In 1949, Jone first introduced the concept of luteal phase
Defect (LPD), which refers to the delayed or stagnant development of the endometrium during the secretory phase or the unsynchronized development of the stroma and glands due to insufficient progesterone secretion or reduced responsiveness of the endometrium to progesterone as a result of luteal hypoplasia or premature degeneration, which is not conducive to fertilized egg implantation and early development and causes infertility, miscarriage and menstrual disorders, and is one of the main causes of female infertility [1]. The natural incidence of LPD is about 5% in women of childbearing age and 10% in infertile women, for which the International Society of Obstetrics and Gynecology has made it a priority research topic. Modern medical treatment of this disease is mainly limited to progestogen replacement therapy and the use of clomiphene and HCG to promote luteal function, which are not effective and have significant side effects. In contrast, Chinese medicine has greatly improved the clinical fertility rate by applying a variety of treatments such as Chinese medicine typing, Chinese medicine manual cycle, Chinese medicine external treatment, Chinese and Western medicine combined with psychological treatment. The conception rate has been greatly improved. The recent literature is reviewed as follows. 1 Etiology and pathogenesis: kidney essence is the root of human growth and development, and any factor that interferes with the yin and yang of the qi and blood of the kidney, tiankui, and the internal organs of the punching chamber, causing the abnormal collection and diarrhea of the uterus and affecting the rhythmical changes of the menstrual cycle, can lead to infertility. Wang’s [3] believes that kidney energy nourishes the five viscera, and kidney deficiency and weakness of qi-transformation depletes the qi and blood of the viscera, affecting the normal operation of qi and blood and causing stasis, and because of the prolonged course of the disease, there is a saying that “long-standing disease is bound to deficiency, and long-standing disease is accompanied by stasis”, and kidney deficiency and stasis is the basis of the pathogenesis. Dang’s [4] and Fan’s [5] argue that LPD is caused by a slow rise in basal body temperature after ovulation or a small rise or a short maintenance of the high temperature phase, a loss of kidney warmth and liver depression during the process of yin to yang, resulting in a delay in the transformation of yin to yang and a failure of yang to reach the normal balance of yin and yang. According to Zhang et al [6], “fullness of essence makes the uterus easy to take in essence, and fullness of blood makes the uterus easy to hold things”, LPD is manifested by kidney deficiency, and the vast majority (92%) also have Qi deficiency, Blood deficiency, or both Qi and Blood deficiency. Modern medicine believes that LPD is caused by various reasons, such as: hyper-PRLemia, endometriosis, increased prostaglandin release from the endometrium after IUD or abortion, unreasonable application of clomiphene and HCG and endometrial receptor deficiency or poor response, and the new term of pseudoluteinizing insufficiency (PLI) was proposed from the perspective of pathophysiology. Dai [7] demonstrated experimentally that endometrial progesterone receptors in patients with LPD were not lower than normal during the luteal phase, and that the appearance of delayed endometrial secretion in them was not related to the endometrial progesterone receptor content during the luteal phase, but rather to the low progesterone produced by the ovaries that resulted in insufficient formation of hormone receptor complexes, which ultimately led to delayed endometrial secretion. the endometrial progesterone receptor content in the mid-luteal phase in patients with PLI was significantly lower than in the normal group. The low progesterone receptors inevitably lead to delayed endometrial secretion and infertility. The treatment is based on the liver, and the patients are classified into Qi stagnation and blood deficiency type, which is treated with Hephuan Wan (Radix Angelicae Sinensis, Radix Rehmanniae, Poria, Radix Paeoniae Alba, Fructus Jujubae, Rhizoma Polygonati, Radix et Rhizoma Glycyrrhizae, etc.); Qi stagnation and blood stasis type, which is treated with Blood Mansions and Blood Stasis Tang (Radix Angelicae Sinensis, Radix Rehmanniae Sinensis, Rhizoma Polygonati, Radix Safflower, Citrus Aurantium, Radix Paeoniae, Radix Bupleurum, Radix Glycyrrhizae, Rhizoma Chuanxiong, Radix Bupleurum, etc.); and Qi stagnation and phlegm For the type of blockage, we use the formula “Medical formula collection and explanation” Qigong pill plus or minus (Chuanxiong, Atractylodes, Semen, Poria, Shenqu, Chenpi, Licorice, etc.); for the type of deficiency of the kidneys with qi stagnation, we use the formula “Fu Qingzheng masters of women’s medicine” Kaiyu seed yu Tang plus or minus (Angelica sinensis, Aromatic herb, Atractylodes, Poria, Paeonia, Cornus, Radix Rehmanniae, etc.). Among the 34 patients, 26 cases were cured, 5 cases improved, and 3 cases were ineffective, with faster relief of symptoms such as premenstrual breast distension, chest congestion and depression, and longer improvement of ovulation and luteal function. and luteal function for a longer period of time. The total effective rate was 94.51% after one to four courses of treatment. This formula can significantly improve the BBT high temperature phase and the endometrial secretion dysphoria. It was also verified by pharmacological efficacy test that it can significantly counteract the elevation of PRL in rats caused by gastric rennet and has the effect of reducing PRL. It can significantly elevate serum E2 and reduce the organ coefficient of rat uterus. Fan’s [5] started to take Wuzi Yanzong Wan plus orally on the 6th day of menstrual cycle (Cuscuta sinensis, Raspberry, Lycium barbarum, Plantago ovata, Schisandra chinensis, Radix rehmanniae, Radix Angelicae Sinensis, Radix et Rhizoma shouwu, Radix paeoniae, Pericarpium chenopodium, Radix et Rhizoma sandy), 1 dose every day for 6 days. 2 days after the rise of BBT, Epimedium, Mugwort, and Zihejiang powder were added, 1 dose every other day, 6 doses in total. 3 menstrual cycles were taken as 1 course of treatment, and 1 to 2 courses of treatment were taken. The effect is remarkable. Pan’s [11] took luteinizing soup (Cuscuta sinensis, Morinda citrifolia, Yam, Agaricus blazei, Astragalus, Xianmao, Xianling spleen, Raspberry, Radix Codonopsis, Glycyrrhiza glabra) on the 15th day of menstrual cycle, 1 dose every day for 10 doses, and the total effective rate was 91% in 3 menstrual cycles. Meng’s [12] started to use Huang-supporting soup (Shu-Di, He Shou Wu, Fructus Lycii, Xuan Shen, Mai Dong, Dan Pi, Yi Mu Cao, Raspberry, Cuscuta, Epimedium, Ba Ji Tian) on the second day after the rise of body temperature until the next menstruation, with a total efficiency of 79.16%. 4 herbal manual cycle treatment: Cai [13] used the sequential treatment of tonifying the kidney and sparing the liver. With 1 dose daily, the pregnancy rate was 71.88% and the total effective rate was 90.63%. Sun’s [14] took Liu Wei Di Huang Tang combined with Er Zhi Wan plus flavor for 6 doses after menstruation, and Liu Wei Di Huang Tang combined with Er Xian Tang plus reduction for 6 doses after ovulation for 3 menstrual cycles (1 course of treatment), with a total effective rate of 97%. Liu [15] and others followed Xia Gui Cheng’s theory of “deficiency of kidney yang” and proposed the method of tonifying the kidney and regulating the week: 7 doses of Nourishing Kidney and Liver Drink (Angelica sinensis, Shu Di Huang, Shan Yao, Cornu Cervi Pantotrichum, Mudan Pi, Fu Ling, Chuan Xuan Zhuan, Bai Zhu, Chai Hu) on the 6th to 12th day of the menstrual cycle; 7 doses of Tonifying Kidney and Promoting Ovulation Soup (Deer Horns, Angelica sinensis, Er Shao, Shan Yao) on the 13th to 19th day of the menstrual cycle. The formula was applied to the menstrual cycle from 20 to 28 days with Yulinzhu Plus and Minus (Deer horn tablet, Radix Rehmanniae, Radix Angelicae Sinensis, Paeonia lactiflora, Radix Angelicae Sinensis, Danggui, Poria, Radix Rehmanniae Sinensis, Atractylodes Macrocephalae, Wu Ling Ling Ling, Aromatic Herb) for 9 doses; the formula for menstruation was applied to the menstrual cycle for 5 doses with Wu Wei Tiao Menstrual San Plus and Minus (Atractylodes Macrocephalae, Aromatic Herb, Danggui, Dangpi, Hawthorn, Salviae Miltiorrhizae, Radix Paeoniae, Zelenia, Wu Ling Ling Ling, Yimu Cao). The total effective rate was 93.75%. Zhong’s [16] advocated warming the kidney and strengthening the spleen to nourish the blood during the follicular phase (Radix et Rhizoma Ginseng, Atractylodes Macrocephalae, Radix Paeoniae Alba, Radix Angelicae Sinensis, Radix Rehmanniae Sinensis, Semen Cuscutae, Semen Cuscutae, Herba Cistanches, Radix Glycyrrhiza Uralensis); if the basal body temperature rises for 18 days, the treatment is to tonify the kidney, benefit the qi, nourish the blood and calm the fetus (Semen Cuscutae, Radix Rehmanniae Sinensis, Radix Rehmanniae Sinensis, Radix Aconite, Radix Aconite); if the basal body temperature rises for 18 days, the treatment is to tonify the kidney, benefit the qi, nourish the blood and calm the fetus (Semen Cuscutae, Radix Rehmanniae Sinensis, If the basal body temperature rises up to 18 days, the treatment is to tonify the kidney, benefit the qi, nourish the blood and calm the fetus (Cuscuta sinensis, Radix et Rhizoma mulberry, Radix et Rhizoma rehmanniae, Colla Corii Asini, Radix et Rhizoma Codonopsis, Rhizoma Atractylodis Macrocephalae, Radix et Rhizoma Paeoniae). 5 Combination of Chinese and Western medicine treatment: Bao [17] used menstrual regulation formula (Radix et Rhizoma Ginseng, Radix Rehmanniae, Radix Rehmanniae, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix et Rhizoma Paeoniae, Rhizoma Saffron, Radix Salviae Miltiorrhizae, Radix Salviae Miltiorrhizae) on days 1-5 of menstruation based on the oral administration of Zi He Che capsule; follicle promotion formula (Radix Angelicae Sinensis, Radix Rehmanniae Sinensis, Cornu Cervi Pantotrichum, Rhizoma Huang Jing, Semen Cuscutae, Rhizoma Atractylodis, Rhizoma Atractylodis) on days 6-10; ovulation promotion formula (Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Rhizoma Dan Shen, Rhizoma Atractylodis) on days 11-15, Radix et Rhizoma lactis, Salviae Miltiorrhizae, Radix et Rhizoma cyperus, Radix et Rhizoma cyperus, Radix et Rhizoma Zeleniae, Radix et Rhizoma Dioscoreae); on day 16-25, use the luteal formula (Radix et Rhizoma lactis, Radix et Rhizoma lactis, Radix et Rhizoma lactis, Radix et Rhizoma Atractylodis Macrocephalae, Rhizoma yam, Rhizoma Amethyst, Rhizoma Polygonati, Rhizoma Cuscutae, Rhizoma Polygonati). With the addition of western medicine (HCG 1000μ,progesterone 10mg), 14 cases were cured and 6 cases improved. Mao’s [18] used a staged approach to identify the symptoms, nourishing and harmonizing the blood during menstruation (Shu Di, Angelica sinensis, Chuanxiong, Bai Shao, Huang Qi, Fructus Lycii, Xiang Shen); warming the yang, tonifying the kidney, promoting blood circulation during ovulation (Xian Ling Spleen, Xian Mao, Ba Ji Ren, Cuscuta, Fructus Lycii, Serpentine, Angelica, Ze Lan, Chai Hu, Soapberry, and Fructus Aromaticus); and adding Gui Lu Er Xian Tang during the luteal phase (Gui Pan, Deer Antler Gum, Xian Ling Spleen, Xian Mao, Fructus Puzzle, Cuscuta, (Guisan, Deer horn gum, Xian Ling Spleen, Xian Mao, Gui Ren, Semen Cuscutae, Cuscutae, Fructus Lycii, Raspberry, Serpentine Seed) or with the addition and subtraction of Jia Wei Yi Yuan San (Chai Hu, Angelicae, Bai Shao, Dampi, Fried Gardenia, Sheng Di, Tao Ren, Safflower, Poria, Atractylodes, Peppermint). Combined with western medicine (clomiphene 50mg/day or HCG 1000μ~5000μ/day), the total effective rate was 88.5%. Zhang [6] et al. compared the Chinese medicine group (oral on the 5th day of menstruation: Cuscuta, Raspberry, Fructus Lycii, Erdi, Cornu Cervi Pantotrichum, Astragalus, Radix Angelicae Sinensis, Bacopa monnieri, Yam, Citrus Aurantium, Chrysanthemum, Radix et Rhizoma; oral after ovulation: Astragalus, Radix Angelicae Sinensis, Cuscuta, Raspberry, Fructus Lycii, Radix Rehmanniae, Zelenia, Rhizoma Ziziphi, Rhizoma Urticae, Yujin, Radix Paeoniae Alba, Cistanches, Cornu Cervi Pantotrichum); Western medicine group (clomiphene 50mg/day The total effective rates of the three groups were 83.9%, 66.6% and 94.7%, respectively. It was concluded that the Chinese medicine and the combination of Chinese and Western medicine groups were significantly better than the Western medicine group, and the clinical TCM symptoms of kidney deficiency with Qi and blood deficiency, symptoms of irregular menstruation, ovulation function and endometrial thickness were significantly improved. Zheng [19] used Chinese herbs to tonify the kidney and activate the blood (Angelica sinensis, Radix Rehmanniae, Deer antler cream, Radix Bacopa monniera, Cistanches, Chuanjian, Fructus Lycii, Semen Cuscutae, Huai Shan, Amethyst, Paeonia lactiflora, etc.); combined with psychological guidance and western medicine (clomiphene, HCG or bromelain, etc.), the overall pregnancy rate was 65.7%. Wang’s [20] self-prepared herbal medicine (amethyst, pepper, chuanxiong, sequestra, cow’s knee, angelica, er shao, made aromatic herb, wolfberry, cuscuta, danpi, gui xin, epimedium) combined with western medicine (clomiphene 50mg/day, ethylene estradiol 0.25mg, HCG 1000iu), with an efficiency of 78.33%. 6 Psychological treatment: As early as in the Nei Jing, it is written that “tell its defeat, talk about its goodness, guide its place, and open its suffering”. Li’s [21] et al. compared the drug-only group with the drug-plus-psychotherapy group and showed that there was a significant difference in the pregnancy rate between the two groups. 7 Other treatments: Liu’s [22] advocated conception during the good biological clock period by taking 6 doses of each for 3 months (male: roasted astragalus, rehmannia, codonopsis, atractylodes, poria, angelica, danshen, wolfberry, cuscuta, sandy nuts, heliotrope leaves, salt ginseng, licorice, bupleurum; female: rehmannia, angelica, bupleurum, shamrock, Chuanjian, wolfberry, turtle gum, deer gum, danshen, salt ginseng). The female side took 3 doses of oral ovulation medicine (Radix Rehmanniae, Radix Angelicae Sinensis, Radix Paeoniae Alba, Peach kernel, Radix Aromaticus, Rhizoma Zeleniae, Rhizoma Azadirachtae, Rhizoma Saffron, Rhizoma Chuanxiong) before ovulation in the third month, and 20 days after the rise of basal body temperature, she took nourishing and calming products (Radix Codonopsis, Rhizoma Atractylodis Macrocephalae, Radix Aconiti, Rhizoma Dulcis, Rhizoma Cuscutae, Rhizoma Chuanbao, Rhizoma Parviflora, Rhizoma Saxifraga, Rhizoma Sandy) with an overall efficiency of 88%, with a maximum age of 43 years. Pang [23] et al. finely grinded Chinese herbs (Cornu Cervi Pantotrichum, Shu Di, Shan Yao, Bai Shao, Licorice, Tortoise, Dry Ginger), mixed into a paste (10g/time) with warm water, applied to the Shen Que point, covered with gauze and fixed with adhesive tape. The medication was started on the 5th day of menstruation, and 8 times as a course of treatment. 86 cases were cured and 46 cases were invalid. 8 Laboratory studies: Yu [24][25] et al. observed 17 patients with LPD of kidney deficiency and spleen weakness, and hysteroscopy revealed increased abnormal changes in their uterine cavity, especially pale and hypertrophic endometrium with localized polyp-like hyperplasia, which may be related to kidney deficiency and lack of qi-transformation, spleen deficiency and dereliction of duty of transportation and transformation, and stagnation of lipid film and water-dampness in the uterus. The application of herbs that warm the kidneys and strengthen the spleen can significantly increase the levels of trace elements Zn and Cu in the blood of this type of patients and reduce the Cu/Zn ratio, which in turn is proposed as one of the objective clinical diagnostic indicators for this type of infertility. Wang [26] studied 418 endometrial biopsies in patients with primary infertility and showed that the normal endometrial phase gradually decreased with age and the progesterone deficient endometrial phase gradually increased, suggesting poor follicular development and a significant age difference in luteal insufficiency. Thus, it was pointed out that patients with primary infertility should seek medical attention as early as possible to avoid missing the optimal physiological period for fertility. Lu [27] studied cervical mucus during ovulation in patients with LPD, in which IL1β levels were significantly elevated, suggesting that the reproductive tract cervical local is in a state of cellular immune activation, which may have a detrimental effect on spermatozoa movement in the female reproductive tract, sperm-egg union and early embryo implantation, which may be closely related to the occurrence of LPD and its infertility; elevated TNFα levels suggest that the reproductive tract of LPD patients during ovulation Local macrophages are in an activated state and locally secreted TNFα may have a negative effect on the reproductive process by affecting sperm and/or embryo function. It is believed that the detection of cervical mucus TNFα and IL1β during ovulation can be used as a test to predict luteal function in infertility patients, which will help to study the etiology, diagnosis and treatment of LPD in depth and is expected to improve the success rate of human assisted conception techniques. 9 Conclusion: LPD infertility is a common and difficult disease in gynecology, which has a tendency to increase year by year with the increasing work pressure and fast pace of life. Although modern medicine continues to reveal the pathogenesis of LPD infertility from microscopic point of view through laboratory studies, it is still unable to find a satisfactory treatment, therefore, Chinese medicine is the first in the treatment field with its good efficacy and very low side effects. However, most of the samples reported in the recent literature are slightly insufficient in content; although emphasis was placed on the establishment of control groups, none of them were blinded in the study, which could not effectively avoid the subjectivity of observers and subjects; the treatment was always administered according to the patients’ menstrual cycle for 30 days, without discussing the individual differences, which undoubtedly affected the objectivity, accuracy and credibility of the study results, and if these deficiencies can be overcome If these shortcomings can be overcome, the findings of TCM for LPD infertility will be more scientific.