In vitro fertilization and embryo transfer (IVF-ET) remains the primary treatment approach for infertility, but with poor success rates despite advancements in ovulation induction and laboratory techniques (Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of EmbryologyESHRE Special Interest Group Embryology, 2011a; Lundin et al., 2023). Embryo quality has been identified as the most critical determinant of IVF outcomes. High-quality embryos can significantly improve the pregnancy and live birth rates (Günther et al., 2022; Sun et al., 2020; Wei et al., 2020; Zou et al., 2023), while poor-quality embryos increase the risk of implantation failure, miscarriage (Xia et al., 2020), and ectopic pregnancy (Anzhel et al., 2022). This holds true even in natural cycle IVF, where embryo quality remains paramount for successful implantation (Tomic et al., 2020). Poor embryo quality remains a major challenge in the assisted reproductive technology (ART), significantly affecting the rate of implantation and live birth. Multiple factors compromise embryo development, such as chromosomal abnormalities associated with advanced maternal age, cellular damage induced by oxidative stress, mitochondrial dysfunction, and impaired cytoplasmic maturation. Additional contributing factors include suboptimal culture conditions, including, but not limited to, deviations in the pH value, suboptimal oxygen tension, and nutrient imbalances, as well as epigenetic alterations arising from hormonal imbalances or exposure to environmental toxins. Moreover, high levels of sperm DNA fragmentation and oocyte spindle defects may further impair fertilization and early embryogenesis.

Given the multifactorial nature of poor embryo quality, comprehensive interventions targeting multiple pathological pathways - including antioxidant, anti-inflammatory, and mitochondrial-supportive strategies - are crucial for high-risk patients. While current approaches predominantly focus on extrinsic interventions such as advanced embryo selection (via time-lapse imaging and AI algorithms) and laboratory optimization (culture media composition and oxygen concentration control) (Rienzi et al., 2011; Hill et al., 1989; Cimadomo et al., 2023; Busnelli et al., 2021), intrinsic factors - particularly genetic abnormalities, mitochondrial dysfunction, and oxidative stress - continue to present major obstacles to optimal embryo development. The development of adjuvant therapies to enhance embryo quality has therefore become a research priority. DACHAO, a commercially available maternal and preconception nutritional supplement with over 3 years of market presence, is formulated from clove ethanol extract, Sophora flower buds, and yam in the ratio of 15:6:10. Researchers have demonstrated its therapeutic potential—in aged mouse models, with the formulation having restored ovarian function through multiple mechanisms including oxidative stress mitigation, anti-inflammatory effects, mitochondrial membrane potential improvement, and serum estradiol elevation (Liu et al., 2022). Its anti-apoptotic properties were evidenced by downregulation of cleaved caspase-3 and PARP, while reduced pro-inflammatory chemokine levels confirmed anti-inflammatory efficacy (Liu et al., 2022). These multi-target mechanisms suggest DACHAO’s promise as a novel intervention for improving human reproductive outcomes.

Our interest in this product stems not only from its robust preclinical efficacy but also from its favorable safety profile as a naturally derived, food-grade botanical extract. Moreover, its oral administration route facilitates prospective clinical research. We therefore conducted a prospective clinical study to evaluate whether DACHAO could improve outcomes in women with prior IVF/ICSI (intracytoplasmic sperm injection) failure and poor embryo quality.

This prospective, self-controlled clinical study investigated the potential of a novel intervention to address poor embryo quality—a significant challenge in the management of female infertility—among IVF-ET patients with a documented history of suboptimal embryological outcomes. Oral supplementation with DACHAO Reco18 for 6 weeks prior to a subsequent treatment cycle was associated with improvements across multiple intermediate endpoints. These included the number of oocytes retrieved, fertilization rates, embryo quality and yield, as well as rates of biochemical pregnancy, clinical pregnancy, and embryo implantation.

Poor embryo quality represents a critical challenge in assisted reproductive technology and typically results from a combination of intrinsic and extrinsic factors. These include advanced maternal age, oxidative stress, mitochondrial dysfunction, and suboptimal follicular microenvironment. Age-related meiotic incompetence in oocytes often leads to chromosomal abnormalities that significantly impair blastocyst formation. Furthermore, excessive reactive oxygen species (ROS) not only disrupt oocyte maturation and early embryonic development, but the accompanying decline in ovarian reserve also exacerbates gonadotropin resistance, further compromising embryo viability.

Clinically, several methods have been used to better embryo quality. Growth hormone supplementation has been shown to improve the embryo quality in poor responders (Yovich and Stanger, 2010; Tesari et al., 2005), primarily through promoting follicular development and oocyte quality. This effect may be mediated by increased FSH/LH receptor expression in granulosa cells (Yovich and Stanger, 2010; Yovich et al., 2019). Importantly, our study demonstrated that DACHAO Reco18 lowered the basal FSH levels while increasing the embryo yield, suggesting similar modes of action. Additionally, antioxidants such as melatonin and coenzyme Q10 have been shown to improve oocyte yield and high-quality embryo rates while reducing gonadotropin dosage requirements (Shang et al., 2024; Yong et al., 2021). In previous studies, CoQ10 pretreatment improved ovarian response to stimulation and embryological parameters in young women with poor ovarian reserve, while in women over 35 years it also improved oxidative metabolism in follicular fluid and oocyte quality (Xu et al., 2018; Giannubilo et al., 2018). It was confirmed that exogenous melatonin, which scavenges ROS via the Sirt1/SOD2 pathway, improved oocyte quality and suppressed aneuploidy both in vitro and in vivo (Zhang et al., 2020). Given its rich content of antioxidant compounds including quercetin, DACHAO Reco18 may confer benefits through comparable antioxidant mechanisms. Thus, DACHAO Reco18 may improve both oocyte yield and embryonic developmental potential/quality in women undergoing assisted reproductive technology cycles by simultaneously reducing ovarian hyper-responsiveness and oxidative stress levels. Dehydroepiandrosterone (DHEA) is a steroid secreted from ovarian theca cells that induce testosterone and estradiol biosynthesis (Burger, 2002), which could enhance gonadotropin responsiveness (Dewailly et al., 2016). A meta-analysis including 1,336 DHEA pretreatment cycles demonstrated that adding DHEA could increase ovarian response in women with DOR but cannot improve clinical pregnancy and live birth rates (Conforti et al., 2025). Myo-Inositol (myo-ins) is an insulin-sensitizing natural molecule that facilitates cellular glucose uptake. Recent studies have demonstrated a positive correlation between elevated levels of myo-Ins in human follicular fluid and satisfactory oocyte quality (Dinicola et al., 2021). A meta-analysis including 935 women with myo-Ins pretreatment concluded that the use of myo-Ins significantly improved the clinical pregnancy rate (p = 0.03), with a significantly reduced abortion rate (p = 0.0006) and a significant increase in the number of grade I embryos (p = 0.02). At the same time, the FSH dosage of participants with myo-Ins was significantly less (p = 0.004) (Zheng et al., 2017).

As we all know, the complete follicular physiology from the primordial to the preovulatory stage spans approximately 90 days. In many studies, the duration of adjuvant treatment lasted for 3 months (Zhang et al., 2014; Kara et al., 2014). To the best of our knowledge, there were few studies designed to explore the duration of adjuvant treatment resulting in differences on IVF outcome (Giannubilo et al., 2018; Feng et al., 2023). A recent meta-analysis hypothesized that there might be a dose- and time-dependent relationship between different GH protocols and IVF outcomes (Shang et al., 2022). According to the high time cost, the pretreatment durations of adjuvant supplements (e.g., CoQ10, DHEA) ranged from 1 to 3 months in many studies (Xu et al., 2018; Conforti et al., 2025; Aragona et al., 2025). A shorter, targeted intervention period (6 weeks) improves patient adherence and facilitates more efficient participant recruitment.

In animal studies, DACHAO was found to improve the fertility in aged mice via several mechanisms, both by in vitro fertilization and natural mating (Liu et al., 2022). DACHAO improves oocyte quality in aged female mice both qualitatively and quantitatively. In addition, DACHAO administration in aged female mice improved the quality of embryos and increased the growth rate of their offspring. The mechanisms were as follow: Firstly, DACHAO administration promoted the proliferation of the granulosa cells around the follicles and reduced the level of apoptosis in the ovaries. Furthermore, DACHAO administration improved the hormone level and increased the expressions of antioxidant factors in aged female mice. Additionally, the mRNA expression levels of ovarian inflammation-related factors in the mice with DACHAO administration were downregulated (Liu et al., 2022).

As a content of the DACHAO, eugenol was shown to improve tissue damage and oxidative stress after ovarian torsion in adult female rats (Barghi et al., 2021). A previous study demonstrated that clove extract enhanced blastocyst development in frozen mouse oocytes derived from in vitro-fertilized embryos (Bahmanpour et al., 2018). Moreover, several in vitro studies on animal and human granulosa cells showed that quercetin treatment reduced the proportion of early apoptotic cells, improved oocyte quality, and promoted subsequent embryo development (Wang et al., 2017; Rashidi et al., 2019; Silva et al., 2018). Furthermore, in vitro maturation of oocytes from humans and aged mice, quercetin subsequently improves the quality of oocytes, promoting both oocyte maturation and early embryonic development in humans and aged mice oocytes (Cao et al., 2020). A novel protein, DOI, isolated from Chinese yam was reported to stimulate estradiol biosynthesis in rat ovarian granulosa cells, with a potential to treat menopausal syndrome (Wong et al., 2015).

We observed a statistically significant reduction in FSH levels. Importantly, this effect was not accompanied by changes in AMH or E₂, suggesting a targeted modulation of the pituitary-ovarian axis rather than direct ovarian stimulation. This subgroup represents a clear and mechanistically supported target population, as lowering FSH in hypergonadotropic women may improve follicular sensitivity and oocyte quality.

This prospective, self-controlled study provides preliminary clinical evidence suggesting that oral supplementation with DACHAO Reco18 may be associated with improved embryological parameters and early pregnancy outcomes in a selected cohort of IVF patients with a documented history of poor embryonic development. Compared to their own previous untreated cycles, participants undergoing the intervention demonstrated notable improvements in key intermediate endpoints, including oocyte yield, fertilization efficiency, and notably, the number and proportion of high-quality embryos. An increase in clinical pregnancy rates was also observed following treatment. The observed associations, though statistically significant, do not establish causality, as potential confounding from inter-cycle variability cannot be entirely ruled out. Nonetheless, the consistent pattern of improvement across multiple developmental stages lends biological plausibility to the notion that the multi-component botanical formulation in DACHAO Reco18 could positively influence the follicular and embryonic microenvironment. This provides a rational basis for future investigation. The primary clinical implication of this pilot study is to justify and inform the design of a larger, randomized, placebo-controlled trial.

Several study limitations should be acknowledged. The relatively small sample size may limit the generalizability of findings, and the limited number of embryo transfer procedures reduced the statistical power of pregnancy outcomes analysis. While significant improvements were observed in implantation and clinical pregnancy rates, this study was not specifically powered for these clinical endpoints due to the sample size. The pregnancy outcomes should therefore be interpreted as promising preliminary signals that require confirmation in larger, adequately powered trials. In addition, the pre-post, self-controlled study design, though appropriate for a preliminary investigation in this refractory population, inherently limits the ability to attribute outcomes solely to the intervention due to potential inter-cycle variability and the absence of a parallel control group. Moreover, enrollment of Chinese patient, no randomization, and no involvement of multiple centers may also produce some publication bias to affect the outcomes and generalization of the study. Future randomized, double-blind, placebo-controlled trial (RCT) with involvement of a larger cohort of patients and multiple centers will be necessary to conclusively establish the clinical value of DACHAO Reco18 supplementation for IVF patients with poor embryo quality.

In conclusion, this prospective self-controlled study indicates that a six-week intervention with DACHAO Reco18 was associated with significant improvements in ovarian response and embryological parameters among IVF patients with a history of poor embryo quality. A reduction in FSH levels was also observed in the hyper-gonadotropic subgroup. While these findings are encouraging, the self-controlled design precludes definitive causal inferences and cannot fully account for inter-cycle variability. Therefore, the results should be interpreted as preliminary evidence supporting the need for further research. Future randomized, placebo-controlled trials are warranted to rigorously evaluate the efficacy and potential role of this botanical formulation as an adjuvant treatment for ART patients with poor embryo quality and compromised pregnancy prognosis.