Recent clinical treatment of anovulatory infertility

  Infertility is defined in China as inability to have children after two years of marriage, cohabitation, normal sexual life, without any contraceptive measures, and 25% to 37% of female causes. Ovulation disorders account for 20% to 40% of all female factors, with persistent anovulation accounting for 15% to 20% and sporadic anovulation for 8% to 10% [1]. In recent years, clinical physicians or in the inheritance of the predecessors on the basis of self-designed soup; or selected Chinese medicine artificial cycle therapy; or Chinese and Western medicine combined treatment, have achieved good results, the following is a review of recent literature: 1 etiology pathogenesis: Suwen. Shanggu tianzhen zhuan” cloud: “the woman seven years old, kidney qi Sheng, teeth more hair long; two seven and day sebum to, Ren vein through, Taichong vein Sheng, menstruation to time down, so there are children”. Female Science. The embryo is tied to the heart package and to the vital gate, the heart is also Yang; the one tied to the vital gate is connected to the kidney, the kidney is also Yin. This shows that the sages believed that the kidney essence is sufficient, yin and yang harmony, in order to maintain normal reproductive function. Although contemporary medical practitioners have subdivided them into deficiency of kidney yang and deficiency of liver and blood [2]; deficiency of kidney yin and deficiency of qi and blood [3]
[4]; kidney deficiency and liver depression [5]
[6]; kidney deficiency, spleen deficiency, liver depression [7]; kidney deficiency-based, deficiency-real mixed [8], and also always treating the kidney beforehand. Huang’s [9] was inspired by the “Essentials of Women’s Medicine” that “women’s childlessness is due to menstrual irregularities, …… the method of seeds is in the regulation of menstruation”, emphasizing the importance of regulating menstruation first to restore ovulatory function. Liu et al [10] combined the different stages of follicular development in the menstrual cycle and suggested that the follicular phase is mainly to nourish Yin and tonify the kidneys to promote follicular development and recovery of kidney Yin, laying the material foundation for ovulation; the ovulatory phase is mainly to tonify the kidneys and invigorate Blood, unblocking the cellular veins and cellular channels, making the Qi and Blood active and enhancing the function and increasing the ovulation rate; the luteal phase is mainly to warm the kidney Yang, benefit the Qi and nourish the Blood to improve the function of the corpus luteum and warm the uterus to nurture pregnancy; the menstrual phase The menstrual period invigorates the Blood, regulates menstruation, removes the old and creates the new, and restores the menstrual cycle to normal.  Tan et al [11] analyzed that the follicles go through three stages, namely recruitment, selection and dominance, from the beginning of the anagenesis period to ovulation. According to Huang [9], the following causes can affect these three stages and lead to ovulation disorders: chronic wasting disorders, severe malnutrition, excessive obesity, mental stress, etc.; dysfunction of the secretory system (hyper- or hypothyroidism, adrenocortical dysfunction, etc.), dysfunction of the gonadal system; ovarian disorders (congenital bilateral ovarian hypoplasia or agenesis, inflammation, tumors, surgical or radiation damage to ovarian tissue, polycystic ovary syndrome, etc.). Wang et al [2] suggested that the normal endometrium allows embryo implantation only for a very short period of time, when the endometrial tolerance is at its highest level and the “implantation window” is open, and the formation of the endometrial cytosolic protrusion is visible under the microscope, which provides the conditions for adhesion of the gestational blastocyst to the endometrium. The key to improving ovulation rate and pregnancy rate is to synchronize ovulation with endometrial development and to maximize endometrial receptivity on the day of implantation.  2.1 Dialectical treatment: Li’s [12] treated 80 cases with the basic formula of pregnancy promotion soup (Shu Di, Cuscuta, Raspberry, Lycium, Fructus Lycii, Radix et Rhizoma, Cornu Cervi Pantotrichum, Radix Angelicae Sinensis, Radix Paeoniae Alba, Radix Astragali, Poria, Yam, Salviae Miltiorrhizae), with the addition of Aconite and Wu Wei Zi for the deficiency of Yin and Blood, Zingiber officinale and Bacopa monniera for the deficiency of Kidney Yang, Chai Hu, Radix Aconite, Yu Jin, Neem and Citrus aurantium for the deficiency of Liver and Qi, and Parsley and Cang Zhi Zi for the deficiency of Spleen and Phlegm. The healing rate was 93.75% after 3 cycles.  2.2 Manual cycle therapy: Huang [9] used the principle of tonifying the kidneys and filling the essence, regulating the flushes, tonifying the liver and kidneys, nourishing the blood and activating the blood to first regulate menstruation for 1 to 2 months, and starting from the third month, follicle promotion soup (Angelica sinensis, Chuanxiong…) was used on the 5th to 11th day of menstruation,
(Angelica sinensis, Chuanxiong, Radix ligustici, Radix rehmanniae, Semen cuscutae, Semen spleen, Radix chinensis, Zeilan, Shouwu, Huaiyang yam, Chicken blood vine) on the 5th to 11th day of menstruation, and Ovulation promotion soup (Angelica sinensis, Chuanxiong, Radix ligustici, Semen cuscutae, Semen spleen, Radix rehmanniae, Semen spleen, Cistanche, Zeilan, Radix rehmanniae, Chicken blood vine) on the 15th to 17th day when ovulation is imminent. Mao’s [7] formula was used to nourish blood, invigorate blood, and soothe the liver during menstruation (Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Rehmanniae, Radix Paeoniae Alba, Radix Kuncao, Radix Zeleniae, Rhizoma Peach Blush, Radix Chai Hu, Radix Neem, Radix Yuan Hu, Radix Niubizi, etc.); and formula No. 2 was used to nourish kidney yin and kidney yang and tonify qi and blood during late menstruation (Radix Astragali, Radix Angelicae Sinensis, Radix Yam, Radix Shou Wu, Radix Rehmanniae Sinensis, Radix Fubenzi, Radix Chasteberry, Radix Cuscutae, Radix Zizyphus, etc.),
In the intermenstrual period, the formula was used to nourish kidney yang, regulate qi and invigorate blood (Xian Ling Spleen, Xian Mao, Semen Cuscutae, Fructus Lycii, Fructus Serpentis, Fubanzi, Fructus Chai Hu, Fructus Aromaticus, Fructus Liu, Fructus Saponariae, Fructus Safflower, etc.), and 88 of 160 patients conceived in one course, with a total efficiency of 85%. Chen’s [6] applied the method of tonifying the kidneys and regulating the cycle, using Chinese herbs (Chai Hu, Yu Jin, Chuan Neem, Angelica sinensis, Chuan Xiong, Red Peony, Radix Aromaticus, Chuan Gui, Niubizi, Radix Shou Wu, Yimu Herb, Chicken Blood Vine) before menstruation and Chinese herbs (Chai Hu, Yu Jin, Green Calyx Plum, Cornu Cervi Pantotrichum, Cuscuta, Golden Cherry, Boneset, Shu Di, Amethyst, Cistanches, Poria, Zedoary) after menstruation to tonify the liver and kidneys and promote ovulation. The pregnancy rate was 100%. It is suggested in the paper that infertility patients have complex physical and psychological crises, psychological threats and emotional tensions, mostly manifested as depression, self-blame, exasperation and personality defects, which can cause impaired pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) and imbalance of folliculopoietin (FSH) and luteinizing hormone (LH), emphasizing the importance of psychological detoxification.  2.3 Single and experimental treatment: Ma et al [8] took oral menstrual regulating and ovulation stimulating punch (Cuscuta, Epimedium, Radix et Rhizoma, He Shou Wu, Fructus Lycii, Ze Lan, Pu Huang, etc.) on the 5th day of menstrual cycle and controlled with clomiphene (CC). The healing rate was 69.23% in the Chinese medicine group and 36.67% in the Western medicine group. The study showed that this formula can selectively regulate FSH, stimulate follicular development, synthesize and secrete estradiol (E2) and inhibin, and induce sufficient LH receptor production, so that LH levels reach peak in time and promote ovulation. After ovulation, granulosa cells and cytosolic cells are controlled to synthesize and secrete E2 and progesterone (P); the synergistic effects of FSH and LH induce the ovaries to secrete E2 and P, which enable their receptors on the endometrium to function normally, improve luteal function, enhance pregnancy and support early pregnancy. It avoids endometrial insensitivity due to anti-estrogen action of CC, delayed pre-implantation endometrial development in the mid-luteal phase and inhibition of cervical mucus secretion. Wang’s [3] treated 36 cases with Dajingyuan decoction plus reduction (Shu Di, Shan Yu Fei, Shan Yao, Fructus Lycii, Radix Angelicae Sinensis, Eucommia Ulmoides, Radix Codonopsis Pilosulae, Glycyrrhiza Uralensis, Cuscutae, Radix et Rhizoma Ligustici) for 15 days starting from the 3rd day of menstruation, and a course of treatment was given for 3 months, and the ovulation rate was 86.1% and the pregnancy rate was 72.2% after 1 year. Wang et al [2] used Zhen Wu Tang combined with Sheng Wei San plus reduction from the 3rd day of menstruation until ovulation and stopped taking it, compared with CC+human chorionic gonadotropin (HCG) group and human menopausal gonadotropin (HMG)+HCG group. The ovulation rates in the three groups were 55.68%, 79.13% and 65.67%, respectively; the pregnancy rates were 32.33%, 21.73% and 35.82%, respectively; 80.80% and 82.80% of the cycles with type A endometrium on the ovulation day in the herbal group and the HMG+HCG group, respectively, but only 40.86% in the CC+HCG group, thus revealing the high pregnancy rates in the herbal group and the HMG+HCG group. HCG group, thus revealing the intrinsic reason for the high pregnancy rate. Huang [13] used Chinese herbs (Angelica sinensis, fried white peony, Cuscuta sinensis, Bacopa monniera, Cistanche cistanche, Radix Rehmanniae, Raspberry, Lycium barbarum, Radix Aromaticus, roasted tortoise shell, Chuanxiong) from clean menstruation to the next menstrual period.
The total effective rate was 74.4% after 3-6 menstrual cycles. Mai et al [14] used sound luteinizing soup (Chuan Guan Guan, Fructus Herba, Semen Cuscutae, Yimu Cao, Cyperus rotundus, Radix Aromaticus, Radix Paeoniae Alba, Radix Paeoniae Alba, Radix Scutellariae), which can be used to tonify the liver and kidneys, activate blood circulation and resolve blood stasis, clear heat and dry dampness, and help kidney ovulation, with a pregnancy rate of 46.66% and an overall effective rate of 76.66%. (Shu Di, Shan Yao, Cornus Officinalis, Dan Pi, Poria, Ze Di, Fructus Lycii, Cuscuta, Raspberry, Wu Wei Zi, Psyllium) on the 7th day of menstruation, together with acupuncture (the main acupuncture point was Qi Hai, San Yin Jiao, Zhong Ji, and the supporting acupuncture point was taken according to the evidence). In Cai et al [16], a course of 3 menstrual cycles was given from day 5 of the cycle with a combination of acupuncture and moxibustion (Guan Yuan, Zi Gong, Kidney Yu, Sanyin Jiao, Baihui, Shuidao, Foot San Li, Tai Xi, Blood Sea, and Spleen Yu) and a course of 3 months after ovulation. Compared with the CC group, the ovulation rate was 71.42% and 67.64% respectively; the pregnancy rate was 53.57% and 29.41% respectively; the total effective rate was 84.61% and 58.33% respectively, and the improvement of menstrual disorders was better in the treatment group than in the control group.  3 Western medical treatment: Hormonal drugs are still used to promote follicular development and induce ovulation. Shin et al [17] controlled the CC group with the CC+vitE (600 mg/d) group, and the ovulation rates in the two groups were 66.7% and 80.0%; the pregnancy rates were 20.0% and 33.3% (5/15 cases); and the incidence of LUF was 26.7% and 20.0%. It was shown that vitE acts directly on hypothalamus and pituitary gland, improves pituitary capillary blood flow, enhances the functional activity of hypothalamus and pituitary gland, regulates their endocrine function, and reduces the incidence of LUF. Ren [18] divided 84 patients into 30 cases in the CC+hexenestrol group,and 54 cases in the CC+hexenestrol+HCG group. The pregnancy rates in the two groups were 36.7% and 77.22%, respectively; ovulation rates were 73.33% and 94.44%. the incidence of LPD and LUF were 20% and 5.56%. Hu et al[19] compared CC+HCG and CC+hexenestrol+HCG, there was no significant difference in ovulation rate and endometrial thickness between the two groups, but the pregnancy rate was significantly higher in the latter (46.46%) than in the former (32.65%), probably because hexenestrol tablets improved the anti-estrogenic effect of CC and thinned the cervical mucus, which facilitated sperm passage. Li et al [20]
investigated the effect of ultrasound-guided immature follicular puncture (IMFP) technique combined with HMG on endocrine and basal sinus follicle counts in patients with anovulatory infertility in PCOs. 37 patients with PCOs had normalized T and LH/FSH ratios after 2-3 punctures, of which 33 (89.2%) had basal sinus follicle counts down to less than 10/ovary, and all were pregnant after 6 months.  4 Combination of traditional Chinese and Western medicine: 4.1 The manual cycle of traditional Chinese medicine combined with Western medicine: Liu’s [21] tonifies the kidney and nourishes yin and regulates the flushing of the ovary (Shu Di, Angelica sinensis, Fructus Lycii, Radix et Rhizoma Polygonati, Cuscuta sinensis, Radix Epimedium, Rhizoma Yam, Radix Seuccium, Amethyst); tonifies the kidney and invigorates blood during ovulation (Sheng Di, Angelica sinensis, Rhizoma Chuanxiong, Radix Qiang Wu, Salviae Miltiorrhizae, Rhizoma Hong Hua, Rhizoma Wang Bu Li Xing); warms the kidney and yang, benefits qi and nourishes blood during the luteal phase ( Radix Rehmanniae Praeparata, Fructus Cynanchum, Epimedium, Herba Cistanches, Rhizoma Polygonati, Semen Cuscutae, Radix Glycyrrhiza Uralensis, Radix Codonopsis Pilosulae); invigorating blood circulation and regulating menstruation during menstruation
(Shengdi, Angelica, Zelenia, Shanzha, Safflower, Yimoucao) + Clomiphene treatment, the total effective rate was 74.3%. Shi’s [22] treated with follicle promoting soup (Shengdi, Er Shao, Fructus Lycii, Cuscuta, Radix et Rhizoma, Huangjing, Cistanches, Huaiyam, Cornu Cervi Pantotrichum, Safflower, Angelicae Sinensis) during follicular phase; ovulation promoting soup (Shudi, Yam, Cornu Cervi Pantotrichum, Xianlingzhi, Xianmao, Cistanches, Eucommiae, Bacopa monnierae, Parviflora) + CC + vinpocetine estradiol + progesterone + HCG during ovulation phase, with an overall effective rate of 78.3%. Zhang’s [5] took 7 doses of Formula 1 Follicle Promotion Soup (Shu Di, Angelicae, Bai Shao, Fructus Lycii, Radix et Rhizoma, Shou Wu, Radix prunus, yam, Cornu Cervi Pantotrichum, Semen Cuscutae, Deer Antler Cream); 5 doses of Formula 2 Ovulation Promotion Soup (Danshen, Radix Paeoniae, Ze Lan, Radix Aromaticae, Fructus Lycii, Radix Angelicae, Semen Cuscutae, Semen Fructus, Xian Mao, Xian Ling Spleen) from the 5th day of menstruation in sequence; 5 doses of Formula 3 Luteal Promotion Soup (Shu Di, Fructus Lycii, Semen Cuscutae, Radix et Rhizoma, Cistanches, Angelicae, Astragalus, Cuscutae, Epimedium, Dazao) for 7 doses + Clomiphene, with a pregnancy rate of 81%. Yin’s [23] used tonification of the kidneys to invigorate blood stasis and tonification of the kidneys to invigorate blood to regulate menstruation combined with CC, HMG, and HCG according to the ovarian cycle, with an overall efficiency of 91.7%. Liu et al [10] used 7 doses to nourish the yin and tonify the kidney and regulate flushing (Shou Wu, Cuscuta, Angelica, Shu Di, Bai Shao, Fructus Lycii, Cyperus, Radix et Rhizoma, Radix et Rhizoma Ligustici, Radix et Rhizoma Drynaria, Yam, Deer Antler Cream, Pericarpium Citri Reticulata, Radix et Rhizoma Sandy) during the follicular phase; 5 doses to tonify the kidney and warm the uterus, invigorate blood circulation and promote ovulation (Cuscuta, Chuan Jian, Fructus Lycii, Shu Di, Shou Wu, Xian Ling Spleen, Radix et Rhizoma Angelica, Radix et Rhizoma Paeoniae, Tao Ren, Safflower, Niubizi, Chuan Xiong, Radix et Rhizoma Glycyrrhizae) during the ovulatory phase; The treatment restored ovulation function in 80% and the pregnancy rate was 68.6%.  4.2 Treatment with Chinese herbal medicine single formula and experimental formula combined with western medicine: Chen et al [24] treated with blood activating and kidney tonifying Chinese herbal medicine (Chai Hu, Er Shao, Ze Lan, Niubizi, Kun Cao, Sheng Pu Huang, Chicken Blood Vine, Lady’s Mantle, Cuscuta, Fructus Lycii, Cistanches, Xian Ling Spleen, Xian Mao, Raspberry; 3 doses each on the 1st to 3rd and 11th to 13th days of menstruation) + western medicine artificial cycle + CC, the efficiency was 73.68%, the pregnancy rate decreased with duration of disease and decreasing with age. Mei et al [25] treated 20 cases with kidney tonic Yulin Tang (Shu Di, Cornu Cervi Pantotrichum, Cuscutae, Eucommiae, Angelicae, Safflower, Amethyst, Lady’s Mantle, Dry Lotus Grass, Dan Pi, Epimedium, Roasted Licorice; taken on alternate days after menstruation) + CC, 12 cases ovulated and 10 cases became pregnant. In Zhang [26], the total effective rate was 81.25% on the 5th day of menstruation and 60.0% in the CC control group when treated with regulating menstruation and promoting ovulation (Cuscuta sinensis, Chuansuansuan, Shouwu, Fructus Lycii, Zeilan, Kuncao, Angelica sinensis, Bai Shao, Xiangxiang, Wu Yao) + CC. Xu et al [27] formulated their own pregnancy aid No. 1 (Cuscuta sinensis, Radix et Rhizoma shouwu, Safflower,
Caulophyllum, Salviae, Caulophyllum, Rose,
Cistanches, Salviae, Salviae, etc.) + CC for 3 months resulted in a pregnancy rate of 82.6% and a significant improvement in menstrual status, E2 and P levels after treatment. Yang’s [4] treated with ovulation promotion soup (Radix Angelicae Sinensis, Radix Rehmanniae, Radix Shou Wu, Fructus Lycii, Fructus Ligustrum, Fructus Ligustrum, Radix Yam, Fructus Chuan Gui, Fructus Xian Mao, Fructus Cuscutae, Fructus Zizyphus) + CC + ethenol + HCG, and the cumulative ovulation rate was 98.4% and the cumulative conception rate was 88.7% after 3 cycles. Wang et al [28] treated with ovulation soup (Cai Hu, Er Shao, Ze Lan, Kun Cao, Gynostemma, Niu Knee, Liu Yao Nuo, Su Mu, Sheng Bo Huang, Lizhen Zi, Fuban Zi, Cuscuta, Lycium, etc.; 3 doses each on days 1 to 3 and 11 to 13 of menstruation) + CC or bromocriptine + HMG, and the clinical pregnancy rate was 50.0%. It is emphasized that overall regulation and dialectical treatment should be carried out under the principle of “tonifying the kidney – activating blood circulation and removing blood stasis – tonifying the kidney – activating blood regulation”. Studies have shown that Chinese and Western medicines play a synergistic role in promoting follicle growth and ovulation, while Chinese medicine compensates for the “anti-estrogen-like effect” of Western medicines, improves cervical mucus score and facilitates sperm passage; improves endometrial tolerance and promotes synchronization of endometrium and blastocyst development while increasing ovulation rate; supports luteal function after ovulation and improves clinical pregnancy rate. clinical pregnancy rate. Huang et al [29] treated with Yulinzhu plus reduction (Ginseng, Atractylodes, Poria, Paeonia lactiflora, Rhizoma Chuanxiong, Salvia, Radix Aromaticus, Zizyphus, Radix Angelicae Sinensis, Radix Rehmanniae, Semen Cuscutae, Eucommia, Xian Ling Spleen, Roasted Dry Herbs; day 5-14 of menstruation) + Clomiphene (day 5-9 of menstruation) + Tonicum (day 10-25 of menstruation), and the conception rate was 58%.  5 Conclusion: In Chinese medicine, the so-called “heavenly sap” is mainly achieved through the regulation of the kidney qi-ren-taichong axis, therefore, the regulation of qi and blood in the renal meridians is the condition for ovulation, and the transformation of yin and yang in the kidney is the key to the pathogenesis of this disease. The key to this disease is to grasp the transformation of yin and yang and the changes in the menstrual cycle, to adjust the functional balance of the transformation of yin and yang, to restore the regulatory role of the ovaries, and to promote ovulation. The author believes that the artificial cycle of traditional Chinese medicine can restore the natural state of the body through the sequential treatment of tonifying the kidneys and filling the essence, de-regulating the flushes, tonifying the liver and kidneys, activating the blood and regulating the menstruation, and then combining with psychological and hormonal drugs to promote ovulation at the right time, which can significantly increase the pregnancy rate while reducing the adverse effects of western drugs alone. However, this method has disadvantages such as a long course of treatment, which needs to be further improved in the future.