With the advancement of modern fertility techniques such as in vitro fertilization and artificial insemination, infertility caused by ovulatory dysfunction due to follicular dysplasia and loss of normal function of the ovulatory system in the ovary has received more attention. In this paper, we have collected the relevant literature in the past 20 years, and the clinical research overview of acupuncture for ovulation promotion is reviewed as follows.
1. Clinical overview of acupuncture treatment
1. 1 acupuncture point selection: modern medicine believes that the pathogenesis of ovarian dysfunctional infertility lies in the suppression of hypothalamic function and decrease in pituitary responsiveness resulting in ovarian dysfunction and endocrine disorders, that is, related to the dysfunction of the hypothalamic-pituitary-ovarian gonadal axis. In the Neijing, it is said that “when the kidney qi is in abundance ……, when the tenebrae pulse is open, and the tai-chong pulse is in abundance, the menstruation is timely.
This means that there is some similarity between the kidney-rheumato-uterine system and the reproductive axis, and that the reproductive function of women is closely related to the liver, spleen and kidney. The liver collects blood, the spleen regulates blood, the kidneys collect essence, and the essence is transformed into heavenly sebum. When the kidney energy is abundant, the two chakras of the Qi and the Ren are in harmony, and the essence and blood infuse the uterus, the menstruation is on schedule, and it is possible to conceive twins.
We summarized and analyzed 25 papers.
25 articles summarized and analyzed (number of occurrences/total literature)
Acupuncture point selection
Treatment method
Overview of clinical studies
Guan Yuan (Zhong Ji) 21/25
Ovary (Uterus) 16/25
Sanyinjiao 20/25
Dialectical point allocation 11/25
Acupuncture 14/25
Electroacupuncture 7/25
Moxibustion 4/25
Chinese medicine 6/25
Ultrasound 15/25
BBT 15/25
CM 7/25
Reproductive hormone 6/25
Most of the literature reports that the main acupuncture points taken are Guan Yuan and Zhong Ji in the localized Chong and Ren Channels of the abdomen; and the ovary and uterus points. The “ovaries” and “uterus” are extra-meridian points that regulate the uterus. “Sanyinjiao” is the meeting point of the three meridians of the liver, spleen, and kidney, so that the formula achieves the purpose of treating the liver and kidney and regulating the punch and the Ren [2]. Chen [3] took “Guan Yuan”, “Zhong Ji”, “Zi Gong”, and “San Yin Jiao points” to promote ovulation in 42 cases. Of the 42 cases, 41 cases (97.6%) were clinically cured; 1 case (2.4%) was ineffective.
According to the clinical manifestations, Kou treated 50 cases of anovulatory infertility with the addition and subtraction of acupuncture points, of which 40 cases were cured and 10 cases were ineffective. The clinical manifestation of qi stagnation and blood stasis was considered to be the most effective, while the liver-depression and kidney deficiency type was the least effective.
The results of 32 cases of female infertility treated by Chang’s acupuncture were 9 cases of pregnancy after 1-3 months of treatment, 22 cases of pregnancy after more than 4 months of treatment, and 1 case of invalidation, with a cure rate of 97%, and it was believed that the efficacy was related to the amount of acupuncture points and acupuncture stimulation; it was also related to the timing of acupuncture, which was performed about 12 days after each menstrual period to favorably promote ovulation and increase the chance of conception. Chen’s [6] took Shen Que acupuncture point to treat ovarian dysfunctional infertility and divided into simple moxibustion therapy, moxibustion therapy with medicine, and Chinese and Western medicine therapy; the treatment results were processed by Q-test and combined with clinical practice, and the clinical efficacy of the three groups was basically the same.
1. 2 Treatment methods
1.2. 1 Acupuncture treatment: Yan [7] acupuncture ovarian acupuncture points to treat ovarian retention syndrome 38 cases, clinical cure 36 cases, accounting for 94.7%; invalid 2 cases, accounting for 5.3%. There were also 30 cases in the Chinese medicine control group. Comparison of the efficacy of the two groups (P<0.01< span="">) showed that the efficacy of the acupuncture group was higher than that of the herbal treatment group. It is believed that acupuncture of ovarian points may have two major effects: overall regulation and local stimulation. Modern experimental studies have confirmed that acupuncture has a bidirectional effect on gonadotropic hormones in vivo; on the other hand, acupuncture of ovarian points can cause ovarian smooth muscle contraction, which promotes ovulation by rupture of the follicle wall.
Electroacupuncture treatment: Wei [8] used electroacupuncture to promote ovulation in 106 cases, 96 cases ovulated after electroacupuncture, with an ovulation rate of 90.6%; 10 cases (9.4%) were ineffective, and it was clinically observed that electroacupuncture for ovulation is not limited by age, nor is it affected by whether infertility is primary or secondary. Fei’s [9] electroacupuncture treatment of ovulation disorder in polycystic ovary syndrome 30 cases, cured 4 cases, effective 22 cases, ineffective 4 cases, with an efficiency of 86.67%.
Yan’s preliminary analysis of the mechanism of electroacupuncture for ovulation has two aspects: one is the local stimulation effect, the points taken in the small abdomen are close to the uterus/ovary, and the treatment with deep pricking, heavy manipulation, and stronger current stimulation may produce some physical stimulation of the ovarian cytosol on the surface of mature follicles, making the follicles easy to rupture and thus inducing ovulation. Secondly, it may cause changes in plasma luteinizing hormone and follicle-stimulating hormone levels, prompting the rupture of mature follicles and ovulation.
1.2.2 Moxibustion treatment: Li [12] treated 42 cases of ovulation disorder with moxibustion, 31 cases were effective, of which 12 cases were pregnant and 11 cases were ineffective, with an efficiency of 73.8%. There were also 40 cases in the herbal group. Compared with the efficiency of the two groups, (P>0.05) their differences were not significant, confirming that moxibustion has a better effect in promoting ovulation and regulating menstruation.
1.2.3 Acupoint injection therapy: Tu [13] applied gonadotropin (HMG) acupoint injection to treat 36 cases of ovulatory disorders of infertility and treated 26 cases with traditional methods as the control group, and the results were observed to promote follicle development and ovulation rate, conception rate of the two groups with similar efficacy (P>0.05), and the differences in the amount of medication and side effects were highly significant (P<0.01< span="">) . It is believed that the results of acupoint injection of HMG are similar to those of the traditional high-dose administration method, and the side effects are significantly reduced.
1.2.4 Acupuncture point buried thread: Chen [14] took Sanyinjiao acupuncture point buried sheep intestine thread to treat 24 non-ovulatory patients, 22 cases were followed up, 18 of which were ovulated, 16 were pregnant and 4 were ineffective, these 4 cases were secondary amenorrhea patients. It is believed that sanyinjiao acupuncture point buried thread is a more ideal method to promote ovulation, and it is clinically observed that one buried thread regulates ovarian function for a long time; in addition to adjusting menstruation and promoting ovulation to treat non-ovulatory infertility, it is also effective in polycystic ovary syndrome.
1.2.5 Acupuncture and medicine: Zheng [15] treated 32 cases of anovulatory infertility with acupuncture plus oral Chinese medicine; 9 cases were cured (conception), 16 cases were effective (ovulation); 7 cases were invalid. There were also 32 cases in the western medicine group (clomiphene control group). The ovulation rate was not significantly different between the two groups by X2 test, P>0.05; the clomiphene used in the control group had estrogen-like effects, so the conception rate was low, and there was a significant difference between the two groups P<0.05< span="">. Clinical observation of the treatment group did not have the side effects of luteinized unruptured follicle development syndrome caused by clomiphene.
Zhu’s acupuncture combined with Chinese herbal medicine induced ovulation in 59 cases, with an overall ovulation rate of 52.5%. And clinical observation was made that there was no significant difference between short-term efficacy in both disease identification and evidence identification (P>0.05); there was no significant difference between the effect of acupuncture plus herbal medicine and the effect of acupuncture alone (P>0.10); there was no significant relationship between the ovulation effect of treatment and the level of EI (Erythrocyte Index) before treatment (P>0.05). The results suggest a complementary relationship between acupuncture and combined herbal treatment to induce ovulation.
Shu treated 27 patients with ovarian dysfunction with the manual cycle method by giving herbs based on kidney tonics plus acupuncture according to the menstrual cycle, and had a western medicine (chlorostigmine) group. The ovulation rate was basically the same in both groups (P>0.7). Preliminarily, it is concluded that Chinese herbs plus acupuncture induced ovulation without the side effect of over-stimulation of ovaries.
2. Overview of clinical studies on acupuncture
The morphological changes characteristic of follicular development and ovulation during the reproductive cycle, and the characteristic changes in reproductive hormones accompanying ovulatory activity and the symptoms, signs and histology caused by hormonal effects on target organs, which can be used as indicators or parameters for ovulation monitoring.
2. 1 Symptomatic hormonal effects
The cyclic changes of sex hormones and the hormonal effects on target organs cause the symptoms and signs changes, which are used as clinical indicators for ovulation monitoring.
2.1.1 Basal body temperature (BBT): Testing BBT in women of reproductive age can indirectly check whether ovarian function is sound. BBT is widely used as a simple method to indirectly determine ovulatory function; to observe the effects of various ovulation-promoting treatments. Biphasic BBT is the clinical manifestation of an ovulatory menstrual cycle. In 63 cases of ovulation promotion by acupuncture by Pu [18], the basal body temperature was clinically observed and monophasic (atypical biphasic) was converted to atypical biphasic (typical biphasic) in 48 cases, with an invalid conversion in 5 cases and an overall efficiency of 92%.
It is suggested that simple acupuncture has a good effect on the regulation of basal body temperature in women of childbearing age. It is believed that acupuncture has an enhancing effect on the thalamus-pituitary-ovarian gonadal axis in terms of self-regulation. Yu [19] observed that the skin temperature of the palm of the fingers of patients with anovulatory menstrual disorders was low, and those who could rise after electroacupuncture treatment had a significantly higher ovulation rate. It was also observed that there was a relationship between changes in skin temperature of the hand and changes in blood ß-endorphin-like immunoreactive substance (ß-EPIS).
It is thought that there may be a correlation between changes in skin temperature of the hand after electroacupuncture and changes in hypothalamic regulation of gonadotropin-releasing hormone to some extent; it may be a predictor of electroacupuncture for ovulation.
2.1.2 Cervical mucus (CM) examination
The secretion of CM is not controlled by nerves, but by ovarian steroid hormones, which can reflect the changes of ovarian endocrine function in vivo. The crystallization of CM is mainly controlled by estrogen, which drives the formation of crystals and has cyclic changes. The lambdoid crystalline test can be used as one of the indicators for estimating estrogen levels, especially as a guide when treating with various ovulation-promoting methods.
In 20 cases of ovulation disorders, the CM crystalline test was performed before acupuncture treatment, and no amniotic crystals were seen. After acupuncture treatment (one to three cycles of treatment), lambdoid crystals were seen in 17 cases, and ovulation was confirmed by the test; five cases were not effective.
2.1.3 Histological features
Although the vaginal epithelium responds to various steroid hormones, it is most sensitive to estrogen and shows cyclic changes. Yu [19] used vaginal exfoliative cell examination (VS) with the Eosin index (EI) as a reference for the level of estrogen action in vivo and observed that patients with anovulatory menstrual disorders with low EI and those whose EI could rise after electroacupuncture treatment had a significantly higher ovulation rate.
Zhu analyzed the relationship between TCM diagnosis classification and EI. 74.2% and 64.3% of those with kidney deficiency and spleen-kidney yang deficiency had EI<< span="">30%, respectively, which were higher than those with liver-kidney yin deficiency (57.1%), which was not statistically significant (P>0.05). It was also concluded that the total ovulation rate was not significantly related to the Erythrocyte Index (EI) before treatment.
2.2 Morphological signs
Recently, high-resolution real-time ultrasound has been applied to the morphological examination of follicular development and ovulation, which is superior to traditional thermometry and blood endocrine examination due to the non-invasive nature of ultrasound, which can be used for continuous dynamic monitoring and its rapid and accurate results. Feng [21] applied ultrasound to monitor acupuncture for ovulation and observed that it could make small follicles develop in those who could not develop to maturity; for those with oversized follicles, it could make them break down and ovulate rapidly.
The results showed that the treatment of infertility with acupuncture therapy was effective in those with normal follicular development, with a success rate of 78.6%; in some cases with impaired follicular development, it was effective in promoting follicular maturation and inducing ovulation. Shu [15] systematically observed follicular development in 10 cases before and after treatment with Chinese medicine plus acupuncture manual cycle method, and the results confirmed that the Chinese medicine group did have the effect of promoting follicular development, which was not significantly different from chlorostigmine treatment.
However, it is well recognized that chlorostigmine treatment can overstimulate the ovaries, and for this reason, none of the 10 cases observed systematically in the TCM group showed multiple identifiable follicles at the same time under ultrasound, and it is proposed that it can be tentatively concluded that there is no side effect of overstimulation of ovulation induced by TCM plus acupuncture. We also reviewed the relevant literature and did not find any reports of ovulation induced by herbs and acupuncture complicated by overstimulation of ovaries.
2.3 Reproductive hormones
2.3.1 Reproductive regulatory hormones of the pituitary gland
The main hormones are follicle stimulating hormone FSH and luteinizing hormone (LH), which are secreted in a biphasic cyclic pattern with a short period of peak secretion before ovulation, i.e., the ovulatory peak. Determining their onset peak and the time of reaching the peak can predict ovulation. Yu [22] tested the changes in blood FSH and LH levels before and after electroacupuncture treatment in 10 patients with confirmed anovulation on the basis of effective electroacupuncture ovulation promotion.
Among them, the blood FSH and LH values and the number of FSH pulse frequency increased after electroacupuncture in 8 patients who were effective after electroacupuncture; there were no significant changes in FSH and LH values in 2 cases of anovulation after electroacupuncture. It is suggested that electroacupuncture is used to regulate FSH and LH secretion through the central nervous system to promote ovulation.
In 98 cases of polycystic ovary syndrome (PCOS) treated with Ma’s acupuncture, serum FSH and LH were measured by radioimmunoassay in all cases, and the serum LH level was significantly increased before treatment and decreased after treatment. , there was a highly significant difference (P<0.001< span="">) when comparing LH/FSH before and after treatment.
And clomiphene treatment was set up for control, and there was a very significant difference in LH between the two groups after treatment (P<0.001< span="">); the difference in LH/FSH comparison was very significant (P<0.01< span="">). This indicates that the adjustment of gonadotropins in PCOS patients by acupuncture treatment is better than that in the control group, which allows the human endocrine function to be adjusted to a new equilibrium state thus restoring normal ovarian function.
Clinical observation of the cure rate and pregnancy rate of the treatment group compared with the control group has, there is a significant difference (P<0.01 , P<0.05< span="">), indicating that the treatment group not only has better efficacy than the control group, but also has a firm pregnancy and is less prone to abortion. It is believed that the treatment group restored ovulation and pregnancy by the therapeutic effect of acupuncture, and the functions of all tissues and organs were restored to normal by the internal regulatory effect. In contrast, the control group produced ovulation and pregnancy under the action of a large amount of external ovulation-promoting drugs (clomiphene). When the action of external drugs ceases, this function is not stable enough and is prone to miscarriage.
2.3.2 Ovarian steroid hormones
The ovaries mainly secrete estrogen and progesterone. Estrogen is most active in estradiol (E2), and the increase of E2 in follicular phase is positively correlated with follicular diameter, so the estrogen level in normal cycle can reflect the stage of follicular development. Estrogen, together with FSH, promotes follicle development and induces the appearance of LH before ovulation, which triggers ovulation, and is an indispensable regulator of follicle development, maturation and ovulation. Progesterone is the most biologically active hormone, and the rise of progesterone before ovulation has the same significance as the measurement of LH peak, which has the value of predicting ovulation.
Blood progesterone is the most variable hormone during the ovulatory cycle and has been used as a common indicator to detect ovulation. Shah [24] treated premature ovarian failure infertility with acupuncture and had a western drug group (clomiphene and haptenestrol) control. The serum E2 in the acupuncture group increased after treatment and 30 and 90 days after treatment, and the difference was highly significant (P<0.001< span="">) compared with that before treatment; the difference was significant (P<0.05< span="">) compared with that at 90 days after treatment and 30 days after treatment. The E2 levels in the Western medicine group were not statistically significant (P>0.05), although they were elevated after treatment and 30 days after treatment compared with those before treatment.
The rise was significant on day 90, with a significant difference compared with pre-treatment (P<0.01< span="">). The difference was not significant at day 90 after treatment compared with day 30 after treatment (P>0.05). It is believed that acupuncture treatment activates its own reproductive endocrine and restores its normal physiological dynamic balance; the effect is relatively long-lasting, and the effect remains significant for a longer period of time after stopping treatment. Western medicine treatment relies on the action of external hormones to restore human hormone levels, and when the external factors disappear, the dynamic balance of human hormones is not stable enough, and although the recent efficacy is more obvious, the effect is not long-lasting after stopping the treatment.
Mo used acupuncture to promote ovulation to achieve good clinical efficacy, and used radioimmunoassay to measure progesterone and other reproductive hormones. Patients with below-normal progesterone returned to the normal range after treatment, with significant differences between pre- and post-treatment comparisons (P<0.01< span="">). It has a bi-directional benign regulatory effect on other hormones FSH, LH and E2. Even though high decreases and makes low increase, the overall tendency is towards the normal range. However, the effect on prolactin (PRL) seems to be insignificant.
3.Summary
Reviewing the relevant literature in the past 20 years, it is proved that acupuncture has better clinical effect on ovulation promotion, and the efficiency and side effects are significantly better than those of western medicine for ovulation promotion. Acupuncture is mostly used to treat this disease with local abdominal acupuncture points: Guan Yuan (Zhongji) and ovaries (uterus); the treatment method mostly uses acupuncture (electroacupuncture). Fast and accurate real-time ultrasound is used to confirm the clinical results, and the simple and easy to use BBT method is used to monitor ovulation.
Laboratory testing of the patient’s reproductive hormones FSH, LH, and E2 has confirmed that acupuncture treatment shows a bi-directional and benign regulation of these hormones. The reviewed literature did not report the occurrence of “ovarian hyperstimulation syndrome (OHSS)”, and acupuncture can be a safe and effective tool in conjunction with modern fertility techniques.
Most of the studies on the mechanism of ovulation promotion by acupuncture have reported changes in reproductive hormones such as FSH, LH and E2 in the H-P-O gonadal axis, citing the traditional Chinese medicine meridian theory; only Zhong [26] reported an experiment with rabbits to observe the response to ovulation promotion by acupuncture. The response of ovulation promotion, changes in the levels of LH and progesterone in blood, and preliminary exploration of the mechanism of ovulation promotion by acupuncture.
In the future, we should follow the progress of modern medical research on the mechanism of ovulation in the H-P-O gonadal axis to further clarify the mechanism of ovulation promotion by acupuncture.