After 3-6 months of intramuscular injection of long-acting GnRH-a (3.75 mg/month) in PCOS patients, the ovarian atrophy, the number of follicles, LH concentration, LH/FSH ratio and androgen level are obviously reduced, but the drug cost is very expensive, about 7000-8000 yuan, and it is only used for refractory infertility in clinic. GnRH-a200-500ug subcutaneous injection for 2-4 weeks can also reduce LH and androgen levels. After pulse treatment with HMG, FSH or GnRH, the ovulation rate and pregnancy rate are improved, and the most important thing is that OHSS and abortion rate are significantly reduced.
For PCOS patients who have ovulated but are not pregnant after applying the standard ovulation cycle for more than 6 months, in vitro fertilization and embryo transfer can be selected. The pregnancy rate of PCOS patients can be similar to that of patients with tubal factors alone. Pay attention to the high incidence of severe ovarian hyperstimulation syndrome and the high rate of multiple pregnancy.
Surgical treatment can also be chosen if drug treatment fails. The disadvantage of wedge-shaped oophorectomy is that 10% patients have adhesion, which leads to mechanical infertility. Its curative effect is not lasting, and symptoms recur after several months. So it is rarely used at present. Laparoscopic electrocautery, diathermy or laser puncture can destroy 15-20 polycystic sites on each side of the ovary, which can cause natural ovulation or increase the sensitivity to clomiphene citrate treatment. This method can cause the decrease of androgen and inhibin, and can also cause wedge resection. The postoperative ovulation rate was 70-92% and the pregnancy rate was 36-86%. However, although laparoscopic surgery is to reduce the adhesion caused by open wedge resection, it can not completely avoid the formation of adhesion, so it is very important to minimize the damage of ovarian capsule and stop bleeding completely during operation. In addition, laparoscopic surgery also has the shortcomings of short duration of curative effect and easy recurrence of symptoms.
Polycystic Ovary Syndrome (PCOS) is an endocrine disease. The ovary is enlarged and contains many fluid-filled cysts, and the androgen level is increased, so it is impossible to ovulate. The main symptom of the patient is menstrual disorder, which is generally rare menstruation, and the amount of menstruation gradually decreases to amenorrhea. Because the androgen level is too high to ovulate, the patient may be infertile. In addition, patients will have hairy, prone to acne, greasy skin, obesity and other manifestations. B-ultrasound examination will find that the ovary is 2-3 times larger than normal, and these typical symptoms often appear in adolescence.
In terms of treatment, we need to start from the following three aspects:
1, general treatment. Patients should actively exercise, reduce the intake of high-fat and high-sugar foods and lose weight. This can promote the decline of androgen level and facilitate the recovery of ovulation.
2. medication. Drug therapy can counteract the effect of androgen and promote ovarian ovulation.
3. Laparoscopic surgery. If the above two methods fail, we need to consider laparoscopic surgery. Under laparoscopy, the level of androgen can be reduced by puncture of follicles, so as to achieve the therapeutic purpose.
The comprehensive theory is as follows:
Polycystic ovary syndrome was first reported by stein and leventhal in 1935, so it is also called stein—leventhal syndrome, which is one of the main factors of infertility in young married women. These patients have symptoms such as sparse amenorrhea, infertility, hirsute acne, obesity, and polycystic ovaries on both sides, which is an important factor causing anovulatory infertility. In addition to infertility, polycystic ovary syndrome has other pathological changes, such as anovulation, endometrial stimulation by estrogen alone, which leads to higher incidence of endometrial cancer than normal people, gland hyperplasia, metabolic changes, increased low-density lipoprotein (LPL) and triglyceride (TG) in blood, and decreased high-density lipoprotein (HDL). It is known that these changes will lead to atherosclerosis and coronary heart disease, so polycystic ovary syndrome is related to.
Etiology of polycystic ovary syndrome
The etiology of polycystic ovary syndrome is not clear, but many scholars believe that its etiology involves genetic and non-genetic theories.
The evidence of genetic theory is that 1.pocs is a family social phenomenon, and family analysis concludes that there are different genetic modes such as autosomal dominance and X-linked dominance. A recent family study shows that pcos is a single-gene autosomal dominant inheritance. 2. Family linkage analysis of candidate genes showed that Pcos was closely linked to a polymorphism in the regulatory region of cholesterol side-chain lyase gene, and the polymorphism and hirsutism were positively correlated with serum total testosterone. Anovulatory pocs are closely linked to type ⅲ variable number tandem repeats in the 5' regulatory region of insulin gene, and this polymorphism has been proved to lead to low expression of insulin gene. 3. The association analysis between candidate genes and diseases found that a polymorphism in the coding region of D3 dopamine receptor gene may be related to hyperandrogenic anovulation and clomiphene resistance.
The evidence of non-genetic theory is as follows: 1. Intrauterine hormone environment affects the endocrine status of adult individuals. Female rats exposed to high concentrations of androgen during pregnancy will have anovulation and polycystic ovary in adulthood. Kaohsiung hormone may change the normal secretion behavior of gonadotropin-releasing hormone by destroying the structure and function of postsynaptic membrane. A recent study reported that women with polycystic ovary with elevated luteinizing hormone (LH) but normal testosterone and weight were associated with longer pregnancy weeks, while obese women with elevated LH and testosterone were associated with maternal obesity and high birth weight, which also indicated that intrauterine environment affected individual secretion. 2. Early life and eating behavior affect individual endocrine status: protein overload in infancy will increase serum IGF-I level, change ovarian hormone production, and lead to polycystic ovary syndrome. Other factors before and after puberty, such as childhood obesity and abnormal adrenal function, can lead to the increase of androgen, thus increasing the transformation of external Zhou Xiong hormone into estrogen. Excessive estrogen levels will affect the functional perfection of synapses and synaptic membranes in arcuate nucleus and other centers in the brain. Lead to abnormal secretion of luteinizing hormone. In addition, patients with eating disorders such as bulimia in adolescence often have polycystic ovary syndrome. 3. Not all identical twins with PCOS are sick, which indicates that a single gene is unlikely to cause the disease, and there may be multiple genes or non-genetic factors. 4. According to a research report, 87% of the sisters of patients with polycystic ovary syndrome are also sick. Even if it is completely dominant (50%), there is no such high proportion, suggesting that there may be non-genetic factors. 5. Familial gregarious diseases are not necessarily hereditary diseases, and a trait may be familial because of the interaction between * * * and environmental factors.
Current research data show that PCOS mainly involves five aspects, namely 1. Abnormal GnRH secretion control II. Primary ovarian diseases III. Hyperandrogenism 4. Insulin resistance. Obesity factors, there is evidence from all sides that PCOS may have genetic factors. However, the diversity of clinical manifestations of PCOS is more like the result of multiple genes, and there may be environmental factors, especially intrauterine factors and nutritional factors.
Pathophysiology of Polycystic Ovary Syndrome
The range of pathological changes is very wide, involving neuroendocrine, glucose metabolism, fat metabolism, protein metabolism and abnormal changes of ovarian local regulatory factors. The exact reason of these changes is not clear, and its characteristic pathophysiological changes mainly include the following aspects: 1. The gonadotropin secretion is abnormal, and follicle stimulating hormone (FSH) and luteinizing hormone (LH) secreted by pituitary gland are two glycoprotein hormones necessary for follicular development and maturation. In pcos patients, LH is relatively increased, while FSH is slightly decreased or equal, resulting in an increase in LH/FSH ratio. The specific performance is that the serum LH of pcos patients is relatively constant at the middle stage of follicular phase of normal female menstrual cycle, and the LH/FSH ratio is often greater than 2. It is believed that this phenomenon is partly the result of the increase of GNRH pulse release frequency in hypothalamus. 2. Hyperandrogenism: One of the main basic pathophysiological changes of pcos is the increase of androgen in the body. Androgen in women mainly includes androsterone (A), testosterone (T), dehydroandrosterone (DHEA), dehydroandrosterone sulfate (DHEA-S) and dihydrotestosterone (DHT). Hyperandrogenism can cause ovarian matrix hyperplasia, accelerate follicular atresia and inhibit the synthesis of estrogen-binding globulin in liver. The increase of dihydrotestosterone leads to female diseases and hirsutism. Hyperandrogenism in Pcos patients can cause lipid metabolism disorder, but it can balance the degenerative effect of long-term amenorrhea on bones. 3. Insulin resistance and hyperinsulinemia. Insulin resistance is characterized by decreased sensitivity of body tissues to insulin. Insulin resistance and glandular hyperplasia are important clinical manifestations of many obese and non-obese pcos women. 4. Obesity About 5% of pcos women are obese, and many of them often gain weight rapidly before the clinical symptoms of pcos appear. The increased fat is mainly distributed in the upper body, especially in the abdomen and viscera, and the waist-hip ratio is greater than 0.85, forming a characteristic centripetal fat distribution. 5. The ovarian local regulatory factors are abnormal, from primordial follicle to early primary follicle, which is not controlled by pituitary gonadotropin, and its development depends on the internal factors of the follicle itself. The number of follicles in polycystic ovary syndrome, including preantral follicles, is higher than that in normal follicles. This phenomenon shows that pcos is inherently different from normal follicles. The primary disease of Pcos may be located in the ovary.
Diagnosis of infertility caused by polycystic ovary syndrome
The diagnosis of infertility caused by polycystic ovary syndrome can be judged according to clinical symptoms, blood hormone level, B-ultrasound examination and infertility. 1. Clinical symptoms: infertility, menstrual changes, such as scanty menstruation, scanty menstruation, amenorrhea, functional uterine bleeding, anovulation and luteal insufficiency. 2. Changes of blood hormone level: LH/FSH is greater than or equal to 2, T is higher and/or A is higher; The F2 level is equivalent to the increase of the volume of the middle follicle, and there are more than or equal to 10 cystic follicles scattered around the ovary, with a diameter of 2-8 mm. The strict diagnostic criteria for the enhancement of interstitial echo are menstrual changes, abnormal blood hormones, multiple follicles, three abnormalities and infertility.
Treatment of infertility caused by polycystic ovary syndrome
There are two treatments for PCOS: medication and surgery. Here is mainly about medication.
1. Anti-androgen therapy is used to treat hyperandrogenism: A: Oral contraceptives are a simple and relatively safe method. At present, the most effective ones are Marvelon and Diane -35, which can adjust the elevation and reduce the effect of estrogen. B, combined use of androgen and progesterone: ethinylestradiol 0.05mg and diethylacetate 100mg, once a month 1 time, for 3 weeks every month, because it can reduce free testosterone and block testosterone receptors. C. Combination of oral contraceptives and glucocorticoids: Oral contraceptives are combined with dexamethasone, 0.75mg per day for three consecutive cycles, which is suitable for patients with elevated testosterone and dehydroandrosterone sulfate.
2. Ovulation-promoting treatment: The purpose is to restore ovulation and menstruation to promote pregnancy. A clomiphene citrate, its usage: take it for 5-9 days after menstruation, 20-20-200 ug per day, and ovulate 7-8 days after taking it. In order to improve the ovulation rate and pregnancy rate, the following measures can be taken: adding estrogen to clomiphene citrate and taking 0.05mg propargyl alcohol once a day for 65,438+00 days, that is, 0. 1. 63% of pcos patients use cc to treat ovulation, but 20%-25% of the treated women have cc resistance. Although the ovulation rate is high, the cumulative pregnancy rate is only 30%, the periodic pregnancy rate is 10%, and the abortion rate is 10%-33.3%. B. Use cc+HMG+HCG, cc in menstrual period (3-8) days, and monitor by B-ultrasound. According to the monitoring results, HMG 150u (2-3) days depend on the results of B-ultrasound. After the follicles mature, intramuscular injection of HCG (5000- 10000u, but at the same time, multiple follicles can develop. However, for those who cannot ovulate with clomiphene citrate, dexamethasone 0.25-0.5mg/ day is added to achieve the purpose of pregnancy. D. Application of gonadotropins (generally due to the high price of such drugs). For pcos patients who have been ovulated for more than 6 months but are not pregnant, gonadotropins can be used. However, due to the high price of gonadotropins, human assisted reproductive technology-in vitro fertilization-embryo transfer (TVF-ET) can be selected. The number of oocytes obtained by patients with polycystic ovary syndrome is higher than that of normal people, and the incidence of OHSS and multiple pregnancy is higher.
3. Surgical treatment: When drug treatment fails, bilateral oophorectomy is feasible. When exploratory laparotomy is carried out, a detailed examination should be carried out first. After diagnosis, 1/3 tissue was removed according to the shape of ovary. Microsurgery can reduce adhesion and improve curative effect. Laparoscopic surgery has the advantages of simple operation and few complications. After ovariectomy, the level of estrogen temporarily drops, FSH secretion increases through feedback, and the ratio of LH/FSH changes, so that follicles mature and ovulate, thus achieving the purpose of pregnancy.