Chinese herbal medicines as complementary therapy to in vitro fertilization-embryo transfer in women with infertility: protocols and applications.

In vitro fertilization-embryo transfer (IVF-ET) is a very common treatment for couples with infertility. However, IVF-ET still has a limited success rate with high costs. Chinese herbal medicines (CHM) have been used as complementary treatments for infertility to improve the reproductive outcomes during different stages of the IVF-ET cycle. This review provides an up to date evidence on CHM treatments. We summarize the treatment protocols based on the stages of IVF-ET cycle and discuss its clinical applications in IVF-ET treatment. The possible underlying mechanisms of CHM include improving ovarian function, promoting endometrial receptivity, regulating immune function, inhibiting oxidation, and reducing mental stress and discomfort during treatment. This review aims to provide information and guidance on the potential clinical applications of CHM as an adjuvant therapy during IVF-ET treatment.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

Protective effects of electroacupuncture on polycystic ovary syndrome in rats: Down-regulating Alas2 to inhibit apoptosis, oxidative stress, and mitochondrial dysfunction in ovarian granulosa cells.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting women at reproductive age. The therapeutic effect of electroacupuncture (EA) on PCOS has been revealed, while the anti-PCOS mechanisms of EA have not been fully explored. In this study, PCOS were induced in rats by daily injection with dehydroepiandrosterone (DHEA) for 20 days and EA treatment was performed for 5 weeks. The mRNA expression profiles in ovarian tissues from control, PCOS, and EA-treated rats were examined by high-throughput mRNA sequencing. 5'-aminolevulinate synthase 2 (Alas2), a vital rate-limiting enzyme of the heme synthesis pathway, was selected to be further studied. PCOS led to the upregulation of Alas2 mRNA, whereas EA treatment restored this change. In vitro, primary ovarian granulosa cells (GCs) were challenged with H2O2 to mimic the oxidative stress (OS) state in PCOS. H2O2 induced apoptosis, OS, mitochondrial dysfunction, as well as Alas2 overexpression in GCs, while lentivirus-mediated Alas2 knockdown evidently restrained the above impairments. In summary, this study highlights the crucial role of Alas2 in cell apoptosis, OS, and mitochondrial dysfunction of PCOS GCs and provides potential therapeutic candidates for further investigation on PCOS treatment.

The efficacy and safety of combined chinese herbal medicine and western medicine therapy for COVID-19: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the clinical efficacy and safety of Chinese herbal medicine (CHM) with and without Western medicine (WM) for different severity of COVID-19. METHODS: CNKI, PubMed, Wanfang Database, ClinicalTrails.gov, Embase, ChiCTR and ICTRP were searched from 01 Jan, 2020 to 30 Jun, 2021. Two authors independently assessed all the randomized clinical trials (RCTs) for trial inclusion, data extraction and quality assessment. Meta-analysis was conducted using Review Manager software (RevMan 5.4.1). Evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Primary outcomes included total effectiveness rate. Secondary outcomes included improvements in symptom improvement and total adverse event rate. Different severity of COVID-19 patients was assessed in subgroup analysis. This study was registered with INPLASY, INPLASY202210072. RESULTS: 22 high quality RCTs involving 1789 participants were included. There were no trial used CHM alone nor compare placebo or no treatment. Compared with WM, combined CHM and WM (CHM-WM) treatment showed higher total effectiveness rate, lower symptom scores of fever, cough, fatigue, dry throat and pharyngalgia, shorter mean time to viral conversion, better Computerized Tomography (CT) image and blood results, fewer total adverse events and worse conditions (P < 0.05). Subgroup analysis showed that the total effectiveness rate of combined CHM-WM group was significantly higher than WM group, especially for mild and moderate patients. No significant differences in mortality and adverse events were found between combined CHM-WM and WM treatment. No serious adverse events and long-term outcomes were reported. CONCLUSION: Current evidence supported the therapeutic effects and safety of combined CHM-WM treatment on COVID-19, especially for patients with mild and moderate symptoms. Long-term effects of therapy are worthy in further study.

Evidence for the Use of Complementary and Alternative Medicine for Pelvic Inflammatory Disease: A Literature Review.

Pelvic inflammatory disease (PID), a common infectious disease of the female reproductive tract, is mainly characterized by abdominal/pelvic pain and tenderness of the uterus, cervix, or adnexa on physical exam. In recent years, its incidence has gradually increased yearly due to numerous factors, including sexually transmitted diseases and intrauterine operations. Based on self-report of PID in the National Health and Nutrition Examination Survey (NHANES) 2013-2014 survey, PID impacts approximately 2.5 million women in the US during their reproductive age. Although empiric treatments such as antibiotics or surgery could alleviate the related symptoms of PID, its unsatisfactory obstetric outcome and high relapse bring heavy physical and psychological burden to women. Complementary and alternative medicine (CAM), a complementary therapy other than Western medicine with a complete theoretical and practical system, has been attached to importance in the world due to its remarkable efficacy. More people are accepting and trying to use CAM to treat gynecological diseases, including infertility, polycystic ovary syndrome, and PID, but its efficacy and mechanism are still controversial. This article reviews the previous literature systematically focusing on the effectiveness, safety, and mechanism of CAM in the treatment of PID to provide an evidence-based basis for the clinical application of CAM in patients with PID.

Associations of Serum Magnesium With Insulin Resistance and Testosterone in Women With Polycystic Ovary Syndrome.

Objective: This article aimed to investigate whether serum magnesium is associated with insulin resistance index and testosterone level in women with polycystic ovary syndrome (PCOS). Materials and Methods: Overall 1000 women with PCOS were enrolled in a randomized controlled trial and a cross-sectional analysis of the association of serum magnesium with glucose metabolism markers and testosterone was performed. Serum magnesium, glucose metabolism markers and testosterone were measured. Insulin resistance was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI). Multivariable linear regression and logistic regression models were used to estimate the association between serum magnesium, insulin resistance and testosterone. Results: In comparative analyses, women with higher quartile of serum magnesium had significantly lower fasting glucose, HOMA-IR and testosterone. Multiple linear regression showed serum magnesium was independently negatively associated with insulin, glucose, HOMA-IR, testosterone and positively associated with QUICKI (P for trend <0.05) after adjusting confounding covariates. Logistic regression showed serum magnesium in quartile 1 and 2 were independently associated with insulin resistance status (Quartile 1: OR: 2.15, 95%CI: 1.35-3.40, P = 0.001; Quartile 2: OR: 1.90, 95%CI: 1.20-3.02, P = 0.006), while quartile 1 was marginally associated with hyperandrogenemia status (Quartile 1: OR: 1.45, 95%CI: 0.99-2.11, P = 0.055) after adjusting confounding covariates. Conclusion: The current findings suggest that lower serum magnesium was associated with aggravated insulin resistance and higher testosterone levels among women with PCOS.

The Apolipoprotein B/A1 Ratio is Associated With Metabolic Syndrome Components, Insulin Resistance, Androgen Hormones, and Liver Enzymes in Women With Polycystic Ovary Syndrome.

Aim: To evaluate the association between the apolipoprotein B/A1 ratio (ApoB/ApoA1) and metabolic and endocrine parameters in women with polycystic ovary syndrome (PCOS). Methods: This study was a secondary analysis of the Acupuncture and Clomiphene for Chinese Women with Polycystic Ovary Syndrome trial (PCOSAct), and 957 subjects with available ApoB and ApoA1 measurements were included. Tests for linear trends and linear regression were used to assess the relation between the ApoB/ApoA1 ratio and metabolic and endocrine parameters. Logistic regression was used to estimate the association between the ratio and risk of metabolic syndrome (MetS) and insulin resistance (IR). The receiver operating characteristics (ROC) curve was used to determine the predictive value of the ApoB/ApoA1 ratio for MetS and IR. Results: The results showed that the ApoB/ApoA1 ratio was positively associated with waist circumference, systolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein, fasting plasma glucose, fasting insulin, homeostatic model assessment-insulin resistance, high free testosterone, high free androgen index, alanine transferase, aspartate transferase, and higher prevalence of MetS and IR, but was negatively correlated with high-density lipoprotein and sex hormone-binding globulin after adjusting for age and body mass index. Logistic regression showed that compared with the ApoB/ApoA1 ratio in first quartile, those in the fourth quartile demonstrated a higher risk of MetS (OR: 24.48, 95%CI: 8.54-70.15, P trend <0.001) and IR (OR: 1.78, 95%CI: 1.10-2.87, P trend <0.05) after adjusting for confounding factors. ROC curve results showed that the AUCMetS was 0.84 (95%CI: 0.81-0.86) and had 86.8% sensitivity and 70.3% specificity with a threshold value of 0.64, and the AUCIR was 0.68 (95%CI: 0.64-0.71) and had 74.3% sensitivity and 58.2% specificity with a threshold value of 0.56. Conclusions: Increased ApoB/ApoA1 ratio was associated with worse MetS components, IR, and elevated androgen hormones and liver enzymes. The ratio might be a useful tool to screen for MetS and IR in PCOS patients.

Effect of Three Androgen Indexes (FAI, FT, and TT) on Clinical, Biochemical, and Fertility Outcomes in Women with Polycystic Ovary Syndrome.

This work sought to evaluate the effects of three androgen indexes of free testosterone (FT), total testosterone (TT), and free-androgen index (FAI) on clinical phenotype, endocrine metabolic disorders, and fertility outcomes in women with polycystic ovary syndrome. The data in this study came from a large, multicenter, randomized double-blind controlled clinical trial involving 1000 infertile PCOS patients. Baseline phenotypic, endocrine, and metabolic parameters and fertility outcomes undergoing ovulation induction were collected. FAI is superior to FT, and FT is superior to TT in terms of their correlation with anthropometric parameters and metabolic profile. FT and TT were significantly positively correlated with LH/FSH. FAI and FT were significantly correlated with the incidence of metabolic syndrome. FAI, FT, and TT were significantly positively correlated with polycystic ovary morphology and menstrual period. FAI was significantly related ovulations per cycle, pregnancy, conception, and live birth rates. After adjusting for age, the increased FT level was significantly related to the decreased rates of ovulations per cycle, conception, and pregnancy. FAI is superior to FT and FT is superior to TT in terms of their correlation with phenotypic and metabolic parameters in PCOS patients. FAI and FT are important factors related to the fertility outcomes of infertile PCOS patients. Clinical trial registration number: NCT01573858.

Phenotypic features and fertility outcomes of women with polycystic ovary syndrome: The effect of quality of life.

AIM: This work sought to evaluate the correlation between the five domains of the Polycystic Ovary Syndrome Questionnaire (PCOSQ) and anxiety and depression scales and the clinical phenotype and fertility outcomes in infertile polycystic ovary syndrome (PCOS) patients and to determine the effect of quality of life (QOL) on the clinical, biochemical and fertility disorders in these patients. METHODS: The data in this study came from a large-scale hospital-based cohort survey of infertile PCOS patients across mainland China. A total of 1000 infertile PCOS subjects diagnosed according to the modified Rotterdam criteria ranging in age from 20 to 40 years in 21 sub-centers (27 hospitals) were enrolled. Baseline anthropometric parameters, endocrine indexes, metabolic panel, QOL questionnaires and the fertility outcomes of ovulation, conception, pregnancy, pregnancy loss and live birth were collected. RESULTS: PCOSQ scores were significantly correlated with most of the baseline parameters. PCOSQ-weight domain scores of National Institute of Health-PCOS group were significantly lower compared with non-National Institute of Health-PCOS group. The five domains scores of PCOSQ were significantly negatively correlated with the body mass index levels of PCOS patients. The serum testosterone levels (total testosterone, free testosterone and free androgen index) were significantly negatively correlated to the scores for the weight, body hair, infertility and emotion domains of PCOSQ. Scores on the anxiety and depression scales were significantly and positively correlated with luteinizing hormone, luteinizing hormone/follicle-stimulating hormone levels. In the low-score group of infertility domain, the rates of conception, pregnancy and live birth decreased significantly. CONCLUSIONS: QOL appears to have an impact on the physical symptoms of PCOS, and the emotional stress of infertility affects fertility outcomes.

Efficacy and Safety of Triazavirin Therapy for Coronavirus Disease 2019: A Pilot Randomized Controlled Trial.

No therapeutics have been proven effective yet for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the efficacy and safety of Triazavirin therapy for COVID-19, we conducted a randomized, double-blinded controlled trial involving hospitalized adult patients with COVID-19. Participants were enrolled from ten sites, and were randomized into two arms of the study with a ratio of 1:1. Patients were treated with Triazavirin 250 mg versus a placebo three or four times a day for 7 d. The primary outcome was set as the time to clinical improvement, defined as normalization of body temperature, respiratory rate, oxygen saturation, cough, and absorption of pulmonary infection by chest computed tomography (CT) until 28 d after randomization. Secondary outcomes included individual components of the primary outcome, the mean time and proportion of inflammatory absorption in the lung, and the conversion rate to a repeated negative SARS-CoV-2 nucleic acid test of throat swab sampling. Concomitant therapeutic treatments, adverse events, and serious adverse events were recorded. Our study was halted after the recruitment of 52 patients, since the number of new infections in the participating hospitals decreased greatly. We randomized 52 patients for treatment with Triazavirin (n = 26) or a placebo (n = 26). We found no differences in the time to clinical improvement (median, 7 d versus 12 d; risk ratio (RR), 2.0; 95% confidence interval (CI), 0.7-5.6; p = 0.2), with clinical improvement occurring in ten patients in the Triazavirin group and six patients in the placebo group (38.5% versus 23.1%; RR, 2.1; 95% CI, 0.6-7.0; p = 0.2). All components of the primary outcome normalized within 28 d, with the exception of absorption of pulmonary infection (Triazavirin 50.0%, placebo 26.1%). Patients in the Triazavirin group used less frequent concomitant therapies for respiratory, cardiac, renal, hepatic, or coagulation supports. Although no statistically significant evidence was found to indicate that Triazavirin benefits COVID-19 patients, our observations indicated possible benefits from its use to treat COVID-19 due to its antiviral effects. Further study is required for confirmation.

The Efficacy and Safety of Triazavirin for COVID-19: A Trial Protocol.

The coronavirus disease 2019 (COVID-19), a pneumonia caused by a novel coronavirus, was reported in December 2019. COVID-19 is highly contagious and has rapidly developed from a regional epidemic into a global pandemic. As yet, no effective drugs have been found to treat this virus. This study, an ongoing multicenter and blind randomized controlled trial (RCT), is being conducted at ten study sites in Heilongjiang Province, China, to investigate the efficacy and safety of Triazavirin (TZV) versus its placebo in COVID-19 patients. A total of 240 participants with COVID-19 are scheduled to be enrolled in this trial. Participants with positive tests of throat swab virus nucleic acid are randomized (1:1) into two groups: standard therapy plus TZV or standard therapy plus placebo for a 7-day treatment with a 21-day follow-up. The primary outcome is the time to clinical improvement of the subjects. Secondary outcomes include clinical improvement rate, time to alleviation of fever, mean time and proportion of obvious inflammatory absorption in the lung, conversion rate of repeated negative virus nucleic acid tests, mortality rate, and conversion rate to severe and critically severe patients. Adverse events, serious adverse events, liver function, kidney function, and concurrent treatments will be monitored and recorded throughout the trial. The results of this trial should provide evidence-based recommendations to clinicians for the treatment of COVID-19.

First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine. OBJECTIVE AND RATIONALE: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. SEARCH METHODS: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. OUTCOMES: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06). WIDER IMPLICATIONS: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.

[Progress of researches on non-specific effect of acupuncture].

Acupuncture therapy is effective in the treatment of quite a lot of clinical conditions. Accumulating evidence demonstrates that acupuncture therapy not only has specific therapeutic effects, but also in a large part has non-specific effects such as the patient's and/or acupuncture practitioner's "unity of form and spirit", "treatment experience and environment" and "expectations and trust", etc. In the present article, we make a review about progresses of recent researches on the non-specific effect of acupuncture therapy and its influencing factors from 1) placebo acupuncture, 2) expectancy effect, 3) Hawthorne effect, and 4) Pygmalion effect. The placebo acupuncture intervention may enhance the therapeutic effect by triggering the cutaneous somatosensory afferents, brainstem, hypothalamus, limbic system, etc. to produce cognitive and emotional responses. The patient's expectancy and belief about acupuncture analgesia are associated with activities of the spino-thalamo-cortical pathway, cingulate gyrus, endogenous opioid system, emotional and reward circuits, etc. Regarding the Hawthorne effect and Pygmalion effect, it is supposed that the patients' behavioral tendency changes and higher expectations for acupuncture treatment may produce a positive impact on the outcomes of treatment. In-depth exploration of the influencing factors and the therapeutic targets of acupuncture treatment will further improve clinical effect, and serve the patients better.

Effects of hyperhomocysteinaemia and metabolic syndrome on reproduction in women with polycystic ovary syndrome: a secondary analysis.

RESEARCH QUESTION: What is the association between hyperhomocysteinaemia (HHCY), metabolic syndrome, and reproductive outcomes among women with polycystic ovary syndrome (PCOS). DESIGN: A secondary analysis of PCOSAct with 21 sites in China. A total of 1000 women with PCOS were enrolled; 936 women with baseline homocysteine (HCY) were analysed. RESULTS: Higher HCY was associated with higher body mass index, free testosterone and lower FSH, fasting glucose (P < 0.001; P < 0.001; P = 0.005; P < 0.001) and ovulation rate among all participants (OR 0.59, 95% CI 0.41 to 0.86; OR 0.57, 95% CI 0.39 to 0.83 tertiles 2 and 3 versus tertile 1, respectively). The HHCY group had lower oestradiol and higher free testosterone (P = 0.04; P < 0.001) than the controls. In the metabolic syndrome group, LH, LH-FSH ratio and sex hormone-binding globulin were lowest in the metabolic syndrome group (all P < 0.001). In the HHCY group, ovulation rate decreased and the second or third trimester pregnancy loss rate increased compared with controls (OR 1.678, 95% CI 1.04 to 2.70; OR 0.03, 95% CI 0.00 to 0.42) with treatment adjustment. Compared with the controls, ovulation, conception, pregnancy, second or third trimester pregnancy loss and live birth rates were statistically lower in the metabolic syndrome group after adjusting treatment (OR 1.76, 95% CI 1.15 to 2.70; OR 1.75, 95% CI 1.15 to 2.65; OR 2.09, 95% CI 1.27 to 3.44; OR 0.02, 95% CI 0.00 to 0.33; OR 2.42 95% CI 1.42 to 4.10), and pregnancy, pregnancy loss and live birth rates remained significantly different after adjusting for treatment and sex-hormone factors (OR 1.77, 95% CI 1.05 to 2.99; OR 0.14, 95% CI 0.02 to 0.82; OR 2.02, 95% CI 1.16 to 3.50). CONCLUSIONS: In women with PCOS, HHCY contributes to increased pregnancy loss and reduced ovulation, and metabolic syndrome was related to defects in ovulation, conception, pregnancy, pregnancy loss and live birth, indicating that the two conditions lead to defects at various reproductive stages.

Acupuncture and clomiphene for Chinese women with polycystic ovary syndrome (PCOSAct): statistical analysis approach with the revision and explanation.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women. Clomiphene is regarded as the first-line medical treatment for ovulation induction in PCOS patients and acupuncture is often used as an alternative and complementary treatment for fertility issues such as those associated with PCOS. The efficacy of acupuncture alone or combined with clomiphene still lacks strong supporting evidence. Factorial 2 × 2 designs can be used for the evaluations of two treatments within a single study, to test the main effects of acupuncture and clomiphene and their interactions. METHODS: PCOSAct was designed to test the effect of clomiphene and acupuncture by three two-group comparisons in the original protocol. However, the trial was designed as a standard factorial trial and the factorial analysis approach for analyzing the data that were actually obtained during the trial was found to be more appropriate and more powerful than the three two-group comparisons described in the original protocol, so the statistical analysis approach and different datasets of PCOSAct in the primary publication were accordingly changed. DISCUSSION: Although the statistical analysis approach used in the primary publication deviated from the statistical analysis planned in the study protocol, focusing on the main effects of the two interventions and their interactions was a more standard approach to a factorial trial and proved to be more suitable and consistent with the characteristics of the trial data. Statistically, the revision is more powerful and precise and should be more useful to the journal and the readers. TRIAL REGISTRATION: Chinese clinical trial registry, ChiCTR-TRC-12002081 . Registered on 20 March 2012. Clinicaltrials.gov, NCT01573858 . Registered on 4 April 2012.

[Protocol optimization and quality control of large-scale acupuncture clinical trial for infertility].

The design of research protocol and quality control are the key to ensure the quality of clinical trial. A randomized clinical trial regarding the effects of medication combined with acupuncture on live birth rate in polycystic ovary syndrome (PCOS), which was initially designed as a comparative effectiveness research, then added with an acupuncture control group and finally became a factorial analysis, is taken as an example to explain the protocol design and optimization process, demonstrating the high level of methodology design and international recognization. By a series of measurements, such as unified purchase of acupuncture equipment, multiple trainings and assessments for acupuncturists' knowledge and operation standardization, in-site supervision of local center experts, the standard operation of acupuncture could be ensured and the credibility and scientificity of research results could be improved.

Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.

Value of qualitative research in polycystic ovary syndrome.

OBJECTIVE: This article aims to introduce the benefits of qualitative research and to discuss how such research can be applied to the study of polycystic ovary syndrome (PCOS). DATA SOURCES: Relevant articles were published in English as of May 2013 from Pubmed. Terms "polycystic ovary syndrome/PCOS, qualitative research and methodology" were used for searching. STUDY SELECTION: Articles studying PCOS with qualitative methods were reviewed. Articles associated with the use of qualitative research in clinical research were cited. RESULTS: Six qualitative studies related to PCOS were found in the literature search. These studies addressed different aspects in PCOS women including their womanhood, lived experience, information need, and experience of treatment with acupuncture. Five of these six studies used phenomenology as guiding theory. CONCLUSION: Quantitative research has been the dominant approach in the field so far, qualitative research is relevant to the advancement of PCOS.