Недостаточность яичников преждевременная: причины, диагностика и современные подходы к лечению.

Primary ovarian insufficiency (POI), also called premature ovarian insufficiency, premature menopause, and premature ovarian failure, is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of follicular (egg producing area) dysfunction or early loss of eggs. POI affects approximately 1 in 10,000 women under age 20, 1 in 1,000 women under age 30, and 1 in 100 of those under age 40. A medical triad for the diagnosis is amenorrhea, hypergonadotropism, and hypoestrogenism. Although 5 to 10% of women with POI may ovulate sporadically and become pregnant without treatment, others may use assisted reproductive technology including in vitro fertilization and egg donation or decide to adopt or remain childless. The causes of POI are heterogeneous and are unknown in 90% of cases. Two to 5% of women with POI and a premutation in FMR1, a genetic abnormality, are at risk of having a child with fragile X syndrome, the most common cause of inherited intellectual disability.

BRCA1 protein plays an essential role in the repair of DNA double strand breaks by homologous recombination. Women with a germline BRCA1 mutation tend to have premature menopause as evidenced by the final amenorrhea appearing at a younger age. BRCA1 mutations are associated with occult POI. Impairment of the repair of DNA double strand breaks due to a BRCA1 defect leads to premature ovarian aging in both mice and humans. In addition to BRCA1, the MCM8 MCM9 protein complex also plays a crucial role in the recombinational repair of DNA double strand breaks. In humans, an MCM8 mutation can give rise to premature ovarian failure, as well as chromosomal instability. MCM9, as well as MCM8, mutations are also associated with ovarian failure and chromosomal instability. The MCM8 MCM9 complex is likely required for the homologous recombinational repair of DNA double strand breaks that are present during the pachytene stage of meiosis I. In women homozygous for MCM8 or MCM9 mutations, failure to repair breaks apparently leads to oocyte death and small or absent ovaries. Results from studies on DHEA in 2010 indicated that DHEA may increase spontaneously conceived pregnancies, decrease spontaneous miscarriage rates and improve IVF success rates in women with POI. This includes women referred for donor eggs or surrogacy in 2009. In 2018, there was no significant improvement in ovarian function by 12 month on DHEA supplementation in women with POI. Ovarian tissue cryopreservation can be performed on prepubertal girls at risk for premature ovarian failure, and this procedure is as feasible and safe as comparable operative procedures in children. In 2013, Kawamura in Japan and his collaborators at Stanford University published treatment of infertility of POI patients by fragmenting ovaries followed by in vitro treatment of ovarian fragments with phosphatidylinositol 3 kinase activators to enhance the AKT pathway followed by autografting. They successfully promoted follicle growth, retrieved mature oocytes, and performed in vitro fertilization. Following embryo transfer, a healthy baby was delivered. A 2020 review covered variations including phosphatidylinositol 3 kinase activators to enhance the AKT pathway, fragmentation of ovarian cortex, combining those two into in vitro activation (IVA), and drug free IVA. Two laparoscopies are needed in conventional IVA and one with drug free IVA. The transdermal estradiol patch also provides the replacement by steady infusion rather than by bolus when taking daily pills. There is also an increased risk with valvular heart disease and cardiomyopathy. To avoid the development of endometrial cancer young women taking estradiol replacement need also to take a progestin in a regular cyclic fashion. The most evidence supports the use of medroxyprogesterone acetate per day for days one through 12 of each calendar month. This will induce regular and predictable menstrual cycles. It is important that women taking this regimen keep a menstrual calendar. If the next expected menses is late it is important to get a pregnancy test. It this is positive, the woman should stop taking the hormone replacement. Approximately 5 to 10% of women with confirmed POI conceive a pregnancy after the diagnosis without medical intervention.

The most common words women use to describe how they felt in the two hours after being given the diagnosis of POI are "devastated", "shocked," and "confused." The diagnosis is more than infertility and affects a woman's physical and emotional well being. Some have advocated formation of a patient registry as well as a community based research consortium with integrative care to better understand the etiology and treatment of the condition, including treatment of its psychological effects. Women with POI perceive lower social support than control women, so building a trusted community of practice for them would be expected to improve their well being. Also, when having that social support, it often helps with reducing stress and having better coping skills. It is important to connect women with POI to an appropriate collaborative care team because the condition has been clearly associated with suicide related to the stigma of infertility.

The prevalence increases with age and is approximately 1 in 10,000 women under age 20, 1 in 1,000 women under age 30, and one percent by age of 40. It occurs in 3.7% of women worldwide and 1% of women in the United States. In the United States, the incidence is 1% in White women, 1.4% in Black and Hispanic women, with lower rates seen in Chinese and Japanese women, at 0.5% and 0.1% respectively.

Fuller Albright et al. in 1942 reported a syndrome with amenorrhea, estrogen deficiency, menopausal FSH levels, and short stature. They used the term "primary ovarian insufficiency" to distinguished POI from ovarian insufficiency secondary to a primary failure of pituitary FSH and other hormonal secretion. POI has been described as a more accurate and less stigmatizing term than premature ovarian failure