Project description:Would letrozole as a primary ovulation induction agent generate better pregnancy rates than clomiphene citrate (CC) in subfertile women with anovulatory polycystic ovarian syndrome (PCOS)?Participants receiving letrozole as a primary treatment achieved a significantly (P = 0.022) higher clinical pregnancy rate per patient (61.2%) compared to CC (43.0%).According to a recent Cochrane systematic review (2014), letrozole appears to improve live-birth (LB) and pregnancy rates in anovulatory women with PCOS, compared to CC. However, the review concluded that the quality of evidence was low due to poor reporting of study methods and possible publication bias.This double-blind randomized controlled trial (RCT) included 159 participants between April 2007 and June 2014. Subjects were randomly allocated to either CC (n = 79) or letrozole (n = 80) in a 1:1 ratio. Both drugs were encapsulated to look identical. Randomization was performed in mixed blocks and stratified by patients' BMI (<30 and 30-35 kg/m2).The trial included subfertile women diagnosed with PCOS. Treatment started with one tablet (CC 50 mg, letrozole 2.5 mg) increasing to two in non-responders and continuing until pregnancy or for up to six ovulatory cycles. Non-responders were crossed over to the other treatment after a 6-week break. Cycles were initially monitored with ultrasound follicle tracking then mid-luteal serum progesterone measurement in subsequent cycles.Amongst the 159 participants included in the intention-to-treat analysis, four women conceived before treatment and six were lost-to-follow-up. The remaining 149 participants (74 on CC and 75 on letrozole) completed at least the first treatment. Women receiving letrozole achieved a significantly (P = 0.022; absolute difference [95% confidence interval] 18% [3-33%]) higher pregnancy rate (61.%) than those on CC (43%). The median number of treatment cycles received until pregnancy was significantly (log rank P = 0.038) smaller with letrozole (4[3-5] cycles) compared to CC (6[4-7] cycles). LB rates were not statistically (P = 0.089) different between the two groups, although there was a trend towards higher rates on letrozole (48.8%) compared to CC (35.4%). After the crossover, pregnancy and LB rates on letrozole (n = 45; 28.9 and 24.4%, respectively) were not statistically (P = 0.539 and P = 0.601) different from CC (n = 31; 22.6 and 19.4%).One possible limitation of this trial may be the exclusion of PCOS women with BMI > 35 kg/m2, which would limit the applicability of the results in this subgroup of PCOS. However, this group of women are generally excluded from treatment in the majority of fertility centres, especially in Europe, due to the associated challenges and risks.The results of this trial are consistent with the recent Cochrane systematic review. However, with its robust design, the current RCT provides more valid and compelling evidence for the superiority of letrozole over CC as a primary ovulation induction agent in PCOS women with 40% increase in pregnancy rates and with a shorter time-to-pregnancy. Furthermore, the participants in this RCT are a good representation of subfertile PCOS population receiving fertility treatment in Europe and worldwide. The results are therefore globally generalizable for clinical practice.This RCT was mainly funded by the R&D Funding Scheme of Derby Hospitals NHS Foundation Trust. The study also received funds from School of Medicine, University of Nottingham. The Trust R&D department was involved in the development of the protocol and the running of the trial. The trial was sponsored and monitored by the University of Nottingham. The authors have no conflicts of interest.www.Clinicaltrials.gov: NCT00478504.Registration was verified on 23/05/2007.25/04/2007.
Project description:BackgroundChinese herbal medicine (CHM) has significant effects that improve the reproductive functions of patients with polycystic ovary syndrome (PCOS). However, the intergenerational effects of CHM on offspring and the underlying mechanism of CHM remain unclear. This study aimed to explore the effects and the underlying mechanism of CHM, specifically the Bu-Shen-Tian-Jing formula (BSTJF), on model rats with polycystic ovary syndrome (PCOS) and the neurobehavioral alterations of female offspring born to PCOS rats administered BSTJF.MethodsHigh-performance liquid chromatography-mass spectrometry (HPLC-MS) and network pharmacology analysis were performed to identify the active ingredients and potential targets of BSTJF. Moreover, PCOS model rats were used to validate the role of BSTJF in reproduction and progeny neural development and to confirm the network pharmacological targets.ResultsA total of 91 constituents were characterized from BSTJF. The 20 most significant KEGG pathways and the high-frequency genes of these pathways were predicted to be putative targets of these molecules. The rat experiment showed that the downregulation of FOS protein expression in the ovarian granulosa cells of the PCOS group was reversed by BSTJF. The target residence time of the 5-week-old female offspring of the BSTJF group was higher than that of the PCOS group in the water maze experiment. Compared to the PCOS group, the changes in dendritic spine density, ultrastructure of neurons and synapses, and Gabrb1 and Grin2b protein expression levels in the hippocampus of female offspring were partially reversed in the BSTJF group.ConclusionsBSTJF can effectively improve ovarian follicle development in PCOS rats and has positive effects on pubertal neurobehavioral alterations in the female offspring of these rats by reversing dendritic spine density, the ultrastructure of neurons and synapses, and the Gabrb1 and Grin2b protein expression levels in the hippocampus.
Project description:As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate < 0.05 and corresponding p value < 5.68e-06), highly consistently replicating biological pathways extensively implicated in immunity and immunity-related inflammatory disorders (false discovery rate < 0.05) that were reportedly regulated in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women.
Project description:BackgroundPolycystic ovary syndrome (PCOS) is one of the most common disorders of reproductive endocrinology in women of reproductive age. Lifestyle intervention and oral contraceptives are the first-line treatments for PCOS. Recent studies have suggested that complementary and alternative medicine (CAM) therapies including acupuncture, herbal medicine, and mind-body therapy have the potential to alleviate the symptoms and/or pathology of PCOS and to improve the quality of life of women with PCOS. This meta-analysis aimed to quantitatively summarize the efficacy and safety of moxibustion combined with oriental herbal medicine (OHM), common CAM therapies, for treating PCOS.MethodsFour databases were searched from their inception to June 22, 2018. Randomized controlled trials (RCTs) and quasi-RCTs using both OHM and moxibustion as experimental intervention, and western medication (WM) as control intervention were included. Studies involving OHM plus moxibustion combined with WM as the experimental intervention were also included. The quality of included studies was assessed using risk of bias tool.ResultsOwing to the heterogeneity of reporting, meta-analysis was only performed for pregnancy rate, rate of normal biphasic basal body temperature (BBT), and total effective rate (TER). The results showed that compared to the WM group, the OHM combined with moxibustion group was associated with significantly higher pregnancy rate (risk ratio [RR] 1.95, 95% confidence interval [CI] 1.55-2.47; I?=?0%), normal biphasic BBT rate (RR 1.66, 95% CI 1.34-2.05; I?=?0%), and TER (RR 1.19, 95% CI 1.08-1.31; I?=?0%). When OHM combined with moxibustion was used as an adjunctive therapy to WM, pregnancy rate (RR 1.65, 95% CI 1.29-2.11; I?=?0%), and TER (RR 1.35, 95% CI 1.13-1.61; I?=?43%) were significantly higher than those of the WM group.ConclusionAccording to current evidence, OHM combined with moxibustion might be beneficial for treating PCOS. Moreover, the treatment might improve the therapeutic effects of conventional WMs including clomiphene citrate, oral contraceptives, and/or metformin. However, the findings should be interpreted with caution, owing to poor methodological quality of the included studies. Further larger, high-quality, rigorous RCTs should be conducted in this regard.
Project description:Objective This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) on ovarian mass, weight, sex hormone disorders, and insulin resistance in animal models of polycystic ovary syndrome (PCOS). Methods This systematic review and meta-analysis was conducted through a comprehensive search in three databases to find studies testing CHM in animal models of PCOS. Two researchers independently reviewed the retrieval, extraction, and quality assessment of the dataset. The pooled effects were calculated using random-effect models; heterogeneity was explored through subgroup analysis; and stability was assessed through sensitivity analysis. In addition, publication bias was assessed using the Egger's bias test. Results Fifteen studies with twelve mice and 463 rats published from 2016 to 2021 met the inclusion criteria. The results of primary outcomes revealed that CHM therapy was significantly different with control animals in ovarian mass and testosterone (SMD, −1.01 (95% CI, −1.58, −1.45); SMD, −1.62 (95% CI, −2.07, −1.16), respectively). The secondary outcomes as well showed an overall positive effect of CHM compared with control animals in weight (SMD, −1.02 (95% CI, −1.39, −0.65)), follicle-stimulating hormone (FSH) (SMD, 0.58 (95% CI, 0.19, 0.97)), luteinizing hormone (LH) (SMD, −0.94 [95% CI, −1.25, −0.64)), homeostasis model assessment-insulin resistance (HOMA-IR) (SMD, −1.24 (95% CI, −1.57, −0.92)). Subgroup analyses indicated that PCOS induction drug, formula composition, random allocation, and assessment of model establishment were relevant factors that influenced the effects of interventions. The stability of the meta-analysis was showed robust through sensitivity analysis. The publication bias was substantial. Conclusions Administration with CHM revealed a statistically positive effect on ovarian mass, weight, sex hormone disorders, and insulin resistance. Moreover, these data call for further high-quality studies investigating the underlying mechanism in more depth.
Project description:IntroductionPolycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders. Evidence of familial aggregation analysis and different clinical traits among different regions and ethnicities indicated that the pathogenesis of PCOS is associated with multiple genetic and environmental factors. Our previous research had identified three susceptibility loci (rs2479106, DENND1A; rs13405728, LHCGR; rs13429458, THADA) for PCOS in Han Chinese women. The overall aim of this study was to investigate the relationship between three susceptibility gene polymorphisms and PCOS in Hui ethnic women.Methods151 patients with PCOS (case group) and 99 healthy women (control group) were recruited from the Reproductive Medicine Center of the General Hospital of Ningxia Medical University. Clinical data and serum hormone characteristics of case and control groups were collected and analyzed. The three susceptibility single-nucleotide polymorphisms have been replicated in both case and control groups. Gene polymorphisms were detected by direct sequencing after polymerase chain reaction.ResultsThe Body Mass Index, LH, LH/FSH ratio and total testosterone were significantly elevated in PCOS patients compared to control group (P<0.05). The frequencies of genotype and allele in rs13405728 were significantly different between the PCOS and the control groups (P<0.05). Of the SNP rs13405728, the PCOS cases with TT genotype stayed at a higher level of total testosterone, TG and LDL than those with the CC and CT genotypes. In contrary, there was no statistical difference between the two groups for SNP rs13429458 and rs2479106 (P>0.05).ConclusionThe present study suggested that the SNP rs13405728 in the LHCGR gene was associated with PCOS in Hui ethnic women, and its TT genotype characterized with higher level of TT, TG and LDL.