Ovarian hyperstimulation syndrome (OHSS) is a major complication of assisted reproduction and can be life-threatening in severe cases. In the literature, the incidence of oHSS during ovulatory treatment and iVF is reported to be 1%-14%, and in severe cases, 0.5-2% [1-3]. The prevention and treatment of this syndrome has progressed with the in-depth study of the pathogenesis of oHSS. The risk factors for oHSS are: (1) ovaries are highly sensitive to ovulation stimulating drugs, i.e. hypersensitive ovaries. (ii) Use of hCG to promote ovulation or maintain the corpus luteum of pregnancy. (iii) Endogenous hCG secretion during early pregnancy. ④Previous history of oHSS. Hypersensitive ovaries are more common in young women (<35 years) and in those with polycystic ovary syndrome (pCOS). Recently, a study by fulghesu et al. showed [6] that the risk of oHSS in hyperinsulinemic pCOS is great, and they compared pCOS cases treated with follicle stimulating hormone (fSH) and found that the incidence of oHSS was significantly higher in the hyperinsulinemic group than in the control group (64.5% versus 23.8%, p < 0.05), and significant differences were seen in ovarian response indicators between the two groups The rate of ovarian growth and the number of immature follicles were higher in the hyperinsulinemic group than in the control group (p < 0.05); the plasma e2 level during ovulation was also higher in the hyperinsulinemic group (p < 0.05). The authors suggested that insulin may have a synergistic effect on fSH, resulting in increased sensitivity of the ovaries to fSH. During iVF, hCG is commonly used to promote follicle maturation and ovulation. Compared with endogenous luteinizing hormone (lH), hCG is more likely to cause oHSS because: (i) hCG preparations have a longer half-life and can produce a post-ovulatory follow-up effect. (ii) hCG preparations have a stronger affinity for lH receptors than endogenous lH. (iii) hCG preparations have both lH and fSH-like effects, which can sustain ovarian stimulation and promote granulosa cell luteinization. In addition to this, oHSS can be exacerbated by endogenous hCG in early pregnancy or by the use of exogenous hCG to maintain the corpus luteum of pregnancy [1, 7]. It has also been clinically observed that the risk of moderate to severe oHSS is higher in those with successful pregnancies during iVF or ovulation promotion therapy. This was also well illustrated in a report by sauer [8], who studied the occurrence of oHSS in egg donors and found that in 400 consecutive cycles of ovulation with human menopausal gonadotropin (hMG) and hCG, no case of severe oHSS occurred after egg retrieval, despite serum e2 levels exceeding the risk value for oHSS. the authors suggested that this could be related to the lack of endogenous hCG. The main pathological feature of oHSS is the increase in capillary hyperplasia and permeability throughout the body, especially in ovarian tissue; this leads to fluid exudation, blood concentration and imbalance in water-electrolyte balance. It is currently believed that the mechanism of this vascular pathology may be related to multiple inflammatory mediators and inflammatory cytokines. (i) Studies of activation of the ovarian reninogen-renin-angiotensin system have shown [1, 9]. Plasma reninogen and renin levels were elevated in oHSS patients and significantly correlated with the severity of their disease; lH and hCG were also found to activate this system and promote the conversion of angiotensin-Ⅰ to angiotensin-Ⅱ. This is further supported by the study of eldor et al [10], who found that reninogen levels in ascites and follicular fluid of oHSS patients were 5-fold higher than in plasma (165 vs. 22 mg/ml? h and 2686 vs. 490 ng/ml? hr). (ii) Inflammatory cytokines Revel et al [11] measured the concentrations of inflammatory cytokines in ascites and serum of 12 patients with severe oHSS by this enzyme-linked immunosorbent assay (eLISA), and the results showed that ascites and serum interleukin-6 (iL-6) concentrations were significantly higher than those of normal controls (p < 0.001 and p < 0.05), and ascites tumor necrosis factor-alpha (tNFα) and interleukin-8 were significantly higher than those of normal controls (p < 0.05). ) and interleukin-8 (iL-8) levels were also increased (p < 0.05); moreover, peritoneal fluid nitric oxide concentrations were significantly lower in oHSS patients (p < 0.004). The authors suggested that inflammatory cytokines may mediate increased capillary permeability and proliferation through the nitric oxide system. mola et al [12] further investigated iL-6 levels in patients with oHSS and found not only that serum and ascitic fluid iL-6 levels were significantly higher in oHSS patients than in normal controls (p < 0.001); but also that follicular fluid iL-6 was significantly higher than serum concentrations with hMG (10.1 ± 4.0 versus 6.3 ± 1.4 pg/ml,p < 0.001). The authors also observed the localization of ovarian tissues by immunohistochemistry and found that both follicular membrane cells and luteal granulosa cells could express iL-6, and their expression intensity was positively correlated with lH and hCG. These results suggest that the ovaries of oHSS patients can produce inflammatory cytokines through autocrine and paracrine mechanisms, leading to local and systemic related pathological changes. (iii) vascular permeability factor (VPF) vPF, vascular endothelial growth factor, not only promotes vascular proliferation, but also increases vascular permeability. Based on the pathological features of oHSS, some authors suggest that vPF may be involved in its pathological mechanism. abramov et al [13] examined serum vPF concentrations in 7 patients with oHSS and the values were significantly higher than in controls (p=0.005); moreover, vPF concentrations correlated significantly with both hematocrit and leukocytes (γ=0.636,p=0.021 and γ0.602,p=0.038), which means that vPF levels correlated with the severity of the disease. krasnow et al [14] observed vPF changes in serum, ascites and follicular fluid during the follicular phase in 8 patients with high-risk oHSS and found that follicular fluid vPF concentrations were approximately 100-fold higher than serum and ascites (171.5±18.5 versus 17±1.3 and 2.5±1.3 pmol/L,P both=0.003); after injection of 10,000 IU hCG in these 8 cases, 4 cases After the injection of 10,000 IU of hCG in these 8 cases, 4 cases developed oHSS, and the serum vPF of oHSS patients increased to 16.2±4.0 pmol/L at the 14th day after the drug administration, while the serum pVF of the other case without oHSS was 0.7±0.6 pmol/L. The difference between the two groups was significant (p<0.05). These results suggest that ovarian tissues can express vPF; and are involved in mediating vascular pathological damage in oHSS. (iv) Hypercoagulability clinical observations showed that the coagulation system was hyperactive and platelet activation was present in oHSS patients. Platelet aggregation and activation can release inflammatory mediators such as prostaglandins, histamine, and 5hydroxytryptamine, leading to vasodilation, increased permeability, and blood concentration, which in turn can lead to thrombosis [1]. Recently, balasch et al [15] studied the blood tissue factor profile in nine patients with severe oHSS and found that plasma thromboxane and fibrin levels were significantly higher in patients than in controls (p < 0.01), and that their values could return to normal levels after remission of oHSS; in addition, the authors analyzed the expression of tissue factors in peripheral blood mononuclear cells by flow cytometry and found that In addition, the authors analyzed the expression of tissue factor in peripheral blood mononuclear cells by flow cytometry and found that the percentage of tissue factor-positive mononuclear cells was significantly higher in oHSS patients compared with controls (40.9% ± 7.6% versus 8.0% ± 3.1%, p < 0.01); the values decreased to normal (8.0% ± 2.4%) once oHSS was controlled. The authors suggested that blood mononuclear cells can express a large number of tissue factors that activate the coagulation system cascade in vivo, which may be related to the occurrence of thromboembolism in oHSS patients. (v) e2Wada et al [16] concluded that serum e2 level is only an indicator of ovarian response and is not a direct causative factor of oHSS; they found a case of 17,20-carbon chain enzyme deficiency in which the ovaries were stimulated to produce only trace amounts of e2, but developed oHSS. This suggests that e2 does not play a decisive role in the pathogenesis of oHSS. Preventive measures oHSS is a disease of medical origin. Serum e2 and ovarian morphological changes can reflect the degree of ovarian stimulation; serum e2 ≥ 11010 pmol/ml (3000 pg/ml) and follicle number ≥ 20 are indicators of ovarian hyperstimulation threshold; therefore, ovarian response should be closely monitored during assisted reproduction. According to brinsden et al [1], serum e2 ≥11010 pmol/ml (3000 pg/ml) and ≥20 follicles ≥12 mm in diameter are threshold indicators of oHSS risk in those undergoing iVF or gamete intrafallopian tube transfer (gIFT), beyond which the risk of oHSS increases significantly. (1) Those with serum e2 ≤ 11010 pmol/ml (3000 pg/ml) and no oHSS manifestations can be directly transferred as embryos. (②E2 in the range of 5505-11010 pmol/m (1500-3000 pg/ml), when luteal support is needed after embryo transfer, progesterone should be used. (③Serum e2 ≥ 20185 pmol/ml (5500 pg/ml) and total follicle count ≥ 40 should not be used for hCG ovulation promotion, but gonadotropin-releasing hormone (gnRH) antagonist can be used to suppress ovarian hyperstimulation, and then low-dose gonadotropin can be used for ovarian stimulation when it returns to normal. In cases with serum e2 between 11010 and 18350 pmol/ml (3000-5000 pg/ml) and follicle counts between 20 and 40, hCG can still be used, but it is advisable to freeze the follicles instead of transferring fresh ones, so as to avoid exacerbation of mild oHSS. Recently, thtinen et al [5] performed blastocyst freezing in 23 high-risk cases of oHSS and only 2 cases of oHSS occurred, 1 mild and 1 severe, with a high success rate of 22.7% for frozen-thawed blastocyst transfer. The effect of albumin was prospectively studied by isik et al [17], who gave 10 g of albumin infusion before egg harvesting, resulting in no moderate to severe oHSS in the treatment group, while there were one severe and four moderate cases in the control group (p < 0.05). They divided 26 cases of high-risk oHSS into two groups of 13 each, with group a receiving frozen-thawed blastocyst transfer and group b receiving 40 g of human albumin at the time of egg collection, repeated 5 d later, followed by fresh blastocyst transfer, resulting in 10 cases of mild oHSS in group a and 9 cases in group b (p < 0.05). No moderate to severe oHSS occurred in both groups. Mochtar et al [5] divided 176 cases after ovulation with gonadotropin-releasing hormone (gnRH) antagonist + hCG and iVF blastocyst transfer into two groups: 89 cases in group a had progesterone placed vaginally and 87 cases in group b had hCG plus progesterone placed vaginally. In the control results, the pregnancy rate was 26% in group a and 15% in group b (oR=0.49, 95% CI=0,18-1.3), the serum e2 value was higher in group b than in group a (p<0.001), and the incidence of oHSS was also higher in group b. The authors concluded that vaginal progesterone placement could both maintain the corpus luteum of pregnancy and reduce the incidence of oHSS. The authors concluded [19] that for patients with a history of severe oHSS with hCG ovulation, a gnRH analogue could be used instead of hCG as ovulation treatment, and they made their own controlled observations in 16 patients with a history of severe oHSS. pCOS is a high risk factor for oHSS. oyesaa found [20] that the ovarian volume of those with severe oHSS before the use of hCG was significantly larger than those without oHSS (271.0±87.0 versus 157.3±54.2 cm3,P<0.01). For this reason, ellenbogen proposed the inability of follicular ultrasound scoring [21] as a predictor of oHSS, and they examined 63 ovulation cycles (hMG+hCG) in 34 pCOS patients using vaginal ultrasound; the scoring was 1 for mean follicular diameter of 5-8 mm, 1.5 for 9-12 mm, 2 for 13-16 mm, and 3 for ≥17 mm The mean follicular diameter was scored as 1, 9-12mm as 1.5, 13-16mm as 2 and ≥17mm as 3. The total score of follicles in both ovaries was accumulated, and it was found that oHSS did not occur in those with a total score <25, and oHSS occurred in all with a total score >30; in addition, the total score was significantly correlated with blood e2 level (γ=0.997). aboulghar [4] suggested that pCOS patients with a history of severe oHSS with previous fSH could be treated with either hMG or recombinant fSH (low-dose incremental method). The pregnancy rates were 20% and 15.4%, respectively. The recombinant fSH has only fSH-like activity, but no lH activity, and the effect is similar to that of hMG, so it is safer to be used in pCOS patients with a history of severe oHSS. The treatment of moderate to severe oHSS should include complete blood cell analysis, liver and kidney function tests, water and electrolyte measurements, pelvic ultrasound and weight measurement. The oHSS may present with elevated blood cell pressure and leukocytes, hyponatremia, hypoproteinemia, enlarged ovaries, follicular or flavin cysts, pelvic effusion, and weight gain on ultrasound. Mild oHSS generally does not require special management and most patients recover within 1 week, but should be monitored on an outpatient basis, and those at risk of exacerbation should continue to be observed for 4-6 d. Moderate oHSS may include significant nausea and vomiting, abdominal distension, abdominal pain, and even dyspnea. Treatment is based on rest and fluid replacement. Most cases resolve within 1 week after egg harvesting or IUI, but those with increased outpatient monitoring should be hospitalized. In severe oHSS, significant fluid loss, abdominal or pleural effusion, hypovolemic shock, oliguria, imbalance of water-electrolyte balance and ovarian enlargement above the umbilicus can be seen. Acute respiratory distress may occur in very severe cases due to massive ascites, pleural fluid, and pericardial effusion, and may also be complicated by complications such as liver and kidney failure and thrombosis. The diagnosis of severe oHSS can be made by hematocrit ≥45%, leukocytes ≥15×109/L, massive ascites, oliguria, and mild hepatic and renal dysfunction. hematocrit ≥55%, leukocytes ≥25×109/L, massive ascites, renal failure, thrombotic phenomenon, and adult respiratory distress syndrome suggest an extremely serious condition. If crystalloid rehydration cannot maintain fluid balance, albumin (50%) or other plasma components should be used, and daily fluid intake and output should be recorded, and fluid balance can also be monitored by central venous pressure. oHSS thrombosis is uncommon. When there is abnormal manifestation, the patient should be encouraged to move the lower extremities, use heparin (5000 IU twice/d) if necessary, and avoid using diuretics. In cases of massive ascites or pleural effusion leading to respiratory distress, abdominal or thoracic drainage can be performed under ultrasound guidance. In most cases, the disease can be alleviated after the mid-luteal phase and complete remission will not occur until after the next menstrual period. Successful pregnancies may have a longer and more severe course of disease.