Volume 43, Issue 2

Endometriosis is one of the most common diseases associated with infertility. It requires different therapeutic approaches, depending on the type, whether superficial, ovarian or deep endometriotic nodules, clinical presentation, age or origin of infertility. Patients with endometriosis should be considered a group of high-risk for infertility and any intervention should be planned taking this consideration into account. For many years, surgery was the only tool in improving fertility outcomes. Nowadays, it remains the gold standard for the treatment of endometriosis, but it should be carefully used because of its harmful potential, leading to premature ovarian insufficiency and further infertility. With the development of modern assisted reproductive techniques (ART), which can offer better results in terms of fertility, the role of surgery progressively decreased. Nowadays, therapeutic approach is complex and multidisciplinary teams should be guiding individual treatment for each woman. Options include medical treatment, surgery, in vitro fertilization (IVF) or oocytes/embryo/ovarian tissue cryopreservation. There is a constant effort in developing diagnostic scores, in order to predict risk of infertility and create standard of practice, offering a long-term approach in terms of fertility preservation and quality of life.

Endometriosis negatively impacts the lives of countless women around the world. When medical management fails to improve the quality of life for women with either previously confirmed or suspected endometriosis often a decision must be made whether or not to proceed with surgery. When deeply infiltrating disease is diagnosed either clinically or by imaging studies often medical management alone will not suffice without excisional surgery. Surgery for endometriosis, especially deeply infiltrating disease, is not without risks. Aside from common risks of surgery endometriosis may also involve pelvic nerves, which can be hard to recognize to the untrained eye. Identification of pelvic nerves commonly encountered during endometriosis surgery is paramount to avoid inadvertent injury to optimize function outcomes. Injury to pelvic nerves can lead to urinary retention, constipation, sexual dysfunction, and refractory pain. However, nerve-sparing surgery for endometriosis has been proven to mitigate these complications and enhance recovery following surgery. Here we review the benefits of nerve-sparing surgery for deeply infiltrating disease.

Endometriosis negatively impacts the lives of countless women around the world. When medical management fails to improve quality of life often women are left making a decision whether or not to proceed with surgery. With endometriomas, patient’s surgical options include complete surgical removal or drainage via laparoscopy. Here, we review the literature to discuss both techniques, excision and drainage of endometriomas, and what the research supports for endometrioma management.

Endometriosis of the diaphragm has been gaining more attention in the practice of gynecologists and thoracic surgeons in recent years. Understanding related symptoms and developing imaging methods have improved their approach. A review of the literature was performed with the aim to report on incidence, diagnosis, treatment and prognosis of diaphragmatic endometriosis. We also cover the issue of the Thoracic Endometriosis Syndrome (TES). Complaints of cyclic chest pain in patients of childbearing age should have as differential diagnosis the presence of thoracic endometriosis. Catamenial pneumothorax is the main manifestation of diaphragmatic endometriosis and Thoracic Endometriosis Syndrome. Other possible manifestations are hemothorax, pulmonary nodules, and diaphragmatic hernia. Despite the possibility of drug treatment, many patients will be submitted to surgical treatment. The minimally invasive approach should be the one of choice. The robotic pathway allows for an easier approach due to its ability to articulate robotic arms, allowing the treatment of lesions in hard-to-reach locations, such as the posterior part of the diaphragm. Multidisciplinary treatment should be used in most cases, as only abdominal approach is not sufficient for the diagnosis and treatment of lesions in the thoracic cavity. The approach of endometriosis of the diaphragm and Thoracic Endometriosis Syndrome should be multidisciplinary, allowing the improvement of quality of life in most patients. Highlights – The incidence of diaphragmatic endometriosis is increasing – Use of MRI and/or CT will allow better diagnosis – Although medical treatment is an option, usually patient will need surgical approach – Minimally invasive approach should be the gold standard (laparoscopy or robotics) – Multidisciplinary management is mandatory – Randomized controlled trials should be done to enhance treatment – Early referral of patients with thoracic endometriosis will allow a better successful treatment rate

Endometriosis is a complex chronic inflammatory condition that can create a multitude of bothersome painful symptoms for women. Bowel endometriosis is often misdiagnosed or overlooked leading to years of suffering for many women. The surgical management of bowel endometriosis varies based on extent of disease as well as surgeon experience. Surgical treatment for bowel endometriosis is complex and a variety of intraoperative and postoperative complications must be considered. Two significant postoperative complications for bowel endometriosis include anastomotic leak and fistula formation. There is continued debate regarding the appropriate surgical treatment for bowel endometriosis. Aggressive surgery with segmental bowel resection is being utilized more cautiously, with an increase in less aggressive shaving or disc excision techniques. Historic beliefs regarding the limitations of shaving and disc excision are being challenged, and with a reduction in morbidity these less aggressive techniques are winning favor among gynecologic surgeons. Shaving, discoid excision, and segmental bowel resection are all feasible surgical management options for bowel endometriosis. Segmental resection is associated with the highest rates of both anastomotic leak and fistula formation, while shaving is associated with the lowest.

Endometriosis is a gynecological disease affecting about 10% of the female population. The multifactorial hormonal, inflammatory, genetic, mental and behavior pathogenesis can result in chronic pelvic pain, blooding disorders and infertility causing disruption of quality of life. Correct diagnosis of the extension and topography is substantial in defining the adequate therapeutic strategy. In an increasing proportion of the cases, endometriosis is being managed medically and para-medically; diagnostic or therapeutic surgery can often be avoided or delayed. Transvaginal sonography is considered being the first-line imaging method in the diagnosis of pelvic endometriosis. The paradigm shift from the belief that endometriosis only affects women of reproductive age has drawn attention to endometriosis in both premenarchal and postmenopausal patients. This review resumes the actually recommended ultrasound signs in the case of patients in menstrual age. Specific diagnostic approaches in adolescent and menopausal patients are highlighted.

Fertility preservation is an important option to consider for young women with low-grade early ovarian cancer. Fertility-sparing surgery (“ FSS ”) permits the conservation of the uterus and one of the ovaries. This technique is considered safe for stages IA G1, G2 and probably safe for IC G1 epithelial and non-epithelial ovarian cancers. There are still uncertainties and FSS is not fully accepted for stage IC G1, G2 and clear cell carcinoma. The difficulty in choosing the best option lies in the fact that there is a lack of prospective randomized studies, due to ethical and organizational issues. Retrospective studies and reviews showed reassuring results for FSS in terms of relapse and long term survival. The spontaneous pregnancy rate seems to decrease after FSS, but chemotherapy does not seem to have an impact on fertility rates. Compared with the general population, assisted reproductive techniques are considered safe and with similar fertility results.

Objectives Genetic testing rates for hereditary breast and ovarian cancer (HBOC) have steadily increased during the past decades resulting in a growing population of young and healthy mutation carriers. Available data on fertility issues in BRCA mutation carriers is rising but the results remain to some extent still conflicting. We have performed a systematic literature review in order to get an overview concerning the current evidence on fertility issues in BRCA mutation carriers. Data were analyzed critically with the aim to deliver physicians a solid basis for (onco) fertility counseling in women with BRCA mutations. Content We present the latest data on cancer risks in women with HBOC and analyze the influence of cancer treatment and preventive surgery on the reproductive potential. Epidemiological studies on fertility issues in BRCA mutation carriers showed heterogeneous results. However, several authors showed a decreased ovarian reserve with lower Anti-Müllerien hormone (AMH) levels and poorer response to ovarian stimulation in BRCA positive women. The diagnosis of BRCA mutations influences reproductive decision-making. Additionally, the shortened reproductive window and the need to complete family planning early has a significant psychological impact. Summary and Outlook This article highlights the importance of fertility counseling in BRCA mutation carriers. Individual fertility counseling is mandatory. Fertility preservation strategies should be discussed. Highlights – BRCA mutation carriers have a shortened fertile window. – Cancer treatment and preventive surgery impair fertility. – Current data indicate decreased ovarian reserve. – Infertility treatment does not increase the risk for breast and ovarian cancer. – Awareness and acceptance rates for PND and PGD are still low. – Fertility counseling and support for young women with BRCA mutations is mandatory. – Mutation carriers should not delay child-bearing.

Borderline ovarian tumors (BOTs) represent around 15% of all epithelial ovarian cancer. Around one third of those patients is under 40 and has not completed childbearing when the tumor is diagnosed. Cancer survivors are more and more concerned about their future fertility since a large proportion of those with BOTs are young. Whatever the tumor stage, information regarding future fertility after treatment and fertility preservation (FP) options must be delivered to all patients before treatment. A multidisciplinary team will discuss and propose personalized treatment and FP strategies. Nowadays, the FP options offered to patients with BOT are the followings: i) minimal invasive conservative surgery, ii) oocyte cryopreservation after controlled ovarian stimulation (COS) or in vitro maturation (IVM) and iii) ovarian tissue cryopreservation. Generally, the most common strategy to preserve future fertility is represented by minimal invasive conservative surgery. However, with the remarkable success and evolution of assisted reproductive technologies (ART) – notably progress and efficiency in COS and oocyte vitrification – have led to offer another potential approach for FP consisting in oocyte cryopreservation. Several COS protocols, such as random start or dual stimulation associating tamoxifen or aromatase inhibitors with gonadotropins provide similar results when compared to standard protocols while providing safety by minimizing the risk of high estrogen exposure. When COS is contraindicated, oocyte cryopreservation can still be possible throw IVM. Even though, oocyte competence after IVM is lower than that obtained after COS. A less used approach is cryopreservation of ovarian tissue, consisting in freezing ovarian cortex fragments for a future thawing and graft. Some concerns and limitations regard the ovarian cortex graft and the risk of reintroducing malignant cells once performed. Nonetheless, the latter it is the only option in prepubertal patients.

Objectives The balance between oxidative stress and antioxidant defense has been reported to differ between women with endometriosis and patients with its malignant transformation. The aim of this study is to investigate changes in redox balance in endometriosis and endometriosis-related ovarian cancer (EAOC) by simultaneously measuring iron-related compounds and bilirubin. Methods This study included 235 patients with a histopathologically confirmed diagnosis of endometriosis (n=178) and EAOC (n=57). Cyst fluid samples were collected in Nara Medical University hospital from January 2013 to May 2019. The levels of iron-related compounds (total iron, heme iron, free iron, oxyhemoglobin [oxyHb], methemoglobin [metHb], and metHb/oxyHb ratio) and bilirubin were measured. Results Total iron, heme iron, free iron, metHb/oxyHb ratio, and bilirubin were significantly elevated in endometriosis compared to EAOC. In both endometriosis and EAOC, iron-related compounds in the cyst were correlated with each other. There was no statistically significant difference in oxyHb and metHb levels between the two groups, but the metHb/oxyHb ratio was significantly higher in endometriosis than in EAOC. Bilirubin was positively correlated with total iron and free iron in EAOC, but there was no correlation between bilirubin and iron-related compounds in endometriosis. Conclusions Iron-induced oxidative stress in endometriosis may exceed bilirubin-dependent antioxidant capability, while redox homeostasis in EAOC can be maintained by at least bilirubin.

Backgrounds Hepatocellular carcinoma (HCC) is a diversity of hepatocellular neoplasms and is more prevalence in people with chronic liver disease and cirrhosis. It has been revealed that modification in miRNA regulation possibly will be elaborated in HCC pathogenesis. Materials and methods In this research 40 samples of HCC subjects and 40 samples of healthy liver were considered. Total RNA was obtained from paraffin-embedded tissue blocks and miR-515, miR-623 and miR-1272 gene expression levels were quantified by Real-Time Quantitative Reverse Transcription PCR. Likewise, the Notch protein quantity was assayed in ffpe materials by immunohistochemistry. Results Our study disclosed that Notch protein deals was ominously elevated in cancer cells than healthy cells (p<0.05). Data analysis also displayed that miR-515, miR-623 and miR-1272 expression levels were 3.8, 4.7, and 2.9 fold in normal tissues, respectively (p<0.05). Furthermore, it was found that expression levels of these genes are not dependent by hepatitis B and hepatic cirrhosis and it could be used as a marker of high specificity and sensitivity for the diagnosis of HCC. Discussions Our study demonstrated main role of miR-515, miR-623 and miR-1272 in HCC pathogenesis and similarly disclosed that these genes expression could be utilized in HCC prognosis.

Objectives To evaluate the anticancer effects of calcitriol and cholecalciferol against different cell lines of breast cancer in monotherapy settings and in combination with raloxifene. Methods The antiproliferative, anti-migratory, and apoptotic induction effects were assessed by MTT, wound healing, and flow cytometry assays, respectively. Results Calcitriol and cholecalciferol exhibited antiproliferative effects against T47D, MCF-7, and MDA-MB-231 in a time and concentration-dependent manner. The IC 50 values of calcitriol were in the range of 0.05–0.25 μM while that for cholecalciferol were in the range of 3–100 μM. Furthermore, the results showed that calcitriol and cholecalciferol exhibited anti-migratory effects on MDA-MB-231, an apoptotic induction effect on MCF-7 cells, and a synergistic effect when combined with raloxifene. Conclusions Calcitriol and cholecalciferol exhibited anticancer effects and may be used as chemosensitizers.

Objectives The purpose of this study was to evaluate serum G protein-coupled estrogen receptor-1 (GPER1) levels in non-pregnant and pregnant with and without gestational diabetes mellitus (GDM). Methods The study comprised 40 pregnant women with (n=20) and without GDM (n=20) and 20 healthy non-pregnant women. Data as maternal age, gestational age, and body mass index (BMI) of participants were recorded and serum samples were collected. Serum GPER1 levels were measured by enzyme-linked immunosorbent assays. Results Serum GPER1 level was significantly higher in GDM (p=0.03) and non-pregnant women (p=0.005) than those of normal pregnancy. There was no significant correlation between the serum GPER1 levels age (r=0.18, p=0.34), gestational age (r=−0.22, p=0.47), and BMI (r=0.004, p=0.975). Conclusions Our results suggest that changes in serum GPER1 levels in pregnancy and GDM may be associated with estrogen. More detailed studies should be conducted to monitor the changes and their interactions in serum sex hormones and serum GPER1 levels during GDM.

Objectives Anorexia, fatigue and pruritus are common complications of hemodialysis (HD) patients. Today, the use of medicinal plants is more than synthetic drugs due to their safety. Therefore, we designed a randomized controlled clinical trial to evaluate the effects of Helichrysum psudoplicatum ( H. psudoplicatum ) supplementation on biochemical parameters, pruritus intensity, fatigue, quality of life and anorexia in HD patients . Methods This randomized, double-blind, placebo-controlled trial was performed on 50 subjects with, aged 55–65 years old. HD patients were randomly divided into two groups. Intervention group received 250 mg/day of H. psudoplicatum supplement capsule for 6 weeks (n=25), and the placebo group was given placebo capsule for the same time duration and dosage (n=25). The serum concentrations of urea, creatinine, albumin and hemoglobin were measured enzymatically methods. Anorexia, pruritus intensity, quality of life the dialysis patients with pruritus and fatigue score was measured using a Simplified Nutritional Appetite Questionnaire (SNAQ), Numerical rating scale (NRS), Fatigue severity scale (FSS) and ItchyQoL questionnaire, respectively. Shapiro–Wilk and independent-samples t-test or Mann–Whitney test were used for the analysis of the data. Results The results showed that the H. psudoplicatum supplementation significantly improved the pruritus intensity, quality of life the dialysis patients with pruritus and fatigue in HD patients, for 6 weeks (p<0.001). However, it did not significantly effect on the anorexia, albumin, hemoglobin, urea, creatinine, arm circumference, and body mass index (p>0.05). Conclusions According to the results of this study, H. psudoplicatum supplementation can be effective as an adjunct therapy to improve pruritus intensity, quality of life, fatigue and relative improvement of anorexia in HD patients.

Objectives Traditional Unani medicine plays a major role in maintaining health in developing countries. For ages, Unani physicians have described many Classical Unani Formulations (CUF) for their anti-cancerous action ( Dāfiʻ-i-saraṭān ) in the human population. These formulations contain various individual drugs which also have anticancer activity. The present study was designed to screen and compare cytotoxic and antioxidant properties of different extracts of  Agaricus albus  L. ( A. albus ), a drug used in the Unani system of medicine on human breast cancer cell lines (MCF-7). Methods Cytotoxic effect was assessed using MTT assay kit and free radical scavenging activity was done by using DPPH assay. Aqueous, hydro-ethanol and methanolic extracts were used at different concentrations. Results All extracts were shown good antioxidant and cytotoxic activity. Among all extracts, maximum cytotoxic effect was observed in methanolic extract and aqueous extract at the concentration of 1,000 μg against MCF-7 cell line in comparison to paclitaxel. The maximum antioxidant activity was observed in the hydroethanolic extract at the concentration of 1,000 μg against the MCF-7 cell line in comparison to ascorbic acid. Conclusions The present study advocates, the anticancer and antioxidant property of A. albus and suggests that this drug may be used as a potential drug for cancer treatment after a successful and detailed preclinical study and clinical trial.

The need for luteal phase support in IVF/ICSI is well established. A large effort has been made in the attempt to identify the optimal type, start, route, dosage and duration of luteal phase support for IVF/ICSI and frozen embryo transfer. These questions are further complicated by the different types of stimulation protocols and ovulation triggers used in ART. The aim of this review is to supply a comprehensive overview of the available types of luteal phase support, and the indications for their use. A review of the literature was carried out in the effort to find the optimal luteal phase support regimen with regards to pregnancy related outcomes and short and long term safety. The results demonstrate that vaginal, intramuscular, subcutaneous and rectal progesterone are equally effective as luteal phase support in IVF/ICSI. GnRH agonists and oral dydrogesterone are new and promising treatment modalities but more research is needed. hCG and estradiol are not recommended for luteal phase support. More research is needed to establish the most optimal luteal phase support in frozen embryo transfer cycles, but progesterone has been shown to improve live birth rate in some studies. Luteal phase support should be commenced between the evening of the day of oocyte retrieval, and day three after oocyte retrieval and it should be continued at least until the day of positive pregnancy test. So, in conclusion still more large and well-designed RCT’s are needed to establish the most optimal luteal phase support in each stimulation protocol, and especially in frozen embryo transfer.

Over the past decades, obesity and infertility in men increased in parallel, and the association between both phenomena have been examined by several researchers. despite the fact that there is no agreement, obesity appears to affect the reproductive potential of men through various mechanisms, such as changes in the hypothalamic-pituitary-testicular (HPT) axis, spermatogenesis, sperm quality and/or alteration of sexual health. Leptin is a hormone produced by the adipose tissue, and its production elevates with increasing body fat. Many studies have supported the relationship between raised leptin production and reproductive function regulation. In fact, Leptin acts on the HPT axis in men at all levels. However, most obese men are insensitive to increased production of endogenous leptin and functional leptin resistance development. Recently, it has been recommended that Kisspeptin neurons mediate the leptin’s effects on the reproductive system. Kisspeptin binding to its receptor on gonadotropin-releasing hormone (GnRH) neurons, activates the mammal’s reproductive axis and stimulates GnRH release. Increasing infertility associated with obesity is probably mediated by the Kisspeptin-GnRH pathway. In this review, the link between obesity, kisspeptin, leptin, and male fertility will be discussed.