Premature ovarian failure (POF) is defined as ovarian hypofunction with amenorrhea due to hypergonadotropic hormones before the age of 40 years, with an incidence of about 1 to 3%. POF leads to a decrease in natural conception rates, but some women with POF can still conceive spontaneously. Therefore, primary ovarian insufficiency is a more appropriate term to describe this group of patients than POF, covering a wide range of dysfunctions and more suitable for clinical application. The most common causes are X chromosome abnormalities, such as Turner syndrome, deletion of the short or long arm of the X chromosome; autosomal abnormalities and crossover ectopics, such as trisomy 13 and 18, which have been found to be associated with ovarian reproductive disorders; and other phenotypic chromosomal abnormalities, such as autoimmune endocrine-related syndrome (APS) types 1 and 2, Perrault syndrome Other phenotypes are associated with autoimmune endocrine-related syndrome (APS) type 1 and 2, Perrault syndrome, ataxia capillaris, and other disorders. Diagnosis Patients are most often seen for primary or secondary amenorrhea and infertility. The first examination should include blood FSH, blood TSH, X chromosome histotype, fragile X chromosome screening, and dual-energy X-ray spectrophotometry. After ruling out other factors of infertility, a thorough examination of the pelvic floor, breast, and pubic hair growth should be performed. Primary amenorrhea is usually due to Turner’s syndrome, congenital dysfunction such as Miller’s duct hypoplasia, androgen insensitivity, gonadal hypoplasia, etc. In secondary amenorrhea, after excluding unplanned pregnancy, tests for prolactin and thyroid hormones are required. After ruling out hyperprolactinemia and thyroid disease, a progesterone test will be performed. If the test is negative, estrogen deficiency or atresia of the genital tract is indicated. FSH levels should be measured or checked at the time of the initial visit. In addition, anti-Miller hormone (AMH) levels below 1.0 ng/Ml can be considered as insufficient ovarian reserve. Therefore, AMH measurement can be used as an early screening test for POF. After the diagnosis of POF is confirmed, the patient should undergo karyotyping. Karyotyping is of great interest in young patients and those who have never been pregnant; in addition, all patients with POF should be recommended for screening for fragile X chromosomes, regardless of age and maternal history. In the long term, patients present with infertility, anxiety and low self-esteem, decreased libido, decreased general well-being, autoimmune dysfunction, osteoporosis, ischemic heart disease, and increased mortality. The consequences of hypoestrogenemia (e.g., osteoporosis, genital atrophy, etc.) are severely detrimental to the quality of life of the patient and are accompanied by a decrease in androgen concentration and consequent sexual dysfunction. POF can be accompanied by autoimmune diseases, the most common of which is hypothyroidism, as well as adrenocortical insufficiency, type 1 diabetes, and pernicious anemia, etc. Patients with POF have a very low chance of conceiving naturally, and their only option is IVF using donor oocytes. Clinicians generally do not recommend pregnancy in patients with Turner syndrome because of the high risk of aortic aneurysm rupture and because the risk cannot be predicted based on the degree of aortic root dilatation. The primary goal is to avoid the development of hypoestrogenemia. Once POF is diagnosed, hormone replacement therapy (HRT) is given, which is mostly used for postmenopausal women. In recent years, oral contraceptive pills (OCPs) have been found to be more effective than HRT. On the one hand, OCPs contain two to four times higher doses of estrogen than postmenopausal HRT; on the other hand, OCPs can be used in conjunction with contraception, which may relieve them of the pressure to have children. Long-term estrogen use was previously thought to increase the risk of breast cancer, cardiovascular disease, and stroke, but the association is not significant for patients with POF. In contrast, some patients with high risk factors for thromboembolism (e.g., smoking) may be switched to transdermal administration. In patients with vaginal atrophy, topical progestin supplementation can be used, which is more than four times more effective locally than intramuscularly or orally. For patients with osteoporosis, calcium and vitamin D supplementation are necessary. Once osteoporosis is diagnosed, bone resorption inhibitors such as bisphosphonates are required: first-line drugs are alendronate, risedronate, zoledronic acid, and denosumab; second-line drugs are ibandronate; and raloxifene is a second- or third-line drug. Screening for autoimmune disease is optional, but TSH testing is still necessary, and other tests such as fasting glucose, blood count, serum calcium, and adrenal 21-hydroxylase are optional additions to differentiate from other autoimmune diseases. Anti-ovarian tissue antibodies are unnecessary and therefore of little clinical relevance and not very helpful in the treatment. In the management of infertility, laparoscopic or transvaginal ovarian biopsy is not useful in the management of infertility, and estrogen prior to IVF is of little significance. In this group of patients, estrogen pretreatment and all types of ovulation treatment are not recommended and IVF with donor oocytes is the most effective method. However, in patients with Turner syndrome, lifelong contraception should be used. In conclusion, a diagnosis of primary ovarian insufficiency will have a serious impact on the physical and mental health of the woman and her long-term outcome. Timely diagnosis, counseling, and intervention may improve these outcomes to some extent.