Ovarian Preservation Research Articles

Impact of haemostasis methods during ovarian cystectomy on ovarian reserve: a pairwise and network meta-analysis

Background Haemostasis during ovarian cystectomy is reported to damage the ovarian reserve, but the comparative impacts of three haemostasis methods (bipolar energy, suture and haemostatic sealant) on ovarian reserve in patients with ovarian cysts are not well known. Methods The Cochrane Library, PubMed and Web of Science databases were searched from the date of inception of the database to June 2022 for literature exploring the impact of haemostasis methods during ovarian cystectomy on ovarian reserve. A traditional meta-analysis was performed using Review Manager software. A network meta-analysis (NMA) was performed using Stata and GemTC software. Results The direct meta-analysis comparison indicated that the mean postoperative reduction of anti-Müllerian hormone (AMH) level was significantly higher in the electrocoagulation (bipolar) group than suture and haemostatic sealant group, both in the overall group and subgroup of women with ovarian endometrioma. In NMA, the reduction of postoperative AMH levels in the electrocoagulation (bipolar) group was higher than the suture group at 6 months with a statistical significance, and at 1, 3 and 12 months without a significant difference. The difference in the postoperative decrease of AMH level did not reach statistical significance between suture and sealant, coagulation and haemostatic sealant. The comprehensive ranking results revealed that suture treatment was, with the highest probability, beneficial to the protection of the ovarian reserve. Conclusions There was insufficient research to detect the optimal haemostasis method for ovarian reserve preservation in ovarian cystectomy. Nevertheless, haemostasis by electrocoagulation (bipolar) should be avoided when possible, and the suture might be considered as the best choice.

Fertility Preservation Strategies in Cancer Patients: A Comprehensive Review

Introduction and purpose. Preserving fertility is crucial for cancer patients, aligning with advancements in oncology. As survival rates improve, addressing treatment-related late effects gains importance. Many young patients, aware of therapy toxicity, consider future conception chances, impacting treatment decisions. With a trend toward delayed childbirth and a growing population facing unplanned family planning disruptions, the demand for fertility preservation is expected to rise. This paper provides a brief review of available methods for preserving fertility in cancer patients. State of knowledge. Freezing semen in liquid nitrogen vapor is a standard method for preserving reproductive potential in male cancer patients. Shielding during total-body radiation limits testicular volume reduction, indicating less damage to the germinal epithelium. Hormone suppression treatments are not protective in male cancer patients. Oocyte and embryo cryopreservation are considered secure methods before anticancer treatments, with oocyte cryopreservation being preferred for post-pubertal women. Ovarian tissue cryopreservation remains an alternative method without preliminary treatment, suitable when time is insufficient for ovarian stimulation. Ovarian transposition beyond the intended radiation area, performed laparoscopically, can retain ovarian function. GnRH agonist administration before and during chemotherapy aims to minimize the likelihood of premature ovarian insufficiency. Summary. Advancements in fertility preservation for cancer patients, ranging from traditional cryopreservation to innovative methods like ovarian tissue preservation, highlight a commitment to empowering individuals facing cancer diagnoses. Ongoing research expands possibilities, ensuring a diverse range of strategies that offer tangible and hopeful prospects at the intersection of cancer and reproductive health.

Prognosis of uterine and extrauterine low-grade endometrial stromal sarcoma: an observational cohort study.

Little is known about the survival differences between uterine and extrauterine low-grade endometrial stromal sarcoma (LGESS). Survival outcomes, consisting of disease-free survivals and overall survivals (OS), were compared in these two entities. From February 2012 to June 2019, all primary LGESS cases and LGESS cases with first recurrence in the study center were reviewed. The clinicopathological characteristics and survival outcomes of extrauterine and uterine LGESS patients were compared for both primary and recurrent diseases. During the study period, 143 patients with primary LGESS and 56 patients with recurrent LGESS were included and followed up to 1 June 2020, among whom 8 (5.6%) and 10 (17.8%) patients were identified as having extrauterine LGESS. Patients with primary and recurrent extrauterine LGESS had similar clinicopathological characteristics to those of patients with uterine LGESS. In primary or in recurrent LGESS cases, in univariate analysis, patients with uterine and extrauterine LGESS had similar disease-free intervals after the last treatment, and they also had similar OSs after the diagnosis. Ovarian preservation led to significantly increased recurrence for primary LGESS [hazard ratio (HR) 4.9, 95% CI: 2.3-10.1, P <0.001) and repeated recurrence for recurrent LGESS (HR 3.1, 95% CI: 1.3-7.3, P =0.009). Surgical treatment for recurrent LGESS decreased repeated recurrence after the first recurrence (HR 0.2, 95% CI: 0.1-0.7, P =0.006). No factors were found to be associated with the OS of primary or recurrent LGESS. The clinical characteristics and survival outcomes of extrauterine LGESS are similar to those of uterine LGESS. Surgery is the treatment of choice for recurrent LGESS. Ovarian preservation is detrimental to disease-free survival but not to OS in both uterine and extrauterine LGESS.

The value of surgery and the prognostic factors for patients with recurrent low-grade endometrial stromal sarcoma: a retrospective study of 38 patients.

As an indolent malignant tumor, the long-term management of low-grade endometrial stromal sarcoma (LGESS) patients required awareness, especially the management of recurrences. Unfortunately, few studies focused on the treatment of recurrent LGESS. Our study aimed to investigate the prognostic factors and the value of recurrent surgery on recurrent LGESS. This retrospective study consecutively recruited patients with pathologically diagnosed recurrent LGESS at our center from April 1, 2004 to April 1, 2020. After a median follow-up of 137.0 months (95% confidence interval=85.4-188.6), the 5-year cumulative survival rate of the cohort of 38 patients with recurrent LGESS was 71.1%. The median overall survival (OS) and post-recurrence survival (PRS) was 156 and 89.0 months. Survival analysis showed that patients with younger age, positive estrogen receptor (ER) and optimal abdominopelvic debulking in the first recurrent surgery had better prognosis (p<0.05). Multivariate analysis showed that optimal abdominopelvic debulking in the first recurrent surgery was the only independent prognostic factor for OS and PRS (OS=216.0/35.0 months, hazard ratio [HR]=5.319, p=0.034; PRS=not reached/4.0 months, HR=10.900, p=0.006). There was no significant difference in OS and PRS between patients recurred only once and those recurred at least twice (p>0.05). The prognosis of recurrent LGESS was favorable. Optimal debulking of no residual tumor in abdominal and pelvic cavity should be the first choice of treatment for recurrent patients, while preservation of ovary or fertility should not be recommended.

Breast Cancer in Young African Women: Unique Challenges and Perspectives

Abstract Breast cancer (BC) in young women is difficult to treat, especially in Africa. This review discusses the gaps and frustrations clinicians face in South Africa and the broader sub-Saharan region. It provides a snapshot of the literature concerning young BC patients and their unique challenges, including age, ancestry, barriers to care, fertility and ovarian preservation options, access to genetic testing and counseling, clinician knowledge and attitudes and specific molecular subtypes. In addition, the review includes insights from specialist oncology surgeons working in the South African public and private healthcare sectors and calls for advocacy. There is an urgent need for multilayered systemic change in the care of young BC patients in sub-Saharan Africa to address the tragic reality of clinicians being unable to offer them the care they deserve.

The association between menopause and dementia risk

AbstractBackgroundWomen have a higher prevalence of Alzheimer’s disease compared to men. Studies are conflicting as to whether an earlier age of menopause or hysterectomy prior to natural menopause, are associated with an increased risk of cognitive impairment. The goal of this study was to determine whether age of menopause and hysterectomy are associated with incident dementia in a group of older, community‐dwelling women.MethodFemale participants from three ongoing Rush cohorts, the Rush Memory and Aging Project, the Religious Orders Study, and the Minority Aging Research Study were included (total n = 3122, mean age = 77 years at baseline, SD = 7.8). Annual clinical assessments allowed for dementia status categorization, based on detailed neuropsychological testing and clinical judgment, using the NINDS‐ADRDA criteria. Age at menopause and hysterectomy status was based on self‐report at baseline. Data on ovarian preservation or removal at time of surgery was not available. Age of menopause was categorized into tertiles (&lt;45, 45‐50, &gt;50). Risk of dementia, with age at dementia diagnosis as the outcome, was evaluated using Cox proportional regression models adjusting for race, early‐life socioeconomic status, education, diabetes, and smoking status.ResultAt the time of these analyses, women were followed for an average of 8.3 years (SD = 5.6). Women in the earliest tertile of menopause age were less likely to be white, more likely to report having diabetes, and have longer hormone therapy use (p&lt;0.01). In fully adjusted models, women with menopause at age 45‐50 (HR 0.80, 95% CI 0.67‐0.96) and age &gt;50 (HR 0.74, 95% CI 0.62‐0.90) had a lower risk of dementia compared to women with menopause at age &lt;45. Hysterectomy prior to natural menopause was not associated with an elevated risk of dementia (HR = 1.01, 95% CI 0.87‐1.19).ConclusionIn a group of older women, earlier age at menopause but not hysterectomy was associated with an elevated risk of dementia. Future research will determine whether these associations differ by race or ethnicity and the factors that may contribute to such differences.Funding: P30‐AG072975, R01‐AG17917, R01‐AG22081

Abstract 15781: Associations Between Hysterectomy and Incident Metabolic Syndrome: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Metabolic syndrome is linked to increased risk of incident atherosclerotic cardiovascular disease (CVD), heart failure, and all-cause mortality. Notable associations exist between hysterectomy with bilateral salpingo-oophorectomy and metabolic syndrome. However, there is emerging evidence that even with ovarian conservation, hysterectomy independently increases long-term risk for CVD. Despite these associations, extant literature on the independent link between ovary-sparing hysterectomy and metabolic syndrome is scarce. We, therefore, examined the associations between hysterectomy with ovarian preservation and metabolic syndrome risk in a multi-ethnic cohort. Methods: We studied 1,355 female MESA participants who had data on self-reported history of hysterectomy, oophorectomy, and hystero-oophorectomy and were free of metabolic syndrome and CVD at exam 1 (2000-2002). Metabolic syndrome was defined by the NCEP Adult Treatment Panel III criteria. We used multivariable Cox regression models to evaluate the associations between hysterectomy/oophorectomy subgroups and incident metabolic syndrome from exams 2 (2002-2004) to 6 (2016-2018). Results: The mean ± SD age was 59.0 ± 9.5 years, with 42% White, 27% Black, 19% Hispanic, and 13% Chinese-American participants. 29% and 22% had a history of hysterectomy and oophorectomy, respectively. Over a median follow-up of 10.5 (3.01-17.62) years, there were 750 metabolic syndrome events. Hysterectomy [HR 1.32; 95% CI (1.01-1.73)] and hystero-oophorectomy [1.40 (1.13-1.74)] were strongly associated with metabolic syndrome (Table) . Conclusion: Hysterectomy with ovarian preservation is independently associated with a higher risk of metabolic syndrome. If our findings are confirmed by other studies, screening and preventive strategies focused on females with ovary-sparing hysterectomy and the pathways driving these associations should be explored.

Recurrent early-stage squamous cell carcinoma cervical cancer presenting with isolated ovary metastasis: a rare case report

Introduction: Ovarian metastatic squamous carcinoma of the cervix is rare, accounting for about 0.4%. This study reports a single case of metastatic recurrent cervical cancer in the ovary. Case presentation: A 46-year-old patient with a history of cervical cancer T1b2N0M0 underwent a radical hysterectomy, bilateral pelvic lymph node dissection, and ovarian preservation. One year later, the patient was admitted to the hospital because of abdominal pain in the left iliac fossa; the abdominal computed tomography image showed a left ovarian tumour. The patient underwent laparoscopic left oophorectomy. Postoperative histopathology confirmed ovarian squamous cell carcinoma. From this case, we would like to review the literature on epidemiology, diagnosis, treatment, and prognosis. Clinical discussion: Ovarian preservation during surgery in patients with cervical cancer offers many benefits, but careful patient selection is required. However, it should be selected carefully and closely monitored. Conclusions: Clinicians should be aware of this situation of ovarian metastasis in patients with early cervical cancer undergoing ovarian-conserving surgery.

Uterine transposition for fertility and ovarian function preservation after radiotherapy

ObjectiveTo evaluate the feasibility of uterine transposition as a method of preserving fertility and ovarian function after pelvic radiation.MethodsThis prospective multicenter observational study included patients with non-gynecologic pelvic cancers who...

Postoperative outcomes of ovarian preserving surgery in premenopausal women with adnexal torsion.

We aimed to determine whether ovarian-preserving surgery for adnexal torsion helps preserve ovarian function without increasing the risk of postoperative complications. We retrospectively evaluated 71 women who were surgically diagnosed with adnexal torsion between January 2015 and December 2019 at Severance Hospital, Yonsei University College of Medicine (ovarian preservation group, 56; oophorectomy, 15). Serum anti-Müllerian hormone (AMH) levels measured within 6 months before surgery were compared to levels measured 6-24 months after surgery. Surgical findings and postoperative complications were compared between the groups. There was a borderline significant difference in the decrease in serum AMH levels between the oophorectomy group and ovarian preservation group before and after surgery. There were no significant differences between the groups in terms of fever, infection, or duration of admission. Discoloration of the twisted ovary was found in 27.3% and 33.3% of the patients in the ovarian preservation and oophorectomy groups, respectively. There was no difference in the decrease in serum AMH levels between patients with and those without discoloration. Ovarian-preserving surgery may not increase postoperative complications in patients with adnexal torsion, even if a twisted mass is suspected to be necrotic. Moreover, the ovarian reserve may not be affected by torsion if the ovary is preserved. Conservative ovarian surgery can be safely performed to preserve the reproductive potential of women with adnexal torsion and cystic masses.

Chronic stress induces meiotic arrest failure and ovarian reserve decline via the cAMP signaling pathway.

Chronic stress is suspected to be a causal factor of female subfertility; however, the underlying mechanisms remain unclear. Here, we found that chronic stress inhibited the cyclic adenosine 3',5'-monophosphate (cAMP) signaling pathway, leading to ovarian reserve decline in mice. A chronic stress model was constructed using restraint stress for 8 weeks. An elongated estrous cycle and a significant increase in the number of atretic follicles were observed in the stress group. We identified a significant increase in meiotic arrest failure (MAF) in oocytes in the stress group, characterized by condensed metaphase chromosomes, assembled spindles, or polar bodies in the oocytes. Whole-mount ovarian reserve estimation at the single-oocyte level using the CUBIC method (clear, unobstructed brain/body imaging cocktails and computational analysis) revealed a significant decrease in quiescent oocytes from 2,261/ovary in the control group to 1,373/ovary in the stress group. The number of growing oocytes also significantly decreased from 220/ovary in the control group to 150/ovary in the stress group. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis of the meiotic arrest maintenance pathways revealed significant downregulation of Gpr3, Nppc, and Npr2 in the stress group. These results indicate that blocking cAMP production contributes to MAF and a decline in ovarian reserve. Overall, we present new insights into the mechanisms underlying chronic-stress-induced oocyte loss and potential targets for ovarian reserve preservation.

Culture of vitrified bovine ovarian tissue on agarose gel inserts maintains follicle integrity.

Ovarian tissue cryopreservation and culture provide an option for fertility preservation without tissue grafting, but need optimization. This study reveals that vitrified bovine ovarian tissue can be cultured on agarose gel and maintain follicle morphology, low activation, and low apoptosis. Ovarian tissue preservation is hitherto a promising fertility insurance option for precious animals. Ovarian tissue vitrification and culture combined approach would eliminate the need of transplanting ovarian tissue to obtain mature oocytes. We aimed at optimizing vitrification and in vitro culture conditions for improved bovine ovarian tissue viability. Ovaries obtained from the slaughterhouse were punched into fragments and divided into three groups. Group 1 (fresh) was divided into two and immediately placed in two-culture systems (culture inserts and agarose inserts). Group 2 was vitrified, warmed, and placed in the two-culture systems, while group 3 was only equilibrated and then placed in the two-culture systems. All cultures were maintained for 6 days and spent media were collected on alternate days for cytokine (interleukin 1β and interleukin 6) evaluation. Fragments were fixed for morphology assessment and immunohistochemistry. Higher percentages (P < 0.05) of grade 1 (morphologically intact) follicles were observed in fragments on agarose compared to those on culture inserts on days 2 and 4 of the culture. Conversely, we found higher (P < 0.05) shifts of primordial follicles to transitional follicles in fragments on culture inserts vis-à-vis agarose inserts which was consistent with a higher proportion of Ki-67 and MCM-7 and activated caspase-3-positive follicles. In conclusion, in vitro culture of bovine ovarian tissue on agarose inserts maintained follicle morphology, low follicle activation, and low apoptosis compared to culture inserts.

Ovarian preservation in gynecologic oncology: current indications and techniques.

Early menopause represents a relevant clinical issue for women. Nevertheless, this issue should be balanced with the risks of ovarian metastasis, ovarian recurrence, and the risk of recurrence in hormone-sensitive gynecological cancers. The purpose of this review was to provide an overview on current indications and techniques of ovarian preservation in patients with gynecological cancers. The potential discussion about ovarian conservation could be proposed to patients with FIGO-stage IA grade 1-2 endometrioid endometrial cancer aged 40 years or less, FIGO-stage IB1-IB2 node-negative cervical cancer with squamous cell carcinoma and HPV-associated adenocarcinoma, FIGO-stage IA-IC grade 1-2 serous, endometrioid, mucinous expansile pattern ovarian cancer, any stage germ cell ovarian tumors, and FIGO-stage IA sex cord-stromal tumors. Technique to perform ovarian transposition in cervix cancer is also reported. Ovarian conservation is a surgical approach that involves preserving one or both ovaries during the treatment of gynecologic cancers. This approach has gained popularity in recent years, as it offers several benefits to the patient, including the preservation of hormonal function and fertility. The decision to perform ovarian conservation depends on several factors, such as the stage and type of cancer, the patient's age, fertility desire, and should be carefully discussed with patients.

Long-acting gonadotropin-releasing hormone agonist trigger in fertility preservation cycles before chemotherapy

Oocytes/embryo cryopreservation and ovarian function suppression with gonadotropin-releasing hormone (GnRH) agonists (GnRHas) are two established strategies for preserving fertility in patients with cancer, frequently both being offered to the same woman. As the first injection of GnRHa should be administered before chemotherapy, it is usually performed in the luteal phase of the urgent controlled ovarian stimulation (COS) cycle. The GnRHa flare-up effect on recently stimulated ovaries may cause ovarian hyperstimulation syndrome (OHSS) and this risk may discourage some oncologists to offer an ovarian function preservation method with proven efficacy. We suggest the long-acting GnRHa as an option to trigger ovulation for egg retrieval in oncological patients, whenever ovarian suppression during chemotherapy is planned. We retrospectively analyzed prospectively collected data from all consecutive ovarian stimulation cases in oncological patients for oocyte cryopreservation from 2016 to 2021 in a single academic referral center. The COS was performed according to good clinical practice standards. Since 2020 long-acting GnRHa trigger was offered to all patients for whom ovarian suppression after cryopreservation was planned. All other patients served as controls, stratified for the triggering method used: highly purified chorionic gonadotrophin 10 000 UI or short-acting GnRHa 0.2 mg. Mature oocytes were collected, with the expected maturation rate, in all the 22 cycles triggered with GnRHa. The mean number of cryopreserved oocytes was 11.1 ± 4, with a maturation rate of 80% (57%-100%), versus 8.8 ± 5.8, 74% (33%-100%) with highly purified chorionic gonadotrophin and 14 ± 8.4, 80% (44%-100%) with short-acting GnRHa. No case of OHSS was observed after long-acting GnRHa triggering and by 5 days after egg retrieval most patients had reached luteinizing hormone levels showing suppression. Our preliminary data show that long-acting GnRHa is efficacious in inducing the final oocytes' maturation, reducing OHSS risk and suppressing ovarian function by the start of chemotherapy.

The value of serum HE4 and CA125 levels for monitoring the recurrence and risk stratification of endometrial endometrioid carcinoma

To evaluate the role of serum human epididymis secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) levels for predicting and monitoring the recurrence of endometrial endometrioid carcinoma (EEC) and assessing preoperative risk stratification in EEC patients. A total of 434 EEC patients were selected for this retrospective study between May 2011 and August 2018. Serum HE4 and CA125 levels were analyzed before the initial treatment, at the first postoperative follow-up, and at recurrence or the last follow-up. Patients were risk stratified according to the European Society for Medical Oncology (ESMO), European Society for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) guideline. We compared the ability of these biomarkers for prediction and monitoring by performing receiver operating characteristic curve analysis and identified optimal cut-off values by determining the Youden index. Kaplan-Meier analyses were also performed to determine prognostic value. Preoperative serum HE4 was identified as a significant predictor for the recurrence of EEC (p = 0.014). Preoperative serum HE4 and CA125 levels were related to depth of myometrial invasion, lymph node status and FIGO stage. Serum HE4 and CA125 levels were both statistically significant markers for monitoring the recurrence of EEC (P = 0.000 for each biomarker). When combined, the two markers showed higher levels of sensitivity and specificity. The two biomarkers were also significant biomarkers for evaluating the risk stratification of patients undergoing lymphadenectomy (P = 0.000 for each biomarker). For premenopausal stage I patients, preoperative serum HE4 and CA125 levels were significant predictors of the need for ovarian preservation (P = 0.000 and P = 0.002, respectively). For premenopausal patients with stage I intramucosal differentiation, preoperative serum levels of HE4 were significant predictors for fertility preservation (P = 0.024). Preoperative serum HE4 level can be used to predict the recurrence of EEC. Postoperative serum HE4 and CA125 levels can be used to monitor the recurrence of EEC and are more sensitive when combined. Preoperative serum levels of CA125 and HE4 levels are of significant value for risk stratification in EEC patients.

Incidence and characteristics of ovarian cancer following endometrial cancer in the emerging era of conservative management of endometrial cancer-Implications for counseling-A SEER analysis.

To assess the ovarian cancer (OC) risk following endometrial cancer (EC) in patients who underwent ovarian preservation as part of the EC staging. With permission of the Surveillance, Epidemiology and End Results (SEER) program of the United States National Cancer Institute, clinicopathological information of women diagnosed with EC and following OC were analyzed. Incidence of OC and survival according to the surgical approach were studied. Primary analysis was conducted in women up to and including the age of 49 years. A total of 116 patients up to the age of 49 years were diagnosed with EC and following OC. In this group of patients, no differences in incidence (IRR 0.9, CI 0.56-1.49, p = 0.66) or survival rates (p = 0.71) were found comparing ovarian preservation and bilateral salpingo-oophorectomy (BSO) performance. In an overall analysis of women diagnosed with EC and following OC at any age, incidence of OC did not differ between groups (IRR 1.07, CI 0.83-1.39, p = 0.59) yet when including patients older than 49 years old survival rates were shorter in ovarian preservation patients compared to patients with BSO performed as part of their EC treatment. Ovarian preservation in EC patients under the age of 49 years may be considered safe, with no impact on OC incidence or survival, benefiting longer natural hormonal status.

P-427 Control of in vitro follicle activation by inhibition of YAP/TAZ activity in mouse ovaries

Abstract Study question Does verteporfin, an inhibitor of YAP/TAZ activity, prevent from the impacts of chemotherapy exposure on signaling pathways governing follicle activation and survival? Summary answer Verteporfin treatment prevents from the chemotherapy-induced impairments of the Hippo pathway but also of PI3K and survival pathways. What is known already The Hippo pathway is a crucial regulator of the ovarian reserve. Disruption of this pathway occurring in non-physiological contexts, such as ovarian processing during ovarian tissue preservation or after chemotherapy exposure, leads to massive uncoordinated follicular growth and depletion of the ovarian stockpile. To prevent from the harmful impact of chemotherapy exposure, several studies assessed the potential of inhibition of the PI3K pathway, the major signaling pathway involved in physiological follicle activation. However, the protective effect of this inhibition appeared to be moderate in vitro, suggesting the involvement of other disrupted mechanisms, as Hippo pathway. Study design, size, duration This study was performed on post-natal day 3 mouse ovaries. Half-cut ovaries were first treated with 0, 0.2, 1.5 and 3 µM Verteporfin (VERT) during 3 hours in vitro culture to establish the efficient dose of VERT. Whole ovaries were then cultured for 24 and 48 hours and exposed to 10 µM 4-hydroperoxycyclophosphamide (4HC) and/or 3 µM VERT to assess the effect of this inhibitor on follicle activation and survival pathways. (N = 3-5) Participants/materials, setting, methods To assess the impacts of sectioning and VERT treatment on follicle activation, gene expression analyses (RT-qPCR) were used to assess Hippo, PI3K/AKT/mTOR and apoptosis signaling pathways. The potential preventive effect of VERT co-treatment with 4HC exposure was evaluated by gene (RT-qPCR) and protein expression (western blot) analyses of these three pathways, and completed with histological staining for DNA damages (TUNEL). Main results and the role of chance Following exposure to increased concentration of VERT for 3 hours, a significant impact of the inhibitor was observed at 3µM on Ccn2 (p = 0.003) and Cmyc (p = 0.045) expression levels compared to control, without impacting on apoptosis genes expression. Exposure to 10 µM 4HC induced a higher YAP/pYAP protein ratio and Ccn2 expression level compared to control after 24 and 48 hours of culture, confirming the Hippo pathway disruption. VERT co-treatment was able to prevent from this increase of protein levels and gene expression, although the impact on Ccn2 expression was moderated after 48 hours of culture. Assessment of PI3K signaling revealed an induction of mTOR signaling following 4HC exposure at both time of culture as shown by the higher pRPS6/RPS6 ratio compared to control. Surprisingly, VERT co-treatment significantly decreased this level compared to 4HC alone at 24 and 48 hours of culture. This result suggests an indirect impact of this inhibitor on the PI3K pathway. Despite Bax and Bcl2 gene levels remained stable among conditions, ovaries exposed to 4HC had a significant higher level of DNA damages at both culture timepoints compared to control. Notably, VERT co-treatment was able to decrease the 4HC-induced gonadotoxicity at 48 hours of culture. Limitations, reasons for caution This study evaluated the impact of an inhibitor to control follicle activation in mouse model, and was limited to the assessment of two main signaling. Although we completed our study with apoptosis analyses, the results should be interpreted with caution as other pathways may be involved into the activation process. Wider implications of the findings Our results suggest that verteporfin is a promising inhibitor to control acute signaling pathway impairments under unphysiological conditions. Moreover, this study sustains the presence of a potential interaction between the two main signaling pathways regulating follicle activation, PI3K and Hippo pathways. Trial registration number Not applicable

Correlation analysis of hysterectomy and ovarian preservation with depression

The relationship between hysterectomy and ovarian preservation and depression is controversial. This study aimed to determine the association of hysterectomy and ovarian preservation with depression using National Health and Nutrition Examination Survey. To assess the association between hysterectomy with or without ovariectomy and depression, we used 3 methods. Method 1: propensity score model (PSM) was established. Method 2 was logistics regression analysis of hysterectomy and depression before and after PSM. Method 3 was a logistics regression analysis of the relationship between hysterectomy and different depressive symptoms. At the same time, in order to evaluate the association between hysterectomy with or without oophorectomy and depression, we explored the effect of four different surgical procedures on depression using logistic regression equations. We enrolled 12,097 women, of whom 2763 underwent hysterectomy, 34.455% were positive for depression. After weighting, 33.825% of the total sample had a PHQ ≥ 5. Finally, a total of 2778 women were successfully matched by propensity score, and 35.537% of them were positive for depression. The OR for PHQ ≥ 5 was 1.236 after crude adjustment of covariates and 1.234 after exact adjustment. This suggests that Hysterectomy is strongly associated with positive depression. Positive depression (PHQ ≥ 5) was associated with little interest, feeling down and trouble concentrating. It was not associated with trouble sleeping, feeling tired, poor appetite, feeling bad, slow moving or speaking, and suicidal thoughts. Oophorectomy-alone is not associated with depression. Hysterectomy-alone is a risk factor for depression, but Hysterectomy combined with Oophorectomy has a stronger correlation with depression than Hysterectomy-alone. Women who have had a Hysterectomy are at higher risk of depression than women who have not had a Hysterectomy, and this risk may be exacerbated if the uterus and ovaries are removed. When clinically appropriate, surgeons should try to preserve the patient's ovaries.

Laparoscopic Excision of Retroperitoneal Adnexal Cyst

To demonstrate the laparoscopic excision of a retroperitoneal adnexal cyst and describe the advanced surgical techniques and anatomic considerations in a patient with previous abdominopelvic surgery. Stepwise demonstration of advanced laparoscopic techniques with narrated video footage. Adnexal masses after hysterectomy are a common reason for repeat abdominal surgery.1 Up to 9% of patients may require future adnexal surgery if ovarian preservation was chosen at the time of hysterectomy.2 Indications for surgery can include persistent adnexal masses, masses with concern for malignancy, chronic pelvic pain, and risk-reducing surgery.2 This patient is a 53-year-old postmenopausal female with a history of a total abdominal hysterectomy and left salpingectomy who underwent excision of an 8 cm retroperitoneal left adnexal cyst (Still 1). Excision of a retroperitoneal adnexal cyst can be performed through a laparoscopic approach with several key strategies: CONCLUSION: Knowledge of retroperitoneal anatomy is crucial in the surgical management of retroperitoneal adnexal masses because dissection can be technically challenging and anatomy may be distorted due to pelvic adhesive disease. Use of advanced laparoscopic techniques and understanding surgical planes are important for safe dissection. High and early ligation of the infundibulopelvic ligament at the pelvic brim and a complete ureterolysis with parametrial excision are often necessary to remove all ovarian tissue to prevent an ovarian remnant.

Impacts of ovarian preservation on the prognosis of neuroendocrine cervical carcinoma: a retrospective analysis based on machine learning

BackgroundNeuroendocrine cervical carcinoma (NECC) is a rare but aggressive malignancy with younger patients compared to other common histology types. This study aimed to evaluate the impacts of ovarian preservation (OP) on the prognosis of NECC through machine learning.MethodsBetween 2013 and 2021, 116 NECC patients with a median age of 46 years received OP or bilateral salpingo-oophorectomy (BSO) and were enrolled in a retrospective analysis with a median follow-up of 41 months. The prognosis was estimated using Kaplan–Meier analysis. Random forest, LASSO, stepwise, and optimum subset prognostic models were constructed in training cohort (randomly selected 70 patients) and tested in 46 patients through receiver operator curves. Risk factors for ovarian metastasis were identified through univariate and multivariate regression analyses. All data processing was carried out in R 4.2.0 software.ResultsAmong 116 patients, 30 (25.9%) received OP and showed no significantly different OS compared with BSO group (p = 0.072) and got better DFS (p = 0.038). After construction of machine learning models, the safety of OP was validated in lower prognostic risk group (p > 0.05). In patients ≤ 46 years, no impacts of OP were shown for DFS (p = 0.58) or OS (p = 0.67), and OP had no impact on DFS in different relapse risk population (p > 0.05). In BSO group, regression analyses showed that later stage, para-aortic LNM, and parametrial involvement were associated with ovarian metastasis (p < 0.05).ConclusionsPreserving ovaries had no significant impact on prognosis in patients with NECC. OP should be considered cautiously in patients with ovarian metastasis risk factors.