Progesterone resistance in endometriosis: A pathophysiological perspective and potential treatment alternatives.

Background: Endometriosis is a common gynecological disease affecting women of reproductive age. Patients with endometriosis frequently experience severe chronic pain and have higher chances to experience infertility. Progesterone resistance is a major problem that develops during the medical treatment of endometriosis, which often leads to treatment failure of hormonal therapies. Previous studies indicated that the dysregulation of progesterone receptors (PR) is the primary factor leading to progesterone resistance in endometriosis. Methods: This review article systematically reviewed and summarized findings extracted from previously published papers available on PubMed, encompassing both experimental studies and clinical trials. Main findings: Various determinants influencing PR expression in endometriosis have been identified, including the environmental toxins, microRNAs, cell signaling pathways, genetic mutations, and the pro-inflammatory cytokines. The selective estrogen/progesterone receptor modulators have emerged as novel therapeutic approaches for treating endometriosis, offering potential improvements in overcoming progesterone resistance. Conclusion: Concerns and limitations persist despite the newly developed drugs. Therefore, studies on unraveling new therapeutic targets based on the molecular mechanisms of progesterone resistance is warranted for the development potential alternatives to overcome hormonal treatment failure in endometriosis.

Autologous PRP therapy for thin endometrium: A self-controlled case series study across menstrual cycles.

OBJECTIVES: Thin endometrium (TE) compromises endometrial receptivity, often leading to implantation failure and lower clinical pregnancy rates. As autologous platelet-rich plasma (PRP) emerges as a potential remedy, the present study focused on its therapeutic effects on TE in infertile women who underwent frozen embryo transfer. STUDY DESIGN: Patients with TE who underwent frozen embryo transfer treatment in our hospital were included. To diminish individual variability, a self-controlled series approach was used. Two menstrual study cycles were arranged for each participant before the actual embryo transfer cycle; PRP treatment was conducted in the second cycle. Key metrics analyzed included endometrial thickness and the expression of specific endometrial biomarkers including HOXA-10, Ki67, and αvß3 integrin. Transvaginal ultrasound was employed to measure endometrial thickness on Days 11 and 14, and an endometrial biopsy was conducted on progesterone Day 5 of the first two cycles. Pregnancy outcomes were observed after the embryo transfer cycle. RESULTS: PRP treatment significantly increased the median endometrial thickness, from 5.8 mm to 6.5 mm (P = 0.0066). Additionally, PRP treatment resulted in a statistically significant increase in the H-score for all endometrial markers. Importantly, during the subsequent embryo transfer cycle with PRP treatment, two patients successfully achieved pregnancies, both culminating in live births. CONCLUSIONS: These findings emphasize the potential of PRP in improving endometrial conditions, especially for individuals grappling with thin endometrium issues, as underscored by this self-comparison methodology.

Physical therapy intervention for breast symptoms in lactating women: a randomized controlled trial.

BACKGROUND: Therapeutic ultrasound, education, and massage are the most common physical therapy interventions provided to mothers with breast symptoms. However, there is insufficient evidence on the effectiveness of the combination of these interventions. This study aimed to explore the effects of the combination of therapeutic ultrasound, education, and massage on breast symptoms in lactating women. METHODS: This study was a single-blind randomized controlled trial. Postpartum lactating women aged from 21 to 45 with breast symptoms were recruited and randomly allocated to one of three groups (ultrasound group, sham group, and usual care group). The severity of breast symptoms (pain, redness, lump, general malaise), breast engorgement, breast hardness, body temperature, breast temperature, and milk volume were assessed at baseline (T1), immediately post-intervention (T2), and at 3 months following baseline (T3). RESULTS: A total of 37 participants were included in the study (ultrasound group n = 12; sham group n = 12; usual care n = 13). The severity of breast symptoms (i.e., pain, lump, and general malaise) as well as breast engorgement, were significantly improved in the ultrasound group at T2 when compared to T1, and these improvements were sustained at T3. The severity of breast engorgement was significantly lower in the ultrasound group when compared to the usual care group at T2. However, no statistically significant differences were found between the ultrasound and sham groups for all outcomes at any assessment time points. CONCLUSIONS: Physical therapy interventions may be beneficial in relieving breast symptoms in lactating women. Larger randomized controlled trials are needed to confirm the findings of this study. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04569136); Date of registration: 29/09/2020.

Improving the diagnosis of endometriosis in Asia-Pacific: Consensus from the Asia-Pacific Endometriosis Expert Panel for Endometriosis.

Endometriosis should be diagnosed as early as possible in the continuum of care; but substantial delays of approximately 6-8 years between symptom onset and endometriosis diagnosis have been widely reported. With the purpose of improving the prompt diagnosis of endometriosis, the Asia-Pacific Endometriosis Expert Panel (APEX) sought to address the reasons for diagnostic delays across the region, and formulate a multi-pronged approach to overcoming these challenges. In the first instance, clinical diagnosis is preferable to surgical diagnosis, in order to facilitate earlier empirical treatment and minimize the negative sequelae of undiagnosed/untreated disease. There should be a high clinical index of suspicion in women presenting with cyclical symptoms, including those involving extrapelvic organs. Diagnostic delays in Asia-Pacific countries are attributable to a variety of patient, physician, and healthcare factors, including poor awareness, normalization/trivialization of pain, individual/cultural attitudes toward menstruation, default use of symptom-suppressing treatments, misdiagnosis, and a lack of diagnostic resourcing or adequate referral pathways in some areas. Suggested initiatives to reduce diagnostic delays are geared toward improving public awareness, improving clinical diagnostic skills, streamlining multidisciplinary care pathways for timely referral, updating and implementing diagnostic guidelines, lobbying policymakers and insurance companies for endometriosis support, and increasing efforts to bridge data gaps and perform further research in this field. Formulating specific action plans and gathering traction are the responsibility of individual countries within local parameters. The APEX group advocates for any initiatives and policies that support the unmet needs of women with endometriosis, to improve patient experience and outcomes.

Feel so bac: is Fusobacterium the suspect causing endometriosis?

Recent work by Muraoka and colleagues reports that the Gram-negative anaerobic bacterium Fusobacterium nucleatum is detected in the uterus of 64% of women with endometriosis. Fusobacterium infection causes macrophage infiltration, transforming growth factor-ß production, and transgelin upregulation in human and mouse endometria as well as endometriotic lesion development in a mouse model of endometriosis.

Effect of atosiban on in vitro fertilization pregnancy outcome among women with endometriosis in presence or absence of adenomyosis.

OBJECTIVE: This study aimed to assess the effect of atosiban on in vitro fertilization (IVF) pregnancy outcome among women with both endometriosis and adenomyosis, and compared it to that of patients with endometriosis but without adenomyosis and that of patients with tubal factor only. MATERIALS AND METHODS: 106 infertile women (176 embryo transfers) from a medical center in Taiwan were included in the analysis, where 34 (54), 34 (66), and 38 (56) cases (embryo transfers) were endometriosis without adenomyosis, endometriosis with adenomyosis, and tubal infertility factor only, respectively. Adenomyosis morphologies were classified using an ultrasound-based classification system. The logistic generalized estimating equation model was used to analyze the association between atosiban use and pregnancy outcomes. RESULTS: The crude pregnancy rates for the endometriosis-only group were significantly higher than those for the endometriosis + adenomyosis group (i.e., biochemical pregnancy: 50.0% versus 29.7%, p = 0.041; ongoing pregnancy: 35.2% versus 16.9%, p = 0.038). Significantly higher chances of biochemical pregnancy and ongoing pregnancy among endometriosis patients without adenomyosis versus those with both endometriosis and adenomyosis were found (odds ratios [95% confidence intervals]: 2.981 [1.307, 6.803]; p = 0.009, 2.694 [1.151, 6.304]; p = 0.022). A significant positive association between atosiban use and biochemical pregnancy existed among endometriosis cases without adenomyosis (a 2.43-fold [1.01, 5.89] increase in successful pregnancy; p<0.05), but not for the other groups. CONCLUSIONS: Poor pregnancy outcomes among adenomyosis-affected women were confirmed. The use of atosiban significantly enhanced IVF pregnancy among endometriosis patients without adenomyosis.

Segmentation of In vitro Fertilization with High-intensity Focused Ultrasound in Repeated Implantation Failure with Adenomyosis.

Adenomyosis is a complex issue in reproductive-age women not only on worsening of quality of life due to severe dysmenorrhea or heavy menstrual bleeding but also on the impact of infertility. A 39-year-old female, gravida 0 para 0, with a history of bilateral ovarian endometrioma post laparoscopic surgery presented to our hospital due to suspected deep infiltrative endometriosis (DIE), adenomyosis, and repeated implantation failure. Initially, gonadotropin-releasing hormone analog treatment for DIE with progestin-primed ovarian stimulation protocol was arranged. Four D5 blastocysts were obtained and freezed. Two frozen embryo transfer were performed after ultrasound-guided high-intensity focused ultrasound (USgHIFU) treatment of adenomyosis. She later had a dichorionic diamniotic twin pregnancy, and two healthy newborns were delivered by Cesarean section at gestational age of 35 weeks due to antepartum hemorrhage with placenta previa and preeclampsia. In conclusion, USgHIFU can be a potential treatment option in segmented in vitro fertilization in future.

Targeting YAP1 ameliorates progesterone resistance in endometriosis.

STUDY QUESTION: Does YAP1 inhibition alleviate progesterone resistance in endometriosis? SUMMARY ANSWER: YAP1 inhibition reduces progesterone resistance in vitro and in vivo. WHAT IS KNOWN ALREADY: Progesterone resistance not only causes treatment failure for endometriosis but also inhibits eutopic endometrial cell proliferation, dysregulates decidualization, and reduces the success rates of pregnancy. Hippo/yes-associated protein 1 (YAP1) signaling pathway plays an important role in the pathogenesis of endometriosis. STUDY DESIGN, SIZE, DURATION: Paraffin-embedded tissues containing paired endometriotic and endometrial specimens (n = 42) and serum samples isolated from normal controls (n = 15) or endometriotic patients with (n = 25) or without (n = 21) prior dienogest treatment were analyzed. A mouse model of endometriosis was also used to evaluate the effects of YAP1 inhibition on progesterone resistance. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary endometriotic and endometrial stromal cells treated with YAP1 inhibitor or miR-21 mimic/inhibitor were used for the in vitro studies including decidualization induction, chromatin immunoprecipitation (ChIP), and RNA immunoprecipitation. Tissue specimens and serum from human and mouse were used for immunohistochemistry staining, exosome isolation, and microRNA (miRNA) quantification, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Herein, we report, by using ChIP-PCR and RNA-IP, that YAP1 inhibits progesterone receptor (PGR) expression through upregulation of miR-21-5p. Upregulation of miR-21-5p not only reduces PGR expression but also inhibits endometrial stromal cell decidualization. Indeed, levels of YAP1 and miR-21-5p are inversely correlated with the level of PGR in human endometrial samples. In contrast, knockdown of YAP1 or treatment with verteporfin (VP), a YAP1 inhibitor, reduces miR-21-5p expression, thus leading to an increase in PGR expression in ectopic endometriotic stromal cells. In the mouse model of endometriosis, treatment with VP increases PGR expression and enhances decidualization. More importantly, VP synergistically increases the treatment effect of progestin in causing the regression of endometriotic lesions and improves the decidualization capability of the endometrium. Interestingly, treatment with dienogest, a synthetic progestin, reduces YAP1 and miR-21-5p expression in human cells and in the mouse model of endometriosis. Patients who received dienogest treatment for 6 months show a significant decrease in serum extracellular vesicle-associated miR-21-5p level. LARGE SCALE DATA: A public dataset (GSE51981) containing a large cohort of endometriotic tissues is available from the Gene Expression Omnibus (GEO). LIMITATIONS, REASONS FOR CAUTION: A large cohort of clinical samples is needed to verify the current diagnostic value of miR-21-5p in future studies. WIDER IMPLICATIONS OF THE FINDINGS: The reciprocal regulation of YAP1 and PGR suggests that combined YAP1 inhibitor and progestin may be a better therapeutic approach for treating endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Ministry of Science and Technology, Taiwan (MOST-111-2636-B-006-012, MOST-111-2314-B-006-075-MY3, and MOST-106-2320-B-006-072-MY3). The authors have no conflict of interest to disclose.

Polymorphisms within the Tumor Necrosis Factor-Alpha Gene Is Associated with Preeclampsia in Taiwanese Han Populations.

Preeclampsia (PE) occurs in women pregnant for more than 20 weeks with de novo hypertension and proteinuria, and is a devastating disease in maternal-fetal medicine. Cytokine tumor necrosis factor (TNF)-α may play a key role in the pathogenesis of PE. We conducted this study to investigate the regulatory regions of the TNF genes, by investigating two promoter polymorphisms, TNFA-308G/A (rs1800629) and -238G/A (rs361525), known to influence TNF expression, and their relationship to PE. An observational, monocentric, case-control study was conducted. We retrospectively collected 74 cases of severe PE and 119 pregnant women without PE as control. Polymerase chain reaction (PCR) was carried out for allele analysis. Higher A allele in women with PE was found in rs1800629 but not rs361525. In this study, we first found that polymorphism at the position -308, but not -238, in the promoter region of the TNF-α gene can contribute to severe PE in Taiwanese Han populations. The results of our study are totally different to previous Iranian studies, but have some similarity to a previous UK study. Further studies are required to confirm the roles of rs1800629 and rs361525 in PE with circulating TNF-α in PE.

Factors associated with utilization of physical therapy services during pregnancy and after childbirth.

Objective: To explore demographic and clinical factors associated with utilization of antepartum/postpartum physical therapy. Methods: This is a secondary analysis of a cross-sectional survey of 298 women who were receiving or had received obstetric care at a medical center in southern Taiwan. Data were collected between May 2021 and May 2022 using an online questionnaire, which included demographic, medical, and obstetric details, the symptom severity questionnaires, management strategies, and experience and perception about physical therapy. Descriptive statistics, independent t-test, chi-square analysis and multivariate logistic regression model were used to analyze data. Results: Among 298 respondents, 190 (63.8%) were pregnant and 108 (36.2%) were postpartum. Thirteen percent of pregnant participants and 27% of postpartum participants had received physical therapy during and/or after childbirth. Multivariate analyses showed that being postpartum, having an associate degree and below, and experiencing depressive symptoms were significantly associated with an increased utilization of physical therapy (postpartum: OR = 3.039, 95% CI = 1.530, 6.035; associate degree and below: OR = 2.521, 95% CI = 1.007, 6.316; depressive symptoms: OR = 3.606, 95% CI = 1.067, 12.185). The odds of utilizing physical therapy decreased with age (OR = 0.935, 95% CI = 0.874, 1.000). Conclusions: Individual factors, such as age, education level, pregnancy status, and experience of depressive symptoms, have a significant association with utilization of antepartum/postpartum physical therapy and should be considered when developing obstetric care pathways to optimize clinical and healthcare utilization outcomes.

Incorporating sperm DNA fragmentation index with computer-assisted semen morphokinematic parameters as a better window to male fertility.

This study aimed to assess (1) the reproducibility of three sperm chromatin dispersion (SCD) assays for sperm DNA fragmentation, i.e., LensHooke R10® (R10), Halosperm G2® (G2), and BASO® (BA); (2) the correlation between computer-assisted semen analyzer (CASA) morphokinematic parameters and sperm DNA fragmentation index (DFI), and (3) the diagnostic value for male reproduction by combining semen morphokinematic parameters and DFI. Total 50 male participants were recruited, and all collected semen samples underwent semen analyses and SCD assays. Intra- and inter-observer variability of DFI data from different SCD measures was tested. In addition, the predictive ability of CASA parameters and DFI (with different cutoffs, i.e., 15% and 20%) for infertility was assessed using receiver operating characteristic curve analysis. We found that the G2 and R10 produced satisfactory variance coefficients (5.53%, 5.67%) compared to BA (14.8%). The DFI data from the R10 had lower intra-observer variability, in terms of higher intra-class coefficient (0.9615), than that of the G2 (0.8847) or BA (0.8824). Inter-observer variability of three SCD kits in scoring the DFI was comparable and satisfactory (concordance correlation coefficients ranging 0.9895-0.9630). The CASA parameters (i.e., total motility [r = -0.57], progression motility [r = -0.55], and rapidly progressive motility [r = -0.55]) were significantly correlated with DFI (P < 0.001). The predictive ability of the 15%-cutoff DFI data was better than that of the 20%-cutoff or continuous DFI data. The model comprising the CASA parameters, 15%-cutoff DFI, and 4%-cutoff normal morphology had the highest area under curve (0.8125) for infertility. For SCD assay, the R10 was the most reliable SCD assay to detect sperm DNA fragmentation. Combining the sperm DFI with CASA parameters might be a better diagnostic tool for male reproduction.

Physical therapists' experiences and perceptions of antepartum and postpartum care.

BACKGROUND: Little is known about the physical therapists' practice and perceptions toward management of pregnancy/postpartum-related disorders in Taiwan. The aim of this study was to document current practice of physical therapy in antepartum and postpartum care in Taiwan. METHODS: An exploratory, cross-sectional study was conducted in registered physical therapists living in Taiwan. An anonymized online survey was designed, piloted, and advertised widely from March 2020 to March 2021. Data were analyzed using descriptive statistics, Chi square analysis and multivariate logistic regression. RESULTS: Of the 364 respondents, 37.6% had experience of treating pregnant or postpartum women in clinical practice. The most commonly treated pregnancy/postpartum-related disorder in practice was low back pain (61.3%). All respondents reported little to moderate level of confidence in their ability to manage pregnancy/postpartum-related disorder. Being female (p < 0.01); working at a regional hospital (p = 0.01), district hospital or district teaching hospital (p < 0.01), clinic (p = 0.01) or physiotherapy clinic (p = 0.01); and having prior experience of treating antepartum or postpartum women (p < 0.01) were significantly associated with willingness to provide customer-oriented service or health education to patients/clients with pregnancy/postpartum-related disorder after controlling for other confounding variables. The most commonly reported barrier was "lack of available training" (81.3%). CONCLUSION: The majority of participating physical therapists indicated a positive attitude to antepartum and postpartum care but were not confident in management of various pregnancy/postpartum-related disorder in practices. The findings of this study highlight the educational needs related to antepartum and postpartum care in clinical practice for physical therapists in Taiwan.

Upregulation of Fibrinogen-Like 1 Expression Contributes to Reducing the Progression of Preeclampsia.

Fibrinogen-like 1 (FGL1) is involved in liver injury and liver regeneration, but its role in placenta and preeclampsia (PE) remains unclear. We assessed FGL1 expression in serum and placenta from L-NAME-induced PE-like mouse and in women with (n = 38) and without (n = 42) PE. For the mouse study, pregnant C57Bl/6 mouse (n = 6/group) were subcutaneously administered L-NAME with or without FGL1 once daily starting on days 7-14 of pregnancy and were sacrificed on gestational day (GD) 20. Maternal body weight, blood pressure, and urinary protein were assessed during GDs 8-20. The weight and length of the placenta and fetus were assessed. The placental structure was evaluated using hematoxylin staining. In the human study, the sera of the pregnant women during the late trimester were assessed with enzyme-linked immunosorbent assays (ELISAs). FGL1 expression in human trophoblast cell lines under L-NAME stimulation was measured using Western blotting and immunofluorescence staining. The detected FGL1 protein levels in serum and placenta were both significantly upregulated in patients and mouse with PE compared with those in the non-PE groups. FGL1 treatment decreased maternal hypertension and proteinuria, decreased fetal weight in mouse with PE, downregulated proinflammatory cytokine (interleukin-1b and interleukin-6) levels, and maintained the balance between antiangiogenic (fms-like tyrosine kinase-1) and proangiogenic (placental growth factor) substances in the placenta. L-NAME-upregulated FGL1 expression was inhibited following overexpression of FoxO3a. In summary, FoxO3a reduction is a potential pathophysiological mechanism leading to upregulated placental FGL1 expression that may play a pivotal role in preventing PE progression.

Pretreatment bowel manipulation during ultrasound-guided high-intensity focused ultrasound therapy for posterior wall uterine masses.

OBJECTIVE: High-intensity focused ultrasound (HIFU) therapy is a noninvasive alternative to conventional abdominal surgery in obstetrics and gynecology. The aim of this study is to evaluate the reduction of pain intensity with bowel manipulation before ultrasound-guided HIFU treatment in women with posterior wall uterine fibroids and/or adenomyosis. MATERIALS AND METHODS: This is a multicenter retrospective observational study. Data from all patients who underwent HIFU therapy at three HIFU clinics (Sichuan Maternal and Child Health Hospital, Xiangya Hospital of Central South University, and Kuo General Hospital) between January 2019 and December 2019 were analyzed. We compared pain intensity with and without bowel manipulation during the HIFU treatment and evaluated tolerability without intravenous sedation. The presence of discomfort or pain during the HIFU procedure was evaluated using the visual analog scale (VAS). RESULTS: A total of 86 women were included in this study. All women underwent HIFU therapy with the PRO-2008 system in the supine position for posterior wall uterine fibroids and/or adenomyosis. Thirty-seven women received pretreatment anal catheterization with a condom and 49 women were not subjected to bowel manipulation. All patients received pretreatment condom-catheter device were well tolerated during the procedure of bowel manipulation. During the HIFU procedure, the women who had received bowel manipulation experienced lower pain intensity, especially less sacrococcygeal pain (VAS score 1.56 ± 1.46 vs 2.89 ± 1.61), target region pain (1.54 ± 1.30 vs 2.53 ± 1.29), and radiating pain (0.13 ± 0.34 vs 0.41 ± 0.54), compared with the women without bowel manipulation. CONCLUSION: Bowel manipulation with anal catheterization before HIFU therapy for posterior wall uterine masses can be safely performed and is effective as a low risk intervention to aid in reducing potential HIFU complications related to nerve involvement.

Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats.

Osteoarthritis (OA) and osteoporosis (OP) are common among older women, especially postmenopausal women. Glucosamine (GlcN) is a common medication for OA, but it may induce insulin resistance and ß-cell dysfunction, especially if ovarian hormones are lacking. Raloxifene (RLX) is a selective estrogen receptor modulator and also an OP drug. Previously, we found that estrogen could improve GlcN-induced insulin resistance in ovariectomized (OVX) rats. Here, we further hypothesized that RLX, similarly to estrogen, can ameliorate GlcN-induced insulin resistance in OVX rats. We used GlcN to induce insulin resistance in OVX rats as a model for evaluating the protective effects of RLX in vivo. We used a pancreatic ß-cell line, MIN-6, to study the mechanisms underlying the effect of RLX in GlcN-induced ß-cell dysfunction in vitro. Increases in fasting plasma glucose, insulin, and homeostasis model assessments of insulin resistance in OVX Sprague Dawley rats treated with GlcN were reversed by RLX treatment (n = 8 in each group). Skeletal muscle GLUT-4 increased, liver PEPCK decreased, pancreatic islet hypertrophy, and ß-cell apoptosis in OVX rats treated with GlcN was ameliorated by RLX. The negative effects of GlcN on insulin secretion and cell viability in MIN-6 cells were related to the upregulation of reticulum (ER) stress-associated proteins (C/EBP homologous protein, phospho-extracellular signal-regulated kinase, phospho-c-JunN-terminal kinase), the expression of which was reduced by RLX. Pretreatment with estrogen receptor antagonists reversed the protective effects of RLX. GlcN can induce insulin resistance, ß-cell dysfunction, and apoptosis in OVX rats and increase ER stress-related proteins in ß-cells, whereas RLX can reverse these adverse effects. The effects of RLX act mainly through estrogen receptor α; therefore, RLX may be a candidate drug for postmenopausal women with OA and OP.

The pro-inflammatory and anti-inflammatory role of hyaluronic acid in endometriosis.

OBJECTIVE: Endometriosis is a bothersome disease affected women worldwide, the mechanism of disease development is still under investigation. Several inflammatory responses after clinical hyaluronic acid (HA) use were reported. Cyclooxygenase (COX)-2 mediated inflammation pathway is involved in the pathogenesis of endometriosis. Thus, we tried to investigate the inflammatory role of hyaluronic acid in endometriosis. MATERIALS AND METHODS: Peritoneal fluid was collected in endometriosis and disease-free patients for the measurement of HA. Endometriotic stromal cells were treated with IL-1ß and HA and expression of COX-2 was evaluated. Mice model of endometriosis was established and treated with fluid or gel form of HA. Endometriotic lesion size and weight were recorded and level of COX-2 was evaluated by immunohistochemistry staining. RESULTS: The level of HA in the peritoneal fluid had no statistically significant difference between normal, early and advanced stage endometriosis patients. The overexpression of COX-2 protein was detected when treating endometriotic stromal cell with HA in the presence of IL-1ß (P < 0.001). The endometriotic lesion size was reduced in mice model when treated with higher concentration gel form HA. It further showed less proportion of strong COX-2 expression compare of gel form HA to fluid form treatment in COX-2 expression score of endometriosis lesion. CONCLUSION: Both proinflammatory evidence, elevated COX-2 expression, and anti-inflammatory result, reduced endometriosis lesion size and COX-2 expression score, were noted in our study after treating HA in in vivo and in vitro models. We hypothesized it is possible that HA may induce an acute proinflammatory response followed by chronic anti-inflammatory reaction in the formation of endometriosis.

Endometriosis-related spontaneous hemoperitoneum in the early second trimester: A case report.

OBJECTIVE: To present a rare case of endometriosis-related spontaneous hemoperitoneum in pregnancy (SHiP) with atypical subacute symptoms, which is likely to be mistaken as an infectious disease initially. CASE REPORT: A 35-year-old primigravid woman presented with diffuse lower abdominal pain and signs of peritoneal irritation for five days at 18 weeks' gestation, and the initial diagnosis was acute peritonitis. An abrupt deterioration with maternal shock and stillbirth of fetus was found in spite of close observation in emergent department. Emergent laparotomy was performed for delay-appeared hemoperitoneum. Bleeding from decidualized endometriotic tissue over posterior uterine surface was found, and hemostasis was achieved with uterine preservation. The patient recovered smoothly. CONCLUSION: SHiP is a serious obstetric complication of endometriosis with diagnostic difficulty. Its initial presentation may mimic infectious disease, so close monitoring for possible abrupt deterioration is crucial. Early detection and timely management are the key to avoid adverse pregnancy outcomes.

Quality of life among infertile women with endometriosis undergoing IVF treatment and their pregnancy outcomes.

OBJECTIVE: We assessed the quality of life (QoL) and pregnancy outcomes of in vitro fertilization (IVF) treatment among infertile women with endometriosis, as compared to infertile women without endometriosis. STUDY DESIGN: Eighty-one (81) endometriosis women (with 142 embryo transfer [ET] cycles) and 605 non-endometriosis women (with 1063 ET cycles) were included. QoL was measured by FertiQoL at the date before ET. Pregnancy outcomes included biochemical pregnancy, ongoing pregnancy and live birth. Generalized estimating equation analyses were performed to assess the association between QoL and IVF pregnancy. RESULTS: Endometriosis-affected women had significantly lower QoL, as indicated by mind/body, treatment environment and total treatment scores, and total scores of FertiQoL (p < .05), compared to those without endometriosis. Among non-endometriosis women, QoL scores were significantly associated with successful IVF pregnancy; with one unit increase in QoL scores as measured by emotional domain of FertiQoL, the probabilities of ongoing pregnancy and live birth significantly increased by 2.5% and 2.8%, respectively (p < .05). This association was also observed among endometriosis women but it did not reach statistical significance. CONCLUSIONS: Lower QoL among women with endometriosis versus non-endometriosis during IVF treatment highlights the importance of developing strategies to improve their QoL, which may enhance following pregnancy rates in this population.