Efficacy and safety of Zi Gui Nv Zhen^® capsules used in TCM for fertility preservation in patients with diminished ovarian reserve

Abstract

Objective

To evaluate for the first time whether Zi Gui Nv Zhen^® capsules (ZGNZC), until now used in traditional Chinese medicine (TCM) for menopausal complaints, can increase the fertility of Chinese women with diminished ovarian reserve (DOR).

Methods

Prospective, randomized, open-labeled 3-monthly study; 109 DOR patients (aged 20–40 years) receiving either ZGNZC (experimental group, n = 75) or not (control group, n = 34). Main outcomes: markers for ovarian function, thickness/type of the endometrium during ovulation, and pregnancy rate. Between-group analysis (A) comparing experimental vs. control group and within-group analysis (B) comparing data at baseline and after study in each of both groups.

Results

(A) Between-group-analysis: patients with ZGNZC had a higher endometrium thickness (0.75 vs. 0.62; p<.05) and higher anti-Müllerian hormone (AMH, 0.50 vs. 0.40; p<.05) than control group. Pregnancy rates were higher in the experimental than the control group (26.7% vs. 14.7%; n.s.). (B) Within-group-analysis: ZGNZC decreased levels of follicle-stimulating hormone (FSH, 11.42 vs. 8.69), increased estradiol-levels (E₂, 56.09 vs. 73.36), and type A endometrium rates (5.3% vs. 39.7%) (all p< .05) and increased antral follicle count (AFC, 2 vs. 3). All hepato-renal biomarkers remained within the norm. The tolerability was good. There were no adverse events.

Conclusions

In women with DOR who wish to conceive, three months' application of ZGNZC can improve ovarian function and oocyte quality by adjusting the neuroendocrine system, can improve endometrial properties and proliferation, necessary for a healthy pregnancy, and increased the clinical pregnancy rate in our prospective randomized observational study.

中药资癸女贞^®胶囊用于卵巢功能减退患者生育保护的疗效和安全性 摘要

目的：首次评价中药治疗绝经症状的资癸女贞^®胶囊（ZGNZC）是否能提高卵巢功能减退（DOR）女性的生育能力。

方法：进行3个月前瞻性、随机、开放标记研究；纳入109名DOR患者（年龄20-40岁）服用ZGNZC（实验组, n = 75）或不服用ZGNZC（对照组, n = 34）。主要结果：卵巢功能、排卵期子宫内膜厚度/类型和妊娠率的指标。组间分析（A）比较实验组和对照组, 组内分析（B）比较两组在基线检查时和研究后的数据。

结果：（A）组间分析：与对照组相比, ZGNZC患者的子宫内膜更厚（0.75比0.62；p < 0.05）, 抗缪勒管激素水平更高（AMH, 0.50比0.40；p < 0.05）。实验组的妊娠率高于对照组（26.7%对14.7%）。（B）组内分析：ZGNZC降低卵泡刺激素水平（FSH, 11.42对8.69）, 增加雌二醇水平（E2, 56.09对73.36）、A型子宫内膜率（5.3%对39.7%）（p < 0.05）, 增加窦卵泡数（AFC, 2比3）。所有肝肾功能指标均在正常范围内。耐受性良好。无不良事件发生。

结论：对于有生育意愿的DOR女性, 服用ZGNZC三个月可通过调节神经内分泌系统改善卵巢功能和卵母细胞质量, 改善子宫内膜特性和增殖, 这是健康妊娠所必需的, 并在前瞻性随机观察研究中提高了临床妊娠率。

Keywords:

• Zi Gui Nv Zhen^® capsule
• diminished ovarian reserve
• fertility preservation
• ovarian function
• clinical pregnancy

Acknowledgements

The authors especially thank Prof. Xingming Li of Capital Medical University (Beijing, China) for his assistance in the data's statistical analysis.

Disclosure statement

All authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by Association for Maternal and Child Health Studies [No. 2018AMCHS011] and Beijing Municipal Administration of Hospitals’ Ascent Plan [No. DFL20181401].