Ovulation disorders are common endocrine disorders, with a prevalence of up to 25-30% in infertility. The clinical manifestations are varied, such as menstrual disorders (hypomenorrhea, thinning and amenorrhea), hirsutism, obesity, and infertility. Due to prolonged anovulation, the endometrium is overproliferated without the counteracting effect of cyclic progesterone, and therefore has a high risk of developing endometrial cancer or breast cancer. Therefore, ovulation treatment is not only a solution to the problem of female fertility, but also a need to prevent and treat women’s diseases. Normal ovulation depends on the regulation of the hypothalamo-pituitary-ovarian axis (HPOA) and the paracrine/autocrine function of the ovaries. The etiology of ovulatory disorders is quite complex and is clinically classified into hypothalamic anovulation, pituitary anovulation, ovarian anovulation and anovulation caused by other endocrine gland function abnormalities. Induced ovulation refers to the use of drugs or surgery to induce ovulation in patients with ovulatory disorders, usually with the aim of inducing the development of a single follicle or a few follicles. Superovulation, also known as controlled ovarian hyperstimulation (COH), refers to the induction of multiple follicle development and maturation by pharmacological means within a controlled range, usually in patients with normal ovulatory function. Ovulation prediction is a clinically important tool in the diagnosis of ovulatory disorders and usually requires several cycles of continuous observation to determine the presence or absence of ovulation more accurately. Commonly used methods to diagnose ovulation include basal body temperature monitoring, cervical mucus examination, reproductive endocrine hormone measurement, ultrasound monitoring and endometrial biopsy. There are many kinds of ovulation-promoting drugs, which act at different levels of the hypothalamic-pituitary-ovarian axis and produce effects through different mechanisms. After systematic screening of the causes of infertility and confirming that ovulation disorders are the only cause of infertility, most infertile couples can achieve satisfactory clinical results after reasonable and systematic drug treatment. The pregnancy rate is almost comparable to that of the normal population, and the earlier the treatment, the better the results. Many infertile women at the primary level have only mild hypothalamic-pituitary-ovarian axis dysfunction, and due to improper treatment, the cure is not only delayed but even aggravated. Therefore, determining the cause and site of the lesion and correctly selecting the appropriate drug therapy is the key to achieving successful ovulation induction. The application of ovulation-promoting drugs must have clear indications and is generally used only in patients with hypothalamic-pituitary-ovarian hypofunction or incoordination, as well as in artificially assisted conception treatment cycles. Ovulation-promoting drugs are not effective in women with ovulation disorders due to systemic disorders or lesions of the ovaries themselves, such as congenital ovarian hypoplasia, postmenopause or premature ovarian failure. Before treatment, a detailed medical history must be taken and a careful physical examination must be performed, especially to clarify the function of important organs and the condition of the fallopian tubes to prevent ectopic pregnancy and to ensure the safety of treatment, and to exclude male infertility factors before implementation. Clomiphene citrate (CC) (a) Chemical structure and preparation Clomiphene, also known as clomid, serophene, has the chemical name of 1-chloro-2-[p-(2,-diethylaminoethoxy)phenyl]-1,2-diphenylethyl citrate. It was first synthesized in 1956 and started to be used clinically in 1960. It is obtained by etherification of 4-hydroxydiphenylketone with diethylaminochloroethane hydrochloride to obtain p-diethylaminooxydiphenylketone, which is added, hydrolyzed, eliminated and chlorinated to make chlorostigmine [(911-45-5)], and finally the product is obtained by citrate salt. (II) Mechanism of action The chemical mechanism formula of clomiphene is similar to that of estrogen. It has a strong anti-estrogenic effect and weak estrogenic activity. It can compete with endogenous estrogen for receptors at the hypothalamus and pituitary levels, release negative feedback from estrogen, increase the frequency of gonadotropin-releasing hormone (GnRH) pulse, which in turn causes the pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and FSH promotes follicle development and maturation, while the rise in estradiol level causes positive feedback, promoting the release of large amounts of GnRH from the hypothalamus and the release of (ii) Indications (iii) Indications There are two prerequisites for the use of CC: firstly, anovulation or sporadic ovulation in patients with certain endogenous estrogen levels, such as those with menstrual cycle, positive progesterone test, or E2>100pg/ml, etc.; secondly, the HPOA axis has a sound positive feedback function. The indications are mainly 1) PCOS. 2) Secondary low or normal gonadotropin amenorrhea, such as hypothalamic amenorrhea, amenorrhea after using contraceptives, etc. 3) Amenorrhea and overflow syndrome when bromocriptine is ineffective, CC can be added. 4) Anovulatory uterine bleeding, especially in patients with anovulatory uterine bleeding and luteal insufficiency during puberty. 5) Fertility assistance techniques, superovulation in combination with other drugs. (D) Contraindications Contraindicated in patients with liver disease, kidney disease, ovarian cysts and other gynecological tumors. （The most common ones are facial flushing, abdominal distension, breast discomfort, nausea, vomiting, visual disturbance, headache and hair loss. The symptoms will disappear naturally after stopping the drug and do not need to be treated. Clomiphene has no teratogenic effect. (vi) Dosage Natural menstrual cycle or artificially induced menstrual cycle starting from day 3 to 5, 50-100mg/d for 5 days. After 2-4 days of discontinuation, the follicle development can be monitored by urine LH test strip or by ultrasound. When LH peak appears, or when the dominant follicle reaches 18-20mm, add HCG 10000IU intramuscularly to promote final follicle maturation and ovulation and maintain luteal function. When ovulation is induced with clomiphene, its anti-estrogenic effect inhibits the pituitary and hypothalamic related estrogen receptors for a long time, which weakens the positive feedback effect of the high E2 level produced by the follicles on the pituitary gland, and can cause the endogenous LH peak formation to be insufficiently high pointed, or the LH peak to appear early but with a low peak due to the development of multiple follicles, resulting in the failure of ovulation and the luteinization of granulosa cells before ovulation. consider the use of HCG to induce ovulation. The patient is instructed to have intercourse or perform IUI on the same day and the next night. If patients fail to conceive with clomiphene alone, a small amount of estrogen may be considered, such as estradiol valerate (Tegretol) 1-4 mg/d for 10 days starting on the fifth day of menstruation, to improve the quality of cervical mucus and increase the thickness of the endometrium for sperm entry and embryo implantation. (vii) Treatment effect: Ovulation rate of 60～80%, pregnancy rate of 11～56%. Clomiphene citrate (CC), by antagonizing ER in hypothalamus pituitary gland, relieves the feedback inhibitory effect of estrogen on hypothalamus/pituitary gland, increases secretion of pituitary gonadotropin and induces follicle growth and development, but also occupies ER in endometrial and cervical tissues and exerts anti-estrogen effect, resulting in insufficient edema of endometrial tissues, incomplete metaphase, and incomplete implantation window. However, it also occupies the endometrium and cervical tissues and plays an anti-estrogenic role, resulting in insufficient edema of endometrial tissues, incomplete metaplasia, reduced drinking vesicles during the implantation window, reduced secretion of cervical mucus, and viscous nature, which does not facilitate sperm penetration and affects pregnancy. However, because of its low cost, ease of use, safety and effectiveness, it is still one of the most commonly used ovulation-promoting drugs in clinical practice. Gonadotropin (Gn) (a) types and physicochemical properties 1. human menopausal gonadotropin (HMG) urinary gonadotropin (Leporte). HMG is a glycoprotein gonadotropin extracted from the urine of menopausal women, each containing 75 IU FSH and 75 IU LH. In 1959, Lunenfeld and others in Israel were the first to use it in clinical practice to induce ovulation and obtain a full-term delivery, and it has been produced and used in China since the 1980s. In recent years, most pharmaceutical companies have purified HMG to ensure the content of FSH, while the content of LH has been greatly reduced. FSH was obtained from the urine of menopausal women by applying immunochromatographic method. 1983 was the first time to obtain a product containing only FSH activity, which is almost free of LH activity and has similar physiological effects to FSH, stimulating follicular growth and development, increasing estrogen levels, and promoting endometrial proliferation. High purity FSH is like a further purified product. Through biotechnology, FSH was aspirated from HMG raw material and in 1993, high purity human FSH was produced with a purity of over 95%. High purity FSH is safer to use, has fewer adverse effects, is easy to administer, and can be self-administered by patients by subcutaneous injection. The most appropriate endometrial thickness is 9-14 mm. there are 3 types of endometrial morphology: A, B and C. Type A (for those with three clear lines): a highly echogenic lateral line formed between the endometrium and the myometrium and a clearly visible highly echogenic central line formed by the two superficial layers of the endometrium in close proximity; Type B: a highly echogenic line formed by the endometrium and the myometrium. Type B: endometrial echogenicity is lower than that of the myometrium and lacks a hyperechoic central line; Type C: endometrial echogenicity is higher than that of the myometrium and lacks a hyperechoic central line. type A endometrial embryo transfer thick pregnancy rate is the highest. The E2 level in the circulation is a pointer to the change in follicular function in the ovary, so it is widely used to monitor follicular development during ovulation promotion. 24 h before the peak of LH, the blood E2 reaches 200-400 Pg/ml, which is called the peak E2, and 24-48 h after the peak E2 ovulation. The E2 value of 3000 pg/ml should alert the occurrence of ovarian hyperstimulation syndrome. (b) LH measurement: LH reaches a peak of 40-200 IU/L before ovulation, which is called peak LH, and ovulation occurs within 24-36 hours after peak LH. 42.4% of ovulation occurs on the day of peak LH and 54.6% on the next day, i.e. about 97% of ovulation occurs within 24 hours after peak LH, so it is a reliable diagnostic method. The urinary LH peak is usually 3-6 hours later than the blood LH peak, and about 1/3 exceeds 6-12 hours. Urinary LH levels up to 20 IU/L suggest the starting point of urinary LH peak, and ≥40 IU/L is the peak. Ovulation 12 to 24 hours after the urinary LH peak. This method is semi-quantitative, simple, economical, non-invasive and easy for patients to self-monitor.