Efficacy and safety of Ding-Kun-Dan for female infertility patients with predicted poor ovarian response undergoing in vitro fertilization/intracytoplasmic sperm injection: study protocol for a randomized controlled trial

Abstract

BackgroundWomen undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) who have a predicted poor ovarian response (POR) present a challenge for reproductive medicine specialists. Traditional Chinese medicine (TCM) is commonly used in China for such patients, in the belief that it will improve the ovarian response and ultimately increase pregnancy rates. However, there is a lack of high-quality evidence about the effect of TCM on improving ovarian response in such patients. The purpose of this study is to evaluate ongoing viable pregnancy rate at 12 weeks’ gestation and related indicators of ovarian response in fertile women who have a predicted poor ovarian response having immediate versus delayed IVF/ICSI after 3 months of Ding-Kun-Dan (DKD) pre-treatment.Methods/designThis study is a multicenter, randomized controlled, parallel-group, phase III, superiority clinical trial. Two hundred and seventy-eight eligible female infertility patients with POR will be included in the study and randomly allocated into an immediate treatment group and a DKD group in a 1:1 ratio. Both groups will receive IVF or ICSI as a standard treatment while in the DKD group, a commercially available Chinese medicine, DKD, will be administrated for 3 months before the IVF/ICSI cycle starts.The primary outcome of the study is the ongoing pregnancy rate at 12 weeks’ gestation. The secondary outcomes include total gonadotropin dosage, duration of stimulation, estradiol (E2) and progesterone (P) levels on human chorionic gonadotropin (hCG) trigger day, cycle cancellation rate, number of oocytes retrieved, high-quality embryo rate, biochemical pregnancy rate, the change of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and E2 levels and all side effects, safety outcomes, and any adverse events.The protocol was approved by the Ethics Committee of the First Teaching Hospital of Tianjin university of TCM (approval no. TYLL2017[K] 004).DiscussionIVF/ICSI is increasingly used to treat couples desiring a baby. Many of these women will have poor ovarian function. In China, DKD is commonly used for these patients prior to undergoing IVF/ICSI. There is no effective treatment for poor ovarian response in Western medicine currently. It is important, therefore, to undertake this randomized control trial to determine whether DKD is effective or not.Trial registrationChinese Clinical Trial Registry, ID: ChiCTR-IOR-17011697. Registered on 19 June 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2511-0) contains supplementary material, which is available to authorized users.

Systematic characterization of the chemical constituents in vitro and prototypes in vivo of Dingkun Dan using ultra‐high‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry combined with the UNIFI™ software

“…Dingkun Dan (DKD), an over-the-counter drug in China, was one of the first-class confidential and reputable TCM formulas listed by the state council in 1957. It is used to promote blood circulation, regulate menstruation, and relieve fatigue and the symptoms of depression (Ma et al, 2018;Ren, Gou, Wei, Gou, & Guo, 2000). It is a large honey pill that consists of 30 flavors of Chinese medicinal materials, including the monarch drugs Ginseng Radix et Rhizoma Rubra (GRERR) and Rehmanniae Radix Praeparata and the minister drugs Croci Stigma and Angelicae Sinensis Radix (ASR) (Chinese Pharmacopoeia Commission, 2015).…”

“…It is a large honey pill that consists of 30 flavors of Chinese medicinal materials, including the monarch drugs Ginseng Radix et Rhizoma Rubra (GRERR) and Rehmanniae Radix Praeparata and the minister drugs Croci Stigma and Angelicae Sinensis Radix (ASR) (Chinese Pharmacopoeia Commission, 2015). In recent years, many studies have investigated its clinical application (Deng et al, 2019;Ma et al, 2018). Previously, a total of 121 components and isomers were tentatively characterized using liquid chromatography Q Exactive accurate mass spectrometry (UHPLC-QE-MS) with automated MetaboLynx analysis (Gao et al, 2019).…”

The ameliorating effects of Bushen Tiaoxue Granules and Kunling Wan on impaired angiogenesis and endometrial receptivity in rats following controlled ovarian hyperstimulation

“…For example, treatment with low-dose aspirin may reduce uterine vascular resistance and elevate local thromboxane production of prostacyclin, thereby improving uterine blood flow. 28,29 Some traditional Chinese medicines have been reported to increase EBF, up-regulate the expression of endometrial receptivity molecules, and improve the pregnancy outcome of ART in animal models. For the most intractable cases, stem cell therapy seems to be a promising strategy; however, more study is required to assess the safety, effectiveness, and cost of this approach.…”

“…27 Compared with western medicine, traditional Chinese medicine has become widely used in ART. 28,29 Some traditional Chinese medicines have been reported to increase EBF, up-regulate the expression of endometrial receptivity molecules, and improve the pregnancy outcome of ART in animal models. [30][31][32] Bushen Tiaoxue Granules and KW are Chinese herbal formulas, which are widely used for treatment of infertility in China.…”

Dehydroepiandrosterone Ameliorates Abnormal Mitochondrial Dynamics and Mitophagy of Cumulus Cells in Poor Ovarian Responders

“…Several strategies, including a variety of COS protocols and various adjuvant supplements, have been proposed to improve the reproductive outcomes in PORs [ 8 , 9 , 10 ]. While some adjuvants show more promise than others do, to date, none have significantly improved pregnancy rates [ 11 , 12 ].…”