Traditional Chinese Medicine Interventions For Fertility Preservation in Diseases Associated With Ovarian Function Decline During The In Vitro Fertilization Period
May 09, 2025
In vitro fertilization and embryo transfer (IVF-ET) has become the primary treatment option for patients with infertility associated with ovarian function decline. Fertility preservation for such patients has emerged as a research hotspot. Traditional Chinese Medicine (TCM) can intervene at various stages of IVF-ET, either as a standalone comprehensive treatment or in combination with IVF-ET, applying a phase-based approach to treatment. TCM can assist IVF-ET at different stages as follows:
Pre-cycle Phase: Identifying the root cause and addressing it-enhancing ovarian reserve function.
Downregulation Phase: Regulating liver and spleen, harmonizing Yin and Yang-alleviating symptoms of low estrogen.
Ovulation Induction Phase: Tonifying the kidney and essence, promoting blood circulation and unblocking meridians-improving the quantity and quality of follicles and reducing adverse reactions.
Post-Transfer Phase: Strengthening the kidney and spleen, warming the kidney, and nourishing the blood-improving endometrial receptivity.
By employing TCM-specific therapies such as acupuncture, auricular point pressing, acupoint application, herbal enema, dietary therapy, etc., it can enhance the quantity and quality of mature eggs, improve endometrial receptivity, and optimize assisted reproduction outcomes. Additionally, TCM can mitigate the adverse effects of assisted reproductive technology and improve the success rate of IVF-ET.
Keywords: Ovarian function decline-related diseases; diminished ovarian reserve; premature ovarian insufficiency; premature ovarian failure; fertility preservation; Traditional Chinese Medicine; in vitro fertilization period
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Diseases Associated with Ovarian Function Decline: Pathological States, Infertility, and TCM Interventions During IVF
Diseases associated with ovarian function decline reflect three distinct pathological states. Early manifestations include frequent or infrequent menstruation, which gradually progresses to reduced menstrual flow or amenorrhea, often accompanied by infertility. For infertile patients with such conditions, early fertility assessment and guidance are essential. When necessary, in vitro fertilization and embryo transfer (IVF-ET) should be employed.
IVF-ET involves retrieving eggs from the female ovaries, fertilizing them with sperm in vitro, and culturing the fertilized eggs for 3-5 days. The embryos, at either the cleavage or blastocyst stage, are then transferred into the uterine cavity for implantation and fetal development. Commonly referred to as "test-tube babies," IVF-ET has become a critical intervention for infertility [1].
Globally, 8%-12% of couples of reproductive age suffer from infertility [2]. Each year, IVF-ET technology is used to address issues such as low ovarian response rates, poor embryo quality, low clinical pregnancy rates, and complications such as Ovarian Hyperstimulation Syndrome (OHSS). The incidence of mild OHSS is 20%-33%, while moderate to severe OHSS occurs in 3%-8% of cases. For high-risk women, such as those with polycystic ovaries or high oocyte yields post-retrieval, the risk of OHSS is even higher [4].
Traditional Chinese Medicine (TCM) offers significant advantages and distinct features in addressing ovarian function decline during the IVF period. TCM plays an active role in preserving fertility for patients. This article reviews the basic concepts of ovarian function decline, TCM pathogenesis and treatment principles, and fertility assessment, summarizing TCM interventions during various stages of IVF-ET. The goal is to provide new therapeutic strategies for phase-based, comprehensive TCM treatments to preserve fertility in such patients.
Overview of Diseases Associated with Ovarian Function Decline
Diseases associated with ovarian function decline include Diminished Ovarian Reserve (DOR), Premature Ovarian Insufficiency (POI), and Premature Ovarian Failure (POF).
DOR refers to a reduction in the quantity and/or quality of oocytes in the ovaries, accompanied by decreased Anti-Müllerian Hormone (AMH) levels, reduced Antral Follicle Count (AFC), and elevated Follicle-Stimulating Hormone (FSH) levels [5]. DOR results in reduced fertility but is not defined by age, etiology, or menstrual status. According to epidemiological surveys, the maximum prevalence rates of DOR are 3.8%, 6.0%, 11.0%, and 28.6% for women aged 20–24, 25–29, 30–34, and 35–39, respectively [6].
POI refers to ovarian function decline occurring before the age of 40, characterized by infrequent or absent menstruation, elevated gonadotropin levels (FSH > 25 U/L), and fluctuating declines in estrogen levels [5]. A meta-analysis revealed a global prevalence rate of 3.5% for POI, with developing countries exhibiting a higher rate (5.3%) than developed countries (3.1%). The prevalence of POI has been increasing over the past 20 years [7].
POF is the final stage of ovarian decline before age 40, manifesting as infrequent menstruation progressing to amenorrhea, with elevated gonadotropin levels (FSH > 40 U/L) and decreased estrogen levels. POF is often accompanied by perimenopausal symptoms [5].
Due to increasing work and family pressures, as well as environmental and immune factors, the incidence of ovarian function decline is trending toward younger ages. If untreated, DOR can progress to POI within 1–6 years, eventually leading to POF [8].
Traditional Chinese Medicine (TCM) Understanding of Ovarian Function Decline
Historical TCM texts do not directly record diseases associated with ovarian function decline. However, based on their clinical manifestations, these conditions can be classified under terms such as "early menstruation", "delayed menstruation", "scanty menstruation", "amenorrhea", "early cessation of menstruation", "infertility", and "perimenopausal symptoms".
In Fu Qingzhu's Gynecology, it is noted:
"A woman's 'heavenly water' ceases at seven times seven years of age. However, some women experience early cessation of menstruation before this age, which is often mistaken as blood deficiency and amenorrhea, when in fact it is due to stagnation of Qi in the heart, liver, and spleen."
This text emphasizes the role of the kidneys in menstruation, stating that treatment for early cessation of menstruation should focus on kidney deficiency while addressing stagnation of Qi in the heart, liver, and spleen.
From a TCM perspective, DOR, POI, and POF represent different stages of ovarian function decline, but their core pathogenesis lies in kidney essence deficiency. Kidney essence deficiency leads to inadequate generation of Qi and blood, resulting in deficiency of the Chong and Ren meridians and the Sea of Blood, which fails to overflow on schedule. This manifests as delayed or scanty menstruation, or even amenorrhea. Kidney essence deficiency also causes kidney Qi to decline, disrupting the balance of Yin and Yang in the kidneys. This leads to symptoms such as hot flashes, night sweats, and five-center heat, commonly seen in perimenopausal syndromes. Since the kidneys govern reproduction, kidney Qi deficiency and inadequate nourishment of the Chong and Ren meridians impair fertility.
TCM Treatment Philosophy
In clinical practice, treatment should not solely focus on replenishing kidney essence. Diagnosis should be based on kidney deficiency as the root cause while considering coexisting conditions. Modern women face increasing pressures from work and family, as well as societal fertility expectations, which often result in liver Qi stagnation. Renowned modern TCM practitioners have diverse insights into the etiology and pathogenesis of these conditions:
Chen Huinong: Believes that ovarian reserve decline stems from kidney Yin deficiency as the root and kidney Yin-Yang imbalance as the overarching framework, involving the heart, liver, and spleen. Treatment includes nourishing blood and Yin, replenishing essence, harmonizing Yin and Yang, soothing and nourishing the liver, tonifying the spleen, and invigorating blood circulation. Chen also emphasizes that POI is caused by early depletion of the "heavenly water," which is attributed to Yin damage in the three burners, loss of regulation in the Sea of Marrow, and deficiency in the Chong and Ren meridians [9–10].
Xiao Chenglong (National TCM Master): Highlights that POF arises from kidney deficiency, insufficient Chong meridian function, and blood deficiency in the Sea of Blood [11].
Xia Guicheng (National TCM Master): Associates the heart with the upper burner, as it governs the mind and corresponds to brain functions like the hypothalamus and pituitary. He asserts that simple kidney supplementation is insufficient and proposes the concept of "heart-kidney disharmony" as a primary pathogenesis. Treatment focuses on harmonizing the heart and kidneys, emphasizing calming the heart to nourish Yin [12–14].
Liu Minru (National TCM Master): Attributes ovarian function decline to deficiencies in kidney Qi (kidney Yin and Yang) and kidney essence, combined with stagnation in the heart, liver, and spleen channels [15]. Liu identifies common syndromes such as kidney Yin deficiency with liver Qi stagnation, kidney Yang deficiency with spleen Yang dysfunction, kidney water depletion with heart blood deficiency, and kidney essence deficiency with Sea of Marrow emptiness [16].
Xu Runshan (National TCM Master): Suggests that POI is often caused by congenital kidney Qi deficiency, excessive labor or childbirth, emotional disturbances, and other factors leading to dysfunction in the liver, spleen, and kidneys. This results in Qi and blood deficiency in the Chong and Ren meridians, blood stasis in the meridians, and ultimately dysfunction in the kidney-heavenly water-Chong and Ren-uterus axis.
Dysfunction of the Chong-Ren-Uterus Axis and Fertility Assessment for Patients with Ovarian Function Decline
Fertility Assessment for Patients with Ovarian Function Decline
For patients with ovarian function decline, fertility assessment and guidance should be conducted as early as possible, taking into account factors such as age, serum hormone levels, medical history, and associated primary diseases. When necessary, in vitro fertilization (IVF) intervention should be considered, as it is clinically significant for preserving fertility. Early fertility assessment and guidance are particularly important for older patients [18–19].
Age is a critical factor affecting ovarian reserve function. As age increases, mitochondrial function declines, leading to reduced fertility. Reports on assisted reproductive technology (ART) indicate that among all treatment cycles, 36.2% of patients are below 35 years old, 23.4% are 35–37 years old, 20.7% are 38–40 years old, 9.5% are 41–42 years old, and 10.1% are above 42 years old. In 2021, the average age of patients undergoing ART in the United States was 36.3 years [20].
Research shows that the natural miscarriage rate for pregnant women aged 35–45 can reach 40%, increasing to 60–65% for women over 45 [21]. Additionally, for women over 35 undergoing ART, the early pregnancy loss rate in fresh cycles is 38.81% [22].
To address these challenges, the "Guidelines for Diagnosis and Treatment of Infertility in Advanced-Age Women" [23] and the "Chinese Clinical Practice Guidelines for Assisted Reproductive Technology in Advanced-Age Infertile Women" [18] recommend ovarian function evaluation and comprehensive infertility examination for women aged ≥35 who have been trying to conceive unsuccessfully for six months or longer without contraception. When necessary, ART is suggested to shorten the time to pregnancy. For women aged ≥40, immediate ovarian reserve evaluation and infertility examination are recommended, with direct IVF intervention to increase pregnancy chances. Preimplantation genetic screening (PGS) and pre-pregnancy counseling on the risks of advanced maternal age are also advised when necessary.
Both guidelines [18, 23] recognize anti-Müllerian hormone (AMH) as a biomarker for assessing ovarian function. AMH levels are categorized into three ranges to indicate ovarian reserve status and response to medication:
AMH < 1.0 ng/mL: Indicates low baseline ovarian reserve, suggesting potential low ovarian responsiveness.
AMH 1.0–3.5 ng/mL: Suggests good responsiveness to gonadotropin stimulation.
AMH > 3.5 ng/mL: Predicts high responsiveness to controlled ovarian hyperstimulation (COH), requiring close monitoring of ovarian changes during COH to prevent ovarian hyperstimulation syndrome (OHSS).
However, there is disagreement regarding the use of inhibin B (INHB) as a marker for ovarian function. The first guideline suggests that INHB is more sensitive than FSH for ovarian function assessment, while the second guideline does not recommend INHB due to its high cost and controversial reliability.
Currently, the most commonly used clinical indicators for ovarian function evaluation are FSH and AMH. Although INHB testing is expensive and its role as an ovarian function marker remains contentious, it is not widely used in clinical practice. Additionally, the FSH/LH ratio can also serve as a marker for ovarian reserve. When the FSH/LH ratio exceeds 3.6, there is a high likelihood of poor ovarian responsiveness, increasing the risk of cycle cancellation.
