Effect of medroxyprogesterone acetate dose in progestin-primed ovarian stimulation on pregnancy outcomes in poor ovarian response patients with different body mass index levels.

Background: For the poor ovarian response (POR) population, the relationship between medroxyprogesterone acetate (MPA) dose in progestin-primed ovarian stimulation (PPOS) and clinical outcome is still unclear. This study aims to explore the effect of MPA dose in PPOS on clinical outcomes in POSEIDON group 3 and 4 patients with different body mass index (BMI) levels, hoping to provide clinical doctors with better options for controlled ovarian hyperstimulation (COH) programs. Methods: This is a retrospective analysis of 253 oocyte retrieval cycles of POSEIDON group 3 and 4 patients who underwent PPOS protocol in IVF/ICSI treatment at the Reproductive Medical Center of Renmin Hospital of Wuhan University from March 2019 to April 2022. The effects of different MPA doses (8 mg/d or 10 mg/d) on pregnancy outcomes were compared in normal BMI (18.5-24 kg/m2) and high BMI (≥24 kg/m2) patients, and multivariate logistic regression analysis was performed to analyze the factors affecting pregnancy outcomes. Results: For normal BMI patients, the 8-mg/d MPA group had a higher embryo implantation rate (33.78% vs. 18.97%, P = 0.012). For high BMI patients, the 10-mg/d MPA group had a higher HCG positive rate (55.00% vs. 25.00%, P = 0.028), clinical pregnancy rate (50.00% vs. 20.00%, P = 0.025), and cumulative pregnancy rate (37.74% vs. 13.79%, P = 0.023) compared with the 8-mg/d MPA group. There was no significant difference in cumulative live birth rate between the 8-mg/d and 10-mg/d MPA groups in patients with normal or high BMI. The results of multivariate logistic regression showed a significant correlation between MPA dose and cumulative pregnancy in the high BMI population (OR = 0.199, 95% CI: 0.046~0.861, P = 0.031). Conclusions: For POR patients with high BMI, 10 mg/d of MPA in the PPOS protocol had a higher cumulative pregnancy rate than 8 mg/d of MPA, but it had no significant effect on the cumulative live birth rate.

Berberine alleviates inflammation in polycystic ovary syndrome by inhibiting hyaluronan synthase 2 expression.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous metabolic and endocrine disorder that causes anovulatory infertility and abnormal folliculogenesis in women of reproductive age. Several studies have revealed inflammation in PCOS follicles, and recent evidence suggests that Berberine (BBR) effectively reduces inflammatory responses in PCOS, however, the underlying mechanisms remain unclear. PURPOSE: To determine the underlying mechanisms by which BBR alleviates inflammation in PCOS. STUDY DESIGN: Primary human GCs from healthy women and women with PCOS, and KGN cells were used for in vitro studies. ICR mice were used for in vivo studies. METHODS: Gene expression was measured using RT-qPCR. HAS2, inflammatory cytokines, and serum hormones were assayed by ELISA. Protein expression profiles were assayed by Western blot. Chronic low-grade inflammatory mouse models were developed by intraperitoneal injection with LPS, and PCOS mouse models were established by subcutaneous intraperitoneal injection of DHEA. BBR and 4-MU were administered by gavage. Ovarian morphologic changes were evaluated using H&E staining. HAS2 expression in the ovary was assayed using Western blot and immunohistochemistry. RESULTS: Our results confirmed that HAS2 expression and hyaluronan (HA) accumulation are closely associated with inflammatory responses in PCOS. Data obtained from in vitro studies showed that HAS2 and inflammatory genes (e.g., MCP-1, IL-1ß, and IL-6) are significantly upregulated in PCOS samples and LPS-induced KGN cells compared to their control groups. In addition, these effects were reversed by blocking HAS2 expression or HA synthesis using BBR or 4-MU, respectively. Furthermore, HAS2 overexpression induces the expression of inflammatory genes in PCOS. These results were further confirmed in LPS- and DHEA-induced mouse models, where inflammatory genes were reduced by BBR or 4-MU, and ovarian morphology was restored. CONCLUSIONS: Our results define previously unknown links between HAS2 and chronic low-grade inflammation in the follicles of women with PCOS. BBR exerts its anti-inflammatory effects by down-regulating HAS2. This study provides a novel therapeutic target for alleviating ovarian inflammation in women with PCOS.

LncRNA AOC4P impacts the differentiation of macrophages and T-lymphocyte by regulating the NF-κB pathways of KGN cells: Potential pathogenesis of polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disease, which is an important cause of female infertility worldwide. PCOS patients are in a state of chronic low-grade inflammation, and immune imbalance is considered as a potential cause of its pathogenesis. METHODS: The expression of AOC4P in PCOS and normal ovarian granulosa cells (GCs) was detected by real-time quantitative PCR. KGN cells were induced by dihydrotestosterone at 500 ng/mL to construct the PCOS model. After lentivirus-infected, KGN cells were constructed with AOC4P overexpression cell lines, the proliferation and apoptosis levels of KGN cells in AOC4P and NC groups were detected. Human monocyte cell line (THP-1)-derived macrophages and peripheral blood mononuclear cells (PBMC) were co-cultured with KGN cells for 48 h, respectively, and the differentiation of macrophages and CD4+ T cells were detected by flow cytometry. RESULTS: Decreased AOC4P expression was found in PCOS patients. After constructing the PCOS cell model, we observed that overexpression of AOC4P promoted KGN cell proliferation and inhibited apoptosis. After co-culture with AOC4P overexpressed KGN cells, M1 macrophages decreased, M2 macrophages increased, T helper cells type 1 (Th1)/Th2 ratio increased, and regulatory T cell (Treg) cells increased. Finally, we found that AOC4P inhibited the activation of the nuclear factor κ B (NF-κB) pathway in KGN cells. CONCLUSIONS: In this study, we found that AOC4P regulated the NF-κB signaling pathway by inhibiting the phosphorylation of P65, thereby affecting the proliferation and apoptosis of GCs, altering the differentiation of macrophages and T cells, thus contributing to the pathogenesis of PCOS.