.8 ± 12.0%). In both sites, biodiversity was greater after COS (p < 0.05), particularly in the endometrial microbiota, as confirmed by Bray-Curtis analysis of the phylogenetic distance among bacteria genera. Bray-Curtis analysis confirmed significant differences also for the paired endometrium-vagina samples at each time point. CONCLUSIONS: Our findings suggest that COS and P supplementation significantly change the composition of vaginal and endometrial microbiota. The greater instability could affect both endometrial receptivity and placentation. If our findings are confirmed, they may provide a further reason to encourage the freeze-all strategy.

Ultrasound and clinical characteristics of uterine smooth muscle tumors of uncertain malignant potential (STUMPs).

OBJECTIVE(S): Smooth muscle tumors of uncertain malignant potential are rare uterine neoplasms. Their identification through imaging is still limited due to the few available descriptions in the scientific literature. The objective of this paper is to provide clinical and ultrasound features that could support an early identification of these neoplasms. STUDY DESIGN: We retrospectively evaluated preoperative sonographic data of patients receiving a histopathological diagnosis of smooth muscle tumors of uncertain malignant potential between 2014 and 2019 at the S. Anna Hospital (Turin, Italy), a tertiary gynecological center. Tumors were characterized on the basis of ultrasound images using terms and definitions according to the morphological uterus sonographic assessment group. RESULTS: A total of fourteen patients with smooth muscle tumors of uncertain malignant potential (20 lesions, including 18 pure and 2 with associated leiomyosarcoma) were identified. The median age was 47 years (range 28-77) and nine (64%) patients were of reproductive age. Six patients (43%) were asymptomatic, two (14%) presented with abdominal pain, two (14 %) with menorrhagia and four (29%) with both symptoms. Two (14%) patients developed local recurrences as uterine smooth muscle tumor of uncertain malignant potential and leiomyosarcoma, respectively. At ultrasound imaging, nine (69%) smooth muscle tumors of uncertain malignant potential were poorly or moderately vascularized and nine (82%) showed both circumferential and intra-lesional flows. Only three (15%) showed shadowing. The outlines were well-defined in seventeen cases (85%) and most (90%) showed isoechoic or mixed echogenicity with microcystic anechoic areas in fourteen (70%) of cases. CONCLUSION(S): Sonographic features of smooth muscle tumors of uncertain malignant potential may vary and a pathognomonic description has not been recognized. However, the identification of single or multiple lesions with specific ultrasound features should raise the suspicion of tumors of uncertain malignant potential. These features include isoechogenicity or mixed echogenicity, regular borders, presence of internal microcystic and anechoic areas, circumferential and intralesional vascularization ranging from minimal to high and absence of shadowing.

A prospective randomized trial comparing corifollitropin-α late-start (day 4) versus standard administration (day 2) in expected poor, normal, and high responders undergoing controlled ovarian stimulation for IVF.

OBJECTIVE: To assess whether corifollitropin-α (CFα) late-start administration (day 4) and standard administration (day 2) can obtain similar oocyte yield and live birth rate. STUDY DESIGN: A randomized controlled trial. SETTING: University Hospital IVF Unit. PATIENTS: One hundred thirteen women undergoing IVF. INTERVENTIONS: Patients distributed in three subgroups (expected poor, normal, or high responders to FSH) were randomized into two treatment arms: (a) CFα late-start: CFα on day 4 + GnRH antagonist from day 8 + (when needed) recFSH from day 11; (b) CFα standard start: CFα on day 2 + GnRH antagonist from day 6 + (when needed) recFSH from day 9. IVF or ICSI was performed as indicated. RESULTS: Considering the whole study group, the late-start regimen obtained comparable oocyte yield (8.9 ± 5.6 vs. 8.8 ± 6.2; p = n.s.), cPR/started cycle (25% vs. 31.6%, p = n.s.), and cumulative live birth rate (LBR)/ovum pickup (OPU) (29.2% vs. 37.7%, p = n.s.) than the standard regimen. The outcome of the two regimens was comparable in the two subgroups of high and normal responders. Differently, in poor responders, oocyte yield was similar, but LBR/OPU was significantly lower with late-start CFα administration that caused 40% cancellation rate due to monofollicular response. ROC curves showed that the threshold AMH levels associated with cycle cancellation were 0.6 ng/ml for late-start regimen and 0.2 ng/ml for standard regimen. CONCLUSION: CFα may be administered on either day 2 or day 4 to patients with expected high or normal response to FSH without compromising oocyte yield and/or live birth rate. Differently, late-start administration is not advisable for expected poor responders with AMH ≤ 0.6 ng/ml. TRIAL REGISTRATION: NCT03816670.

Practical Clinical and Diagnostic Pathway for the Investigation of the Infertile Couple.

Capsule: This expert opinion summarizes current knowledge on risk factors for infertility and identifies a practical clinical and diagnostic approach for the male and female partners of an infertile couple aimed to improve the investigation and management of fertility problems. Background: Infertility represents an important and growing health problem affecting up to 16% of couples worldwide. In most cases, male, female, or combined factor can be identified, and different causes or risk factors have been related to this condition. However, there are no standardized guidelines on the clinical-diagnostic approach of infertile couples and the recommendations concerning infertility are sometimes lacking, incomplete, or problematic to apply. Objective: The aim of this work is to provide an appropriate clinical and diagnostic pathway for infertile couples designed by a multidisciplinary-team of experts. The rationale is based on the history and physical examination and then oriented on the basis of initial investigations. This approach could be applied in order to reduce variation in practice and to improve the investigation and management of fertility problems. Methods: Prominent Italian experts of the main specialties committed in the ART procedures, including gynecologists, andrologists, embryologists, biologists, geneticists, oncologists, and microbiologists, called "InfertilItaly group", used available evidence to develop this expert position. Outcomes: Starting from the individuation of the principal risk factors that may influence the fertility of females and males and both genders, the work group identified most appropriate procedures using a gradual approach to both partners aimed to obtain a precise diagnosis and the most effective therapeutic option, reducing invasive and occasionally redundant procedures. Conclusions: This expert position provides current knowledge on risk factors and suggests a diagnostic workflow of infertile couples. By using this step-by-step approach, health care workers involved in ART, may individuate a practical clinical management of infertile couples shared by experts.

Clinico-pathological features of gynecological myopericytoma: a challenging diagnosis in an exceptional location.

Myopericytomas (MPC) are rare mesenchymal tumors, originating from the perivascular myoid cells. They predominantly occur in the skin and superficial soft tissues of the extremities, while visceral involvement is rare. Histological features and clinical course are usually benign. To the best of our knowledge, MPC is still an uncharacterized tumor entity of the female internal genital tract. We describe three MPC cases involving the female internal genital tract: (1) a uterine wall MPC arising in a 49-year-old woman with progressive pelvic/abdominal pain; (2) a cervix MPC of a 49-year-old woman who presented with metrorrhagia, and (3) a MPC presenting as a simple ovarian cyst in a 26-year-old woman with pain located in the left iliac fossa. All patients were surgically treated, and recurrence occurred in two cases. The histological and immunohistochemical findings, supporting the diagnosis of MPC, are presented; in particular, one case showed characteristics pointing towards an uncertain biological behavior/low-grade malignancy. A literature search was conducted to identify previous reports of gynecological MPC and for possible alternative diagnoses. Leiomyoma, epithelioid leiomyoma, angioleiomyoma, perivascular epithelioid cell tumor, solitary fibrous tumor, and low-grade endometrial stromal sarcoma should be considered in the differential diagnosis. Awareness of possible occurrence of this rare neoplasm in the female genital tract is important to reach a correct diagnosis in the spectrum of mesenchymal tumors. Considering the risk of recurrence, we recommend careful evaluation of surgical margins and complete surgical removal whenever possible.

Empty follicle syndrome revisited: definition, incidence, aetiology, early diagnosis and treatment.

In this review, the definition, incidence and possible causes of empty follicle syndrome (EFS), including molecular mechanisms that may underlie the syndrome, are discussed, along with prevention and treatment options. EFS is the complete failure to retrieve oocytes after ovarian stimulation, despite apparently normal follicle development and adequate follicular steroidogenesis. Two variants of EFS have been described: the 'genuine' form (gEFS), which occurs in the presence of adequate circulating HCG levels at the time of oocyte aspiration, and the 'false' form (f-EFS), which is associated with circulating HCG below a critical threshold. Heterogeneous HCG concentration thresholds, however, have been used to define gEFS, and to date no standardization exist. The situation is unclear when GnRH-analogues are used for ovulation trigger, as the threshold circulating LH and progesterone levels used to define EFS as 'genuine' are not established. The cause of fEFS has been clearly identified as an error in HCG administration at the time of ovulation trigger; in contrast, the cause of gEFS is still unclear, although some pathogenetic hypotheses have been proposed. Optimal treatment and prognosis of these patients are still poorly understood. Large, systematic multi-centre studies are needed to increase the understanding of EFS.