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JKM > Volume 43(1); 2022 > Article
Lee, Choi, Noh, Min, and Kim: East Asian Herbal Medicine (EAHM) Alone for the Treatment of Women with Diminished Ovarian Reserve (DOR): A Systematic Review and Meta-analysis

Abstract

Objectives

The aim of this study was to find out whether east asian herbal medicine (EAHM) treatment alone is effective in improving pregnancy-related indicators compared to conventional medicine in women with Diminished Ovarian Reserve (DOR).

Methods

We searched eligible studies from PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure Database, CiNii, Korean Medical Database, Korean Studies Information Service System, Oriental Medicine Advanced Searching Integrated System, ScienceOn. GRADE pro was used to evaluate the current evidence of the study.

Result

A total of 5 studies, 325 women with DOR were included. EAHM showed a significant effect on improvement of pregnancy rate (n=270, RR 2.13 [95% CI 1.44 to 3.15], Z=3.78, p=0.0002, I2=0%) and Anti-Mullerian Hormone (AMH) level (n=211, SMD 0.82 [95% CI 0.40 to 1.25], Z=3.80, p=0.0001) compared to conventional medicine. In ovulation rate (n=156, RR 0.86 [95% CI 0.70 to 1.06], Z=1.43, p=0.15, I2=0%), Antral Follicle Count (n=245, SMD 0.27 [95% CI −0.25 to 0.79], Z=1.01, p=0.31), and follicle stimulating hormone (n=245, SMD 0.29 [95% CI −0.13 to 0.70], Z=1.36, p=0.17) level, EAHM showed similar effects to conventional medicine. In this study, the most frequently used herbal medicines were Cuscutae Semen, Dipsaci Radix, and Angelicae Gigantis Radix.

Conclusion

This meta-analysis showed that EAHM could improve pregnancy rates and AMH levels in women with DOR. However, more well-designed RCTs will have to be performed further in the future.

Fig. 1
The PRISMA Flow Diagram of Study Selection
jkm-43-1-136f1.gif
Fig. 2
Summary of Risk of Bias in All Included Studies
jkm-43-1-136f2.gif
Fig. 3
Forest Plot of Pregnancy Rate
jkm-43-1-136f3.gif
Fig. 4
Forest Plot of Secondary Outcome (a) Ovulation Rate (b) Anti-Mullerian Hormone (c) Antral Follicle Count (d) Follicle Stimulating Hormone (e) Ovarian Volume
jkm-43-1-136f4.gif
Table 1
Summary of the Studies Included
Included study
Study year
Country
Types of infertility Trial design Number of participants; Age(mean+SD, years) Interventions Course of treatment; Follow up period Outcome measures Intergroup differences
Trial Control Trial Control
Wang 201211)
China
DOR RCT 17
37.53, 35–42y
17
38.00, 35–42y
Xianziyizhen No1 3 capsules, No2 4 capsules tid DHEA 25mg tid 3 menstrual cycle period
3months
  1. Pregnancy rate

  2. AMH

  3. AFC

  4. FSH

  1. p>0.05

  2. NR

  3. p>0.05

  4. p>0.05

Guan 201612)
China
DOR RCT 30
24–49y
25
24–49y
kidney and liver blood chinese traditional medicine oral granule bid estradiol valerate (Climen) qd 3 menstrual cycle period
NR
  1. AMH

  2. AFC

  3. FSH

  4. ovarian volume

  1. p<0.05

  2. p<0.05

  3. p>0.05

  4. p>0.05

Wang 202013)
China
DOR RCT 30
20–40y
26
20–40y
Bushen Culuan Formula Decoction 250ml qd estradiol valerate (Climen), Clomiphene qd 3 menstrual cycle period
3months
  1. Pregnancy rate

  2. Ovulation rate

  3. AMH

  4. AFC

  5. FSH

  1. p>0.05

  2. p>0.05

  3. p>0.05

  4. p<0.05

  5. p<0.05

Duan 202114)
China
DOR RCT 40
33.4, 21–39y
40
32.8, 20–39y
Zhuyun Tang Granule, Guchong Tang Granule qd estradiol valerate qd, Dydrogesterone bid 3 menstrual cycle period
1year
  1. Pregnancy rate

  2. AMH

  3. AFC

  4. FSH

  1. NR

  2. p<0.001

  3. p<0.001

  4. p<0.001

Ma 202115) China DOR RCT 50
34.18±3.91
50
33.50±4.16
Bushen Huoxue Culuan Formula Decoction 200ml bid estradiol valerate (Climen), Clomiphene bid 3 menstrual cycle period
2years
  1. Pregnancy rate

  2. Ovulation rate

  3. AMH

  4. AFC

  5. FSH

  1. p<0.05

  2. p<0.05

  3. p<0.05

  4. p>0.05

  5. p<0.05

DOR: Diminished Ovarian Reserve ; RCT: Randomized Clinical Trial ; DHEA: Dehydroepiandrosterone ; AMH: Anti-Mullerian Hormone ; AFC: Antral Follicle Count : FSH: Follicle Stimulating Hormone ; NR: Non Reported

Table 2
Summary of Finding
Intervention and comparator intervention Outcomes Participants (n) (studies) Relative effect (95% CI) Anticipated absolute effects: Risk difference with EAHM Heterogeneity (I2, p) Quality of the evidence
EAHM alone vs Conventional medicine Pregnancy rate 270 (4 RCTs) RR 2.13 [1.44, 3.15] 221 more per 1,000 (from 86 more to 420 more) I2=0%, p=0.84 ⊕⊕⊕⊕
High
Pregnancy success rate 100 (1 RCT) RR 6.25 [2.35, 16.65] 420 more per 1,000 (from 108 more to 1000 more) - ⊕○○○
Very low
Ovulation rate 156 (2 RCTs) RR 0.86 [0.70, 1.06] 105 fewer per 1,000 (from 225 fewer to 45 more) I2=0%, p=0.54 ⊕⊕⊕⊕
High
AMH 211 (3 RCTs) - SMD 0.82 higher (0.4 higher to 1.25 higher) I2=53%, p=0.12 ⊕○○○
Very low
AFC 245 (4 RCTs) - SMD 0.27 higher (0.25 lower to 0.79 higher) I2=74%, p=0.008 ⊕○○○
Very low
FSH 245 (4 RCTs) - SMD 0.3 higher (0.12 lower to 0.71 higher) I2=60%, p=0.06 ⊕○○○
Very low
Ovarian volume 55 (1 RCT) - SMD 0.48 lower (1.02 lower to 0.06 higher) - ⊕⊕○○
Low

EAHM: East Asian Herbal Medicine, AMH: Anti-Mullerian Hormone, AFC: Antral Follicle Count, FSH: Follicle Stimulating Hormone, CI: confidence interval; RR: risk ratio; SMD: standardized mean difference

Table 3
Ingredients of EAHM used in clinical trials
References EAHM prescription name Ingredients of herb prescription (Latin name) Ingredients of EAHM prescription (scientific name) Types of preparation
Wang 201211) Xianziyizhen No.1 Morindae Radix, Epimedii Herba, Angelicae Gigantis Radix, Lycii Fructus, Dipsaci Radix, Astragali Radix Morinda officinalis How, Epimedium koreanum Nakai, Angelica gigas Nakai, Lycium chinense Miller, Dipsacus asperoides C. Y. Cheng et T. M. Ai, Astragalus membranaceus Bunge Capsule
Xianziyizhen No.2 Rehmanniae Radix Preparata, Ligustri Fructus, Ecliptae Herba, Dipsaci Radix, Cuscutae Semen, Epimedii Herba, Rehmannia glutinosa Liboschitz ex Steudel,, Ligustrum japonicum Thunb., Eclipta prostrata Linné, Dipsacus asperoides C. Y. Cheng et T. M. Ai, Cuscuta chinensis Lamark, Epimedium koreanum Nakai Capsule
Guan 201612) Bushen Shugan Yangxue Recipe Cuscutae Semen, Rehmanniae Radix Preparata, Uncariae Ramulus cum Uncus, Curcumae Radix, Dipsaci Radix, Cyperi Rhizoma, Angelicae Gigantis Radix, -, Spatholobi Caulis, Salviae Miltiorrhizae Radix, Rosae Rugosae Flos, Hordei Fructus Germinatus Cuscuta chinensis Lamark, Rehmannia glutinosa Liboschitz ex Steudel, Uncaria sinensis Havil, Curcuma longa Linné, Dipsacus asperoides C. Y. Cheng et T. M. Ai, Cyperus rotundus Linné, Angelica gigas Nakai, Rhodiola rosea L., Spatholobus suberectus Dunn, Salvia miltiorrhiza Bunge, Rosa rugosa Thunberg, Hordeum vulgare Linné var. hexastichon Aschers Granule
Wang 202013) Bushen Culuan Formula Cuscutae Semen, Ligustri Fructus, Lycii Fructus, Loranthi Ramulus Et Folium, Dipsaci Radix, Achyranthis Radix, Angelicae Gigantis Radix, Paeoniae Radix, Lycopi Herba, Typhae Pollen, Salviae Miltiorrhizae Radix, Cyperi Rhizoma, Cuscuta chinensis Lamark, Ligustrum japonicum Thunb., Lycium chinense Miller, Loranthus parasticus Merr., Dipsacus asperoides C. Y. Cheng et T. M. Ai, Achyranthes japonica Nakai, Angelica gigas Nakai, Paeonia lactiflora Pallas, Lycopus lucidus Turczaininov, Typha orientalis Presl, Salvia miltiorrhiza Bunge, Cyperus rotundus Linné Decoction
Duan 202114) Zhuyun Tang Cuscutae Semen, Lycii Fructus, Rubi Fructus, Morindae Radix, Epimedii Herba, Cervi Parvum Cornu, Dipsaci Radix, Eucommiae Cortex, Mori Fructus, Polygoni Multiflori Radix, Fluoritum, Araliae Continentalis Radix Cuscuta chinensis Lamark, Lycium chinense Miller, Rubus coreanus Miquel, Morinda officinalis How, Epimedium koreanum Nakai, Cervus canadensis, Dipsacus asperoides C. Y. Cheng et T. M. Ai, Eucommia ulmoides Oliver, Morus alba Linné, Polygonum multiflorum Thunberg, -, Aralia continentalis Kitagawa Granule
Guchong Tang Cuscutae Semen, Lycii Fructus, Rubi Fructus, Morindae Radix, Epimedii Herba, Cervi Parvum Cornu, Dipsaci Radix, Eucommiae Cortex, Ecliptae Herba, Ligustri Fructus, Dioscoreae Rhizoma, Cuscuta chinensis Lamark, Lycium chinense Miller, Rubus coreanus Miquel, Morinda officinalis How, Epimedium koreanum Nakai, Cervus canadensis, Dipsacus asperoides C. Y. Cheng et T. M. Ai, Eucommia ulmoides Oliver, Eclipta prostrata Linné, Ligustrum japonicum Thunb., Dioscorea batatas Decaisne Granule
Ma 202115) Bushen Huoxue Culuan Formula Ligustri Fructus, Cuscutae Semen, Epimedii Herba, Morindae Radix, Salviae Miltiorrhizae Radix, Angelicae Gigantis Radix, Cnidii Rhizoma, Paeoniae Radix, Lycopi Herba, Typhae Pollen, Ligustrum japonicum Thunb., Cuscuta chinensis Lamark, Epimedium koreanum Nakai, Morinda officinalis How, Salvia miltiorrhiza Bunge, Angelica gigas Nakai, Cnidium officinale Makino, Paeonia lactiflora Pallas, Lycopus lucidus Turczaininov, Typha orientalis Presl Decoction

EAHM : east asian herbal medicine; NR: not reported

Table 4
Frequency of Use of Herbs
Herb name (Latin) Frequency Amount (g)
Cuscutae Semen 4.5 12–30
Dipsaci Radix 4 10–12
Angelicae Gigantis Radix 3.5 10–15
Salviae Miltiorrhizae Radix 3 12–30
Epimedii Herba 3 10
Ligustri Fructus 3 10–20
Lycii Fructus 2.5 12–20
Morindae Radix 2.5 10–12
Cyperi Rhizoma 2 10
Lycopi Herba 2 15
Paeoniae Radix 2 15
Typhae Pollen 2 15
Rehmanniae Radix Preparata 1.5 15

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