Premature ovarian failure refers to the appearance of amenorrhea, low blood estrogen levels, high gonadotropin concentrations, sometimes accompanied by menopausal symptoms such as hot flashes and sweating in women after pubertal development and before the age of 40 years, named because it is very similar to physiological menopause, also called early menopause or early onset menopause. 1.Diagnosis Diagnosis is based on clinical findings, blood or urine hormone measurements, and pathological histological examination. In addition, the relevant medical history is also of great reference value for the diagnosis. (1) Clinical findings The age of menarche is often abnormal, and menstrual disorders may occur, followed by amenorrhea; or menstruation may start regularly and then become irregular; there are also cases of sudden amenorrhea (those who have had pregnancy and delivery). About 20% to 70% of patients have vasodystrophic syndrome such as facial flushing. Although atrophy of reproductive organs is rare, if premature ovarian failure occurs in early adolescence, the secondary sexual characteristics are not obvious. (2) Endocrinological examination: follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) should be measured in amenorrheic patients with negative progesterone test. LH concentrations may be normal or >50u/L, and estrogen levels are generally low, but there are also normal cases. It has also been suggested that systematic endocrinological examinations should be performed in patients with premature ovarian failure, including daily measurement of FSH, LH and estradiol (E2) for 1 month and luteinizing hormone-releasing hormone (LH-RH) excitation test, if there is a fluctuating increase or decrease in FSH with a temporary increase in E2, there may be a chance to resume ovulation. If the E2 value exceeds the level of menopausal women and LH is increased and LH/FSH=2:1, it indicates the existence of hormonal feedback mechanism and ovulation induction therapy may be successful. (3) Pathological histological examination According to the histological examination, patients can be divided into two categories: (1) no follicles are seen, completely occupied by fibrotic mesenchyme; (2) only normal primordial to primary follicles are present, and they do not develop even if large amounts of gonadotropins are given, which is called anti-ovarian syndrome. In most cases, the first histologic finding is that the atrophied ovary has no follicles or only atretic follicles, and the diagnosis is made if fibrous degeneration is seen in the interstitial part of the ovary as in menopausal patients. Laparoscopic ovarian biopsy has its limitations in that some follicles are deeply buried in the interstitial part of the ovary, so it is usually appropriate to remove the deep ovarian tissue for examination by dissection. Laparoscopic observation of the ovaries is also helpful for diagnosis. The vast majority are bilateral ovarian atrophic or striated ovaries. Only 15% have small or normal ovaries either unilaterally or bilaterally. Atrophic or striated ovaries have no follicles present. (4) Relevant medical history Chromosomal abnormalities, viral and bacterial infections, history of exposure to physical and chemical factors, immune disorders and family history are all associated with the development of this disease. For example, Tumer syndrome (45, XO) is caused by the complete loss of the primordial follicle in the fetus, gonadal dysgenesis, and the absence of the chimeric X chromosome or its long arm. The ovaries of those with previous mumps are susceptible to failure of function. In addition, pelvic infections or harmful substances accumulating in the ovaries, radiation therapy or drug treatment, Addison’s disease, thyroiditis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, myasthenia gravis, diabetes mellitus, pernicious anemia and other autoimmune diseases, as well as family genetic factors (about 10% of patients have a family history of menopause before the age of 30 years in their mother and grandmother) are associated with the disease. The above mentioned conditions, combined with clinical and examination will help in the diagnosis. 2. Treatment Premature ovarian failure currently lacks ideal treatment. Most of these patients present with symptoms of amenorrhea or require fertility. In young women, those with low estrogen amenorrhea should undergo artificial cycle replacement therapy. The goal is to eliminate menopausal symptoms, expect fertility and improve sexual function. Estrogen therapy can increase FSH receptors and promote residual follicle development, as well as prevent metabolic abnormalities caused by estrogen deficiency, such as osteoporosis and coronary artery lesions. Combined estrogen 1.25 mg/d for 24 days, and progesterone 10 μg/d on the last 10 days. 4 mg of nil estrol can also be taken on days 5 and 14 of menstruation, and 5 mg/d of gynecomastia tablets on days 21-25 for 5 days. This therapy is recommended because it is convenient to take orally with less frequent doses, has almost no gastrointestinal adverse effects, and can avoid the carcinogenic effects of estrogens in general. For those who have follicles and require fertility, ovulation induction therapy can be tried. Although the possibility of fertility is small, it is not sterilization. The specific methods are as follows. (1) Estrogen cycle therapy, at least 3 cycles, with pregnancy reported in domestic and foreign literature. (2) Gonadotropin therapy, because there are a few residual follicles in the ovary, and pregnancy can be obtained by treatment with large amounts of menopausal gonadotropin (hMG), or by LH-RH pulse method. (3) Combination therapy with clomiphene and hexenestrol, the former 50 mg/d for 5 days and the latter 0.5-1.0 mg/d for 20 days. (4) Combined treatment with chorionic gonadotropin (HCG) and hexestrol: 0.5-1.0 mg/d for 20 days for hexestrol and 10,000 u/d for 5 days for HCG during the cycle. (5) Oral contraceptive treatment. Oral contraceptives inhibit gonadotropins, which gradually increase the FSH and LH receptors on the granular follicular membrane cells and cause conception in response to endogenous sex hormones. (6) The use of IVF or gamete fallopian tube transplantation, the technique of egg donation has opened up new avenues to solve the fertility problems of those with premature ovarian failure. The patient is treated with estrogen and progestin to alter the endometrium in a secretory phase, which must be synchronized with that of the donor. The donor will be treated with ovulation promotion, the mature eggs will be retrieved at the right time, the sperm of the patient’s husband will be fertilized with the eggs of the donor in vitro, and then the fertilized eggs will be transplanted into the uterine cavity of the patient at the right time (gametes can also be transplanted into the fallopian tubes), and the appropriate estrogen and progestogen supplementation will stop at about 20 weeks of gestation. In conclusion, it is advisable to diagnose premature ovarian failure before complete menopause with a view to early treatment, and hormone replacement therapy should be given intermittently to prevent the onset of menopausal syndrome, osteoporosis and other metabolic disorders.