p,p'-DDT induces apoptosis in human endometrial stromal cells via the PI3K/AKT pathway and oxidative stress.

Objective: Bis-[4-chlorophenyl]-1,1,1-trichloroethane (DDT), one of the most widely used synthetic pesticides, is an endocrine-disrupting chemical with the potential to interfere with the human reproductive system. The effects of DDT and one of its metabolites, p,p'-DDT, on human endometrial stromal cells (ESCs) and health outcomes remain unknown. In this study, we investigated whether p,p'-DDT induces an imbalance in cell proliferation and apoptosis in human ESCs via oxidative stress. Methods: We assessed apoptosis in ESCs by quantifying the expression of markers associated with both intrinsic and extrinsic pathways. Additionally, we measured levels of reactive oxygen species (ROS), antioxidant enzyme activity, and estrogen receptors (ERs). We also examined changes in signaling involving nuclear factor kappa-light-chain-enhancer of activated B cells. Results: Following treatment with 1,000 pg/mL of p,p'-DDT, we observed an increase in Bax expression, a decrease in Bcl-2 expression, and increases in the expression of caspases 3, 6, and 8. We also noted a rise in the generation of ROS and a reduction in glutathione peroxidase expression after treatment with p,p'-DDT. Additionally, p,p'-DDT treatment led to changes in ER expression and increases in the protein levels of phosphatidylinositol 3-kinase (PI3K), phospho-protein kinase B (phospho-AKT), and phospho-extracellular signal-regulated kinase (phospho-ERK). Conclusion: p,p'-DDT was found to induce apoptosis in human ESCs through oxidative stress and an ER-mediated pathway. The activation of the PI3K/AKT and ERK pathways could represent potential mechanisms by which p,p'-DDT prompts apoptosis in human ESCs and may be linked to endometrial pathologies.

Oleuropein suppresses endometriosis progression and improves the fertility of mice with endometriosis.

BACKGROUND: Endometriosis is an estrogen-dependent inflammatory reproductive disease. Therefore, systematic estrogen depletion and anti-inflammatory drugs are the current treatment for endometriosis. However, current endometriosis treatments have low efficacy and cause adverse effects in endometriosis patients. Consequently, alternative endometriosis treatments targeting endometriosis-specific factors are in demand. In this context, ERß was selected as a druggable target for endometriosis due to its critical role in progression. Therefore, selective targeting of ERß without inhibiting ERα activity would be a new paradigm for endometriosis treatment to overcome the low efficacy and adverse effects of hormonal endometriosis therapy. METHODS: Cell-based ERß and ERα activity assay systems were employed to define a selective ERß-inhibiting chemical product from a library of natural products. A surgically induced endometriosis mouse model was used to determine whether an ERß inhibitory drug suppressed endometriosis progression. Mice with endometriosis were randomly separated and then orally treated with vehicle or 25 mg/kg oleuropein (once a day for 21 days), an ERß inhibitory drug. The volume of endometriotic lesions or luciferase activity of endometriotic lesions was examined to define the growth of ectopic lesions in mice with endometriosis. The metabolite and levels of metabolic enzymes of the liver and kidney were determined in the serum of female mice treated with vehicle and oleuropein (25 mg/kg, once a day for 21 days) to define the toxicity of oleuropein. The in vitro decidualization assay was conducted with normal human endometrial stromal cells and endometriotic stromal cells to determine whether oleuropein overcomes decidualization in endometriosis patients. The pregnancy rate and pup numbers of C57BL/6 J female mice with endometriosis treated with vehicle or oleuropein (n = 10/group) were determined after mating with male mice. The cytokine profile in endometriotic lesions treated with vehicle and oleuropein (25 mg/kg) was determined with a Mouse Cytokine Array Kit. RESULTS: Among natural products, oleuropein selectively inhibited ERß but not ERα activity in vitro. Oleuropein treatment inhibited the nuclear localization of ERß in human endometrial cells upon estradiol treatment. Oleuropein (25 mg/kg) treatment suppressed the growth of mouse (6.6-fold) and human (sixfold) ectopic lesions in mice with endometriosis compared to the vehicle by inhibiting proliferation and activating apoptosis in endometriotic lesions. Oleuropein treatment did not cause reproductive toxicity in female mice. Additionally, mice with endometriosis subjected to oleuropein treatment had a higher pregnancy rate (100%) than vehicle-treated mice (70%). Furthermore, oleuropein treatment partially recovered the decidualization impact of human endometriotic stromal cells from endometriotic lesions compared to the vehicle. Oleuropein-treated mice with endometriosis exhibited significantly lower levels of cytokines directly regulated by ERß in ectopic lesions than vehicle-treated mice, illustrating the improvement in the hyperinflammatory state of mice with endometriosis. CONCLUSIONS: Oleuropein is a promising and novel nutraceutical product for nonhormonal therapy of endometriosis because it selectively inhibits ERß, but not ERα, to suppress endometriosis progression and improve the fertility of mice with endometriosis.

Triphenyl phosphate activates estrogen receptor α/NF-κB/ cyclin D1 signaling to stimulate cell cycle progression in human Ishikawa endometrial cancer cells.

OBJECTIVE: Triphenyl phosphate (TPHP) is one of the most commonly used organophosphorus flame retardants that may accumulate in the environment. However, its effects on human reproductive organs have not been well studied. We aimed to investigate the in vitro effects of TPHP in human Ishikawa endometrial cancer cells to elucidate how TPHP exposure disrupts intracellular signaling and cell proliferation in reproductive tissues. METHODS: Human Ishikawa endometrial cancer cells were exposed to TPHP. RESULTS: Exposure to TPHP elevated the levels of estrogen receptor (ER) α and progesterone receptor-B and reduced ER ß in human Ishikawa endometrial cancer cells. TPHP stimulated phosphoinositide 3-kinase/protein kinase B and mitogenactivated protein kinase/ extracellular signal-regulated kinases 1/2 kinase signaling, which may contribute to the activation of ER function and induce nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in human Ishikawa endometrial cancer cells. Activated ER and NF-κB stimulate the expression of cyclin D1/ cyclin-dependent kinase (CDK) 4/CDK6, indicating cell cycle progression and proliferation. CONCLUSION: This report may provide new information on the molecular mechanisms underlying how TPHP exposure dysregulates the cellular physiology of the human endometrium.

The recurrence rate of ovarian endometrioma in women aged 40-49 years and impact of hormonal treatment after conservative surgery.

The aim of this study was to evaluate the rate of and risk factors for recurrence ovarian endometrioma after conservative surgery in patients aged 40-49 years. This retrospective, single-center study included 408 women between January 2008 and November 2018. All patients underwent ovarian cyst enucleation, were pathologically diagnosed with ovarian endometrioma and were followed up for ≥ 6 months. Recurrence was defined as a cystic mass with diameter ≥ 2 cm detected by sonography. Recurrence rate after conservative surgery and risk factor of recurrence were analyzed. The median follow-up duration after surgery was 32.0 ± 25.9 months (range 6-125 months). Ovarian endometrioma recurred in 34 (8.3%) of included women and median time to recurrence was 22.4 ± 18.2 months. The cumulative recurrences rate at 12, 24, 36, and 60 months were 3.7%, 6.7%, 11.1%, and 16.7%, respectively. Recurrence was correlated with multilocular cysts (p = 0.038), previous surgical history of ovarian endometrioma (p = 0.006) and salpingectomy (p = 0.043), but not use or duration of post-operative medication. In multivariate analysis, large cyst size (> 5.5 cm) was only risk factor for recurrence in this age group. Post-operative medication did not reduce disease recurrence rate, and thus may be administered for endometriosis-associated pain rather than to prevent recurrence in patients aged 40-49 years.

Atypical endometriosis is related to a higher recurrence rate.

OBJECTIVES: The aims of this study were to evaluate the clinical characteristics and recurrence rate of atypical endometriosis (AE)1 compared to typical endometriosis (TE) in addition to the malignant transformation rate among a large cohort. STUDY DESIGN: The medical records of 2681 patients who had undergone surgical treatment of ovarian endometrioma between January 2008 and September 2019 were retrospectively reviewed. The patients were divided into AE (n = 86) and TE (n = 2595) groups. Patients' characteristics and recurrence rates were evaluated and compared between the two groups. RESULTS: The mean size of ovarian cysts was significantly larger in the AE group (7.6 ± 3.5 cm vs 6.7 ± 3.3 cm, p = 0.01) and the proportion of nulliparous women was significantly lower in AE group (65.1 % vs 77.8 %, p = 0.008). Otherwise, there were no statistically significant differences in patient characteristics between the two groups. After Cox regression analyses with IPTW was adjusted, the risk factors for recurrent endometrioma were higher preoperative CA125 level >48 U/mL (hazard ratio [HR] = 2.741; 95 % confidence interval [CI] = 1.517-4.952; p < 0.001), multilocular cyst (HR = 1.909; 95 % CI = 1.128-3.230; p = 0.016), and atypical endometriosis (HR = 2.666; 95 % CI = 1.659-4.284; p < 0.001). The AE group displayed a significantly higher cumulative recurrence rate than the TE group (p = 0.0057, log-rank test). No patients were diagnosed with atypical endometriosis to malignant transformation during the follow-up periods. However, two typical endometriosis patients experienced borderline malignancy and serous carcinoma, respectively. CONCLUSION: Recurrence rates for AE were higher than for TE. Although the AE group included no patient with malignant transformation in this study, considering the higher recurrence as well as the possibility of malignant transformation, long-term close surveillance is warranted.

Bis-Indole-Derived Nuclear Receptor 4A1 (NR4A1, Nur77) Ligands as Inhibitors of Endometriosis.

Endometriosis is an inflammatory disease that primarily affects women during their reproductive years, and since current hormonal therapies are of concern, new hormone-independent treatment regimens are needed. The orphan nuclear receptor 4A1 (NR4A1, Nur77) is expressed in patient-derived (stromal) endometriotic cells and also epithelial cell lines, and we observed that knockdown of NR4A1 in patient-derived ectopic endometrium-isolated ovarian endometrioma (ESECT)-7 and ESECT-40 cells decreased cell proliferation and induced apoptosis. Moreover, the treatment of these cells with bis-indole derived NR4A1 ligands 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) and its buttressed 3-chloro-5-methoxy analog (DIM-C-pPhOH-3-Cl-5-OCH3) inhibited cell growth and induced apoptosis and related genes. The compounds exhibit NR4A1 antagonist activities in both functional and transactivation assays whereas these effects were not observed in normal endometrial cells. We also observed that NR4A1 knockdown and treatment with NR4A1 antagonists decreased fibrosis, α-smooth muscle actin, and related pro-fibrotic genes in ESECT-7 and ESECT-40 cells, and similar results were observed in epithelial-derived endometriotic cell lines. Moreover, in an endometriosis mouse model with auto-transplantation and also in severe combined immune deficiency mice transplanted with human endometriotic cells treatment with 25 mg/kg/day DIM-C-pPhOH-3-Cl-5-OCH3 significantly inhibited growth and expansion of endometriotic lesions. Thus, bis-indole-derived NR4A1 ligands represent a novel class of drugs as nonhormonal therapy for endometriosis.

Nonpersistent endocrine disrupting chemicals and reproductive health of women.

Nonpersistent endocrine disrupting chemicals (npEDCs) are exogenous chemicals or mixtures of industrial agents that can interfere with the normal action of hormone with a shorter half-life and lower liposolubility. These are commonly found in plastics, medical equipment, detergents, and cosmetics. Recently, role of npEDCs on the changes of ovary and/or uterus development and alterations in hormonal signaling has been emphasized. However, many controversial results exist on the effects of npEDCs and reproductive health of women. Thus, we have focused to review the scientific evidence of a causal relationship between exposure to npEDCs and representative female reproductive issues such as menstrual cycle, endometriosis, uterine fibroids, polycystic ovarian syndrome and infertility/subfertility. Though not all studies indicated a positive correlation of npEDCs with female reproductive issues, the reviewed data illustrated that the majority of the available data strengthen the evidence of reproductive health-related actions of npEDCs. In future, recommendations should be made in order to reduce human exposure to npEDCs and to protect from steadily increasing reproductive health risks.

Clinical experience of uterine smooth muscle tumor of uncertain malignant potential in two gynecological centers: Oncological and obstetrical aspects.

OBJECTIVES: To evaluate the clinical characteristics and obstetrical and oncological outcomes of patients with uterine smooth muscle tumors of uncertain malignant potential (STUMP) and analyze the risk factors for recurrence. STUDY DESIGN: A retrospective cohort study was performed at two gynecological centers using data collected between January 2008 and August 2018. All the patients enrolled were diagnosed with STUMP and had been followed up for at least 6 months. The patients' characteristics, treatment methods, recurrence rate, and subsequent pregnancy outcomes were evaluated. RESULTS: The mean age of the 62 patients was 36.1 ±â€¯9.1 years (median 35, range 20-55 years) and mean follow-up duration was 36.3 ±â€¯26.8 months (29.5, 6-130). All the patients were of premenopausal status. Fourteen patients (22.6 %) were initially treated by hysterectomy and 48 (77.4 %) by myomectomy. During the study period, three patients (4.8 %) experienced recurrence. However, there was no statistical difference between myomectomy and hysterectomy in terms of the rate of recurrence of STUMP or sarcoma, and all patients survived even after recurrence. Multivariate analysis revealed that a history of previous myomectomy was the sole independent risk factor for recurrence (odds ratio = 51.071; 95 % confidence interval = 2.743-950.726; p = 0.008). Subsequent pregnancies were successful in 10 of 19 women (52.6 %) who tried to conceive. Two of them had ongoing pregnancies at the time of last follow-up; the remaining eight women experienced a total of 14 subsequent pregnancies. CONCLUSIONS: The recurrence rate of STUMP was similar between hysterectomy and myomectomy. Therefore, fertility sparing myomectomy can be considered in women diagnosed with STUMP with close monitoring.

Efficacy of nerve-sparing radical hysterectomy vs. conventional radical hysterectomy in early-stage cervical cancer: A systematic review and meta-analysis.

The aim of the present study was to compare the oncological outcome of nerve-sparing radical hysterectomy (NSRH) and conventional radical hysterectomy (CRH) for early-stage cervical cancer using a meta-analysis. A systematic review and meta-analysis was conducted, including 4 randomized controlled trials (RCT), 8 case-control and 11 comparative cohort studies comparing the morbidity, pelvic dysfunctions and oncological outcome between the two surgical methods. A total of 23 studies were included in this meta-analysis. The studies reported data of patients affected by cervical cancer; were written in English; included ≥20 patients; and reported data of patients with a comparison of clinical outcomes between NSRH and CRH. Data were extracted and risk of bias was assessed by four independent reviewers. A total of 1,796 patients were included: 884 patients (49.2%) undergoing NSRH and 912 (50.8%) undergoing CRH. The meta-analyses were conducted using Review Manager version 5.3 software, which is designed for conducting Cochrane reviews. As regards perioperative parameters, NSRH was found to be associated with a lower intraoperative blood loss and a shorter length of hospital stay in comparison with CRH. Patients undergoing NSRH experienced lower incidence of urinary, colorectal and sexual dysfunction compared with patients undergoing CRH. However, the resected parametrial width was favorable in patients with CRH, suggesting that NSRH was inferior to CRH in terms of radicality. The 5-year disease-free and overall survival rates were similar between the two groups. In this systematic review and meta-analysis, the collected data to date demonstrated that the nerve-sparing approach guarantees minimized surgical-related pelvic dysfunction, with similar oncological outcomes as CRH. However, further RCTs should be conducted to confirm the superiority and safety of NSRH.

Genomic Function of Estrogen Receptor ß in Endometriosis.

Estrogen receptor (ER) ß plays a critical role in endometriosis progression because cytoplasmic ERß stimulates proinflammatory signaling in ectopic lesions and prevents apoptosis to promote their survival. However, the role of "nuclear ERß" in endometriosis progression is not known. This critical knowledge gap obscures our understanding of the full molecular etiology of ERß-mediated endometriosis progression. To fill this void, we generated an ERß-regulated transcriptome and ERß cistrome in ectopic lesions and the eutopic endometrium of mice with endometriosis by using a new endometrium-specific FLAG-tagged human ERß overexpression mouse model. The integration of these omics data sets revealed that ERß stimulated the proliferation activities of ectopic lesions and the eutopic endometrium by directly upregulating MYC and E2 transcription factor target genes and genes associated with the G2/M transition. Additionally, ERß stimulated gene expression associated with TNFα/nuclear factor κB (NF-κB) signaling, epithelial-mesenchymal transition, reactive oxygen species signaling, IL-6/Janus kinase (JAK)/signal transducer and activator of transcription (STAT)3 signaling, and hypoxia signaling and suppressed IFNα signaling in ectopic lesions to enhance endometriosis progression. ERß also stimulated gene expression associated with the unfolded protein response and IL-6/JAK/STAT3 inhibitory signaling and suppressed TNFα/NF-κB signaling in the eutopic endometrium to cause endometriosis-associated endometrial dysfunction. Therefore, nuclear ERß-regulated gene networks provide critical clues to understand the molecular etiology and complexity of endometriosis and endometriosis-associated endometrial dysfunction.

Comparison of vaginal hysterectomy and laparoscopic hysterectomy: a systematic review and meta-analysis.

BACKGROUND: There are various surgical approaches of hysterectomy for benign indications. This study aimed to compare vaginal hysterectomy (VH) and laparoscopic hysterectomy (LH) with respect to their complications and operative outcomes. METHODS: We selected randomised controlled trials that compared VH with LH for benign gynaecological indications. We included studies published after January 2000 in the following databases: Medline, EMBASE, and CENTRAL (The Cochrane Library). The primary outcome was comparison of the complication rate. The secondary outcomes were comparisons of operating time, blood loss, intraoperative conversion, postoperative pain, length of hospital stay and duration of recuperation. We used Review Manager 5.3 software to perform the meta-analysis. RESULTS: Eighteen studies of 1618 patients met the inclusion criteria. The meta-analysis showed no differences in overall complications, intraoperative conversion, postoperative pain on the day of surgery and at 48 h, length of hospital stay and recuperation time between VH and LH. VH was associated with a shorter operating time and lower postoperative pain at 24 h than LH. CONCLUSIONS: When both surgical approaches are feasible, VH should remain the surgery of choice for benign hysterectomy.

Clinical application of serum anti-Müllerian hormone in women.

Anti-Müllerian hormone (AMH), a peptide growth factor of the transforming growth factor-ß family, is a reliable marker of ovarian reserve. Regarding assisted reproductive technology, AMH has been efficiently used as a marker to predict ovarian response to stimulation. The clinical use of AMH has recently been extended and emphasized. The uses of AMH as a predictive marker of menopause onset, diagnostic tool for polycystic ovary syndrome, and assessment of ovarian function before and after gynecologic surgeries or gonadotoxic agents such as chemotherapy have been investigated. Serum AMH levels can also be affected by environmental and genetic factors; thus, the effects of factors that may alter AMH test results should be considered. This review summarizes the findings of recent studies focusing on the clinical application of AMH and factors that influence the AMH level and opinions on the use of the AMH level to assess the probability of conception before reproductive life planning as a "fertility test."

Bisphenol A modulates inflammation and proliferation pathway in human endometrial stromal cells by inducing oxidative stress.

Bisphenol A (BPA) has been implicated in altered human reproductive function. The oxidative stress or change of inflammatory signaling may appear a key factor in the biological changes of the human endometrium. Using MTT assay we assessed BPA mediated modulation of oxidative stress and inflammation responses in human endometrial stromal cells (ESCs). According to the results, reactive oxygen species (ROS) generation was highest upon exposure to 1000 pmol BPA. Increased mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were demonstrated. Gene expression and release of inflammatory cytokines were increased. Upon BPA exposure, elevated estrogen receptor (ER)-α expression levels in ESCs correlated with changes in oxidative stress, inflammatory gene expression and signal changes in cellular proliferation signaling. These findings support that BPA induces oxidative stress and activates inflammatory signals in cultured ESCs via ER-α. Together, this result may provide insight into the association between BPA exposure and endometrium-related disorders.

Assessment of the effects of prostaglandins on myometrial and leiomyoma cells in vitro through microRNA profiling.

It is well known that prostaglandin (PG) E2 and PGF2α are secreted in copious amounts from the menstruating uterus. The aim of the present study was to determine whether PGs affect the growth of uterine leiomyomas (ULs) to the same extent as estrogen or progesterone (P4). The present study evaluated the expression of eight microRNAs (miRNAs) by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) through treatment with estradiol (E2), P4, PGE2, PGF2α and each antagonist or cyclooxygenase­2 (COX­2) inhibitor of cultured leiomyoma and myometrial cells (LC and MC, respectively). The eight miRNAs were divided into two groups according to their primary biological action, namely apoptosis­regulating miRNAs (let­7a, miR­21, miR­26a and miR­200a) and inflammation­regulating miRNAs (miR­29b, miR­93, miR­106b and miR­100b). PGE2 induced significantly higher expression of the 3 anti­apoptotic miRs, let­7a, miR­16a and miR­200a, in LC when compared with the non­treated control or E2. PGE2 significantly promoted a greater expression of let­7a and miR­26a in LC when compared with P4. Overall, PGE2 exerted the highest anti­apoptotic and anti­inflammatory effect in LC, which was comparable with E2. It was not observed among the inflammation­regulating miRNAs in LC. PGF2α did not exert effects as prominent as those of PGE2. In MC, PGs and sex steroids exerted no similar effects on MC compared with LC. The present study demonstrated that PGE2 levels during menstruation may affect the growth of preexisting ULs without affecting the normal myometrium. Therefore, the control of secretion of PGs from the menstruating uterus or the administration of antagonists may be an alternative therapy for inhibiting the growth of ULs.

Bufalin suppresses endometriosis progression by inducing pyroptosis and apoptosis.

The steroid receptor coactivator (SRC)-1 isoform/estrogen receptor (ER)-ß axis has an essential role in endometriosis progression. In this context, therefore, bufalin was employed as a 'tool compound' to evaluate inhibitors of SRC in alternative endometriosis treatment. Bufalin effectively suppressed the growth of primary human endometrial stroma cells isolated from endometriosis patients compared to women without endometriosis and immortalized human endometrial epithelial and stromal cells expressing the SRC-1 isoform compared to their parental cells in vitroIn vivo, compared to the vehicle, bufalin treatment significantly suppressed the growth of endometriotic lesions in mice with surgically induced endometriosis because bufalin disrupted the functional axis of SRC-1 isoform/ERß by increasing SRC-1 isoform protein stability, hyperactivating the transcriptional activity of the SRC-1 isoform and degrading the ERß protein by proteasome 26S subunit, non-ATPase 2 in endometriotic lesions. Bufalin treatment elevated the apoptosis signaling in epithelial cells of endometriotic lesions. In stromal cells of endometriotic lesions, bufalin treatment increased the levels of pyroptosis markers (caspase 1 and the active form of interleukin 1ß) and reduced proliferation. In addition, bufalin treatment increased the expression levels of endoplasmic reticulum-stress (ERS) markers (PKR-like ER kinase, protein disulfide isomerase and binding immunoglobulin) in endometriotic lesions. Collectively, the bufalin-induced disruption of the SRC-1 isoform/ERß axis might induce apoptosis, pyroptosis and ERS signaling in endometriotic lesions, causing the suppression of endometriosis. Therefore, future generations of SRC-modulators could be employed as an alternative medical approach for endometriosis treatment.

Dysfunctional signaling underlying endometriosis: current state of knowledge.

Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity. It affects approximately 5-10% of women of reproductive age. Endometriosis is associated with dysmenorrhea, dyspareunia and, often, severe pelvic pain. In addition to pain, women with endometriosis often experience infertility. Defining the molecular etiology of endometriosis is a significant challenge for improving the quality of women's lives. Unfortunately, the pathophysiology of endometriosis is not well understood. Here, we summarize the potential causative factors of endometriosis in the following three categories: (1) dysregulation of immune cells in the peritoneal fluid and endometriotic lesions; (2) alteration of apoptotic signaling in retrograde menstrual tissue and cytotoxic T cells involved in endometriosis progression and (3) dysregulation of oxidative stress. Determining the molecular etiology of these dysregulated cellular signaling pathways should provide crucial clues for understanding initiation and progression of endometriosis. Moreover, improved understanding should suggest new molecular therapeutic targets that could improve the specificity of endometriosis treatments and reduce the side effects associated with current approaches.

Recurrence of Ovarian Endometrioma in Adolescents after Conservative, Laparoscopic Cyst Enucleation.

STUDY OBJECTIVE: To evaluate the cumulative recurrence rate of endometriomas after a laparoscopic endometriotic cyst enucleation in adolescents and to find the factors associated with recurrence. DESIGN: A multicenter retrospective cohort study. SETTING: Three university hospitals. PARTICIPANTS: One hundred five patients surgically treated with laparoscopic enucleation of endometriotic cysts younger than 20 years of age were selected. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Endometrioma recurrence was considered when transvaginal or transrectal sonography indicated a cystic mass with a diameter of 20 mm or greater. Recurrence rate of endometrioma and median time to recurrence were evaluated. RESULTS: In total, 105 patients were followed for 47.3 (±44.3) months (range, 3-161 months). Seventeen patients (16.2%) experienced recurrence after the first-line surgery and 8 patients (7%) underwent a second surgery. The median time to recurrence was 53.0 (±8.5) months (range, 8-111 months). Using Kaplan-Meier method, the cumulative recurrence rates of endometrioma per patient at 24, 36, 60, and 96 months after the first-line surgery were 6.4%, 10%, 19.9% and 30.9%, respectively. Surgical characteristics, such as the diameter of the cyst, revised American Society for Reproductive Medicine stage, unilateral or bilateral involvement, and coexistence of deep endometriosis were not associated with recurrence in this age group. CONCLUSION: Although the short-term recurrence rate in adolescents after first-line surgery is relatively low, the recurrence rate appears to be higher according to the follow-up duration. Long-term and continuous follow-up is needed for patients who have undergone surgical treatment for endometriosis in the adolescent period.

Internal jugular vein thrombosis with OHSS.

Ovarian hyperstimulation syndrome (OHSS) includes ovarian enlargement and ascites. It is usually mild but can be, rarely, fatal. Deep vein thrombosis (DVT) is among the potentially fatal complications of OHSS. During pregnancy, DVT is more common in the lower extremities than in the upper part of the body, but OHSS-related DVT occurs more frequently in the upper part. Internal jugular vein thrombosis is considered rare, and duplex ultrasound is the appropriate examination for its diagnosis. We present a rare case of internal jugular vein thrombosis following OHSS. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:450-452, 2017.

The efficacy of long-term maintenance therapy with a levonorgestrel-releasing intrauterine system for prevention of ovarian endometrioma recurrence.

OBJECTIVE: To evaluate the cumulative recurrence rates of ovarian endometrioma among patients using a levonorgestrel-releasing intrauterine system (LNG-IUS) after conservative laparoscopic surgery. METHODS: A retrospective review was conducted of premenopausal women who underwent conservative laparoscopic surgery for ovarian endometrioma and subsequent treatment with LNG-IUS at two gynecologic surgery centers in South Korea between January 1, 2007, and September 30, 2014. Eligible patients had no residual ovarian lesions before LNG-IUS insertion, underwent insertion within 12 months of primary surgery, and were followed up for at least 6 months afterwards. Recurrence was defined as a cystic mass (≥2 cm in diameter) detected by transvaginal ultrasonography. RESULTS: Overall, 61 patients were included. The mean duration of follow-up was 42.9 ± 22.0 months (range 8-98). Recurrence of ovarian endometrioma was detected among 7 (11%) of the patients. On Kaplan-Meier analysis, the cumulative recurrence rates were 4.0%, 6.3%, and 25.5% at 24, 36, and 60 months after surgery, respectively. In multivariate analysis, nulliparity at surgery was the only risk factor for recurrence (hazard ratio 5.892, 95% confidence interval 1.139-30.484; P=0.034). CONCLUSION: Long-term maintenance therapy with LNG-IUS after conservative surgery might be a treatment option to consider to prevent ovarian endometrioma recurrence among premenopausal women.