Journal of Ovarian Research最新文献

Background: Epidemiological studies regarding the correlation between anti-Müllerian hormone (AMH) and insulin resistance (IR) in polycystic ovarian syndrome (PCOS) remain inconsistent. The primary aim of this study was to determine the correlations between AMH and IR in patients with PCOS and to explore the selected factors that influence the correlations.

Methods: We conducted systemic searches of online databases (PubMed, Science Direct, Taylor and Francis, Scopus, and ProQuest) from inception to December 20, 2023 and manual searches of the associated bibliographies to identify relevant studies. We then performed subgroup and sensitivity analyses to explore the sources of heterogeneity, followed by a publication bias risk assessment of the included studies using the Joanna Briggs Institute critical appraisal tool. We used a random-effects model to estimate the pooled correlations between AMH and the homeostatic model assessment for insulin resistance (HOMA-IR) in patients with polycystic ovarian syndrome (PCOS).

Results: Of the 4835 articles identified, 22 eligible relevant studies from three regions were included and identified as low risk of bias. The random-effects pooled correlation estimate was 0.089 (95% confidence interval [CI]: -0.040, 0.215), with substantial heterogeneity (I² = 87%; τ² = 0.0475, p < .001). Subgroup analyses showed that the study region did not influence the correlation estimates, and sensitivity analysis showed no significant alteration in the pooled correlation estimate or 95% CI values. No publication bias was observed.

Conclusion: There was a weak, statistically insignificant correlation between AMH and HOMA-IR in patients with PCOS. The correlation estimates did not vary according to the study participants' regions.

Background: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis.

Methods: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL.

Results: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR.

Conclusion: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

Introduction: The incidence of infertility caused by diminished ovarian reserve has become a significant problem worldwide. The beneficial effect of PRP treatment of the ovaries has already been described, but the high-level evidence of its effectiveness has not yet been proven.

Materials and methods: A systematic search was performed in five databases, until March 12th, 2024. Both randomized and non-randomized studies that compared PRP treatment of the ovaries to self-control among women with diminished ovarian reserve were eligible for inclusion. Hormonal levels (Anti-Müllerian hormone (AMH), Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Estradiol (E2), In-vitro fertilization parameters (Antral follicle count, oocyte, and embryo count), biochemical and spontaneous pregnancy and livebirth were measured.

Results: 38 eligible studies were identified reporting on 2256 women. The level of AMH rised, the level of FSH decreased significantly after the PRP treatment. AMH 1 month MD 0.20 (n = 856, p > 0.001, 95% CI: [0.12;0.28]), 2 months MD 0.26 (n = 910, p = 0.013, 95% CI: [0.07;0.44]), 3 months MD 0.36 (n = 881, p = 0.002,95% CI: [0.20;0.52]). FSH 1 month MD -10.20 (n = 796, p > 0.039, 95% CI: [-19.80;-0.61]), 2 months MD -7.02 (n = 910, p = 0.017, 95% CI: [-12.48; -1.57]), 3 months MD -8.87 (n = 809, p = 0.010, 95% CI: [-14.19; -3.55]). The antral follicle count elevated significantly MD 1.60 (n = 1418, p =  < 0.001, 95% CI: [0.92; 2.27]). Significant improvement was observed in the number of retrieved oocytes MD 0.81 (n = 802, p = 0.002, 95% CI: [0.36; 1.26]), and embryos created MD 0.91 (n = 616, p = 0.001, 95% CI: [0.45;1.36]). The incidence of spontaneous pregnancy following PRP treatment showed a rate with a proportion of 0.07 (n = 1370, 95% CI: 0.04-0.12), the rate of biochemical pregnancy was 0.18 (n = 1800, 95% CI: 0.15-0.22), livebirth was 0.11 (n = 1482, 95% CI: 0.07-0.15).

Conclusions: Our meta-analysis showed that based on protocolized analysis of the widest scientific literature search to date, containing predominantly observational studies, PRP treatment resulted in a statistically significant improvement in the main fertility parameters of diminished ovarian reserve women. Further multicenter, randomized trials, with large patient numbers and a longer follow-up period are needed to certify our results and develop the most effective treatment protocol.

Background: Fragile X-associated primary ovarian insufficiency (FXPOI), characterized by amenorrhea before age 40 years, occurs in 20% of female FMR1 premutation carriers. Presently, there are no molecular or biomarkers that can help predicting which FMR1 premutation women will develop FXPOI. We previously demonstrated that high FMR4 levels can discriminate between FMR1 premutation carriers with and without FXPOI. In the present study the relationship between the expression levels of FMR4 and the ovarian reserve markers was assessed in female FMR1 premutation carriers under age of 35 years.

Methods: We examined the association between FMR4 transcript levels and the measures of total antral follicle count (AFC) and serum anti-müllerian hormone (AMH) levels as markers of ovarian follicle reserve.

Results: Results revealed a negative association between FMR4 levels and AMH (r = 0.45) and AFC (r = 0.64). Statistically significant higher FMR4 transcript levels were found among those FMR1 premutation women with both, low AFCs and AMH levels.

Conclusions: These findings reinforce previous studies supporting the association between high levels of FMR4 and the risk of developing FXPOI in FMR1 premutation carriers.

Ovarian cancer is a major gynecological cancer that has poor prognosis associated mainly to its late diagnosis. Cisplatin is an FDA approved ovarian cancer therapy and even though the therapy is initially promising, the patients mostly progress to resistance against cisplatin. The underlying mechanisms are complex and not very clearly understood. Using two different paired cell lines representing cisplatin-sensitive and the cisplatin-resistant ovarian cancer cells, the ES2 and the A2780 parental and cisplatin-resistant cells, we show an elevated proto-oncogene c-Myb in resistant cells. We further show down-regulated lncRNA NKILA in resistant cells with its de-repression in resistant cells when c-Myb is silenced. NKILA negatively correlates with cancer cell and invasion but has no effect on cellular proliferation or cell cycle. C-Myb activates NF-κB signaling which is inhibited by NKILA. The cisplatin resistant cells are also marked by upregulated stem cell markers, particularly LIN28A and OCT4, and downregulated LIN28A-targeted let-7 family miRNAs. Whereas LIN28A and downregulated let-7s individually de-repress c-Myb-mediated cisplatin resistance, the ectopic expression of let-7s attenuates LIN28A effects, thus underlying a c-Myb-NKILA-LIN28A-let-7 axis in cisplatin resistance of ovarian cancer cells that needs to be further explored for therapeutic intervention.

Background: Shikonin (SK), a naphthoquinone with anti-tumor effects, has been found to decrease production of tumor-associated exosomes (exo). This study aims to verify the treatment effect of SK on ovarian cancer (OC) cells, especially on the production of exo and their subsequent effect on macrophage polarization.

Methods: OC cells SKOV3 and A2780 were treated with SK. The exo were isolated from OC cells with or without SK treatment, termed OC exo and SK OC exo, respectively. These exo were used to treat PMA-induced THP-1 cells (M0 macrophages). M2 polarization of macrophages was determined by measuring the M2 specific cell surface markers CD163 and CD206 as well as the secretion of M2 cytokine IL-10. The functions of galectin 3 (LGALS3/GAL3) and β-catenin in macrophage polarization were determined by gain- or loss-of-function assays. CB-17 SCID mice were subcutaneously injected with SKOV3 cells to generate xenograft tumors, followed by OC exo or SK OC exo treatment for in vivo experiments.

Results: SK suppressed viability, migration and invasion, and apoptosis resistance of OC cells in vitro. Compared to OC exo, SK OC exo reduced the M2 polarization of macrophages. Regarding the mechanism, SK reduced exo production in cancer cells, and it decreased the protein level of GAL3 in exo and recipient macrophages, leading to decreased β-catenin activation. M2 polarization of macrophages was restored by LGALS3 overexpression but decreased again by the β-catenin inhibitor FH535. Compared to OC exo, the SK OC exo treatment reduced the xenograft tumor growth in mice, and it decreased the M2 macrophage infiltration within tumor tissues.

Conclusion: This study suggests that SK reduces M2 macrophage population in OC by repressing exo production and blocking exosomal GAL3-mediated β-catenin activation.

Background: Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder with multiple metabolic abnormalities. Most PCOS patients have concomitant metabolic syndromes such as insulin resistance and obesity, which often lead to the development of type II diabetes and cardiovascular disease with serious consequences. Current treatment of PCOS with symptomatic treatments such as hormone replacement, which has many side effects. Research on its origin and pathogenesis is urgently needed. Although improving the metabolic status of the body can alleviate reproductive function in some patients, there is still a subset of patients with metabolically normal PCOS that lacks therapeutic tools to address ovarian etiology.

Methods: The effect of IL-22 on PCOS ovarian function was verified in a non-metabolic PCOS mouse model induced by dehydroepiandrosterone (DHEA) and rosiglitazone, as well as granulosa cell -specific STAT3 knockout (Fshr^cre+Stat3^f/f) mice (10 groups totally and n = 5 per group). Mice were maintained under controlled temperature and lighting conditions with free access to food and water in a specific pathogen-free (SPF) facility. Secondary follicles separated from Fshr^cre+Stat3^f/f mice were cultured in vitro with DHEA to mimic the hyperandrogenic environment in PCOS ovaries (4 groups and n = 7 per group) and then were treated with IL-22 to investigate the specific role of IL-22 on ovarian function.

Results: We developed a non-metabolic mice model with rosiglitazone superimposed on DHEA. This model has normal metabolic function as evidenced by normal glucose tolerance without insulin resistance and PCOS-like ovarian function as evidenced by irregular estrous cycle, polycystic ovarian morphology (PCOM), abnormalities in sex hormone level. Supplementation with IL-22 improved these ovarian functions in non-metabolic PCOS mice. Application of DHEA in an in vitro follicular culture system to simulate PCOS follicular developmental block and ovulation impairment. Follicles from Fshr^cre+Stat3^f/f did not show improvement in POCS follicle development with the addition of IL-22. In DHEA-induced PCOS mice, selective ablation of STAT3 in granulosa cells significantly reversed the ameliorative effect of IL-22 on ovarian function.

Conclusion: IL-22 can improve non-metabolic PCOS mice ovarian function. Granulosa cells deficient in STAT3 reverses the role of IL-22 in alleviating ovary dysfunction in non-metabolic PCOS mice.

With increasingly used assisted reproductive technology (ART), the acquisition of high-quality oocytes and early embryos has become the focus of much attention. Studies in mice have found that the transition of chromatin conformation from non-surrounded nucleolus (NSN) to surrounded nucleolus (SN) is essential for oocyte maturation and early embryo development, and similar chromatin transition also exists in human oocytes. In this study, we collected human NSN and SN oocytes and investigated their transcriptome. The analysis of differentially expressed genes showed that epigenetic functions, cyclin-dependent kinases and transposable elements may play important roles in chromatin transition during human oocyte maturation. Our findings provide new insights into the molecular mechanism of NSN-to-SN transition of human oocyte and obtained new clues for improvement of oocyte in vitro maturation technique.

Ovarian Hyperstimulation Syndrome (OHSS) is a systemic condition marked by the enlargement of the ovaries and heightened vascular permeability. And hypothyroidism (HT) emerges as a potential risk factor for OHSS occurrence. This review presented a comprehensive summary of pertinent case reports involving patients diagnosed with both HT and OHSS. Detailed exploration was conducted into their clinical presentations, diagnostic methodologies, and treatment modalities. Additionally, the review delved into potential interaction mechanisms between HT and OHSS, encompassing various aspects including hormone levels. Moreover, management strategies for mitigating the risk of OHSS in HT patients were thoroughly reviewed and the importance of monitoring thyroid function in those experiencing OHSS was emphasized. This review indicated that the association between HT and OHSS, underscoring its multifaceted complexity. It could accentuate the ongoing necessity for rigorous research and clinical refinement to deepen our comprehension of this association and to bolster diagnostic and therapeutic methodologies for optimal patient care. In conclusion, this review offered valuable insights for future research directions and clinical practices for patients afflicted with OHSS and HT.

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.