premature ovarian insufficiency:

Insuffisance ovarienne prématurée : évaluation de l'acupuncture

1. Systematic Reviews and Meta-Analysis

☆☆☆ Evidence for effectiveness and a specific effect of acupuncture
☆☆ Evidence for effectiveness of acupuncture
Limited evidence for effectiveness of acupuncture
Ø No evidence or insufficient evidence

1.1. Generic Acupuncture

1.1.1. Li 2020 ☆

Li Y, Xia G, Tan Y, Shuai J. Acupoint stimulation and Chinese herbal medicines for the treatment of premature ovarian insufficiency: A systematic review and meta-analysis. Complement Ther Clin Pract. 2020. [215434]. doi

Background and purposeAcupoint stimulation and Chinese herbal medicines (CHM) are widely used in the treatment of premature ovarian insufficiency (POI), but the efficacy and safety remain controversial. This systematic review aims to evaluate the efficacy and safety of acupoint stimulation and CHM for POI.
Methods Seven databases were searched and collected studies comparing acupoint stimulation and CHM with hormone replacement therapy (HRT) from inception to July 31, 2019. The methodological quality of the included trials was assessed in line with the criteria of the Cochrane risk of bias assessment tool.
Results Meta-analysis was performed in 14 trials, which contained a total of 1030 women with POI. The acupoint stimulation and CHM presented advantages in normalizing of menstrual cycle (RR 2.06, 95% CI 1.62 to 2.61, P < 0.00001) and improving perimenopausal symptoms (RR 2.00, 95% CI 1.56 to 2.56, P < 0.00001) when compared with HRT. After treatment, compared with HRT, acupoint stimulation and CHM effectively decreased the level of follicle stimulating hormone (MD -2.88, 95% CI -5.00 to -0.76, P = 0.008) and increased the level of estradiol (SMD 0.88, 95% CI 0.06 to 1.71, P = 0.04). By contrast, there were no significant between-group differences in the level of luteinizing hormone (MD -3.24, 95% CI -6.77 to 0.29, P = 0.07) and adverse effects (RR 0.31, 95% CI 0.04 to 2.54, P = 0.28).
Conclusion This meta-analysis suggested that acupoint stimulation and CHM can serve as complementary therapies to alleviate menstrual disorders, perimenopausal symptoms, and serum sex hormone levels in POI females.

1.1.2. Xu 2020 ☆

Xu Yuanbo. [Acupuncture combined with traditional Chinese medicine in the treatment of premature ovarian failure: A meta-analysis ]. Modern Chinese Clinical Medicine. 2020. [212891].

ObjectiveTo compare the efficacy and safety between acupuncture combined with traditional Chinese medicine and hormone replacement therapy for premature ovarian failure.
Methods Articles up to October, 2019 about the randomized controlled trails on the efficacy of treating the premature ovarian failure with acupuncture combined with herbal medicine were included in the electronic retrieval library, which were from China national knowledge infrastructure (CNKI), China Science and Technology Journal Database (VIP), WanFang Database, China Biology Medicine disc (CBM), Pubmed, Cochrane Library, and EMBase. Studies screening and data extraction were performed by two researchers separately. The quality evaluation and risk assessment of the inclusion were carried out by using the criteria provided by the Cochrane. Meta-analysis was conducted with RevMan 5. 3.
Results A total of 14 randomized controlled trials were included, involving 879 individual. The meta-analysis showed that: 1) The total effective rate for the treatment of premature ovarian failure was higher in acupuncture combined with traditional Chinese medicine than in the hormone replacement therapy [OR=3. 41, 95% CI (2. 38, 4. 89), P<0. 05]; 2) The improvement of laboratory indexes (E2, FSH, LH) in patients who received treatment of acupuncture combined with traditional Chinese medicine were superior to those with hormone replacement therapy (SMD=0. 86, -0. 95, -0. 82, P<0. 05); 3) The improvement of the Kupperman score in patients with acupuncture combined with traditional Chinese medicine was superior to those with hormone replacement therapy (SMD=-0. 99, P<0. 05); 4) The main adverse reactions reported were gastrointestinal symptoms, dizziness and nausea. The adverse effects rate were similar in both oacupuncture combined with traditional Chinese medicine group and hormone replacement therapy group [OR=0. 13, 95% CI (0. 01, 1. 17), P=0. 07].
Conclusions Our analysis found that acupuncture combined with traditional Chinese medicine showed better efficacy than hormone replacement therapy in the treatment of premature ovarian failure. However, the quality of the enrolled studies is low. Consequently, more high-quality randomized controlled trials would be needed in future.

1.1.3. Yin 2020 ☆

Yin Ya-qian, Xu Huan-fang. Acupuncture for premature ovarian insufficiency: a systematic review and meta-analysis. Journal of Acupuncture and Tuina Science. 2020;18(1):24-32. [209302]. doi

ObjectiveTo analyze the effect of acupuncture versus hormone replacement therapy (HRT) for premature ovarian insufficiency (POI).
MethodsChina National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), Web of Science, Cochrane Library, PubMed, and Excerpta Medica Database (EMBASE) were searched up to January 31st, 2019 to identify randomized controlled trials (RCTs) evaluating the effect of acupuncture for POI. The primary outcome was the level of basal serum follicle-stimulating hormone (FSH). Secondary outcomes included serum levels of luteinizing hormone (LH), estradiol (E2) and anti-Müllerian hormone (AMH). Two authors extracted data independently and assessed the risk of bias and the methodological quality using the Cochrane’s tool. Meta-analysis was conducted by RevMan version 5.3.
ResultsEight eligible RCTs with a total of 496 POI patients were included in the meta-analysis. The pooled results showed that there was a significant reduction in the basal serum FSH level (MD=−5.82, 95%CI: −9.76 to −1.87, I2=82%, P=0.004) and a remarkable elevation in the basal E2 level (SMD=0.93, 95%CI: 0.34 to 1.52, I2=88%, P=0.002) in the acupuncture group when compared with the control. Subgroup analysis showed that compared with HRT, a significant decrease in the FSH level was observed in both acupuncture alone (MD=−4.53, 95%CI: −8.96 to −0.10, I2=73%, P=0.04) and acupuncture plus HRT (MD=−9.60, 95%CI: −17.60 to −1.61, I2=50%, P=0.02), while a remarkable elevation of E2 was only found in acupuncture plus HRT (SMD=1.43, 95%CI: 1.03 to 1.82, I2=0%, P<0.00001). There was no significant difference in the LH level between acupuncture and HRT (MD=−3.16, 95%CI: −9.41 to 3.10, I2=0%, P=0.32), only one trial reported AMH, and no significant difference was found between acupuncture and HRT.
Conclusion The present study indicated that acupuncture had an advantage over HRT in reducing serum FSH level and increasing serum E2 level in women with POI. However, evidence supporting the finding is limited due to the small sample size, potential methodological flaws and significant heterogeneity. Hence, this conclusion still needs to be verified by high-quality RCTs.

1.1.4. Zhang 2020

Zhang J, Huang X, Liu Y, He Y, Yu H. A comparison of the effects of Chinese non-pharmaceutical therapies for premature ovarian failure: A PRISMA-compliant systematic review and network meta-analysis. Medicine (Baltimore). 2020;99(26). [211175]. doi

Background Premature ovarian failure (POF) is commonly treated with hormone replacement therapy (HRT). Many patients with POF choose acupuncture as a complementary therapy over HRT, due to possible adverse reactions. This systematic review and network meta-analysis (NMA) compares the efficacy of different forms of acupuncture therapies for POF.
Methods Seven databases including PubMed, the Cochrane Library, Embase, Wanfang database, China National Knowledge Infrastructure database, VIP Chinese Science, and Chinese Biomedical Database were searched for randomized controlled trials (RCTs) of various acupuncture treatments for POF. This time spanned from the date of database inception to January 13, 2020. RevMan 5.3 was used to assess the bias risk of the studies. A NMA of the included studies was performed using Stata14.0.
Results A total of 408 items were searched in this study, and finally this NMA included 16 RCTS, involving 1,307 patients. It showed that acupuncture (OR:1.35,95%1.24 to 1.47) has the best effectiveness among the four acupuncture (standardized mean difference [SMD]-16.30,95% -31.33 to -1.28) is the most effective and the best in reducing follicle-stimulating hormone levels among the four acupuncture treatments. Acupuncture (SMD 26.67,95%5.95 to 47.40) and acupoint embedding (SMD41.14,95%11.90 to 70.37) were ranked in the top 2 positions, in improving estradiol, whereas acupuncture (SMD-4.90,95% -8.10 to -1.70) was than acupoint embedding and HRT, in reducing luteinizing hormone level. In addition, our conclusions have not changed significantly after the sensitivity analysis.
Conclusion With clinical evidence summarized by NMA, it is observed that acupuncture is the most promising therapy for improving menopausal symptoms, decreasing serum follicle-stimulating hormone and luteinizing hormone level. Therefore, acupuncture could be effective for patients with POF, who are intolerant to the adverse effects of hormone replacement therapy or who would prefer non-drug therapies. Further multi-center and high-quality RCT studies should be conducted to make our conclusion more rigorous.

1.1.5. Zhang 2020 ☆

Zhang Jinhuan. [Systematic Evaluation and Meta-analysis of Acupuncture-Moxibustion Alone in Treating Premature Ovarian Failure]. Journal of Guangzhou University of TCM. 2020. [212934].

ObjectiveTo systematically evaluate the clinical efficacy of acupuncture-moxibustion alone for the treatment of premature ovarian failure.
Methods The literature about randomized control trials (RCTs) of acupuncture-moxibustion treatment for premature ovarian failure were searched out from CNKI, VIP, Wanfang, CBM, PubMed, Cochrane Library, and Embase databases. The included RCTs were given quality evaluation by Cochrane bias risk assessment tool. Meta-analysis was carried out by RevMan 5. 3 software.
Results A total of 16 literature according with standard were included, involving 1 102 cases of patients. The Mata-analysis results showed that the overall response rate of acupuncture-moxibustion treatment for premature ovarian failure was superior to that of the western medicine group [OR = 4. 70, 95% CI (3. 34, 6. 61), P < 0. 000 01]. Compared with the western medicine group, the acupuncture-moxibustion alone decreased follicle stimulating hormone (FSH)level [MD =-3. 3, 95% CI (-5. 88, -0. 72), P = 0. 01], decreased luteinizing hormone (LH)level [MD =-5. 81, 95% CI (-7. 42, -4. 20), P < 0. 000 01], and elevated estradiol (E2)level [MD = 24. 15, 95% CI (12. 82, 35. 48), P < 0. 000 1], showing that the effect was superior to that of the western medicine group.
Conclusion Acupuncture-moxibustion alone treatment for premature ovarian failure is significantly effective for enhancing the response rate and improving hormone level, and has less adverse reactions. But due to the less sample size and lower quality of the included RCTs, the above results need to be verified by more large-scale and high-quality RCTs.

1.1.6. Yang 2017 (network meta-analysis) ☆

Yang Hui-sheng, Fang Yi-gong, Xu Huan-fang, Li Xiao-tong, Shang Jie, Yin Ya-qian. Systematic evaluation on the clinical efficacy of acupoint stimulation therapy for treatment of premature ovarian insufficiency on the basis of network Meta-analysis World Journal of Acupuncture-Moxibustion. 2017;27(3):26-39. [52294].

Objective To systematically evaluate the effectiveness and safety of acupoint stimulation therapy for treatment of premature ovarian insufficiency (POI).
Methods Computer retrieval was carried out in such databases as PubMed, Embase, Cochrane Library, web of science, Chinese biomedicine database (CBM), China National Knowledge Infrastructure (CNKI), WanFang and VlP in order to collect the randomized controlled trials (RCT) concerning acupoint stimulation therapy for treatment of POI. Software R 3. 40 and stata 14. 0 were used for Meta-analysis and network Meta-analysis, and RevMan 5. 3 was used for plotting the risk bias diagrams.
Results Forty three RCTs were included in total, involving 3046 POI patients and 18 acupoint stimulation therapies and comprehensive therapies. Metaanalysis showed: ① The curative effects of acupoint stimulation therapy (RR=1. 25, 95%CI [L07, 1. 45]), acupoint stimulation therapy+Chinese herbal medicine (RR=1. 25, 95%CI [1. 18, 1. 32]) and acupoint stimulation therapy+hormone replacement therapy (HRT) (RR=1. 20, 95%CI [1. 12, 1. 29]) were all superior to that of HRT, indicating that the differences were statistically significant (Z=2. 90, P=0. 04; Z=7. 56, P<0. 000 01; Z=4. 06, P<0. 000 01). ② Compared with HRT, the occurrence rate of adverse effect of acupoint stimulation therapy was lower, and the safety was superior to that of HRT (RR=0. 18, 95%CI [0. 08, 0. 41]), indicating that the differences were statistically significant (Z=4. 08, P<0. 000 1). Forty-two direct comparisons and 110 indirect comparisons were generated according to network Meta-analysis, among which, 38 comparisons were statistically significant. Network Metaanalysis results with HRT as control showed: the therapeutic measures ranking top 3 according to the curative effect sequence were catgut embedment in acupoint, moxibustion and warming-needle moxibustion, successively, and all the 3 measures were monotherapies without reflecting the advantages of comprehensive therapy. HRT ranked 17th among the 18 included therapeutic measures.
Conclusion On the basis of current evidences, acupoint stimulation therapy has a better clinical efficacy and safety for treatment of POI when compared with HRT. The acupoint stimulation therapies ranking the top 3 have more significant curative effects, but the long-term efficacy and the effect on the ovarian function still need to be further explored. In addition, the conclusion of this study still needs to be verified through a large number of RCTs with reasonable designs and appropriate methods.

1.1.7. Pang 2016 ☆

Pang Yong, Huang Yanyan. [Meta-analysis the effect of acupuncture in treating premature ovarian failure]. Clinical Journal of Traditional Chinese Medicine. 2016;1:108-112. [186968].

ObjectiveTo assess the therapeutic effect of acupuncture and moxibustion for premature ovarian failure (POF).
Methods Based on Cochrance system assessment methods, the search engine Pub Med, CNKI and databases (till Sept, 2015) including Wan Fang data and VIP database were used to retrieve. The randomized controlled trial of treating POF with the method of acupunture and moxibustion were inserted, the quality of adopted literature were evaluated one by one and valid data were extracted. Meta-analysis was conducted with the assistance of RevMan5. 2 software.
ResultsNine randomized controlled trials (RCTs) involving 719 patients in all with POF were on meta-analysis. Results of meta-analysis indicated: After treatment, there was statistical difference between acupuncture and Western medicine groups on effective rate (P<0. 01)The results of Follicle-stimulating Hormone (FSH) and estrogen (E2) after therapy were better in the acupuncture group than those in the Western medicine group, which had statistical significance (P<0. 05). Four of the 9 literatures referred to reported outcomes of Luteinizing-hormone (LH) and their differences had no statistical significance.
Conclusions During the treatment to POF, by observing clinically and analyzing the improvement of clinical efficacy and the level of serum hormone, the clinical efficacy of the method of acupuncture and moxibustion is better than that of the method of Western medicine. Since it’s difficult to achieve double-blind in the treatment of acupuncture and moxibustion and adopted literatures include some of low quality, so it remains to look forward to that high-quality experiments will provide high-quality evidence.

1.1.8. Jo 2015 ∅

  • Jo J, Lee YJ, Lee H. Effectiveness of Acupuncture for Primary Ovarian Insufficiency: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med. 2015;:842180. [144903]. doi
  • Junyoung Jo, Yoon Jae Lee, Jinmoo Lee, Hyangsook Lee. Effectiveness of Acupuncture for Primary Ovarian Insufficiency: A Systematic Review and Meta-analysis. Integrative Medicine Research. 2015;5(1) supp: 39. [204729]. doi
ObjectiveThis systematic review aimed to assess current evidence from randomized controlled trials (RCTs) on the effects of acupuncture for patients with primary ovarian insufficiency (POI).
MethodsWe searched twelve databases to identify relevant studies published before July 2014. The outcomes were serum follicle-stimulating hormone (FSH) levels and resumption of menstruation. Two reviewers independently assessed the risk of bias using the Cochrane's tool, extracted the results, and evaluated the overall level of the evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.
ResultsEight RCTs were selected. Acupuncture significantly lowered serum FSH levels and more women receiving acupuncture reported resumption of menses. However, the results should be interpreted with caution due to a small number of participants, high risk of bias for blinding, and likely publication bias. The level of evidence for FSH level and resumption of menses were assessed as “low” using GRADE.
ConclusionThe current evidence on acupuncture for POI is insufficient to draw a firm conclusion due to scarcity of studies with a low risk of bias and likely publication bias. Further rigorously designed and conducted studies are needed to confirm the effectiveness and safety of acupuncture in patients with POI.

1.2. Specific outcome

In vitro fertilization

1.2.1.1. Jang 2020

Jang S, Kim KH, Jun JH, You S. Acupuncture for in vitro fertilization in women with poor ovarian response: a systematic review. Integr Med Res. 2020;9(2). [208640]. doi

Background Poor ovarian response (POR) is one reason for infertility. In vitro fertilization (IVF) is frequently used to help achieve pregnancy, and performing acupuncture before IVF may promote ovulation and reduce egg retrieval pain. The purpose of this systematic review was to evaluate the effectiveness of acupuncture on clinical pregnancy rates (CPR) after IVF in women with POR.
MethodsEight electronic databases were searched in January 2020, and reference lists of retrieved articles and previous review articles were hand-searched. Randomized controlled trials (RCTs) using any type of acupuncture for women with POR undergoing IVF were considered. Risk of bias was assessed using the Cochrane risk of bias standards.
Results Three RCTs were included in this review. CPR and the number of retrieved oocytes were measured in two studies, while the values of anti-Mullerian hormone (AMH) and antral follicle count (AFC) were only reported in one study. In two studies, CPR was higher in the intervention group than the control group [37.8 % vs 24.3 %]. We did not conduct a meta-analysis, as there was a high level of heterogeneity in interventions among the included trials.
Conclusions This study suggests that acupuncture may improve CPR, AMH, AFC and the number of retrieved oocytes in women with POR undergoing IVF. However it is difficult to conclude that acupuncture is more effective than conventional treatment. Additionally, more clinical trials are needed to evaluate the effectiveness of acupuncture on CPR and other outcomes of POR.

1.2.2. Comparison of acupuncture techniques

1.2.2.1. Zhang 2020

Zhang J, Huang X, Liu Y, He Y, Yu H. A comparison of the effects of Chinese non-pharmaceutical therapies for premature ovarian failure: A PRISMA-compliant systematic review and network meta-analysis. Medicine (Baltimore). 2020;99(26). [211175]. doi

BackgroundPremature ovarian failure (POF) is commonly treated with hormone replacement therapy (HRT). Many patients with POF choose acupuncture as a complementary therapy over HRT, due to possible adverse reactions. This systematic review and network meta-analysis (NMA) compares the efficacy of different forms of acupuncture therapies for POF.
MethodsSeven databases including PubMed, the Cochrane Library, Embase, Wanfang database, China National Knowledge Infrastructure database, VIP Chinese Science, and Chinese Biomedical Database were searched for randomized controlled trials (RCTs) of various acupuncture treatments for POF. This time spanned from the date of database inception to January 13, 2020. RevMan 5.3 was used to assess the bias risk of the studies. A NMA of the included studies was performed using Stata14.0.
ResultsA total of 408 items were searched in this study, and finally this NMA included 16 RCTS, involving 1,307 patients. It showed that acupuncture (OR:1.35,95%1.24 to 1.47) has the best effectiveness among the four acupuncture (standardized mean difference [SMD]-16.30,95% -31.33 to -1.28) is the most effective and the best in reducing follicle-stimulating hormone levels among the four acupuncture treatments. Acupuncture (SMD 26.67,95%5.95 to 47.40) and acupoint embedding (SMD41.14,95%11.90 to 70.37) were ranked in the top 2 positions, in improving estradiol, whereas acupuncture (SMD-4.90,95% -8.10 to -1.70) was than acupoint embedding and HRT, in reducing luteinizing hormone level. In addition, our conclusions have not changed significantly after the sensitivity analysis.Protocol registration number: CRD42020150508.
ConclusionWith clinical evidence summarized by NMA, it is observed that acupuncture is the most promising therapy for improving menopausal symptoms, decreasing serum follicle-stimulating hormone and luteinizing hormone level. Therefore, acupuncture could be effective for patients with POF, who are intolerant to the adverse effects of hormone replacement therapy or who would prefer non-drug therapies. Further multi-center and high-quality RCT studies should be conducted to make our conclusion more rigorous.

2. Clinical Practice Guidelines

⊕ positive recommendation (regardless of the level of evidence reported)
Ø negative recommendation, (or lack of evidence)

2.1. Haute Autorité de Santé (HAS, France) 2021 Ø

  • Insuffisance Ovarienne Prématurée (IOP) : argumentaire. Saint-Denis La Plaine: Haute Autorité de Santé (HAS). 2021:104P. [216176]. URL
  • Insuffisance Ovarienne Prématurée (IOP) : Protocole National de Diagnostic et de Soins (PNDS) Saint-Denis La Plaine: Haute Autorité de Santé (HAS). 2021:48P. [211336]. URL
Une étude a suggéré que l'acupuncture pourrait, soulager l'anxiété, réduire le stress et améliorer les symptômes de la ménopause (57). Il n’y a pas d’étude randomisée à ce jour prouvant l’efficacité de cette technique.

2.2. European Society of Human Reproduction and Embryology (ESHRE) 2015 Ø

Management of women with premature ovarian insufficiency. European Society of Human Reproduction and Embryology. 2015:161p. [196761].

The other non-pharmacological therapies discussed in the review (homeopathy, vitamin E, magnetic devices and acupuncture) showed no significant benefit. In all studies, side effects were inconsistently reported (Rada, et al., 2010). Women should be informed that for most alternative and complementary treatments evidence on efficacy is limited and data on safety are lacking. Grades of recommendations: B.