Giant Borderline Phyllodes Tumor of the Breast: A Case Report.

Borderline phyllodes tumor is a rare and benign form of breast cancer with malignant potential. According to the World Health Organization (WHO), phyllodes tumor is classified into three categories: benign, borderline, and malignant. The treatment of phyllodes tumor is wide focal excision combined with radiotherapy and chemotherapy in certain cases. Herein, we report a 47-year-old female who presented with a giant borderline mass approximately 19.5 x 16.9 x 9.3 cm in size. From medical history, we noticed that the mass begun to develop during puberty. Wide focal excision of the tumor and immediate implant-based reconstruction with free nipple graft was performed, with the tumor specimen measuring 16.5 x 14.2 x 8.7 cm. Histological examination reported a borderline phyllodes tumor, and in this case, the patient did not undergo adjuvant treatment.

The Impact of Stress and Depression on the Outcome of Human Gestation.

Many researchers have reported on the high prevalence of anxiety and depression during pregnancy as well as the influence on delivery outcomes during the past decade. Preterm birth and premature labor, bleeding, higher frequency of cesarean section (CS), low birth weight, preeclampsia, stillbirth, miscarriage, NICU hospitalization, and a low Apgar score are the most commonly referenced outcomes assessed. Clarifying the relationship between exposure and result may help us to understand the risk factors and guide us to future clinical and research practices. The purpose of this narrative review is to search the following databases: PubMed, Research Gate, Scopus, Medline Plus, and present the most recent, comprehensive literature on the effects of stress and anxiety on pregnancy outcomes. Articles published from 01/01/2000 to 26/11/2022 were obtained from the previous databases. Anxiety and depression-related disorders are common nowadays, and they are frequently correlated with poor pregnancy outcomes. These problems are caused by a number of factors, including health social determinants, the individual obstetric situation, access to healthcare facilities, etc. The effects of each of these factors on birth outcomes range from major, such as preterm labor, congenital deformities, and low birth weight, to minor, such as mutations in the fetal epigenome. Both direct and indirect pathways of substantial interactions between depression, anxiety and stress, risk variables, and delivery problems were identified. Women's health practitioners and mental physicians must provide adequate support to these women in order to improve outcomes for both mothers and infants.

Myomectomy in adult women of reproductive age: a propensity score-matched study for pregnancy rates.

PURPOSE: To study whether it is better to perform or not a myomectomy, in terms of surgical and reproductive outcomes in patients of advanced reproductive age, by an observational prospective study in university-affiliated and Community Hospitals. MATERIALS AND METHODS: 40 years and older patients affected by non-submucous symptomatic uterine fibroids and desiring future fertility were enrolled and treated by laparoscopic intracapsular myomectomy by (LIM) or by open laparotomy (OIM), or by a non-surgical management as control group, while attempting to conceive. The primary outcome measures were fibroid characteristics, pre- and post-surgical parameters, pregnancy achievement; the secondary outcome measures were the spontaneous or ART pregnancy outcomes, eventual week of abortion and type of delivery. Propensity scores have been calculated with logistic regression for binary and continuous variables. RESULTS: 202 patients completed the study: 112 operated by LIM, 40 by OIM and 50 patients as control group. Patients undergoing OIM have a worse surgical outcome than LIM. No difference was seen in pregnancy either after myomectomy or control group during follow-up. In the LIM group, there were 44 pregnancies (39.2%), and in the OIM group, there were 9 (22.5%) and 16 in the control group (32%). The weeks of delivery were statistically greater for the control group versus the surgical groups, with no difference in Apgar score between the 3 groups. CONCLUSION: Patients aged over 40 years did not show substantial differences in reproductive outcome, whether operated or not. Myomectomy in over 40-year-old patients has no detrimental effect on future pregnancy rates and over when compared to expectant management.

Asynclitism and Its Ultrasonographic Rediscovery in Labor Room to Date: A Systematic Review.

Asynclitism, the most feared malposition of the fetal head during labor, still represents to date an unresolved field of interest, remaining one of the most common causes of prolonged or obstructed labor, dystocia, assisted delivery, and cesarean section. Traditionally asynclitism is diagnosed by vaginal examination, which is, however, burdened by a high grade of bias. On the contrary, the recent scientific evidence highly suggests the use of intrapartum ultrasonography, which would be more accurate and reliable when compared to the vaginal examination for malposition assessment. The early detection and characterization of asynclitism by intrapartum ultrasound would become a valid tool for intrapartum evaluation. In this way, it will be possible for physicians to opt for the safest way of delivery according to an accurate definition of the fetal head position and station, avoiding unnecessary operative procedures and medication while improving fetal and maternal outcomes. This review re-evaluated the literature of the last 30 years on asynclitism, focusing on the progressive imposition of ultrasound as an intrapartum diagnostic tool. All the evidence emerging from the literature is presented and evaluated from our point of view, describing the most employed technique and considering the future implication of the progressive worldwide consolidation of asynclitism and ultrasound.

Dystocic Labor and Adrenergic and Noradrenergic Neurotransmitters: A Morphological Experimental Study.

Authors investigated the catecholaminergic neurotransmitters (chNs) quantitative modifications in pregnant uterine Lower Uterine Segment (LUS) during prolonged labor (PL) with the fetus in an occiput-posterior position (OPP), in occiput transverse position (OTP) and in fetal head asynclitism, all diagnosed by Intrapartum Ultrasonography (IU). The chNs neurotransmitters, particularly adrenaline (or epinephrine-A) and noradrenaline (or norepinephrine-N), were evaluated in LUS fragments sampled during CS of 34 patients undergoing urgent cesarean section (CS) in PL, compared to chNs fibers in the LUS of 36 women submitted to elective CS. All results were statistically analyzed to understand the differences in neurotransmitters morphological analysis by scanning electronic microscopy examination (SEM). The LUS fragments analysis revealed a reduction of A and N fibers in LUS during PL, compared with the expression of A and N fibers in LUS during elective CS. The PL for OPP, the OTP and asynclitism, all positions causing dystocia in labor lead to a reduction in neurotransmitters in LUS, with a uterine vascularization modification and a reduction in the contractility of smooth uterine cells. The A and N neurotransmitters reduction observed in PL negatively interferes with uterine contraction during labor.

Inguinal endometriosis: A systematic review.

Inguinal endometriosis is a very rare entity with uncertain pathophysiology, that poses several diagnostic and therapeutic challenges. This study aimed to summarize published literature on the diagnosis and treatment of this condition. Thus, a systematic literature search was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library. An effort was made to numerically analyze all parameters included in case reports and retrospective analyses, as well. The typical and atypical features of this condition, investigations used, type of treatment and histopathology were recorded. More specifications about the surgical treatment, such as operations previously performed, type of surgery and treatment after surgery have been acknowledged. Other sites of endometriosis, the presence of pelvic endometriosis and the follow-up and recurrence have been also documented. Overall, the search yielded 61 eligible studies including 133 cases of inguinal endometriosis. The typical clinical presentation includes a unilateral inguinal mass, with or without catamenial pain. Transabdominal or transvaginal ultrasound was typically used as the first line method of diagnosis. Groin incision and exploratory surgery was the treatment indicated by the majority of the authors, while excision of part of the round ligament was reported in about half of the cases. Chemotherapy and radiotherapy were initiated in cases of coexisting endometriosis-related neoplasia. Inguinal recurrence or malignant transformation was rarely reported. The treatment of inguinal endometriosis is surgical and a long-term follow-up is needed. More research is needed on the effectiveness of suppressive hormonal therapy, recurrence rate and its relationship with endometriosis-associated malignancies.

Prevalence of Intrauterine Adhesions after Myomectomy: A Prospective Multicenter Observational Study.

OBJECTIVES: The aim of this study was to evaluate intrauterine adhesion formation after laparoscopic and laparotomic myomectomy. DESIGN: This is a prospective, multicenter, observational study (ClinicalTrials.gov ID: NCT04030273). METHODS: We included patients after laparotomic and laparoscopic myomectomy. All patients underwent postsurgical diagnostic hysteroscopy, after 3 months. The intrauterine adhesion rate and associated factors were investigated. RESULTS: Between January 2020 and December 2020, 38 and 24 consecutive patients underwent laparoscopic and laparotomic myomectomy, respectively. All diagnostic hysteroscopies were performed in the office setting without complications. Intrauterine adhesions were identified in 19.4% of women (95% CI: of 9-29%). Factors univariately associated (p < 0.2) with the presence of intrauterine adhesions after myomectomy were previous uterine surgery, the surgical approach (laparoscopic or laparotomic), the number of removed fibroids, the type and diameter of the largest myoma, and the opening of the uterine cavity. In the multivariable analysis, only the opening of the uterine cavity (odds ratio [OR] 51.99; 95% confidence interval [CI]: 4.53-596.28) and the laparotomic approach (OR, 16.19; 95% CI: 1.66-158.35) were independently associated with the identification of intrauterine adhesions after myomectomy. LIMITATIONS: One of the main limitations of our study is that we used uterine manipulator only in the laparoscopic group; in addition, we did not perform a preoperative hysteroscopy to evaluate the rate of intrauterine adhesions potentially present even before the myomectomy. CONCLUSIONS: The prevalence of intrauterine adhesions after 3 months from surgery was significantly associated with the opening of the uterine cavity and the laparotomic approach.

Uterine rupture during pregnancy: The URIDA (uterine rupture international data acquisition) study.

OBJECTIVE: To describe the characteristics and peripartum outcomes of patients diagnosed with uterine rupture (UR) by an observational cohort retrospective study on 270 patients. METHODS: Demographic information, surgical history, symptoms, and postoperative outcome of women and neonates after UR were collected in a large database. The statistical analysis searched for correlation between UR, previous uterine interventions, fibroids, and the successive perinatal outcomes in women with previous UR. RESULTS: Uterine rupture was significantly associated with previous uterine surgery, occurring, on average, at 36 weeks of pregnancy in women also without previous uterine surgery. UR did not rise exponentially with an increasing number of uterine operations. Fibroids were related to UR. The earliest UR occurred at 159 days after hysteroscopic myomectomy, followed by laparoscopic myomectomy (251 days) and laparotomic myomectomy (253 days). Fertility preservation was feasible in several women. Gestational age and birth weight seemed not to be affected in the subsequent pregnancy. CONCLUSION: Data analysis showed that previous laparoscopic and abdominal myomectomies were associated with UR in pregnancy, and hysteroscopic myomectomy was associated at earlier gestational ages. UR did not increase exponentially with an increasing number of previous scars. UR should not be considered a contraindication to future pregnancies.

Prediction Models of Adnexal Masses: State-of-the-Art Review.

IMPORTANCE: Several predictive models and scoring systems have been developed to differentiate between benign and malignant ovarian masses, in order to guide effective management. These models use combinations of patient characteristics, ultrasound markers, and biochemical markers. OBJECTIVE: The aim of this study was to describe, compare, and prioritize, according to their strengths and qualities, all the adnexal prediction models. EVIDENCE ACQUISITION: This was a state-of-the-art review, synthesizing the findings of the current published literature on the available prediction models of adnexal masses. RESULTS: The existing models include subjective assessment by expert sonographers, the International Ovarian Tumor Analysis models (logistic regression models 1 and 2, Simple Rules, 3-step strategy, and ADNEX [Assessment of Different NEoplasias in the adneXa] model), the Risk of Malignancy Index, the Risk of Malignancy Ovarian Algorithm, the Gynecologic Imaging Reporting and Data System, and the Ovarian-Adnexal Reporting and Data System. Overall, subjective assessment appears to be superior to all prediction models. However, the International Ovarian Tumor Analysis models are probably the best available methods for nonexpert examiners. The Ovarian-Adnexal Reporting and Data System is an international approach that incorporates both the common European and North American approaches, but still needs to be validated. CONCLUSIONS: Many prediction models exist for the assessment of adnexal masses. The adoption of a particular model is based on local guidelines, as well as sonographer's experience. The safety of expectant management of adnexal masses with benign ultrasound morphology is still under investigation.

Laparoscopic Intracapsular Myomectomy in Women 40 Years Old and Over with Symptomatic Uterine Fibroids. A Pilot Study.

Authors evaluated the impact of laparoscopic intracapsular myomectomy (LIM) in women 40 years of age and over with desire of future fertility compared with medical management of symptomatic fibroids, by a prospective cohort study in University affiliated Hospitals. This study includes a cohort of women 40 years of age and older with symptomatic intramural fibroids with desire of future fertility. Women with symptomatic fibroid uterus were offered to undergo LIM or medical management. They were encouraged to attempt conception either spontaneously or by assisted reproductive technology (ART) according to their individual preference. All women were followed for 2 years. Fibroid characteristics, pre- and post-surgical variables, including surgical complications, days of hospitalization, pregnancy rate, and obstetrical outcomes were collected. A total of 100 patient were included in the analysis. Fifty patients were assigned to the LIM group and 50 to the medical treatment group (MT). Groups were similar regarding age (43.5 ± 2.4 and 43.5 ± 2.4, p = 0.99), body mass index (23.8 ± 3.1 and 24.2 ± 3.1, p = 0.54), parity (0.46 ± 0.09 and 0.58 ± 0.09, p = 0.37), fibroid number (1.38 ± 0.6 and 1.46 ± 0.6, p = 0.53), and fibroid size (5.92 ± 1.62 cm vs. 5.94 ± 1.49 cm, p = 0.949). Of the patients who underwent LIM, 62% conceived within the study period compared with 56% in the control group ( p = 0.54). Pregnancy was achieved by ART in 44% of the patients of the LIM group and 30% in control group. There was no significant difference in pregnancy rates among the two groups regarding spontaneous pregnancy rate ( p = 0.332), nor in pregnancies obtained by ART with own eggs ( p = 0.146) and oocyte or embryo donation ( p = 0.821). The take home baby rate was 65% (20/31) in the LIM group and 61% (17/28) in the control group ( p = 0.7851). Both groups had similar rate of miscarriage ( p = 0.748). Patients 40 years old and over with symptomatic fibroid uterus who undergo LIM have similar subsequent fertility and obstetrical outcomes than women treated with medical management. LIM has no detrimental impact on future fertility in women 40 years old and over.

Follicle inhibition at the primordial stage without increasing apoptosis, with a combination of everolimus, verapamil.

The aim of the present study was to test whether inhibition of ovarian primordial follicles and subsequent activation can be achieved by transient mTOR inhibition. In this preclinical investigation, forty-five female immature Wistar rats were randomized in 5 groups. The control group received subcutaneous saline injections. The other groups received Everolimus, Everolimus plus Verapamil, Everolimus plus Fisetin, and Fisetin alone. Primary and secondary outcomes were measured in the left ovary after a treatment period of 8 weeks. Ten days later, animals received 35 IU FSH for 4 days and 35 IU of hCG on the 5th day. The same parameters were examined in the right ovary. AMH, estradiol, and progesterone levels were assessed at the end of both interventions. Significantly, more primordial and less atretic follicles were observed in the Everolimus plus Verapamil group. AMH and progesterone levels were substantially lower in the Everolimus group. Interestingly, after ovarian stimulation higher levels of AMH and progesterone were observed in the Everolimus plus Verapamil group. Immunoblot analysis of ovarian extracts revealed that the administration of Everolimus led to a significant reduction in the mTORC1-mediated phosphorylation of the 70-kDa ribosomal protein S6 kinase 1. This decrease was reversed in the presence of FSH after stopping drug administration. The expression of the anti-apoptotic molecule Bcl2 as well as of LC3-II and ATG12 was increased after removal of the Everolimus plus Verapamil combination, indicating reduced apoptosis and increased autophagy, whereas the levels of the proliferation marker PCNA in the granulosa cells were elevated, consistent with initiation of follicular growth.Thus, the combination of Everolimus plus Verapamil is capable of increasing the number of competent primordial follicles while reducing atresia.

Myomectomy during pregnancy: A systematic review.

OBJECTIVE: Uterine fibroids affect 2-10 % of pregnant women. Although usually asymptomatic, they may be associated with pregnancy complications. Myomectomy is preferably avoided antenatally, however, it has been reported in symptomatic cases that did not respond to conservative management. The aim of this study was to summarize the published literature and present the reported outcomes and associated risks of this procedure. STUDY DESIGN: A systematic research of the literature was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library, including case reports and case series. An effort was made to numerically analyse all parameters included in the case reports. RESULTS: Overall, 54 relevant articles were identified, including 97 patients. The median gestational age at diagnosis was 13 (range 6-26) weeks, while the median age at myomectomy was 16 (range 6-26) weeks. Abdominal pain, not responding to medical treatment was the most common indication for surgery. The median number of fibroids removed per patient was one (range 1-5). Most of them were subserous pedunculated or subserous and fundal. Laparotomy (78.4 %) was the principal surgical approach, however, laparoscopic and vaginal operations were also reported. The median duration of surgery was 53 (range 20-150) min. The histopathology revealed necrosis and degeneration as the main findings of removed fibroids. The pregnancy outcome was favourable in most of the cases, with few complications reported. CONCLUSION: Based on the limited published data, myomectomy during pregnancy appears as a safe procedure in cases of symptomatic uterine fibroids not responding to conservative management and therefore it may be considered, following appropriate counselling regarding the associated risks.

Pathways Involved in Premature Ovarian Failure: A Systematic Review of Experimental Studies.

Premature ovarian failure (POF), which may be undetectable for a long time, is associated with impaired fertility. The mechanisms involved in the pathogenesis of POF as well as the concomitant treatments are still unclear. Although many data exist, mainly produced by the study of transgenic animals under various experimental conditions, they remain fragmented. A systematic review of the pathways involved in premature ovarian failure was conducted. Data extraction was performed from experimental studies until 2019. The molecular processes and their correlation with the follicular developmental stage have been described. Furthermore, the effects in other cells, such as oocytes, granulosa and theca cells have been reported. An overall estimation was conducted.

Adrenergic and Cholinergic Uterine Innervation and the Impact on Reproduction in Aged Women.

In recent years, the development of Assisted Reproductive Technique, the egg and embryo donation changed substantially the role of the uterus in recent years. It provided a higher chance for a pregnancy even in women over 45 years or post-menopause. In fact, the number of aged patients and in peri/post-menopause in pregnancy is nowadays increasing, but it increases obstetrical and neonatal related problems. The human uterus is richly innervated and modified especially during pregnancy and labor, and it is endowed with different sensory, parasympathetic, sympathetic and peptidergic neurofibers. They are differently distributed in uterine fundus, body and cervix, and they are mainly observed in the stroma and around arterial vessel walls in the myometrial and endometrial layers. Many neurotransmitters playing important roles in reproductive physiology are released after stimulation by adrenergic or cholinergic nerve fibers (the so called sympathetic/parasympathetic co-transmission). Immunohistochemical study demonstrated the localization and quantitative distribution of neurofibers in the fundus, the body and cervix of young women of childbearing age. Adrenergic and cholinergic effects of the autonomous nervous system are the most implicated in the uterine functionality. In such aged women, the Adrenergic and AChE neurofibers distribution in the fundus, body and cervix is progressively reduced by increasing age. Adrenergic and AChE neurotransmitters were closely associated with the uterine arteries and myometrial smooth muscles, and they reduced markedly by ageing. The Adrenergic and AChE neurofibers decreasing has a dramatical and negative impact on uterine physiology, as the reduction of pregnancy chance and uterine growth, and the increase of abortion risk and prematurity.

The Biological Impact of Ulipristal Acetate on Cellular Networks Regulating Uterine Leiomyoma Growth.

Uterine Fibroids (UFs), or leiomyomas, represent the most frequent pelvic tumor in reproductive-aged women. Although of benign origin, UFs decrease fertility and cause significant reproductive dysfunctions. Compared to normal myometrium, UFs are characterized by a clinical and molecular heterogeneity as demonstrated by the presence of multiple genetic alterations and altered signaling pathways. Recently, selective progesteronereceptor modulators (SPRM), as ulipristal acetate (UPA), have demonstrated their clinical benefits by reducing tumor growth and extracellular matrix deposition. For these reasons, UPA is used in the clinical practice as an intermittent treatment for women symptomatic for UFs or, sometimes, before a myomectomy. However, drug effects on signaling pathways frequently upregulated in UFs remain largely unknown. In fact, the mechanisms of action of the UPA on UFs and on the surrounding areas are not yet understood. To learn more about UPA molecular mechanisms, UF samples were treated ex vivo with UPA and profiled for drug effects on selected markers. During this preliminary ex vivo UPA administration, significant changes were observed in the expression levels of proteins related to cell cycle regulation, cytoskeleton remodeling, and drug resistance. The UPA administration reduced cofilin, Erk and Src phosphorylation, p27 and ezrin protein levels, but not Akt phosphorylation and cyclin D1 and ß-catenin levels. This preliminary ex vivo biological analysis provided new insights into the mechanism of action of UPA in the treatment of UFs, which could better explain the biological functioning of the drug on UFs.

Submucous Fibroids, Fertility, and Possible Correlation to Pseudocapsule Thickness in Reproductive Surgery.

BACKGROUND AND OBJECTIVES: Fibroids are related to infertility. Fibroid pseudocapsule is a neurovascular bundle surrounding leiomyomas rich of neurofibers involved in myometrial biology. Authors evaluated, by a case-control study, the fibroid pseudocapsule (FP) thickness by ultrasound (US) and the histological measurements, according to uterine location of fibroids. METHODS: 137 consecutive patients undergoing hysterectomy for uterine myomas were enrolled and 200 myomas were evaluated. Before surgery, patients underwent an ultrasound (US) investigation to evaluate the number, the size, and the location of fibroids. After surgery, myoma-pseudocapsule-myometrium specimens were measured and evaluated by a single expert pathologist. Both US and histological data were collected and statistically analyzed. RESULTS: Our results confirm the relevant difference of FP thickness, particularly represented under the endometrium for submucous LMs. FPs near the endometrial cavity were considerably thicker than those of both intramural fibroids and subserous fibroids measured by US (P=0.0001) and histology (P=0.0001). A clear cut-off measurement at 2 mm (P=0.0001) was found between endometrial FPs and all other FPs for either US or histology measurements. CONCLUSION: The thickness of FP is considerably higher near the endometrial cavity when compared to those of both intramural and subserous LMs, suggesting a potential role either in fertility or in myometrial healing.

Laparoscopic cholecystectomy versus transvaginal natural orifice transluminal endoscopic surgery cholecystectomy: results of a prospective comparative single-center study.

BACKGROUND AND AIMS: Laparoscopic cholecystectomy (LC) in female individuals has been challenged recently by transvaginal natural orifice transluminal endoscopic surgery cholecystectomy (TVC). TVC has not been widely accepted as a standard procedure, even though it is reported to be a safe and painless alternative to LC. This prospective comparative study aims to not only prove equality of TVC and LC but to underline the advantages of TVC over LC with regard to postoperative pain. METHODS: This study presents an analysis of a single-center and single-surgeon study with 226 unselected consecutive cholecystectomies performed as either TVC or LC. RESULTS: A total of 226 female patients underwent surgery with either LC (136 cases) or TVC (90 cases). There were no postoperative adverse events. Twenty-two patients (24.2%) in the TVC group indicated 0 (no pain) on a visual analog scale postoperatively, whereas only 5 patients (3.7%) did so in the LC group (P = < .0001). Overall consumption of non-steroidal anti-inflammatory drugs was significantly less (P < .0001; t test) in the TVC group (mean, 1.2 ± 0.11 g) compared with the LC group (mean, 2.1 ± 0.1 g). Twenty-three patients (25.5%) in the TVC group needed no postoperative analgesics at all. CONCLUSIONS: TVC is a safe and painless procedure for patients with symptomatic cholelithiasis who are from various ethnic and cultural origins. This benefit, along with an equal safety profile compared with LC, should pave the way for wider application of TVC in women.

The combination of Everolimus with Verapamil reduces ovarian weight and vascular permeability on ovarian hyperstimulation syndrome: a preclinical experimental randomized controlled study.

The efficacy of pathways inhibition and the combined effect of Everolimus (mTOR inhibitor) and Verapamil (CYP3A inhibitor) in ovarian hyperstimulation syndrome (OHSS) need to be tested. Therefore, the impact of a leucotriene receptor antagonist, an anticoagulant, a GnRH antagonist as well as Everolimus plus Verapamil (at various doses and days of administration) on an OHSS rat model was tested. Sixty three female Wistar rats were randomly divided into seven groups. The control group received saline, while the OHSS group received rec-FSH for four consecutive days. The other five groups received rec-FSH for four days and Montelukast daily, Heparin daily, GnRH antagonist daily, Everolimus plus Verapamil in the last two days (half days group) and Everolimus plus Verapamil (half dose group) daily, respectively. All groups received also hCG at the fifth day. Significantly reduced ovarian weight was observed in the Everolimus plus Verapamil groups (half days and half-dose groups) and the Montelukast group compared to the OHSS group (p = 0.001 and p = 0.001, respectively). The vascular permeability was significantly reduced in the Everolimus plus Verapamil group (half dose group) and the GnRH antagonist group compared to the OHSS group (p < 0.001 and p = 0.011, respectively). However, estradiol and progesterone levels did not differ significantly between the groups. Studying the inhibition of different pathways, we concluded that the co-administration of Everolimus and Verapamil (at half dose) is beneficial for reducing ovarian weight and vascular permeability in an OHSS animal model.

The ovarian response to standard gonadotropin stimulation is influenced by AMHRII genotypes.

The aim of the current study was to explore whether anti-Müllerian hormone receptor II (AMHRII) genetic variants influence the hormonal profile and the ovarian response to standard gonadotropin stimulation of women undergoing medically assisted reproduction. Three hundred in vitro fertilization or intracytoplasmic sperm injection patients constituted the study population, while 300 women with at least one spontaneous pregnancy participated as controls. The follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and AMH levels were determined at the third day of the menstrual cycle. AMHRII 10A > G (rs11170555), 1749C > T (rs2071558) and -482A > G (rs2002555) polymorphisms were genotyped. The follicle and oocyte numbers, the follicle size and the clinical pregnancies were recorded. Regarding the AMHRII 1749C > T polymorphism, 1749CT women presented with higher total follicle and small follicle numbers compared to 1749CC women (p = 0.04 and p = 0.01, respectively). Whereas, as concerns the -482A > G polymorphism, -482AG women were characterized by higher total follicle and small follicle numbers comparing with -482AA women (p = 0.07 and p = 0.004, respectively). Finally, -482AG women presented with increased FSH levels compared to -482AA women (p < 0.05). However, no associations of AMHRII gene polymorphisms with serum AMH levels or clinical pregnancy rates were observed. AMHRII 1749C > T and -482A > G genetic variants were associated with the ovarian response to standard gonadotropin stimulation, affecting mainly the follicular growth.