Association of pelvic inflammatory disease (PID) with ovarian cancer: a nationwide population-based retrospective cohort study from Taiwan.

BACKGROUND: Pelvic inflammatory disease (PID) is an important health issue for women. Infection and inflammation play an important role in carcinogenesis and PID has been reported to be associated with ovarian cancer in some small scale studies. AIM: We sought to determine whether PID is associated with an elevated risk of ovarian cancer in Asian women. METHODS: Using data from Taiwan's National Health Insurance Research Database (NHIRD), our retrospective cohort study included women diagnosed with PID (cases) between the years of 2000 till 2012. Each case was matched with two women without PID (controls) by age and the year of first entry into the database. Both study cohorts were followed-up until the first event of ovarian cancer, withdrawal from the NHI program, death, or the end of the study period (December 31, 2012). Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios (HRs and aHRs) with their corresponding 95% confidence intervals (95% CIs) for the association of PID and ovarian cancer risk, with and without adjusting for potential confounders. RESULTS: During an approximate 10 years of follow-up, cases were significantly more likely than controls to develop ovarian cancer (incidence rates of 0.27 and 0.16 per 1,000 person-years, respectively; P < 0.001). Women with a history of PID had a 1.49-fold elevated risk for ovarian cancer (aHR, 1.49; 95% CI, 1.21-1.84; P < 0.001). CONCLUSION: Our study evidence supports the contention that PID increases the risk of developing ovarian cancer among Taiwanese women. Gynecologists should undertake careful assessments and closely follow patients with PID, who are at long-term risk of developing ovarian cancer. Our findings need further verification in other international cohorts.

Association between hypertensive pregnancy disorders and future risk of stroke in Taiwan: a Nationwide population-based retrospective case-control study.

BACKGROUND: The incidence of female stroke has increased gradually and has begun occurring at a younger age in recent years. Given that women live longer than men, stroke would cause more negative and longer-term impacts on the rest of the lives of women. There are few related studies on Asian women. We aimed to evaluate stroke risk in Asian women following hypertensive pregnancy disorders. METHODS: Using the Taiwan National Health Insurance database, we designed a retrospective study that included pregnant women between 2000 and 2013. We selected an age-matched control group of women without hypertensive pregnancy disorders at a 1:3 ratio. The endpoint was any episode of stroke; otherwise, the patients were tracked until December 31, 2013. After the index date until the end of 2013, Cox proportional hazards analysis was used to compare the risk of incident stroke. The risk factors for stroke were determined using Cox proportional regression to calculate the hazard ratio (HR) compared with the control group. RESULTS: During the follow-up period, the Kaplan-Meier analysis indicated that patients with hypertensive pregnancy disorders had a significantly higher risk of developing stroke than did patients without hypertensive pregnancy disorders (log-rank test P < 0.001). Multivariate Cox regression analysis demonstrated that the case group had a 2.134-fold increased risk of stroke (HR = 2.134; 95% CI = 1.817-2.505; P < 0.001). CONCLUSION: Our study provided evidence of an increased risk of stroke in patients with hypertensive pregnancy disorders. Compared with those without such disorders, the patients who had experienced the disorders had a 2.134-fold (P < 0.001) higher risk of developing stroke in the future.

Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-α H score.

Prediction of local relapse and distant metastasis in patients with definitive chemoradiotherapy-treated cervical cancer by deep learning from [18F]-fluorodeoxyglucose positron emission tomography/computed tomography.

BACKGROUND: We designed a deep learning model for assessing 18F-FDG PET/CT for early prediction of local and distant failures for patients with locally advanced cervical cancer. METHODS: All 142 patients with cervical cancer underwent 18F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. In each round of k-fold cross-validation, a well-trained proposed model and a slice-based optimal threshold were derived from a training set and used to classify each slice set in the test set into the categories of with or without local or distant failure. The classification results of each tumor were aggregated to summarize a tumor-based prediction result. RESULTS: In total, 21 and 26 patients experienced local and distant failures, respectively. Regarding local recurrence, the tumor-based prediction result summarized from all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively. CONCLUSION: This is the first study to use deep learning model for assessing 18F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. KEY POINTS: • This is the first study to use deep learning model for assessing 18 F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. • All 142 patients with cervical cancer underwent 18 F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. • For local recurrence, all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively.

Low-dose, prophylactic, extended-field, intensity-modulated radiotherapy plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes, and negative para-aortic lymph nodes.

OBJECTIVE: The objective of this study was to assess prospectively the clinical outcomes of low-dose prophylactic extended-field, intensity-modulated radiotherapy (IMRT) plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes (PLNs), and negative para-aortic lymph nodes (PALNs). METHODS: Thirty-two patients with stage IB2-IIIB cervical cancer with positive PLN and negative PALN were included prospectively. All lymph nodes were assessed with positron emission tomography. The PALN field, including lymphatics from the superior border of L1 to the L4-L5 interphase, was irradiated concurrently with pelvic IMRT with a prescribed dose of 40 Gy in 25 fractions. Chemotherapy consisted of cisplatin delivered weekly at a dose of 40 mg/m. Using historical controls treated with pelvic radiotherapy, the survival curves were compared to assess the difference between the 2 treatment periods. RESULTS: Thirty-one patients completed the allocated extended-field IMRT, and all finished the planned pelvic IMRT and brachytherapy. Acute ≥ grade 3 gastrointestinal, genitourinary, and hematologic toxicities were seen in 2, 1, and 18 patients, respectively. During a median follow-up of 33 months, 5 patients developed out-field distant recurrences. One patient had a late grade 3 gastrointestinal complication, and 1 patient had genitourinary toxicity. The 3-year actuarial overall survival, disease-free survival, and distant metastasis-free survival for the study cohort and historic controls were 87% versus 62% (P = 0.02), 82% versus 54% (P = 0.02), and 79% versus 57% (P = 0.01), respectively. CONCLUSIONS: Extended-field IMRT of 40 Gy to the PALN plus concurrent cisplatin can effectively eradicate subclinical disease at the PALN and improve the outcome for patients with PLN-positive stage IB2-IIIB cervical cancer.

Primary treatment and prognostic factors of carcinosarcoma of the ovary, fallopian tube, and peritoneum: a Taiwanese Gynecologic Oncology Group Study.

OBJECTIVE: This study aimed to determine the clinical prognostic factors involved in carcinosarcoma of the ovary, fallopian tube, and peritoneum. MATERIALS AND METHODS: This retrospective study was undertaken by the Taiwanese Gynecologic Oncology Group. The retrieved clinical data included demographic characteristics, medical disease, tumor status, extent of surgery, and adjuvant chemotherapy. RESULTS: In total, 63 patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum were identified. Sixty-one patients with complete data were enrolled for further data analysis. The mean follow-up period was 1.0 year, and the mean overall survival was 15.4 months. By log-rank tests, age, menopausal status, parity, hypertension, diabetes, primary tumor size, para-aortic lymph node metastasis, pretreatment CA-125, preceding diagnostic surgery, hysterectomy, lymphadenectomy, other surgeries, and paclitaxel use were not predictive of overall survival.Omentectomy, no gross residual implants after surgery, platinum treatment, and no pelvic lymph node metastasis had a trend toward better survival. Early diagnosis at stage I and cisplatin/ifosfamide regimen were significant associated with a better overall survival in log-rank and simple Cox regression tests. Bilateral ovarian tumors and metastatic tumors larger than 2 cm were significantly associated with a poorer overall survival. CONCLUSIONS: Early diagnosis at stage I, unilateral ovarian tumor, metastatic tumors less than 2 cm, and cisplatin/ifosfamide regimen were predictive of a better survival.Omentectomy and complete debulking surgery also showed a trend toward better survival. Thus, these treatment strategies should be applied in patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum.

Complementary Chinese Herbal Medicine Treatment is Associated with a Reduction of Surgical Rate in Patients with Dysfunctional Uterine Bleeding: A Propensity-Score Matched Cohort Study.

Background: Many patients with dysfunctional uterine bleeding (DUB) seek traditional medicine consultations. This study intended to investigate the association of complementary Chinese herbal medicine (CHM) with the surgery rate in patients with DUB in Taiwan. Methods: We enrolled 43,027 patients with newly diagnosed DUB (ICD-9-CM codes 626.8) from the National Health Insurance Research Database in Taiwan during the period of 1997 to 2010. Among them, 38,324 were CHM users, and 4703 did not receive CHM treatment. After performing a 1:1 propensity-score match based on patients' age (per 5 years), comorbidities, conventional drugs, childbirth status, duration from the diagnosis year of DUB and index year, there were an equal number (n=4642) of patients in the CHM cohort and non-CHM cohort. The outcome measurement was the comparison of incidences of surgical events, including hysterectomy and endometrial ablation, in the two cohorts before the end of 2013. Results: CHM users had a lower incidence of surgery than non-CHM users (adjusted HR 0.27, 95% CI: 0.22-0.33). The cumulative incidence of surgery was significantly lower in the CHM cohort during the follow-up period (Log rank test, p < 0.001). A total of 146 patients in the CHM cohort (4.99 per 1000 person-years) and 485 patients in the non-CHM cohort (20.19 per 1000 person-years) received surgery (adjusted HR 0.27, 95% CI: 0.22-0.33). CHM also reduced the risk of surgery in DUB patients with or without comorbidities. Regardless of childbirth status or whether patients took NSAIDs, tranexamic acid or progesterone, fewer patients in the CHM cohort underwent surgery than in the non-CHM cohort. The most commonly prescribed single herb and formula were Yi-Mu-Cao (Herba Leonuri) and Jia-Wei-Xiao-Yao-San, respectively. Conclusion: The real-world data revealed that CHM is associated with a reduced surgery rate in DUB patients. This information may be provided for further clinical investigations and policy-making.

Ovarian clear cell carcinoma with uterine intramural recurrence: Case report of ovarian clear cell carcinoma with fertility sparing treatment.

OBJECTIVE: Ovarian clear cell carcinoma has a poor prognosis in comparison with other pathological types of epithelial ovarian carcinoma. It also has relative resistance to first-line platinum-based chemotherapy with a great risk of recurrence. CASE REPORT: We report a case of recurrent ovarian clear cell carcinoma status after left salpingo-oophorectomy (fertility-sparing debulking operation) and six courses of adjuvant chemotherapy (paclitaxel (175 mg/m2)/carboplatin (AUC 6)). However, two years after diagnosis, elevated CA-125 accompanied by an intrapelvic mass was noted. Uterine intramural recurrence was found during the second laparotomy. She was treated with right salpingo-oophorectomy and abdominal hysterectomy combined with systemic chemotherapy administration (paclitaxel (175 mg/m2)/carboplatin (AUC 6)) and maintenance therapy (bevacizumab (7.5 mg/kg)). There was no other recurrence until one and a half years postoperatively, and the patient was tumor free with regular follow-up. CONCLUSION: In young patients with stage I ovarian clear cell carcinoma, fertility-sparing surgery was considered. Most patients will suffer from tumor recurrence, and also intrauterine recurrence rarely happen.

Does initial 45Gy of pelvic intensity-modulated radiotherapy reduce late complications in patients with locally advanced cervical cancer? A cohort control study using definitive chemoradiotherapy with high-dose rate brachytherapy.

BACKGROUND: Comparing initial 45 Gy of pelvic intensity-modulated radiation therapy (IMRT) and non-IMRT in terms of the late toxicities associated with advanced cervical cancer that has also been treated with definitive concurrent chemoradiotherapy and high-dose rate intracavitary brachytherapy (HDRICB). PATIENTS AND METHODS: This retrospective study included 320 stage IB2-IIIB cervical cancer patients treated with CCRT (83 IMRT and 237 non-IMRT). The two groups had similar stage and HDRICB ratings. Following 45 Gy to the pelvis, HDRICB of 24 Gy in four courses was prescribed. Late toxicities, including rectal complications (RC), bladder complications (BC) and non-rectal intestinal injury (NRRII), were scored by the Common Terminology Criteria for Adverse Events. A logistic regression was used to estimate the odds ratio (OR) of the complications. RESULTS: With a median follow-up duration of 33 and 77 months for IMRT and non-IMRT, 33 patients had Grade 2 or higher late RC (7.2% IMRT, 11.4% non-IMRT), whereas that for BC was 40 (9.6% IMRT, 13.5% non-IMRT) and for NRRII was 48 (12.0% IMRT, 16.0% non-IMRT). The cumulative rate for total grade 3 or higher gastrointestinal or genitourinary toxicities was 8.4% and 11.8% (p = 0.33). IMRT did not reduce the OR for all endpoints; however, the ORs for rectum and bladder reference doses to Point A were associated with RC and BC. CONCLUSIONS: Locally advanced cervical cancer patients treated with initial 45Gy of pelvic IMRT and HDRICB have similar treatment-related late toxicities as those treated with non-IMRT. Optimization of the brachytherapy scheme is essential to minimize late toxicities.

Establishment of the fetal-maternal interface: developmental events in human implantation and placentation.

Early pregnancy is a complex and well-orchestrated differentiation process that involves all the cellular elements of the fetal-maternal interface. Aberrant trophoblast-decidual interactions can lead to miscarriage and disorders that occur later in pregnancy, including preeclampsia, intrauterine fetal growth restriction, and preterm labor. A great deal of research on the regulation of implantation and placentation has been performed in a wide range of species. However, there is significant species variation regarding trophoblast differentiation as well as decidual-specific gene expression and regulation. Most of the relevant information has been obtained from studies using mouse models. A comprehensive understanding of the physiology and pathology of human implantation and placentation has only recently been obtained because of emerging advanced technologies. With the derivation of human trophoblast stem cells, 3D-organoid cultures, and single-cell analyses of differentiated cells, cell type-specific transcript profiles and functions were generated, and each exhibited a unique signature. Additionally, through integrative transcriptomic information, researchers can uncover the cellular dysfunction of embryonic and placental cells in peri-implantation embryos and the early pathological placenta. In fact, the clinical utility of fetal-maternal cellular trafficking has been applied for the noninvasive prenatal diagnosis of aneuploidies and the prediction of pregnancy complications. Furthermore, recent studies have proposed a viable path toward the development of therapeutic strategies targeting placenta-enriched molecules for placental dysfunction and diseases.

Image-guided brachytherapy following external-beam radiation therapy for patients with inoperable endometrial cancer.

OBJECTIVE: To investigate the outcomes of definitive external-beam radiation therapy (EBRT) plus image-guided brachytherapy (IGBT) in patients with endometrial cancer (EC) unsuitable for surgery. METHODS: A total of 50 patients with inoperable EC were included. The patients received EBRT in a median dose of 45 Gy to the pelvis over 5 weeks. Thereafter, the patients received brachytherapy using tandem and ovoid applicators. High-risk clinical target volume (HR-CTV) and gross tumor volume in brachytherapy (GTVp) were defined by the assistance of patients' pre-IGBT magnetic resonance imaging. RESULTS: The medical records of the 50 patients were analyzed. The main causes of inoperability were anesthesia contraindications, namely medical comorbidities and obesity. The median cumulative D90s (the minimum dose delivered to 90% of the volume) in EQD2 (equivalent dose in 2-Gy fractions) to the HR-CTV and GTVp were 72.9 Gy10 (range, 64.9 to 80.3) and 166.2 Gy10 (range, 123.0 to 189.8), respectively. Over a median follow-up period of 27 months, 8 of the patients died of cancer. The 2-year overall and cancer-specific survival rates were 75% and 83%, respectively. The cumulative incidences of pelvic and distant failure were 4% (n = 2) and 16% (n = 8), respectively. Gastrointestinal complications of grade 2 or above were noted in 2 patients (4%), and a grade 2 genitourinary complication was noted in one. CONCLUSIONS: For patients with inoperable EC, EBRT followed by IGBT is an effective approach for achieving high local control without a high risk of complications.

Risk factors for 5-year complications after midurethral sling surgery for stress urinary incontinence: a retrospective cohort study from Taiwan.

Midurethral sling surgery is the current gold standard worldwide for stress urinary incontinence (SUI) surgery, with over 90% of surgeons worldwide using the midurethral sling for SUI between 2008 and 2018. However, concerns surround mesh-related adverse events associated with the midurethral sling. The decision to use the midurethral sling for surgical treatment has become a challenging one for clinicians, surgeons and patients. We sought to determine the factors for 5-year complications after midurethral sling surgery, to improve the clinical decision-making process. Records were reviewed from a total of 1961 female patients who underwent their first midurethral sling surgery for SUI between 2003 and 2018 at a single teaching hospital in Taiwan. A multivariable Cox proportional hazard model calculated the hazard ratios of risk factors for surgical complications, after adjusting for confounders. Surgical complications (i.e., secondary surgery and urinary retention) occurred in 93 (4.7%) patients within 5 years following the index operations. These patients were more likely to be older, to have a history of menopausal syndrome within 1 year prior to the index operation, a medication history of oral antidiabetic drug use, hormone replacement therapy (HRT), slower average flow rate, and longer voiding time compared with patients without surgical complications. In the multivariate analysis, HRT (adjusted hazard ratio, 1.787; 95% confidence interval, 1.011-3.158, p = 0.04) was significantly associated with surgical complications at 5 years, after adjusting for age, gender, diabetes, menopause syndrome, average flow rate, and sling type. Our findings suggest that a medication history of HRT may be a risk factor associated with surgical complications, especially urinary retention, at 5 years in women undergoing midurethral sling surgery for SUI.

Finding of the optimal preparation and timing of endometrium in frozen-thawed embryo transfer: a literature review of clinical evidence.

Frozen-thawed embryo transfer (FET) has been a viable alternative to fresh embryo transfer in recent years because of the improvement in vitrification methods. Laboratory-based studies indicate that complex molecular and morphological changes in endometrium during the window of implantation after exogenous hormones with controlled ovarian stimulation may alter the interaction between the embryo and endometrium, leading to a decreased implantation potential. Based on the results obtained from randomized controlled studies, increased pregnancy rates and better perinatal outcomes have been reported following FET. Compared to fresh embryo transfer, fewer preterm deliveries, and reduced incidence of ovarian hyperstimulation syndrome were found after FETs, yet there is a trend of increased pregnancy-related hypertensive diseases in women receiving FET. Despite the increased application of FET, the search for the most optimal priming protocol for the endometrium is still undergoing. Three available FET protocols have been proposed to prepare the endometrium: i) natural cycle (true natural cycle and modified natural cycle) ii) artificial cycle (AC) or hormone replacement treatment cycle iii) mild ovarian stimulation (mild-OS) cycle. Emerging evidence suggests that the optimal timing for FET using warmed blastocyst transfer is the LH surge+6 day, hCG administration+7 day, and the progesterone administration+6 day in the true natural cycle, modified natural cycle, and AC protocol, respectively. Although still controversial, better clinical pregnancy rates and live birth rates have been reported using the natural cycle (true natural cycle/modified natural cycle) compared with the AC protocol. Additionally, a higher early pregnancy loss rate and an increased incidence of gestational hypertension have been found in FETs using the AC protocol because of the lack of a corpus luteum. Although the common clinical practice is to employ luteal phase support (LPS) in natural cycles and mild-OS cycles for FET, the requirement for LPS in these protocols remains equivocal. Recent findings obtained from RCTs do not support the routine application of endometrial receptivity testing to optimize the timing of FET. More RCTs with rigorous methodology are needed to compare different protocols to prime the endometrium for FET, focusing not only on live birth rate, but also on maternal, obstetrical, and neonatal outcomes.

MUC2 polymorphisms are associated with endometriosis development and infertility: a case-control study.

BACKGROUND: Mucins are highly glycosylated proteins protecting and lubricating epithelial surface of respiratory, gastrointestinal and reproductive tracts. Members of the mucin protein family have been suggested to play an important role in development of endometriosis and infertility. This study investigates genetic association of mucin2 (MUC2) with the risk of endometriosis and endometriosis-related infertility. METHODS: This case-control study was conducted at China Medical University Hospital, with 195 endometriosis patients and 196 healthy controls enrolled. Genotyping of six SNPs (rs2856111, rs11245936, rs10794288, rs10902088, rs7103978 and rs11245954) within MUC2 gene were performed by using Taqman genotyping assay; individual SNP and haplotype associations with endometriosis and endometriosis-related infertility were assessed by χ² test. RESULTS: Endometriosis patients exhibit significantly lower frequency of the rs10794288 C allele, the rs10902088 T allele and the rs7103978 G allele (P = 0.030, 0.013 and 0.040, respectively). In addition, the rs10794288 C allele and the rs10902088 T allele were also less abundant in patients with infertility versus fertile ones (P = 0.015 and 0.024, respectively). Haplotype analysis of the endometriosis associated SNPs in MUC2 also showed significantly association between the most common haplotypes and endometriosis or endometriosis-related infertility. CONCLUSIONS: MUC2 polymorphisms, especially rs10794288 and rs10902088, are associated with endometriosis as well as endometriosis-related infertility. Our data present MUC2 as a new candidate involved in development of endometriosis and related infertility in Taiwanese Han women.

Brain metastases from epithelial ovarian carcinoma: evaluation of prognosis and managements - a Taiwanese Gynecologic Oncology Group (TGOG) study.

OBJECTIVE: To evaluate the characteristics and outcome of patients with brain metastases from epithelial ovarian carcinoma. METHODS: The clinical and pathologic characteristics, treatment and outcome of patients with brain metastases from epithelial ovarian carcinoma were analyzed from eight medical centers in Taiwan under the TGOG (Taiwanese Gynecologic Oncology Group). RESULTS: A total of 64 patients were recruited in this study. The incidence of brain metastases from epithelial ovarian carcinoma seemed to be increasing in recent years. The median survival from the diagnosis of brain metastases was 8 months (range: 0-72). Prior cancer relapse before the diagnosis of brain metastases, number of brain metastases and multimodal treatment were related to the duration of survival. CONCLUSIONS: The prognosis for patients with brain metastases from epithelial ovarian carcinoma is generally poor. However, clinicians should keep alert to the neurological complaints of ovarian cancer patients and the patients might benefit from aggressive multimodal treatments.

Protective effect of Flos carthami extract against ethylene glycol-induced urolithiasis in rats.

Flos carthami (FC), also known as Carthamus tinctorius, is a traditional Chinese herbal plant that has been prescribed since centuries for treating various symptoms related to blood circulation improvement. This study aimed to investigate the effects of FC on calcium oxalate (CaOx) formation in ethylene glycol (EG)-fed rats. A total of 50 male Sprague-Dawley rats were divided into the following 6 groups: group 1, as the normal control (n = 5); group 2 received gastric gavages of starch and 0.75% EG (placebo, n = 5) as a stone inducer; group 3 (n = 10) received EG and potassium citrate as positive controls; group 4 (n = 10) received 0.75% EG and 300 mg/day FC; group 5 (n = 10) was treated with EG and 600 mg/day FC; group 6 (n = 10) received with EG and 1,200 mg/day FC. For all experimental animals, 24-h urine and blood samples were analyzed at the beginning and end of the experiment. Kidney tissue was histopathologically examined using a polarized light microscope, and crystal deposits were evaluated by a semi-quantitative scoring method; these scores were significantly lower in the FC groups (600 and 1,200 mg/day) than in the placebo group. Thus, FC administration appeared to inhibit the deposition of CaOx crystal EG-fed rats. We, therefore, consider that FC may be effective for preventing stone disease, albeit with certain side effects, such as a bleeding tendency. Further clinical trials are needed for evaluating its benefits and possible side effects.

Cervical pregnancy: a case report of hysteroscopic resection and balloon compression combined with systematic methotrexate treatment.

OBJECTIVE: Cervical pregnancy is a rare type of ectopic pregnancy. When the pregnancy is terminated, it will sometimes lead to persistent bleeding. In some cases, hysterectomy is inevitable and the patient loses fertility. Therefore, early diagnosis and targeted management with systemic or local injection of methotrexate is the first-line treatment. Multiple interventions of cervical pregnancy were used to prevent massive hemorrhage, including dilatation and curettage, laparoscopic resection, hysteroscopic resection combined with uterine artery embolization, or uterine artery clip. CASE REPORT: We report a case of cervical pregnancy with a high beta-hCG level accompanied by a visible fetal heartbeat that was successfully treated with hysteroscopic cervical tissue resection and balloon compression combined with systemic administration of methotrexate. CONCLUSION: Efficacy and safety with preserved fertility were important issues in the management of cervical pregnancy. We provide a safe, simple and effective treatment of cervical pregnancy.

Growth hormone in fertility and infertility: Mechanisms of action and clinical applications.

Secreted by the anterior pituitary gland, growth hormone (GH) is a peptide that plays a critical role in regulating cell growth, development, and metabolism in multiple targeted tissues. Studies have shown that GH and its functional receptor are also expressed in the female reproductive system, including the ovaries and uterus. The experimental data suggest putative roles for GH and insulin-like growth factor 1 (IGF-1, induced by GH activity) signaling in the direct control of multiple reproductive functions, including activation of primordial follicles, folliculogenesis, ovarian steroidogenesis, oocyte maturation, and embryo implantation. In addition, GH enhances granulosa cell responsiveness to gonadotropin by upregulating the expression of gonadotropin receptors (follicle-stimulating hormone receptor and luteinizing hormone receptor), indicating crosstalk between this ovarian regulator and the endocrine signaling system. Notably, natural gene mutation of GH and the age-related decline in GH levels may have a detrimental effect on female reproductive function, leading to several reproductive pathologies, such as diminished ovarian reserve, poor ovarian response during assisted reproductive technology (ART), and implantation failure. Association studies using clinical samples showed that mature GH peptide is present in human follicular fluid, and the concentration of GH in this fluid is positively correlated with oocyte quality and the subsequent embryo morphology and cleavage rate. Furthermore, the results obtained from animal experiments and human samples indicate that supplementation with GH in the in vitro culture system increases steroid hormone production, prevents cell apoptosis, and enhances oocyte maturation and embryo quality. The uterine endometrium is another GH target site, as GH promotes endometrial receptivity and pregnancy by facilitating the implantation process, and the targeted depletion of GH receptors in mice results in fewer uterine implantation sites. Although still controversial, the administration of GH during ovarian stimulation alleviates age-related decreases in ART efficiency, including the number of oocytes retrieved, fertilization rate, embryo quality, implantation rate, pregnancy rate, and live birth rate, especially in patients with poor ovarian response and recurrent implantation failure.

New Efficient Method for Hysteroscopic Isthmoplasty: Four Simple Steps Lead to a Significant Improvement in Bleeding Status.

We demonstrate an effective reduction in postmenstrual spotting after our novel hysteroscopic isthmoplasty. This study included 66 patients with isthmocele-related postmenstrual spotting confirmed by sonography and diagnostic hysteroscopy between 2000 and 2017. Our new interventions included the following four steps: (1) make a resection gradient of the distal edge of the isthmocele from the ape of the isthmocele down to the cervical outer orifice; (2) resect the distal and proximal niches of the isthmocele; (3) electrocauterize the distal and proximal sides (not only the niche bottom) of the small cave on the scar side of the isthmocele; (4) manage the isthmocele until it is largely connected to the cavity. In our results, all patients underwent extensive hysteroscopic repair of newly hysteroscopic isthmoplasty without any intra- or postoperative complications. After final hysteroscopic repair modification, prolonged menstrual spotting was significantly decreased in 98.2% (53/54) of the patients, and the total number of bleeding days per menstrual cycle significantly decreased from a mean of 15.38 ± 3.3 days to 6.4 ± 1.9 days postoperatively (p < 0.001). Our four-step hysteroscopic technique successfully resolved prolonged menstrual spotting in over 90% of the patients, exceeding the resolution rates of 60−85% achieved with other hysteroscopic techniques used to treat symptomatic isthmocele. No patients experience recurrence after long-term follow up. Four simple steps led to a significant improvement in bleeding status.

Hysteroscopic transcervical resection. A straightforward method corrects bleeding related to cesarean section scar defects.

Cesarean section defect had been found to be one of the causes of prolonged bleeding in women with previous cesarean delivery. Lin's hysteroscopy (TCR)-metroplasty method had focused on 4 predisposed anatomical defects, which ensured correction of the cesarean section defect. With this simple procedure, the patients had greatly improved their quality of life, as well as discomfort.