PANoptosis, a newly defined form of cell death, is characterized by the simultaneous occurrence and crosstalk of apoptosis, pyroptosis, and necroptosis. It has emerged as a promising therapeutic target for various diseases. Ovarian dysfunction is marked by oligomenorrhea or amenorrhea, elevated gonadotropin levels, and diminished estrogen levels, often accompanying subfertility or infertility. Additionally, it can manifest with perimenopausal syndrome and increase the risks of osteoporosis, cardiovascular disease, and cognitive impairments, seriously impacting patients' quality of life. While current studies have reported that ovarian hypofunction is associated with apoptosis, pyroptosis, or necroptosis, a systematic investigation into the relationship between PANoptosis and ovarian hypofunction is still absent. This review aims to elucidate the potential link between these two phenomena, providing new insights into the mechanisms underlying ovarian hypofunction and potential treatment strategies.
Humans ; Female ; Ovary/metabolism* ; Apoptosis ; Animals ; Necroptosis ; Ovarian Diseases/physiopathology*

OBJECTIVE: To observe the therapeutic effect of electroacupuncture at acupoints of liver meridian in patients with diminished ovarian reserve (DOR) of liver depression. METHODS: A total of 62 patients with DOR of liver depression were randomly divided into an electroacupuncture group (31 cases, 1 case discontinued) and a western medication group (31 cases, 1 case was eliminated). Electroacupuncture was applied at bilateral Taichong (LR 3), Ligou (LR 5), Ququan (LR 8), Jimai (LR 12) in the electroacupuncture group, with continuous wave, in frequency of 2 Hz and current of 0.5-1.0 mA, 30 min each time, once every other day, 3 times a week. Femoston was taken orally in the western medication group, oral estradiol tablets were taken for the first 14 days, followed by oral estradiol/progesterone complex tablets for the rest 14 days, 1 tablet a day. Both groups were treated for 3 consecutive menstrual cycles. Before and after treatment, the scores of TCM syndrome, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed, serum levels of follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were detected, and antral follicle count (AFC), peak systolic velocity (PSV) and resistance index (RI) of ovarian artery were measured by color Doppler ultrasound in the two groups, and the clinical efficacy was evaluated after treatment. RESULTS: After treatment, the scores of primary symptom and secondary symptom, as well as the total scores of TCM syndrome were decreased compared with those before treatment (P<0.01), the scores of SAS and SDS, as well as the serum FSH levels and RI of ovarian artery were decreased compared with those before treatment (P<0.01), while the serum AMH levels, AFC and PSV of ovarian artery were increased compared with those before treatment (P<0.05, P<0.01) in the two groups. After treatment, in the electroacupuncture group, the primary symptom score of TCM syndrome was higher than that in the western medication group (P<0.01), the secondary symptom score of TCM syndrome and the scores of SAS and SDS were lower than those in the western medication group (P<0.05, P<0.01). The total effective rate was 70.0% (21/30) in the electroacupuncture group and 73.3% (22/30) in the western medication group respectively, there was no significant difference in the total effective rate between the two groups (P>0.05). CONCLUSION Electroacupuncture at acupoints of liver meridian can effectively improve the clinical symptoms, anxiety and depression, regulate the serum sex hormone levels, increase AFC and improve ovarian blood supply in DOR patients of liver depression.
Humans ; Female ; Electroacupuncture ; Adult ; Acupuncture Points ; Meridians ; Ovarian Reserve ; Young Adult ; Liver Diseases/physiopathology* ; Liver/metabolism* ; Ovary/physiopathology* ; Treatment Outcome ; Depression/therapy*

Objective To assess the value of the MRI-based ovarian-adnexal reporting and data system (O-RADS MRI) for the diagnosis of adnexal masses. Methods A total of 407 patients who underwent dynamic contrast enhancement (DCE)-MRI and pathological examination (gold standard) at the Department of Radiology,Central Hospital of Wuhan between May 2017 and December 2022 were enrolled in this study.Two radiologists performed the O-RADS MRI scoring of adnexal masses according to MRI features and calculated the malignancy rate of adnexal masses by O-RADS MRI score,enhancement type,and mass type.Moreover,receiver operating characteristic curves were established to further evaluate the diagnostic values of O-RADS MRI score,enhancement type,and mass type for adnexal masses. Results A total of 502 adnexal masses were identified in the 407 patients enrolled in this study,including 364 benign masses and 138 malignant masses (including junctional masses).Radiologist 1 reported the malignancy rates of 0,0,5.4%,80.0%,and 89.7% and radiologist 2 reported the malignancy rates of 0,0,5.8%,86.2%,and 83.0% for the adnexal masses with the O-RADS MRI scores of 1-5,respectively.With O-RADS MRI ≥4 indicating malignant masses,the sensitivity,specificity,accuracy,positive predictive value,negative predictive value,false negative rate,and false positive rate were 94.2%,93.6%,93.8%,84.9%,97.7%,2.3%,and 15.1% for radiologist 1 and 93.4%,93.6%,93.6%,85.4%,97.4%,3.6%,and 14.6% for radiologist 2,respectively.The malignancy rates of the adnexal masses presenting no enhancement,cystic wall enhancement,type Ⅰ curve,type Ⅱ curve,and type Ⅲ curve were 0,1.3%,5.7%,81.2%,and 89.0% as reported by radiologist 1 and 0,1.2%,11.3%,87.6%,and 80.0% as reported by radiologist 2,respectively.The malignancy rates of the adnexal masses that were cystic lesions,cystic segregated lesions,solid lesions,cystic solid lesions,and cystic solid segregated lesions were 0,7.1%,38.7%,79.1%,and 89.8% as reported by radiologist 1 and 0,8.1%,37.8%,72.4%,and 89.6% as reported by radiologist 2,respectively.With type Ⅱ and type Ⅲ curves as the criteria for malignancy,the sensitivity of radiologists 1 and 2 was lower for cystic segregated lesions,both at 50.0%.For the masses containing solid components,radiologists 1 and 2 demonstrated low specificity,which was 57.7% and 56.5%,respectively.False-positive masses contained solid components and were mostly fibroadenomas or adnexal leiomyomas,while false-negative masses were mostly junctional cystadenomas with no or few solid components. Conclusions The O-RADS MRI risk stratification has a high diagnostic value for adnexal masses.Further evaluation and refinement are needed to reduce the false-positive rate.
Humans ; Female ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Adnexal Diseases/diagnosis* ; Ovarian Neoplasms/diagnosis* ; Ovary/pathology* ; Sensitivity and Specificity ; Middle Aged ; Adult ; Adnexa Uteri/diagnostic imaging* ; Young Adult ; Data Systems ; Aged

OBJECTIVES: International Ovarian Tumor Analysis (IOTA) working group proposed a logistic regression (IOTA LR2) model. It is served as a risk prediction model for benign and malignant adnexal tumors. This study aims to compare the diagnostic efficiency between the IOTA LR2 model and doctors' subjective assessment on diagnosing benign and malignant adnexal mass. METHODS: The ultrasonographic images of 616 adnexal masses were retrospectively analyzed by the senior doctors' group and the junior doctors' group using the IOTA LR2 model and subjective assessment. The postoperative pathological diagnosis was used as the gold standard to compare the diagnostic efficiency of the 2 methods. RESULTS: The area under the curves of subjective assessment and IOTA LR2 model for diagnosing malignant adnexal masses were 0.86 and 0.90 for the senior doctors' group and 0.79 and 0.88 for the junior doctors' group, respectively. The sensitivity and specificity of subjective assessment for diagnosing the malignant adnexal masses were 81.0% and 91.3% for the senior doctors' group and 70.1% and 88.7% for the junior doctors' group, respectively. The sensitivity and specificity of the IOTA LR2 model for diagnosing the malignant adnexal masses were 79.6% and 88.1% for the senior doctors' group, and 79.6% and 81.7% for the junior doctors' group, respectively.There were no significant difference in the sensitivities between the senior doctors' group and junior doctors' group using the IOTA LR2 model and the senior doctors' group using subjective assessment (both P>0.05). CONCLUSIONS The diagnostic efficiency of the IOTA LR2 model is equal to the senior doctors' experiences. This model can help junior doctors to reduce the missed diagnosis of malignant adnexal masses.
Adnexal Diseases/pathology* ; Diagnosis, Differential ; Female ; Humans ; Ovarian Neoplasms/diagnostic imaging* ; Retrospective Studies

OBJECTIVE: To explore the effect of electroacupuncture on endometrial receptivity and the pregnancy outcomes of in vitro fertilization and embryo transfer (IVF-ET) in the patients with diminished ovarian reserve (DOR). METHODS: Sixty-eight patients of DOR undertaken IVF-ET were randomized into an observation group (34 cases, 2 cases dropped off) and a control group (34 cases, 1 case dropped off). In the control group, endometrial preparation was performed according to the routine protocol. In the observation group, on the base of the treatment as the control group, acupuncture was applied to Geshu (BL 17), Shenshu (BL 23), Mingmen (GV 4), Shiqizhui (EX-B 8), Ciliao (BL 32), Zhongliao (BL 33), Tianshu (ST 25), Qihai (CV 6) and Guanyuan (CV 4), etc. Electric stimulation was given at Ciliao (BL 32)-Zhongliao(BL 33), Tianshu (ST 25)-Zigong (EX-CA 1), with disperse-dense wave, 2 Hz/15 Hz in frequency and tolerable current in intensity. Electroacupuncture was given once every two days, 3 times weekly, lasing 3 menstrual cycles till 1 day before embryo transfer. The endometrial thickness and morphology were observed on the day of human chorionic gonadotropin (HCG) of egg retrieval cycle, the day of endometrial transformation in frozen-thawed embryo transfer (FET) cycle and the day of embryo transfer in both groups successively; as well as HCG positive rate, clinical pregnancy rate, embryo implantation rate and live birth rate. RESULTS: In the observation group, the proportion of type A endometrium on the embryo transfer day was higher than those on HCG day of the egg retrieval cycle and the endometrial transformation day of FET cycle (P<0.05), and also higher than that of the control group (P<0.01). In the observation group, HCG positive rate, clinical pregnancy rate, embryo implantation rate and live birth rate were 75.0% (24/32), 71.9% (23/32), 47.4% (27/57) and 56.3% (18/32) respectively, and all higher than 36.4% (12/33), 30.3% (10/33), 18.0% (11/61) and 15.2% (5/33) in the control group separately (P<0.01). CONCLUSION Electroacupuncture improves the endometrial receptivity and IVF-ET pregnancy outcomes in the patients of diminished ovarian reserve.
Chorionic Gonadotropin ; Electroacupuncture ; Endometrium ; Female ; Fertilization in Vitro ; Humans ; Ovarian Diseases ; Ovarian Reserve ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate

OBJECTIVE: To explore the correlation between Fragile X mental retardation gene-1 (FMR1) gene CGG repeats with diminished ovarian reserve (DOR). METHODS: For 214 females diagnosed with DOR, DNA was extracted from peripheral blood samples. FMR1 gene CGG repeats were determined by PCR and capillary electrophoresis. RESULTS: Three DOR patients were found to carry FMR1 premutations, and one patient was found to carry gray zone FMR1 repeats. After genetic counseling, one patient and the sister of another patient, both carrying FMR1 permutations, conceived naturally. Prenatal diagnosis showed that both fetuses have carried FMR1 permutations. CONCLUSION FMR1 gene permutation may be associated with DOR. Determination of FMR1 gene CGG repeats in DOR patients can provide a basis for genetic counseling and guidance for reproduction.
Female ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/genetics* ; Humans ; Ovarian Diseases ; Ovarian Reserve/genetics* ; Primary Ovarian Insufficiency/genetics* ; Trinucleotide Repeats/genetics*

OBJECTIVE: To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea.METHODS: We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013–2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR).RESULTS: Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923–1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group.CONCLUSIONS: The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533
Alopecia ; Carboplatin ; Cohort Studies ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Hand-Foot Syndrome ; Humans ; Korea ; Ovarian Neoplasms ; Paclitaxel ; Peripheral Nervous System Diseases ; Platinum ; Prognosis ; Recurrence ; Retrospective Studies

OBJECTIVE: To observe the clinical efficacy of " acupuncture" and oral estradiol and dydrogesterone tablets (femoston) on premature ovarian insufficiency of kidney deficiency. METHODS: A total of 50 patients with premature ovarian insufficiency of kidney deficiency were randomized into an observation group and a control group, 25 cases in each one.In the observation group, " acupuncture" was applied at Baihui (GV 20), Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Zhongji (CV 3), Yaoyangguan (GV 3), Yaoshu (GV 2), Mingmen (GV 4), etc. once every 2 days, 1 month as a course. In the control group, femoston was prescribed for oral administration, one tablet per time, once a day, 1 month as a course. Both of the two groups were given consecutive treatment for 3 courses. Before and after treatment, the clinical symptoms, menstrual improvement as well as the changes of estradiol (E), luteotrophic hormone (LH) and follicle-stimulating hormone (FSH) in serum were observed in the two groups. RESULTS: After treatment, the clinical symptoms and menstrual conditions were improved (<0.01), the levels of FSH and LH were significantly reduced (<0.01), and the levels of E were significantly increased in the two groups (<0.01). There were no significant difference in menstrual improvement rate and menstrual improvement time between the observation group and the control group (<0.05), the recurrence rate of menopause and clinical symptom score improvement in the observation group were superior to the control group (<0.05). In the observation group, the level of E in serum was lower and the levels of FSH and LH in serum were significantly lower than those in the control group (<0.05, <0.01). In the observation group, the rate of adverse reaction was 4.0% (1/25), which was lower than 36.0% (9/25) in the control group (<0.05). CONCLUSION " acupuncture" has better therapeutic effect for premature ovarian insufficiency of kidney deficiency. It is superior to femoston in improving clinical symptoms and recurrence rate of menopause as well as reducing the levels of FSH and LH.
Acupuncture Points ; Acupuncture Therapy ; Female ; Follicle Stimulating Hormone ; Humans ; Kidney Diseases ; therapy ; Primary Ovarian Insufficiency ; therapy

OBJECTIVE: The objective was to identify risk factors that were associated with the progression from endometriosis to ovarian cancer based on medical insurance data. METHODS: The study was performed on a dataset obtained from the National Health Insurance Research Database, which covered all the inpatient claim data from 2000 to 2013 in Taiwan. The International Classification of Diseases (ICD) code 617 was used to screen the dataset for the patients who were admitted to hospital due to endometriosis. They were then tracked for subsequent diagnosis of ovarian cancer, and available biological, socioeconomic and clinical information was also collected. Univariate and multivariate analyses were then performed based on the Cox regression model to identify risk factors. C-index was calculated and cross validated. RESULTS: A total of 229,617 patients who were admitted to hospital due to endometriosis from 2000 to 2013 were included in the study, out of whom 1,473 developed ovarian cancer by the end of 2013. A variety of factors, including age, residence, hospital stratification, premium range, and various comorbidities had significant impact on the progression (p < 0.05). Among them, age, urbanization of residence, hospital stratification, premium range, post-endometriosis childbearing, pelvic inflammation, and depression all had independent, significant impact (p < 0.05). The validated C-index was 0.69. CONCLUSION: For a woman diagnosed with endometriosis, increased age, residing in a highly urbanized area, low or high income, depression, pelvic inflammation, and absence of childbearing post-endometriosis all put her at high-risk to develop ovarian cancer. The findings may be of help to gynecologists to identify high-risk patients.
Cohort Studies* ; Comorbidity ; Dataset ; Depression ; Diagnosis ; Endometriosis* ; Female ; Humans ; Inflammation ; Inpatients ; Insurance* ; International Classification of Diseases ; Multivariate Analysis ; National Health Programs ; Ovarian Neoplasms* ; Risk Factors* ; Taiwan ; Urbanization

OBJECTIVE: The impact of beta blockers (BBs) on survival outcomes in ovarian cancer was investigated. METHODS: By using Korean National Health Insurance Service Data, Cox proportional hazards regression was performed to analyze hazard ratios (HRs) with 95% confidence intervals (CIs) adjusting for confounding factors. RESULTS: Among 866 eligible patients, 206 (23.8%) were BB users and 660 (76.2%) were non-users. Among the 206 BB users, 151 (73.3%) were non-selective beta blocker (NSBB) users and 105 (51.0%) were selective beta blocker (SBB) users. BB use in patients aged ≥60 years, longer duration use (≥1 year), in patients with Charlson Comorbidity Index (CCI) ≥3, and in cardiovascular disease including hypertension was associated with better survival outcome. These findings were observed in both NSBB and SBB. When duration of medication was analyzed based on number of days, NSBB (≥180 days) was associated with improved overall survival (OS) with a relatively shorter period of use compared to SBB (≥720 days). In multivariate Cox proportional hazards model, longer duration of BB medication (≥1 year) was an independent favorable prognostic factor for both OS and disease-specific survival in ovarian cancer patients. CONCLUSION: In our nationwide population-based cohort study, BB use was associated with better survival outcomes in ovarian cancer in cases of long term duration of use, in older patients, and in cardiovascular and/or other underlying disease (CCI ≥3).
Adrenergic beta-Antagonists ; Cardiovascular Diseases ; Cohort Studies* ; Comorbidity ; Humans ; Hypertension ; National Health Programs ; Ovarian Neoplasms* ; Proportional Hazards Models ; Treatment Outcome