BMAL1 positively correlates with genes regulating steroidogenesis in human luteinized granulosa cells.

In brief: In this study, we examined the relationship between BMAL1 expression and the genes regulating steroid biosynthesis in human luteinized granulosa cells. BMAL1 function is crucial for steroid production and proper ovarian function, highlighting the importance of circadian clock regulation in female reproductive health. Abstract: Human luteinized granulosa cells were collected to analyze circadian clock gene expression and its effect on the genes regulating steroid biosynthesis. We used siRNA to knock down the expression of BMAL1 in KGN cells. We measured the expression levels of genes regulating steroid biosynthesis and circadian clock RT-qPCR. We demonstrated that BMAL1 expression positively correlates with genes regulating steroid biosynthesis (CYP11A1, CYP19A1, STAR, and ESR2). The knockdown of BMAL1 in KGN cells revealed a significant decrease in steroid synthase expression. In contrast, when BMAL1 was overexpressed in KGN and HGL5 cells, we observed a significant increase in the expression of steroid synthases, such as CYP11A1 and CYP19A1. These results indicated that BMAL1 positively controls 17ß-estradiol (E2) secretion in granulosa cells. We also demonstrated that dexamethasone synchronization in KGN cells enhanced the rhythmic alterations in circadian clock genes. Our study suggests that BMAL1 plays a critical role in steroid biosynthesis in human luteinized granulosa cells, thereby emphasizing the importance of BMAL1 in the regulation of reproductive physiology.

Toward the Establishment of a Harmonized Physicochemical Profiling Platform for Therapeutic Oligonucleotides: A Case Study for Aptamers Where the Higher-Order Structure Influences Physical Properties.

Oligonucleotides are short nucleic acids that serve as one of the most promising classes of drug modality. However, attempts to establish a physicochemical evaluation platform of oligonucleotides for acquiring a comprehensive view of their properties have been limited. As the chemical stability and the efficacy as well as the solution properties at a high concentration should be related to their higher-order structure and intra-/intermolecular interactions, their detailed understanding enables effective formulation development. Here, the higher-order structure and the thermodynamic stability of the thrombin-binding aptamer (TBA) and four modified TBAs, which have similar sequences but were expected to have different higher-order structures, were evaluated using ultraviolet spectroscopy (UV), circular dichroism (CD), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). Then, the relationship between the higher-order structure and the solution properties including solubility, viscosity, and stability was investigated. The impact of the higher-order structure on the antithrombin activity was also confirmed. The higher-order structure and intra-/intermolecular interactions of the oligonucleotides were affected by types of buffers because of different potassium concentrations, which are crucial for the formation of the G-quadruplex structure. Consequently, solution properties, such as solubility and viscosity, chemical stability, and antithrombin activity, were also influenced. Each instrumental analysis had a complemental role in investigating the higher-order structure of TBA and modified TBAs. The utility of each physicochemical characterization method during the preclinical developmental stages is also discussed.

Ovarian Mesonephric-like Adenocarcinoma Recurring With a Rhabdomyosarcoma Component: A Case Report.

Mesonephric-like adenocarcinoma (MLA) has recently been described as a tumor of the endometrium or ovaries, which, morphologically and immunohistochemically, resembles mesonephric adenocarcinoma arising mostly in the uterine cervix. Herein, we report, to our knowledge, the first case of ovarian MLA that developed into an extremely rapidly growing recurrent mesonephric-like carcinosarcoma, as confirmed by a genomic profiling test. A 51-year-old woman underwent chemotherapy with complete debulking surgery for ovarian carcinoma. Pathologically, the patient was diagnosed with stage IVB ovarian MLA. Subsequent to 15 months of complete remission, an enhanced computed tomography scan revealed a solid tumor of 10 cm diameter in the abdominal cavity. Secondary surgery was terminated with a 2 cm 2 tumor biopsy specimen collection considering perioperative complications. Histologically, the tumor consisted of short spindle cells, and immunohistochemical staining revealed a rhabdomyosarcomatous profile without an epithelial component. Despite treatment for the sarcoma, she died 3 months after the detection of the tumor. The genomic profiling of the primary ovarian carcinoma and secondary resected tumor biopsy specimens revealed an identical KRAS mutation in both. Therefore, we concluded that the ovarian MLA recurred with a rhabdomyosarcoma component.

Retrospective comparative study of robot-assisted surgery, laparoscopic surgery, and laparotomy for endometrial cancer in patients with a low risk of recurrence.

AIM: Minimally invasive surgeries for endometrial cancer are increasing worldwide. In Japan, some articles have examined surgical outcomes, but only a few have addressed oncological outcomes. This study aims to compare robot surgery, laparoscopic surgery, and laparotomy in terms of surgical and oncological outcomes within a low-risk group for endometrial cancer recurrence. METHODS: This study included patients with endometrial cancer deemed to be at low risk of recurrence and who underwent surgery between January 2011 and December 2020. We studied 99 patients who underwent robot surgery, 85 patients who underwent laparotomy, and 77 patients who underwent laparoscopic surgery. Surgical and oncological outcomes were compared retrospectively for these groups of patients. RESULTS: The median follow-up period was 47, 61, and 60 months in the laparotomy, laparoscopy, and robotic groups, respectively. The three groups had similar perioperative and pathological data. No significant differences in overall survival and disease-free survival were observed among the groups. Univariate and multivariate analyses conducted on the overall study population for disease-free survival and overall survival showed that the surgical approach did not have any influence. Minimally invasive surgery groups had longer operating times compared to the laparotomy group, but they had significantly less blood loss. The number of resected pelvic lymph nodes was similar, and the complication rate was not significant. CONCLUSIONS: Robot-assisted surgery and laparoscopic surgery were found to be less invasive and showed similar oncologic outcomes compared to laparotomy surgery for endometrial cancer in patients with a low risk of recurrence.

Regulatory action of PGRMC1 on cyclic AMP-mediated COX2 expression in human endometrial cells.

Human endometrial stromal cells (ESCs) undergo differentiation, known as decidualization, and endometrial epithelial cells mature around the embryo implantation stage. In the uterus, cyclooxygenase 2 (COX2), the rate-limiting enzyme that produces prostaglandin E2, is expressed in endometrial stromal and epithelial cells, and promotes decidualization of the former cells. Our recent study demonstrated that progesterone receptor membrane component 1 (PGRMC1) is downregulated during decidualization and may be involved in cellular senescence associated with decidualization via the transcription factor forkhead box protein O1 (FOXO1). Therefore, we investigated the role of PGRMC1 in COX2 expression during differentiation and maturation of endometrial stromal and epithelial cells. Inhibition or knockdown of PGRMC1 significantly enhanced differentiation stimuli-induced COX2 expression in both cell types. However, this COX2 expression was suppressed by FOXO1 knockdown or nuclear factor-kappa B (NF-κB) inhibition. Silencing of COX2 expression inhibited PGRMC1 knockdown-induced expression of decidual markers in ESCs. Thus, PGRMC1 may be linked to FOXO1- and NF-κB-mediated COX2 expression in endometrial cells. Taken together, our data suggest that downregulation of PGRMC1 expression facilitates differentiation of endometrial cells, i.e., decidualization and glandular maturation, via upregulation of COX2 expression.

COVID-19 mRNA vaccination status and concerns among pregnant women in Japan: a multicenter questionnaire survey.

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women. METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively. RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination. CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.

Effect of a web-based fertility preservation training program for medical professionals in Japan.

BACKGROUND: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation. METHODS: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program. RESULTS: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity. CONCLUSION: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors.

The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship.

The circadian rhythm, which is necessary for reproduction, is controlled by clock genes. In the mouse uterus, the oscillation of the circadian clock gene has been observed. The transcription of the core clock gene period (Per) and cryptochrome (Cry) is activated by the heterodimer of the transcription factor circadian locomotor output cycles kaput (Clock) and brain and muscle Arnt-like protein-1 (Bmal1). By binding to E-box sequences in the promoters of Per1/2 and Cry1/2 genes, the CLOCK-BMAL1 heterodimer promotes the transcription of these genes. Per1/2 and Cry1/2 form a complex with the Clock/Bmal1 heterodimer and inactivate its transcriptional activities. Endometrial BMAL1 expression levels are lower in human recurrent-miscarriage sufferers. Additionally, it was shown that the presence of BMAL1-depleted decidual cells prevents trophoblast invasion, highlighting the importance of the endometrial clock throughout pregnancy. It is widely known that hormone synthesis is disturbed and sterility develops in Bmal1-deficient mice. Recently, we discovered that animals with uterus-specific Bmal1 loss also had poor placental development, and these mice also had intrauterine fetal death. Furthermore, it was shown that time-restricted feeding controlled the uterine clock's circadian rhythm. The uterine clock system may be a possibility for pregnancy complications, according to these results. We summarize the most recent research on the close connection between the circadian clock and reproduction in this review.

Anthropometric measurements of term singletons at 6 years of age born from fresh and frozen embryo transfer: A multicenter prospective study in Japan.

Purpose: The purpose of this study is to compare anthropometric measurements between term singletons conceived via fresh embryo transfer (FreET) and frozen embryo transfer (FET) and those born via natural conception (NC) or fertility treatments milder than assisted reproductive technology (non-ART) at 6 years of age. Methods: A total of 8149 children were enrolled, and questionnaires about anthropometric measures (weight, height, BMI) were addressed to parents, when the children were 1.5, 3, and 6 years of age. A total of 3299 term singletons were enrolled at birth: 533, 476, 916, and 1374 in the NC, non-ART, FreET, and FET groups, respectively. Results: A total of 1635 term singletons (290, 176, 467, and 702 in the NC, non-ART, FreET, and FET groups respectively) were enrolled until 6 years of age (follow-up rate, approximately 50%). When non-ART group was used as control, the FreET children were 1.0 cm taller than the non-ART children at 6 years of age, after adjusting for confounding factors. However, no differences were observed in the anthropometric data among the non-ART, ART, and NC children at 6 years of age. Conclusion: At 6 years of age, term singletons were taller in the FreET group than in the non-ART group, after adjusting for confounders.

A case of recurrent endometrial cancer with long-term complete remission following pembrolizumab-induced severe immune-related adverse event colitis.

Endometrial cancer is generally diagnosed at an early stage and has a good prognosis, although once it recurs, the prognosis is poor because of few therapeutic options. Since endometrial cancer has a high frequency of microsatellite instability-high/mismatch repair deficiency, the anti-PD-1 antibody pembrolizumab is expected to be one of the key therapeutic agents for recurrent endometrial cancer. Immune-related adverse events (irAEs) are autoimmune-like unique and occasionally life-threatening side effects of immune checkpoint inhibitors. Here, we report a rare case of recurrent endometrial cancer that showed long-term complete remission after developing relapsing severe irAE colitis following the introduction of pembrolizumab.

Feasibility of a mobile cardiotocogram device for fetal heart rate self-monitoring in low-risk singleton pregnant women.

AIM: This study aimed to clarify the feasibility of a mobile cardiotocogram (CTG) device for self-monitoring fetal heart rate (FHR) in low-risk singleton pregnant women. METHODS: This study was conducted at six university hospitals and seven maternity clinics in Japan. Using a mobile cardiotocogram device (iCTG, Melody International Ltd., Kagawa, Japan), participants of more than 34 gestational weeks measured the FHR by themselves at least once a week until hospitalization for delivery. We evaluated the acquisition rate of evaluable FHR recordings and the frequency of abnormal FHR patterns according to the CTG classification system of the Japan Society of Obstetrics and Gynecology (JSOG). The participants also underwent a questionnaire survey after delivery to evaluate their satisfaction level of self-monitoring FHR using the mobile CTG device. RESULTS: A total of 1278 FHR recordings from 101 women were analyzed. Among them, 1276 (99.8%) were readable for more than 10 min continuously, and the median percentage of the total readable period in each recording was 98.9% (range, 51.4-100). According to the JSOG classification system, 1245 (97.6%), 9 (0.7%), 18 (1.4%), and four (0.3%) FHR patterns were classified as levels 1, 2, 3, and 4, respectively. The questionnaire survey revealed high participant satisfaction with FHR self-monitoring using the iCTG. CONCLUSION: The mobile CTG device is a feasible tool for self-monitoring FHR, with a high participant satisfaction level.

Human Chorionic Villous Differentiation and Placental Development.

In humans, the placenta provides the only fetomaternal connection and is essential for establishing a pregnancy as well as fetal well-being. Additionally, it allows maternal physiological adaptation and embryonic immunological acceptance, support, and nutrition. The placenta is derived from extra-embryonic tissues that develop rapidly and dynamically in the first weeks of pregnancy. It is primarily composed of trophoblasts that differentiate into villi, stromal cells, macrophages, and fetal endothelial cells (FEC). Placental differentiation may be closely related to perinatal diseases, including fetal growth retardation (FGR) and hypertensive disorders of pregnancy (HDP), and miscarriage. There are limited findings regarding human chorionic villous differentiation and placental development because conducting in vivo studies is extremely difficult. Placental tissue varies widely among species. Thus, experimental animal findings are difficult to apply to humans. Early villous differentiation is difficult to study due to the small tissue size; however, a detailed analysis can potentially elucidate perinatal disease causes or help develop novel therapies. Artificial induction of early villous differentiation using human embryonic stem (ES) cells/induced pluripotent stem (iPS) cells was attempted, producing normally differentiated villi that can be used for interventional/invasive research. Here, we summarized and correlated early villous differentiation findings and discussed clinical diseases.

Possible Roles of Calreticulin in Uterine Decidualization and Receptivity in Rats and Humans.

Previous in vitro studies have suggested that calreticulin (CALR), which is responsible for the folding and quality control of glycoproteins, may be associated with decidualization. However, its precise role in regulating decidualization has not been explored in vivo. Here, we used pregnant rat models to examine endometrial CALR expression during the peri-implantation period. We also examined whether polypectomy, a procedure that could ameliorate infertility, alters the endometrial expression levels of CALR and several implantation factors in women diagnosed as infertile. In rats, uterine CALR was expressed at a high level at the implantation site, and a marked increase in CALR expression was observed in decidual cells of normal pregnancy. In addition, endometrial CALR expression was enhanced by either administration of estradiol-17ß in the delayed implantation rat model or the artificial induction of decidualization in the pseudopregnant rat. In cultured stromal cells, siRNA-mediated silencing of CALR inhibited the decidual stimulus-induced expression of prolactin, decidual/trophoblast prolactin-related protein, and connexin 43. In humans, the endometrial expression levels of the mRNAs encoding CALR and the implantation-related factor insulin-like growth factor binding protein (IGFBP)-7 tended to increase after polypectomy. The strongest positive correlation between expression levels before polypectomy was observed for IGFBP-7 and CALR, and the strength of this correlation increased after the surgery. Thus, endometrial CALR may play a role in the formation of decidua, and the polypectomy of infertile patients may result in the co-operative expression of endometrial factors, including CALR, that could enhance endometrial receptivity.

Investigation of clinicopathological features of vulvar cancer in 1068 patients: A Japanese Gynecologic Oncology Group (JGOG) nationwide survey study.

OBJECTIVE: Vulvar cancer is a rare malignancy in the aging population, and optimizing treatment strategies requires large-scale investigation of the clinicopathological features of this disease. In Japan, no such surveys have been conducted in the past 30 years. This large-scale retrospective multi-center study aimed to examine the clinicopathological features of vulvar cancer in Japan. METHODS: Upon obtaining ethical approval by the participating institutions' review boards, the medical records of patients with vulvar cancer, who were treated between 2001 and 2010 were reviewed. The impact of clinicopathological factors on overall survival (OS) was investigated using a multivariate Cox regression model. RESULTS: After applying the inclusion and exclusion criteria, 1068 patients treated in 108 centers were included. The median age was 72 years. The disease was in stage I in 402 patients (37.6%), stage II in 249 patients (23.3%), stage III in 252 patients (23.6%), and stage IV in 165 patients (15.4%). Squamous cell carcinoma, Paget's disease, adenocarcinoma, and other diseases were diagnosed in 773 (72.4%), 154 (14.4%), 59 (5.5%), and 82 (7.7%) patients, respectively. Positive inguino-femoral lymph nodes were found in 265 (24.8%) patients. The 5-year OS rate for stage I, II, III, and IV vulvar cancer were 85.6%, 75.1%, 48.8%, and 40.0%, respectively. CONCLUSION: Our study shows that advanced age, disease stage, histological diagnosis, tumor diameter, and lymph node metastases significantly affect the OS of patients with vulvar cancer in Japan.

Early feasibility surveillance of gynecologic robotic-assisted surgeries in Japan.

AIM: To evaluate the clinical relevance of robotic-assisted surgeries (RAS) for gynecologic malignancies in a Japanese multi-institutional cohort. METHODS: A retrospective review of perioperative outcomes of 357 gynecologic RAS procedures was conducted in 24 hospitals accredited to perform RAS by the Japanese Society of Obstetrics and Gynecology (JSOG) over a 4-year period, January 2014 to December 2017. RESULTS: More than 25 (high), 10-24 (middle) and less than 10 cases (low) were enrolled from 3, 8 and 13 hospitals, respectively. A total of 247 patients underwent RAS for malignant indications. Radical hysterectomy (RH) was conducted for 200 patients, while para-aortic node excision (PAN) for 47 patients. RAS with RH or PAN was more feasible in high-volume centers with significantly shorter operation time and lesser blood loss than that in middle-volume centers. The total rate of perioperative injury and complications in RAS with PAN reached 33.3% in high-volume centers, which was almost equal to those in middle-volume centers (35.5%) but much higher than RAS without PAN (8.5%). CONCLUSION: Perioperative surveillance demonstrated high feasibility of gynecologic RAS procedures conducted in JSOG accredited hospitals for these 4 years. It is mandatory for RAS conducting hospitals to have careful attitudes to realize their learning curves in conducting advanced procedures.

Exchange protein directly activated by cAMP (EPAC) promotes transcriptional activation of the decidual prolactin gene via CCAAT/enhancer-binding protein in human endometrial stromal cells.

Protein kinase A (PKA) signalling accompanies elevated intracellular cAMP levels during endometrial stromal cell (ESC) decidualisation. Exchange protein directly activated by cAMP (EPAC), an alternate mediator of cAMP signalling, promotes PKA analogue-induced decidualisation; however, the precise mechanism by which EPAC and PKA co-operatively stimulate decidualisation has not been characterised. To examine the role of CCAAT/enhancer-binding protein (C/EBP) in EPAC- and PKA-mediated decidualisation of primary human ESCs, a reporter plasmid containing the 332bp region upstream from the transcription initiation site of the decidual prolactin (dPRL) gene was generated and the promoter activity was evaluated using a luciferase assay. The dPRL promoter activity was increased by treatment of transfected ESCs with the PKA-selective cAMP analogue N6-phenyl-cAMP (Phe) and enhanced further by co-treatment with the EPAC-selective cAMP analogue 8-(4-chlorophenyltio)-2'-O-methyl cAMP (CPT). Treatment with forskolin, an adenylyl cyclase activator, had a similar effect on reporter activity. Site-directed mutagenesis of the C/EBPß- and/or C/EBPδ-binding site in the dPRL promoter abolished Phe/CPT-mediated elevation of the reporter activity. EPAC2 knockdown markedly reduced Phe-stimulated C/EBPß and C/EBPδ mRNA levels, as well as forkhead box O1 (FOXO1) protein levels. These results suggest that EPAC signalling enhances PKA-mediated dPRL expression in ESCs by acting on C/EBP response elements in the promoter region of the gene.

Ultrasound Elastography can Detect Placental Tissue Abnormalities.

BACKGROUND: In this prospective cohort study, we examined the utility of elastography to evaluate the fetus and placenta. PATIENTS AND METHODS: Pregnant women in their third trimester of pregnancy, by which time the placenta has formed, were included in this study. A total of 111 women underwent ultrasound examinations, including elastography. Elastographic evaluation was performed using two protocols. First, the placental index (PI) was measured, which quantitatively assesses the hardness of tissue. Second, regions of interest (ROI) were categorized into 3-step scores according to the frequency of the blue area (hardness of placental tissue score [HT score]), which is a qualitative method. After delivery, 40 of the 111 placentas were pathologically examined. RESULTS: The average PI was 44.3 (± 29.4) in the in utero SGA group, which was significantly higher than that in the normal group (8.8 (± 10.0); p < 0.01) during pregnancy. There was a significant correlation between the PI and z score for estimated fetal weight (EFW) (r = -0.55; p < 0.01). Moreover, a significant positive correlation was observed between the PI and the z score of birth weight (r = -0.39; p < 0.01). Pathological ischemia findings of the placenta were identified in 67% of the HT score 3 group, representing 6 of the 9 patients, and in 20% of the HT score 1 group, representing only 3 of the 15 patients. CONCLUSIONS: Placental hardness, as determined by elastography, correlates with both lower estimated fetal body weight and birth weight. These results suggest that ultrasound elastography in the placenta may be an additional marker of intrauterine fetal well-being.

MicroRNA and gynecologic cancers.

AIM: Gynecologic malignancies are serious problems in female health. Here we aim to discuss the involvement of microRNA (miRNA) in the pathogenesis of gynecologic cancers and use of miRNA profiles for diagnosis of diseases. METHODS: In order to obtain information needed for this review, we searched the PubMed database with the following keywords: miRNA and ovarian cancer; miRNA and cervical cancer; and miRNA and endometrial cancer. RESULTS: Recent explosive investigations in the field have dramatically expanded our knowledge of the roles of miRNA in the pathology of gynecologic malignancies. In ovarian cancer, miRNA participates in the development of drug resistance. In cervical cancer and endometrial cancer, miRNA play essential roles in important oncogenic processes, including cell proliferation, migration and metastasis. miRNA also have high potentials to be used as biomarkers in these diseases. CONCLUSION: Further validation of the studies and improvement of the methods will result in the broader use of miRNA in the diagnosis of diseases as well as in understanding of the pathomechanisms of gynecologic cancers.

Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis.

AIM: Although there are various hormone therapies, including gonadotropin-releasing hormone agonist, danazol, levonorgestrel-releasing intrauterine system, dienogest, and low-dose estrogen progestin, no consensus opinion has been reached in terms of which medication should be used and for how long it should be administered. We aimed to determine whether dienogest or goserelin is the better postoperative therapy to prevent recurrence of endometriosis. METHODS: A prospective cohort randomized study were conducted, including 198 patients diagnosed as having endometriosis. A total of 111 patients were randomly assigned into two groups: the dienogest-administered group (n = 56) and the goserelin-administered group (n = 55). Patients were followed for 24 months after laparoscopic surgery. Those who gave consent but desired no postoperative therapy were assigned to the non-treatment group (n = 79). Recurrence, side-effects, degrees of menstrual pain and chronic pelvic pain measured by the Visual Analogue Scale were compared among the three groups: the dienogest, goserelin, and non-treatment groups. RESULTS: No significant difference was observed in the postoperative recurrence rate between the dienogest and goserelin groups. No significant difference was found in the recurrence rate between the goserelin group and non-treatment group; however, a significant difference was found in the recurrence rate between the dienogest group and the non-treatment group (P = 0.027). Menstrual pain and chronic pelvic pain were significantly improved in both treatment groups. Side-effects were markedly observed in the goserelin group as compared with the dienogest group. CONCLUSION: Dienogest is available for prolonged administration of more than 6 months, so it is more useful than goserelin, which is available only for short-term administration.

Robot-assisted laparoscopy for deep infiltrating endometriosis: international multicentric retrospective study.

BACKGROUND: This study aimed to assess the interest in robot-assisted laparoscopy for deep infiltrating endometriosis and to investigate the perioperative results. METHODS: From November 2008 to April 2012, 164 women with stage 4 endometriosis who underwent robot-assisted laparoscopy (da Vinci Intuitive Surgical System) were included by to eight international participating clinical centers. This study evaluated the procedures performed, the duration of the intervention, the complications, the recurrence, and the impact on fertility. RESULTS: The average operative time was 180 min. The main complications were laparotomy (n = 1, 0.6%), sutured bowel injury (n = 2, 1.2%), transfusion for a 2,300-ml bleed (n = 1), prolonged urinary catheterization (n = 1, 0.6%), ureter-bladder anastomotic leak (n = 1, 0.6%), and ureteral fistula after ureterolysis (n = 2, 1.2%). The reoperation rate was 1.8% (n = 3). The mean follow-up period was 10.2 months. A full recovery was experienced by 86.7% (98/113) of the patients. After surgery, 41.2% (42/102) of the patients had a desire for pregnancy, and 28.2% (11/39) of them became pregnant. CONCLUSION: This study analyzed the largest series of robot-assisted laparoscopies for deep infiltrating endometriosis published in the literature. No increase in surgical time, blood loss, or intra- or postoperative complications was observed. The interest in robot-assisted laparoscopy for deep infiltrating endometriosis seems to be promising.