Premature ovarian failure (POF) is a severe illness, characterized by premature menopause with a markedly decrease in ovarian function, which leads to infertility. Si-Wu-Tang (SWT), also called "the first prescription of gynecology" by medical experts in China, is widely used as the basic formula in regulating the menstrual cycle and treating infertility. However, the potential effect and underlying mechanisms of action of SWT on the treatment of POF have not yet been elucidated. This study aimed to explore the therapeutic effect and underlying molecular mechanism of action of SWT on the treatment of POF in C57BL/6 mice. The main compounds of SWT were identified by high-performance liquid chromatography (HPLC). POF model groups were established by a single intraperitoneal injection of cyclophosphamide (Cy, 100 mg/kg). SWT or dehydroepiandrosterone (DHEA) were administered via oral gavage for 28 consecutive days. Ovarian function and pathological changes were evaluated by hormone levels, follicular development, and changes in angiogenesis. Furthermore, statistical analyses of fertility were also performed. Treatment with SWT significantly improved estrogen levels, the number of follicles, antioxidant defense, and microvascular formation in POF mice. Moreover, SWT significantly activated the Nrf2/HO-1 and STAT3/HIF-1α/VEGF signaling pathways to promote angiogenesis, resulting in a better fertility outcome when compared to the model group. Our findings indicated that SWT protected ovarian function of Cy-induced POF mice by improving the antioxidant ability and promoting ovarian angiogenesis, thereby providing scientific evidence for the treatment of POF using SWT.

OBJECTIVE: To estimate the effect of letrozole and clomiphene citrate in women with infertility and polycystic ovarian syndrome (PCOS). METHODS OF STUDY SELECTION: MEDLINE through PubMed, Web of Science, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched for relevant studies from inception to February 1, 2022. Two reviewers retrieved, filtered, and extracted data independently using the bibliographic software EndNote X9 and Excel workbook. We included randomized controlled trials (RCTs) reporting ovulation induction outcomes in women with infertility and PCOS treated with either letrozole or clomiphene citrate followed by timed intercourse or intrauterine insemination. The data were merged into a mean difference or risk ratio (RR) with 95% CI, depending on variable types. TABULATION, INTEGRATION, AND RESULTS: Data collection and organization were conducted in accordance with the 2020 PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Twenty-nine RCTs were eligible, which included 3,952 women and 7,633 ovulation induction cycles. We acquired evidence from 22 RCTs for the ovulation rate, 28 RCTs for the clinical pregnancy rate, and eight RCTs for live-birth rate. Pooled analysis indicated that letrozole treatment prevailed against clomiphene citrate in ovulation rate (RR 1.14, 95% CI 1.06–1.21, P<.001), clinical pregnancy rate (RR 1.48, 95% CI 1.34–1.63, P<.001), and live-birth rate (RR 1.49, 95% CI 1.27–1.74, P<.001). CONCLUSIONS: Letrozole was associated with improved ovulation, pregnancy, and live-birth rates compared with clomiphene citrate. We recommend letrozole over clomiphene citrate as an ovulation induction drug in women with infertility and PCOS, although the quality of the evidence is mixed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022308777.

Premature ovarian insufficiency (POI) is a prevalent condition that impacts female reproductive health and overall well-being. It is characterized by ovarian dysfunction, estrogen deficiency, and increased gonadotropin levels in women under 40 years old. The exact etiology and pathogenesis of POI remain incompletely understood, posing significant challenges for its treatment and prevention. This review article examines the pathogenic factors and mechanisms involved in POI, with a particular focus on the impact of environmental toxicants such as atmospheric particulate matter, endocrine-disrupting chemicals, pesticides, microplastics, heavy metals, and cigarette smoke on the development of POI. Furthermore, the treatments for POI are outlined, encompassing hormone replacement therapy, stem cell and exosome therapy, melatonin therapy, traditional Chinese medicine, in vitro activation, platelet-rich plasma therapy, and ovarian tissue cryopreservation. The primary objective is to raise awareness about the potential detrimental effects of environmental toxicant exposure on ovarian function and reserve, urging individuals to minimize their exposure to harmful substances and advocate for environmental protection. This review also aims to serve as a valuable resource for the prevention and management of POI.

Si-Wu-Tang (SWT) has become a common basic prescription for supplementing blood and regulating menstruation, and enjoys the reputation of "the first prescription in gynecology". It is often reported in the treatment of premature ovarian failure (POF). However, knowledge of its specific mechanism is still limited. This study aimed to identify the potential effects and underlying mechanisms of SWT on POF. After confirming the therapeutic effect of SWT on POF mice induced by cyclophosphamide, we further clarified the promoting effect of SWT on ovarian follicle development by detecting the expression of key factors related to follicle development in the ovary in different ways.Then, network pharmacology and gene expression profiling of POF from the GEO database were used to clarify the underlying mechanisms. Molecular biology and molecular docking analysis were applied for final mechanism verification. Our results showed that SWT increased body weight, ovarian index, reversed disordered serum hormone levels, and menstrual cycle in POF mice. After SWT treatment, the number of follicles at all levels in mice with POF also recovered. Using molecular biology techniques, it was proven that SWT can improve follicle development and angiogenesis in the microenvironment. The network pharmacology and gene expression profiling from the GEO database indicated that the PI3K/Akt signaling pathway may be the reason why SWT improves ovarian function in mice with POF. Subsequently, further Western blot and immunoprecipitation indicated that SWT indeed inhibited the PI3K/Akt signaling pathway in mice with POF. In addition, this conclusion was further confirmed by molecular docking experiments. SWT can improve ovarian function in POF mice induced by cyclophosphamide, and its mechanism is related to the inhibition of the PI3K/Akt signaling pathway.

Bushen Huoxue recipe (BSHXR) is a classic Chinese herbal prescription for nourishing the kidney and activating blood circulation. It consists of six herbs: Astragali radix, Angelicae sinensis radix, Ligustici Chuanxiong Rhizoma, Cuscutae semen, Taxilli Herba, and Dipsaci Radix, and the main active constituents of BSHXR are ferulic acid, calycosin-7-glucopyranoside, hyperoside, quercitrin, and asperosaponin VI. In clinical practice, BSHXR is traditionally used to treat failed pregnancy and its complications. However, little is known about the underlying mechanism of BSHXR for the treatment of implantation loss during early pregnancy. In the current study, controlled ovarian hyperstimulation was induced in mice as our implantation loss model, and we evaluated the effects of BSHXR on implantation, decidualization, decidual angiogenesis, and reproductive outcome. We showed that BSHXR could regulate the supraphysiological levels of serum estrogen and progesterone observed in these mice, and also act on estrogen and progesterone receptors in the stroma and epithelium. BSHXR also enhanced FGF2 expression in the vascular sinus folding area of the decidua, thus potentially reducing implantation loss during early pregnancy and contributing to placentation and survival of the fetuses. Taken together, our findings provide scientific evidence for the application of BSHXR in the clinic as a treatment for implantation loss during early pregnancy, and warrant further investigation of BSHXR as an effective treatment for failed pregnancy and its complications.

Gestational diabetes mellitus (GDM) is an intractable issue that negatively impacts the quality of pregnancy. The incidence of GDM is on the rise, becoming a major health burden for both mothers and children. However, the specific etiology and pathophysiology of GDM remain unknown. Recently, the importance of gut microbiota and related metabolic molecules has gained prominence. Studies have indicated that women with GDM have significantly distinct gut microbiota and gut metabolites than healthy pregnant women. Given that the metabolic pathways of gut flora and related metabolites have a substantial impact on inflammation, insulin signaling, glucose, and lipid metabolism, and so on, gut microbiota or its metabolites, such as short-chain fatty acids, may play a significant role in both pathogenesis and progression of GDM. Whereas the role of intestinal flora during pregnancy is still in its infancy, this review aims to summarize the effects and mechanisms of gut microbiota and related metabolic molecules involved in GDM, thus providing potential intervention targets.