BACKGROUND

Managing low ovarian response remains challenging despite advancements in assisted reproductive technology (ART). Although several approaches have been proposed, there is no strong evidence that a particular stimulation protocol is superior over the other in terms of improving reproductive outcomes in this group of women. The double stimulation protocol (DuoStim) suggests ovarian stimulation during both the follicular phase and the luteal phase of the same ovarian cycle; hence, facilitating two oocyte retrievals in the shortest amount of time.

This study assessed the effect of the double stimulation protocol (DuoStim) on poor ovarian responders in terms of cumulative live birth rates and clinical pregnancy rates, and compared these outcomes to conventional stimulation protocols.

This is a systematic review and meta-analysis of randomized controlled trials (RCT), cohort and cross-sectional studies in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Data from eligible journals were tabulated and analyzed using Cochran’s Q and I² tests.

Eight studies involving poor ovarian responders were included in the meta-analysis. Pooled analysis demonstrated no significant difference between DuoStim and conventional ovarian stimulation protocols in clinical pregnancy rate (OR 0.99, 95% CI 0.75–1.30) and cumulative live birth rate (OR 0.87, 95% CI 0.59–1.28). Fertilization rates were likewise comparable between groups. Nevertheless, several included studies reported higher oocyte yield and greater numbers of mature oocytes and blastocysts with DuoStim

Current evidence does not demonstrate significant superiority of DuoStim over conventional ovarian stimulation protocols in terms of clinical pregnancy rates, cumulative live birth rates, or fertilization rates among poor ovarian responders. However, DuoStim appears to be an effective strategy for increasing oocyte yield within a shorter treatment timeframe. Its use may be particularly relevant in selected patients with diminished ovarian reserve, advanced maternal age, or urgent fertility preservation needs. Further high-quality prospective trials are warranted to clarify its impact on reproductive outcomes.

Introduction: Primary ovarian pregnancy is a rare ectopic gestation (<1% of ectopic pregnancies), usually presenting with first-trimester rupture. Progression to term with live birth is exceedingly rare and requires pathologic confirmation to exclude secondary implantation. Case Presentation: A 32-year-old multigravida underwent exploratory laparotomy for suspected ectopic pregnancy at term. A placenta-bearing mass involving the right ovary was identified, with a grossly normal ipsilateral fallopian tube. Right oophorectomy was performed, delivering a live female infant weighing 3,060 grams with Apgar scores of 8 and 9. Gross examination showed a large hemorrhagic placenta-like mass replacing the ovary with peripheral residual ovarian tissue. Histology revealed mature chorionic villi with syncytial knots, stromal fibrosis, calcifications, and abundant intervillous blood, directly implanted within ovarian stroma containing luteinized cells and corpus albicans remnants, with no tubal or endometrial tissue identified. Discussion: Advanced primary ovarian pregnancy is extremely rare and may mimic secondary abdominal or tubal implantation. Diagnosis relies on the Spiegelberg criteria, including an intact ipsilateral fallopian tube, ovarian location of the gestation, attachment through the ovarian ligament, and histologic demonstration of chorionic villi within ovarian stroma, confirming true ovarian implantation. Conclusion Clinical, gross, and microscopic findings fulfill the Spiegelberg criteria, confirming primary ovarian pregnancy. This rare term pregnancy highlights the crucial role of surgical pathology in establishing the definitive diagnosis and excluding secondary implantation.
Female ; Pregnancy ; Ovary ; Pregnancy, Ovarian

Introduction: Ovarian lymphoma is rare and often misdiagnosed, as its clinical presentation can be similar to other more frequent tumors. It accounts for <1% of all non-Hodgkin lymphomas, with high-grade B-cell lymphoma being the most frequently implicated subtype. Case Description: A 48-year-old woman presented with bilateral ovarian masses, elevated CA-125, and extensive abdominal and thoracic lymphadenopathy. She was managed as advanced ovarian cancer and underwent TAHBSO. Grossly, both ovaries were enlarged and nodular. Histology showed a round cell neoplasm composed predominantly of medium-sized, cleaved lymphocytes, admixed with scattered larger atypical cells. Initial immunohistochemistry panel demonstrated diffuse CD45 positivity and negativity for AE1/AE3, Inhibin, SALL4, Desmin, and Calretinin. Subsequently, CD20 and PAX5 showed diffuse reactivity. CD10, BCL2, and BCL6 highlighted neoplastic follicles. CD3 was negative. High-grade B-cell lymphoma was considered; however, the Ki-67 proliferative index was 38%, and c-MYC expression was low (5%). A final diagnosis of follicular lymphoma involving both ovaries was rendered. Discussion: The clinical presentation strongly suggested advanced ovarian carcinoma. However, histologic and immunophenotypic evaluation established lymphoma. Although aggressive subtypes are more common in advanced cases, indolent entities such as follicular lymphoma should also be considered, particularly in resource-limited settings where delays in diagnosis occur. Distinguishing lymphoma from carcinoma is critical, as management differs significantly and misclassification may lead to overtreatment. Conclusion Recognition of ovarian lymphoma is critical, as accurate diagnosis alters management and prevents unnecessary radical surgery.
CA-125 Antigen ; Immunohistochemistry ; Lymphoma, Follicular ; Ovarian Neoplasms

OBJECTIVE: To study the clinical efficacy of Wenyang Lishui Formula (WYLSF) in preventing ovarian hyperstimulation syndrome (OHSS) and explore the suitable range of estradiol (E₂) on the human chorionic gonadotropin (HCG) day in patients with OHSS using WYLSF. METHODS: Part I: eligible patients at high risk for OHSS undergoing ovulation induction between January and December, 2023 were randomized into 2 groups based on the actual treatment. The treatment group received 200 mL WYLSF formula twice daily for 5 days after oocyte retrieval in a combination of lifestyle coaching (LC) intervention including regular diet and exercise, whereas the LC group received LC intervention alone. The incidence of OHSS, OHSS self-assessment scales, changes in E₂ levels on HCG day and 5 days after oocyte retrieval, ovarian morphology changes, and menstrual recovery were compared between the two groups. Part II: patients at high risk for OHSS treated with WYLSF were studied. The optimal E₂ threshold on the HCG day was determined using the maximum selection test, and a multivariate analysis was adopted to compare the relationship between different E₂ levels on HCG day and hospitalization rate, incidence of moderate to severe OHSS, and self-assessment scales, to explore the preventive effect of WYLSF on OHSS in patients with varying E₂ levels. RESULTS: A total of 120 patients were included in the Part I analysis. The treatment group (60 cases) showed a significant reduction in the incidence, duration, and severity of abdominal distension, as well as the incidence of vomiting compared with the LC group (P<0.05). The post-retrieval E₂ levels in the treatment group decreased significantly more (P=0.032). Among 1,652 patients treated with WYLSF in the Part II, 90 patients with ⩽ 10092 pmol/L, 159 with >31074 pmol/L, and 1,403 in the middle range group were formed based on E₂ levels on HCG day in Part two analysis. Univariate and regression analyses showed that patients with E₂ levels >31073 pmol/L had a significantly higher incidence of moderate to severe OHSS compared to those with E₂ levels ⩽ 10092 pmol/L (P<0.05). CONCLUSIONS WYLSF can effectively reduce specific symptoms in high-risk OHSS patients after ovulation induction and significantly lower E₂ levels. It may be more suitable for high-risk OHSS patients with E₂ levels <31073 pmol/L on HCG day. (Registration No. MR-11-23-032493, https://www.medicalresearch.org.cn/login ).
Humans ; Ovarian Hyperstimulation Syndrome/blood* ; Female ; Adult ; Prospective Studies ; Drugs, Chinese Herbal/pharmacology* ; Estradiol/blood* ; Ovulation Induction ; Chorionic Gonadotropin

OBJECTIVES: Ovarian cancer is a common gynecologic malignancy, with poor prognosis in advanced stages. This study aimed to identify differentially expressed long noncoding RNA (lncRNA) associated with ovarian cancer prognosis and to explore the effects of lncRNA RP11-499E18.1 on the malignant biological behavior of ovarian cancer cells. METHODS: Ovarian cancer-related lncRNA datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed and prognostically relevant tumor-suppressive lncRNAs were screened using lncRNA sequencing combined with clinical data. Reverse transcription PCR (RT-PCR) was used to detect the expression of lncRNA RP11-499E18.1 in ovarian cancer tissues, adjacent normal tissues, the IOSE80 normal ovarian epithelial cell line, and various ovarian cancer cell lines. Fluorescence in situ hybridization (FISH) was performed to determine its subcellular localization. Ovarian cancer cell lines CaOV3 and SKOV3 were divided into 3 groups: a negative control (NC) group, a knockdown (si-RP11-499E18.1) group, and a overexpression (pcDNA-RP11-499E18.1) group. Methyl thiazolyl tetrazolium (MTT) and Transwell assays were used to assess the effects of lncRNA RP11-499E18.1 on cell proliferation and migration. Western blotting was used to evaluate its effect on epithelial-mesenchymal transition (EMT)-related molecules. BALB/c nude mice were injected with CaOV3 cells transfected with pcDNA-RP11-499E18.1 (experimental group) or empty vector (control group), and tumor growth was monitored. Immunohistochemistry was used to assess the expression of Caspase 3 and Ki67 in tumor tissues. RESULTS: LncRNA sequencing identified RP11-499E18.1 as a differentially expressed and associated with prognosis. GEO data analysis showed that low RP11-499E18.1 expression was correlated with shorter overall and progression-free survival (both P<0.05). Its expression was significantly lower in ovarian cancer tissues and cell lines compared to normal controls (P<0.05 or P<0.001), and it was localized in both the nucleus and cytoplasm. In CaOV3 and SKOV3 cells, proliferation rates increased significantly in the si-RP11-499E18.1 group and decreased in the pcDNA-RP11-499E18.1 group (P<0.05 or P<0.001). Cell migration was enhanced in the si-RP11-499E18.1 group and suppressed in the pcDNA-RP11-499E18.1 group. Overexpression increased E-cadherin and decreased vimentin expression, while knockdown had the opposite effect. Tumor volume in the mouse model was significantly smaller in the experimental group (P<0.001), with increased Caspase 3 and decreased Ki67 expression in tumor tissues (both P<0.05). CONCLUSIONS LncRNA RP11-499E18.1 inhibits proliferation, migration, and EMT of ovarian cancer cells, and its low expression is associated with poor prognosis.
Female ; Humans ; RNA, Long Noncoding/physiology* ; Ovarian Neoplasms/pathology* ; Cell Line, Tumor ; Animals ; Mice ; Mice, Nude ; Cell Proliferation ; Prognosis ; Mice, Inbred BALB C ; Gene Expression Regulation, Neoplastic ; Cell Movement ; Epithelial-Mesenchymal Transition

OBJECTIVES: Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer. METHODS: The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes. RESULTS: Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm. CONCLUSIONS Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female ; Ovarian Neoplasms/metabolism* ; Animals ; Carcinoma, Ovarian Epithelial ; Disease Models, Animal ; Humans ; Neoplasms, Glandular and Epithelial/metabolism* ; Ovary/pathology*

OBJECTIVES: Platelet-rich plasma (PRP) treatment has been reported to improve ovarian function in women, but the relationship between the dose and frequency of PRP treatment and its therapeutic effect remains unclear. This study aims to evaluate the efficacy of single and double PRP treatments for diminished ovarian reserve (DOR). METHODS: A total of 65 patients treated at the Reproductive Center of Xiangtan Central Hospital from September 2020 to October 2022 were randomly divided into 4 groups: A single PRP treatment group (21 patients, PRP treatment once), a double PRP treatment group (15 patients, PRP treatment twice), a blank control group (15 patients), and an artificial cycle control group (14 patients, treated with estrogen and progesterone). The differences in baseline follicle-stimulating hormone (FSH), antral follicle count (AFC), ovarian volume, number of oocytes retrieved, number of good quality embryos, and pregnancy outcomes before and after treatment were compared among the 4 groups. RESULTS: Compared to before treatment, both single and double PRP treatment groups showed a significant reduction in FSH, and an increase in AFC, ovarian volume, numbers of oocytes retrieved, and number of MII oocytes (all P<0.05). Compared to the blank control group, the single and double PRP groups showed a decrease in FSH, with an increase in AFC, number of oocytes retrieved, and number of MII oocytes (all P<0.05). The rates of good quality embryos, clinical pregnancy rate, and live birth rate in the single and double PRP groups were higher than those in the blank control group and artificial cycle control groups, but the differences were not statistically significant (all P>0.05). Compared to the single PRP treatment group, the double PRP group had lower FSH and higher AFC, but the differences were not statistically significant (both P>0.05). CONCLUSIONS Both single and double PRP ovarian injections can effectively improve ovarian reserve function in DOR patients and enhance ovarian response. Compared to single PRP ovarian injection, double PRP ovarian injection shows a trend of better improvement in ovarian reserve function.
Humans ; Female ; Platelet-Rich Plasma ; Ovarian Reserve/physiology* ; Adult ; Pregnancy ; Follicle Stimulating Hormone/blood* ; Pregnancy Rate ; Ovary ; Ovulation Induction/methods* ; Ovarian Follicle ; Oocyte Retrieval

Herlyn–Werner–Wunderlich Syndrome (HWWS) is a rare congenital Mullerian duct anomaly, characterized by the presence of an obstructed hemivagina with uterus didelphys and an ipsilateral renal anomaly (OHVIRA). Ovarian serous adenocarcinoma is a type of epithelial ovarian cancer and accounts for about 90% of all ovarian cancers. The incidence of Müllerian duct anomalies associated with ovarian cancer is unknown. Due to its rarity of these conditions, diagnosis and management are challenging. In this paper, we present a case of a 53-year-old, nulligravid woman who presented with an acute abdomen. A transrectal and transabdominal sonography showed an ovarian mass with malignant features. Immediate surgical intervention was performed, and removal of the ovarian mass was done. Intraoperatively, findings of obstructed hemivagina, uterine didelphys, and the absence of one kidney were noted, suggestive of HWWS. Biopsy of the mass revealed borderline serous cystadenocarcinoma of the right ovary.

INTRODUCTION: Premature ovarian insufficiency (POI) refers to loss of ovarian activity before the age 40 years. POI has significant detrimental effects on health (infertility, cardiovascular diseases, type 2 diabetes, reduced bone density, dementia), well-being and longevity. This summary is a practical toolkit for health-care professionals (HCPs) looking after women with POI. METHOD: A workgroup comprising specialists in gynaecology, reproductive medicine, endocrinology, genetics and family medicine reviewed relevant guidelines and literature on POI to establish recom-mendations for the diagnosis and management of POI in Singapore. RESULTS: A summary to assist HCPs manage POI was produced, outlining: (1) the aetiology and conse-quences of POI; (2) making the diagnosis; (3) hormone therapy (HT) prescribing options including for those with additional medical conditions; (4) counselling women with POI about HT; and (5) long-term management of POI. CONCLUSION Timely diagnosis and management of POI is vital to prevent long-term adverse consequences, except infertility. HT is the mainstay of treatment and there are no alternatives as effective. Contraindications are very few; estrogen-sensitive cancer is the main contraindication, and caution in prescribing may be needed with established coexisting cardiovascular disease. Estrogen dosage is higher than when treating normal menopause, and as a result, the patient might require more progestogen for endometrial protection. Minimising cardiovascular risk factors by following a healthy lifestyle is important. POI is a significant public health issue and it is imperative that women have affordable access to appropriate HT. Large-scale research on POI in Asian women is needed.
Humans ; Primary Ovarian Insufficiency/drug therapy* ; Female ; Estrogen Replacement Therapy ; Singapore ; Adult

BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival