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Abstract Background Despite the recent progress of fertility preservation technique, achievement of pregnancy in women with ovarian tumor is still challenging. Here, we report a case of OTO-IVM (ovarian tissue oocyte in-vitro maturation) resulting in a successful delivery. Case presentation The patient, a 33-year-old woman with a history of left borderline ovarian tumor (BOT) who underwent left salpingo-oophorectomy three years ago, presented with an enlarged right ovary during infertility treatment, indicating the recurrence of BOT. Because the patient disagreed with curative surgery and normal part-preservation surgery, we eventually performed OTO-IVM. A right salpingo-oophorectomy was first performed. Eight immature oocytes were immediately aspirated not only from visible follicles, but also from entire cortex for invisible follicles, of the removed ovary. In addition, IVM procedure generated six mature oocytes, and were subjected to intracytoplasmic sperm injection (ICSI). Accordingly, three embryos were obtained and cryopreserved. Three months after surgery, hormone replacement therapy was initiated, and a frozen-thawed embryo was transferred, resulting in a successful pregnancy. Although a cesarean section was performed at 36 weeks due to maternal ileus, the baby was delivered without complications. Conclusions This report indicates this treatment to be an effective approach for fertility preservation in BOT patients, especially, the importance of collecting oocytes from the entire ovarian cortex was suggested.

Abstract Objective To describe the characteristics of children and adolescents with borderline ovarian tumors (BOTs) and evaluate the efficacy and safety of fertility-sparing surgery (FSS) in these patients. Methods Patients with BOTs younger than 20 years who underwent FSS were included in this study. Results A total of 34 patients were included, with a median patient age of 17 (range, 3–19) years; 97.1% (33/34) of cases occurred after menarche. Of the patients, 82.4% had mucinous borderline tumors (MBOTs), 14.7% had serous borderline tumors (SBOTs), and 2.9% had seromucinous borderline tumor (SMBOT). The median tumor size was 20.4 (range, 8–40)cm. All patients were at International Federation of Gynecology and Obstetrics stage I and all underwent FSS: cystectomy (unilateral ovarian cystectomy, UC, 14/34, 41.2% and bilateral ovarian cystectomy, BC, 1/34, 2.9%), unilateral salpingo-oophorectomy (USO; 18/34; 52.9%), or USO + contralateral ovarian cystectomy (1/34; 2.9%). The median follow-up time was 65 (range, 10–148) months. Recurrence was experienced by 10 of the 34 patients (29.4%). One patient with SBOT experienced progression to low-grade serous carcinoma after the third relapse. Two patients had a total of four pregnancies, resulting in three live births. The recurrence rate of UC was significantly higher in MBOTs than in USO (p = 0.005). The 5-year disease-free survival rate was 67.1%, and the 5-year overall survival rate was 100%. Conclusions Fertility-sparing surgery is feasible and safe for children and adolescents with BOTs. For patients with MBOTs, USO is recommended to lower the risk of recurrence.

Abstract Objective To explore the association between ovulation induction drugs and ovarian cancer. Design Systematic review and meta-analysis. Setting Not applicable. Patient(s) Women without ovarian cancer who ever or never underwent ovarian induction. Intervention(s) An extensive electronic search of the following databases was performed: PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library and CNKI, from inception until January 2022. A total of 34 studies fulfilled our inclusion criteria and were included in the final meta-analysis. The odds ratio (OR) and random-effects model were used to estimate the pooled effects. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Funnel plots and Egger tests were used to assess publication bias. Main outcomes New diagnosed borderline ovarian tumor (BOT) and invasive ovarian cancer (IOC) between ovulation induction (OI) group and control (CT) group considering fertility outcome, OI cycles and specific OI drugs. Results Primarily, there was no significant difference in the incidence of IOC and BOT between the OI and CT groups. Secondly, OI treatment did not increase the risk of IOC and BOT in the multiparous women, nor did it increase the risk of IOC in the nulliparous women. However, the risk of BOT appeared to be higher in nulliparous women treated with OI treatment. Thirdly, among women exposed to OI, the risk of IOC and BOT was higher in nulliparous women than in multiparous women. Fourthly, the risk of IOC did not increase with increasing OI cycles. Lastly, exposure to specific OI drugs also did not contribute to the risk of IOC and BOT. Conclusion Overall, OI treatment did not increase the risk of IOC and BOT in most women, regardless of OI drug type and OI cycle. However, nulliparous women treated with OI showed a higher risk of ovarian cancer, necessitating their rigorous monitoring and ongoing follow-up.

Abstract Background There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs. Methods The study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated. Results The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45–15.43, p=0.01). Conclusions Results suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required.

Abstract Background This study aimed to examine the performance of the four risk of malignancy index (RMI) in discriminating borderline ovarian tumors (BOTs) and benign ovarian masses in daily clinical practice. Methods A total of 162 women with BOTs and 379 women with benign ovarian tumors diagnosed at the Second Affiliated Hospital of Harbin Medical University from January 2012 to December 2016 were enrolled in this retrospective study. Also, we classified these patients into serous borderline ovarian tumor (SBOT) and mucinous borderline ovarian tumor (MBOT) subgroup. Preoperative ultrasound findings, cancer antigen 125 (CA125) and menopausal status were reviewed. The area under the curve (AUC) of receiver operator characteristic curves (ROC) and performance indices of RMI I, RMI II, RMI III and RMI IV were calculated and compared for discrimination between benign ovarian tumors and BOTs. Results RMI I had the highest AUC (0.825, 95% CI: 0.790–0.856) among the four RMIs in BOTs group. Similar results were found in SBOT (0.839, 95% CI: 0.804–0.871) and MBOT (0.791, 95% CI: 0.749–0.829) subgroups. RMI I had the highest specificity among the BOTs group (87.6, 95% CI: 83.9–90.7%), SBOT (87.6, 95% CI: 83.9–90.7%) and MBOT group (87.6, 95% CI: 83.9–90.7%). RMI II scored the highest overall in terms of sensitivity among the BOTs group (69.75, 95% CI: 62.1–76.7%), SBOT (74.34, 95% CI: 65.3–82.1%) and MBOT (59.18, 95% CI: 44.2–73.0%) group. Conclusion Compared to other RMIs, RMI I was the best-performed method for differentiation of BOTs from benign ovarian tumors. At the same time, RMI I also performed best in the discrimination SBOT from benign ovarian tumors.

Abstract Low-grade ovarian cancers represent up to 8% of all epithelial ovarian carcinomas (EOCs). Recent studies demonstrated that epithelial-mesenchymal transition (EMT) is crucial for the progression of EOCs. EMT plays a key role in cancer invasion, metastasis formation and chemotherapy resistance. An array of novel EMT transcription factors from the zinc finger protein family have been described recently, among them zinc finger protein 143 (ZNF143) and zinc finger protein 281 (ZNF281). The study included tissue specimens from 42 patients. Based on histopathological examination of surgical specimens, eight lesions were classified as serous borderline ovarian tumors (sBOTs) and 34 as low-grade EOCs. The proportions of the ovarian tumors that tested positively for ZNF143 and ZNF281 were 90 and 57%, respectively. No statistically significant differences were found in the expressions of ZNF143 and ZNF281 transcription factors in SBOTs and low-grade EOCs. Considering the expression patterns for ZNF143 and ZNF281 identified in this study, both sBOTs and low-grade EOCs might undergo a dynamic epithelial-mesenchymal interconversion. The lack of statistically significant differences in the expressions of the zinc finger proteins in sBOTs and low-grade serous EOCs might constitute an evidence for common origin of these two tumor types.

Abstract Background Prior small studies have shown increased expression of sperm protein 17 (Sp17) in epithelial ovarian cancer (EOC) tissue and suggest Sp17 as a potential biomarker for EOC. However, how Sp17 expression varies with histology, grade, and stage of EOC and its expression in other ovarian neoplasms has not been defined. It is unknown whether patients with EOC have elevated serum Sp17 levels or if Sp17 expression is associated with survival outcomes. Methods The study included 982 patients with benign, borderline, and malignant ovarian neoplasms and normal ovary. There were 878 patients with tissue only, 39 with serum only, and 65 with matching serum and tissue. Immunohistochemical (IHC) staining with anti-Sp17 antibody was performed on tissue specimens and the intensity scored as weak, moderate, or strong. A sandwich enzyme-linked immunosorbent assay (ELISA) was performed to measure Sp17 sera concentrations. Results Sp17 expression was most commonly seen in serous cystadenomas (83%) and serous borderline tumors (100%). Of the 773 EOC specimens, 223 (30%) expressed Sp17. Grade and histology were significantly associated with Sp17 expression among EOC specimens (p

Abstract Background This study was to determine age-specific impact of fertility preserving surgery on disease-specific survival in women with stage I borderline ovarian tumors (BOTs). Patients diagnosed during 1988–2000 were selected from The Surveillance, Epidemiology, and End Results (SEER) database. The age-specific impact of fertility preserving surgery and other risk factors were analyzed in patients with stage I BOTs using Cox proportion hazard regression models. Data from our hospital were collected during 1996–2017 to determine the prevalence of patients who had undergone fertility preserving surgery. Results Of a total 6295 patients in the SEER database, this study selected 2946 patients with stage T1 BOTs who underwent fertility preserving or radical surgery. Their median age at diagnosis was 45.0 years and the median follow-up time was 200 months. Fertility preserving surgery was performed in 1000/1751 (57.1%) patients

Abstract Background The lack of consensus around best practices for management of borderline ovarian tumors (BOT) is, in part, to the lack of available data and of clarity in interpreting relationships among various factors that impact outcomes. The objective of this study was to identify clinicopathological factors that impact prognosis of patients with borderline ovarian tumors (BOT) and to address features of this disease with the objective of providing clarity in decision making around management of BOT. Results A total of 178 BOT patients were included in this study, with a median age of 43 years and a median follow-up time of 37 months. Thirty-two (18.0%) recurrences and 5 (2.8%) deaths were observed in this study group. Multivariate analysis showed that fertility-preserving surgery (P = 0.0223 for bilateral cystectomy) and invasive implants (P = 0.0030) were significantly associated with worse PFS, whereas lymphadenectomy (P = 0.0129) was related to improved PFS. No factors were found to be associated with OS due to the limited number of deaths. In addition, patients with serous BOT more commonly had abnormal levels of CA125, while patients with mucinous BOT more commonly had abnormal levels of CEA. Patients with abnormal levels of CA125, or CA19-9, or HE4 had significantly larger tumor sizes. Conclusions Our study reveals the impact of certain types of fertility-preserving surgery, lymphadenectomy and invasive implants on PFS of BOT patients. Blood cancer markers may be associated with histology and size of BOT. Our findings may assist in selection of optimum treatment for BOT patients.

Abstract Background Borderline ovarian tumors (BOTs) are a subset of epithelial ovarian tumors with low malignant potential but significant risk of relapse (10% to 30%). Unfortunately, surgical prognostic factors for BOT relapse have not been clearly identified, probably due to the use of heterogeneous surgical definitions and limited follow-up. The aim of this study was to assess potential relapse risk factors using standard surgical definitions and long follow-up. Methods All patients diagnosed with BOT for a period of more than 10 years in a single institution were included in the analysis. Complete surgical staging was defined as the set of procedures that follow standard guidelines for staging surgery (except lymphadenectomy), performed either with one or two interventions. Fertility-sparing surgeries that preserved one ovary and the uterus but included all the remaining procedures were classified as complete staging. The relationship between potential risk factors and time to BOT relapse was assessed by log-rank tests corrected for multiple comparisons and Cox regression. Results Forty-six patients with a median follow-up of 5.4 years were included, of whom 91.3% had been diagnosed as FIGO stage I disease and 45.7% had received complete staging surgery. Five relapses were detected (10.9%), all of them in women who had been diagnosed with stage I disease and had received incomplete staging surgery. Log-rank tests confirmed the association between incomplete staging surgery and shorter time to BOT relapse. Conclusions Complete staging surgery should be considered a cornerstone of BOT treatment in order to minimize the risk of relapse.