Acupuncture as Treatment for Female Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effects of acupuncture on female infertility remain controversial. Also, the variation in the participant, interventions, outcomes studied, and trial design may relate to the efficacy of adjuvant acupuncture. The aim of the study is to systematically evaluate the efficacy and safety of acupuncture for female with infertility and hopefully provide reliable guidance for clinicians and patients. METHODS: We searched digital databases for relevant studies, including EMBASE, PubMed, Cochrane Library, and Web of Science, and the Cochrane Library up to April 2021, for randomized controlled trials (RCTs) evaluating the effects of acupuncture on women undergoing IVF and other treatment. We included studies with intervention groups using acupuncture and control groups consisting of no acupuncture or sham (placebo) acupuncture. Primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Meta-regression and subgroup analysis were conducted on the basis of ten prespecified covariates to investigate the variances of the effects of adjuvant acupuncture on pregnancy rates and the sources of heterogeneity. Results: Twenty-seven studies with 7676 participants were included. The results showed that the intervention group contributes more in outcomes including live birth rate (RR = 1.34; 95% CI (1.07, 1.67); P < 0.05), clinical pregnancy rate (RR = 1.43; 95% CI (1.21, 1.69); P < 0.05), biochemical pregnancy rate (RR = 1.42; 95% CI (1.05, 1.91); P < 0.05), ongoing pregnancy rate (RR = 1.25; 95% CI (0.88, 1.79); P < 0.05), adverse events (RR = 1.65; 95% CI (1.15, 2.36); P < 0.05), and implantation rate (MD = 1.19; 95% CI (1.07, 1.33); P < 0.05) when compared with the control group, and the difference is statistically significant. In terms of the number of oocytes retrieved, good-quality embryo rate, miscarriages, and ectopic pregnancy rate, the difference between the acupuncture group and the control group was not statistically significant. Conclusions: Our analysis finds a benefit of acupuncture for outcomes in women with infertility, and the number of acupuncture treatments is a potential influential factor. Given the poor reporting and methodological flaws of existing studies, studies with larger scales and better methodologies are needed to verify these findings. More double-blind RCTs equipped with high quality and large samples are expected for the improvement of the level of evidence.

Effect of acupuncture and metformin on insulin sensitivity in women with polycystic ovary syndrome and insulin resistance: a three-armed randomized controlled trial.

STUDY QUESTION: Does acupuncture improve insulin sensitivity more effectively than metformin or sham acupuncture in women with polycystic ovary syndrome (PCOS) and insulin resistance (IR)? SUMMARY ANSWER: Among women with PCOS and IR, acupuncture was not more effective than metformin or sham acupuncture in improving insulin sensitivity. WHAT IS KNOWN ALREADY: Uncontrolled trials have shown that acupuncture improved insulin sensitivity with fewer side effects compared with metformin in women with PCOS and IR. However, data from randomized trials between acupuncture and metformin or sham acupuncture are lacking. STUDY DESIGN, SIZE, DURATION: This was a three-armed randomized controlled trial enrolling a total of 342 women with PCOS and IR from three hospitals between November 2015 and February 2018, with a 3-month follow-up until October 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged from 18 to 40 years with PCOS and homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.14 were randomly assigned (n = 114 per group) to receive true acupuncture plus placebo (true acupuncture), metformin plus sham acupuncture (metformin, 0.5 g three times daily) or sham acupuncture plus placebo (sham acupuncture) for 4 months, with an additional 3-month follow-up. True or sham acupuncture was given three times per week, and 0.5 g metformin or placebo was given three times daily. The primary outcome was change in HOMA-IR from baseline to 4 months after baseline visit. Secondary outcomes included changes in the glucose AUC during an oral glucose tolerance test, BMI and side effects at 4 months after baseline visit. MAIN RESULTS AND THE ROLE OF CHANCE: After 4 months of treatment, the changes of HOMA-IR were -0.5 (decreased 14.7%) in the true acupuncture group, -1.0 (decreased 25.0%) in the metformin group and -0.3 (decreased 8.6%) in the sham acupuncture group, when compared with baseline. True acupuncture is not as effective as metformin in improving HOMA-IR at 4 months after baseline visit (difference, 0.6; 95% CI, 0.1-1.1). No significant difference was found in change in HOMA-IR between true and sham acupuncture groups at 4 months after baseline visit (difference, -0.2; 95% CI, -0.7 to 0.3). During the 4 months of treatment, gastrointestinal side effects were more frequent in the metformin group, including diarrhea, nausea, loss of appetite, fatigue, vomiting and stomach discomfort (31.6%, 13.2%, 11.4%, 8.8%, 14.0% and 8.8%, respectively). Bruising was more common in the true acupuncture group (14.9%). LIMITATIONS, REASONS FOR CAUTION: This study might have underestimated the sample size in the true acupuncture group with 4 months of treatment to enable detection of statistically significant changes in HOMA-IR with fixed acupuncture (i.e. a non-personalized protocol). Participants who withdrew because of pregnancy did not have further blood tests and this can introduce bias. WIDER IMPLICATIONS OF THE FINDINGS: True acupuncture did not improve insulin sensitivity as effectively as metformin in women with PCOS and IR, but it is better than metformin in improving glucose metabolism (which might reduce the risk of type 2 diabetes) and has less side effects. Metformin had a higher incidence of gastrointestinal adverse effects than acupuncture groups, and thus acupuncture might be a non-pharmacological treatment with low risk for women with PCOS. Further studies are needed to evaluate the effect of acupuncture combined with metformin on insulin sensitivity in these women. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants 2017A020213004 and 2014A020221060 from the Science and Technology Planning Project of Guangdong Province. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov number: NCT02491333. TRIAL REGISTRATION DATE: 8 July 2015. DATE OF FIRST PATIENT'S ENROLLMENT: 11 November 2015.

A multicenter randomized trial of personalized acupuncture, fixed acupuncture, letrozole, and placebo letrozole on live birth in infertile women with polycystic ovary syndrome.

BACKGROUND: Traditional Chinese medicine (TCM) usually involves syndrome differentiation and treatment. Acupuncture, one form of TCM, requires the selection of appropriate acupoints and needling techniques, but many clinical trials on acupuncture have used fixed acupuncture protocols without accounting for individual patient differences. We have designed a multicenter randomized controlled trial (RCT) to evaluate whether personalized or fixed acupuncture increases the likelihood of live births in infertile women with polycystic ovary syndrome (PCOS) compared with letrozole or placebo letrozole. We hypothesize that letrozole is more effective than personalized acupuncture, which in turn is more effective than fixed acupuncture, and that placebo letrozole is the least effective intervention. Moreover, we hypothesize that personalized acupuncture is more likely to reduce the miscarriage rate and the risk of pregnancy complications compared with letrozole. METHODS/DESIGN: The study is designed as an assessor-blinded RCT. A total of 1100 infertile women with PCOS will be recruited from 28 hospitals and randomly allocated to 4 groups: personalized acupuncture, fixed acupuncture, letrozole, or placebo letrozole. They will receive treatment for 16 weeks, and the primary outcome is live birth. Secondary outcomes include ovulation rate, conception rate, pregnancy rate, pregnancy loss rate, changes in hormonal and metabolic parameters, and changes in quality of life scores. Adverse events will be recorded throughout the trial. All statistical analyses will be performed using IBM SPSS Statistics version 21.0 software (IBM Corp., Armonk, NY, USA), and a P value < 0.05 will be considered statistically significant. DISCUSSION: This study will be the first multicenter RCT to compare the effect of personalized or fixed acupuncture with letrozole or placebo letrozole on live birth in infertile women with PCOS. The findings will inform whether personalized acupuncture therapy can be considered an alternative treatment to improve the live birth rate in infertile women with PCOS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03625531. Registered on July 13, 2018. Chinese Clinical Trial Registry, ChiCTR1800017304. Registered on July 23, 2018.

Cryptotanshinone Regulates Androgen Synthesis through the ERK/c-Fos/CYP17 Pathway in Porcine Granulosa Cells.

The aim of the study is to investigate the molecular mechanism behind androgen reduction in porcine granulosa cells (pGCs) with Salvia miltiorrhiza Bunge extract cryptotanshinone. PGCs were isolated from porcine ovaries and identified. Androgen excess model of the pGCs was induced with the MAPK inhibitor PD98059 and then treated with cryptotanshinone. The testosterone level was measured by radioimmunoassay in the culture media. The protein levels of P-ERK1/2, c-Fos, and CYP17 in the cells were measured by western blot. Cryptotanshinone decreased the concentration of testosterone and the protein level of CYP17 and increased the protein levels of P-ERK1/2 and c-Fos in the androgen excess mode. After the c-Fos gene was silenced by infection with c-Fos shRNA lentivirus, we measured the mRNA expression by quantitative RT-PCR and protein level by western blot of P-ERK1/2, c-Fos, and CYP17. This showed that the mRNA expression and protein level of P-ERK1/2 and c-Fos were significantly reduced in the shRNA-c-Fos group compared to the scrambled group, while those of CYP17 were significantly increased. So we concluded that cryptotanshinone can significantly reduce the androgen excess induced by PD98059 in pGCs. The possible molecular mechanism for this activity is regulating the ERK/c-Fos/CYP17 pathway.