Effects of Zishen Yutai Pills on <italic style="font-style: italic">in vitro</italic> Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study

LI Xiu-fang; WANG Zhong-qing; XU Hai-yan; LIU Hong; SHENG Yan; XU Jin; LI Yuan-mei; LIAN Fang

doi:10.1007/s11655-023-3546-y

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Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study

Original Article | Updated：2023-04-05

- Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study
- Chinese Journal of Integrative Medicine Vol. 29, Issue 4, Pages: 291-298(2023)
- Affiliations：
  
  1.The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan (250014), China
  2.Center for Reproductive Medicine, Shandong University, Jinan (250021), China
  3.Medical College of Optometry and Ophthalmology, Shandong University of Traditional Chinese Medicine, Jinan(250014), China
  4.Department of Traditional Chinese Medicine, Jinan Golden Time Health Nursing Hospital, Jinan (250000), China
  5.Reproductive and Genetic Center of Integrated Traditional and Western Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan (250011), China
- Author bio：
  
  Prof. LIAN Fang, E-mail: fang_lian123@163.com
- Funds：
- DOI：10.1007/s11655-023-3546-y
  CLC：
- Published：2023-04，
  
  Published Online：21 February 2023，
  
  Accepted：06 December 2022
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LI Xiu-fang, WANG Zhong-qing, XU Hai-yan, et al. Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study. [J]. Chinese Journal of Integrative Medicine 29(4):291-298(2023)
DOI：

LI Xiu-fang, WANG Zhong-qing, XU Hai-yan, et al. Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study. [J]. Chinese Journal of Integrative Medicine 29(4):291-298(2023) DOI： 10.1007/s11655-023-3546-y.

摘要

目的:

探讨滋肾育胎丸对体外受精-胚胎移植(IVF-ET)周期中卵巢储备功能减退(DOR)患者卵母细胞和胚胎质量及妊娠结局的影响

同时观察滋肾育胎丸对骨形态发生蛋白15(BMP15) 和生长分化因子9(GDF9)表达水平的影响.

方法:

将120例DOR患者随机分为治疗组和对照组

以1: 1比例进入其中一组. 两组患者均采用GnRH拮抗剂方案

治疗组(60例)在前一个月经周期黄体中期开始服用滋肾育胎丸

对照组(60例)未服药. 主要观察指标为获卵数和优质胚胎数. 次要观察指标包括其他胚胎指标及妊娠结局指标. 通过异位妊娠、妊娠并发症、流产率及早产评估不良事件发生情况. 采用ELISA法测定卵泡液中BMP15和GDF9表达量.

结果:

与对照组比较

治疗组患者获卵数和优质胚胎数明显增加(均

0.05)

滋肾阴胎丸治疗后可上调血清E2及P水平(

值分别为0.014和0.008) . 两组胚胎种植率、生化妊娠率、临床妊娠率、活产率和流产率未见明显差异 (均

0.05) . 滋肾阴胎丸的使用未增加不良事件的发生率. 治疗组卵泡液中BMP15和GDF9表达水平均明显上调 (均

0.05) .

结论:

在IVF治疗周期中应用滋肾育胎丸可以提高DOR患者获卵数和优质胚胎数

上调卵泡液中BMP15和GDF9表达. 然而

滋肾育胎丸对妊娠结局的影响则需要更大样本量的临床试验中进一步研究. 本试验在中国临床试验注册中心注册 (ChiCTR2100048441).

Abstract

Objective:

To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos

as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving

in vitro

fertilization-embryo transfer (IVF-ET). The possible mechanisms

involving the regulation of bone morphogenetic protein 15(BMP15) and growth differentiation factor 9 (GDF9)

were also investigated.

Methods:

A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1: 1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy

pregnancy complications

pregnancy loss

and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay.

Results:

Compared with the control group

the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both

0.05). After treatment with ZYPs

a significant regulation of serum sex hormones was observed

including progesterone and estradiol. Both hormones were up-regulated compared with the control group (

=0.014 and 0.008)

respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates

biochemical pregnancy rates

clinical pregnancy rates

live birth rates

and pregnancy loss rates (all

0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both

0.05).

Conclusions:

ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET

resulting in increments of oocytes and embryos

and up-regulation of BMP15 and GDF9 expressions in the FF. However

the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).

关键词

Keywords

Zishen Yutai Pillsdiminished ovarian reservein vitro fertilization-embryo transferoocytesembryos

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Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences

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First College of Clinical Medicine, Guangzhou University of Traditional Chinese Medicine

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Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study

DOI：10.1007/s11655-023-3546-y

摘要

Abstract

关键词

Keywords

references