The overall incidence rate of OHSS was 3.1%~8.0% in IVF-ET cycle, and the incidence rate of high-risk patients could be as high as 20%. According to the World Health Organization(WHO), the incidence of moderate OHSS is 3 ~ 6%, and the incidence of severe OHSS is 0.1 ~ 2%.
The pathogenesis of OHSS is not fully understood, which may be related to the production of various vasoactive substances in the ovaries stimulated by HCG[9–10]. The increase of hCG level in OHSS patients triggers the mutation of FSH receptor, which leads to the increase of corresponding downstream hormones. In addition, hCG is highly sensitive to mutant FSH receptor (FSHR) and glycoprotein hormones with the same subunits are over secreted. However, pregnancy patients themselves also produce more endogenous HCG, which may also be another possible mechanism of OHSS. Recent studies have also shown that all FSHR gene activation mutations are associated with OHSS[13–14].
The main pathological changes of OHSS were multiple follicles and multiple corpus luteum cysts with interstitial edema, which caused ovarian enlargement and abnormal volume. In addition, increased capillary permeability causes fluid to flow into the extravascular cavity, leading to pleural effusion, ascites, pericardial effusion, and even systemic edema. These changes can lead to hypovolemia and the increase of blood drug concentration, which can easily lead to the formation of intravascular thrombosis, renal perfusion insufficiency, and then oliguria and electrolyte disorder[16–17].
The key to prevent OHSS is early identification of high-risk factors, including youth, low body mass index, polycystic ovary syndrome, hypothyroidism, rapid increase of serum E2 levels and previous history of OHSS[18–20]. We should pay attention to the clinical intervention before the treatment of COH cycle in high-risk groups. During ovulation induction, we should closely monitor blood E2 and B-ultrasound, monitor the size and quantity of follicles. The stimulation program and the dosage of Gn should be adjusted in time to prevent the occurrence of OHSS. Mild OHSS is mostly self-healing. The main purpose of moderate and severe OHSS treatment is capacity expansion and symptomatic and supportive treatment. Early and timely give human serum albumin, low molecular dextran andother intravenous drip to correct blood volume and improve microcirculation. For patients with a large amount of hydrothorax and ascites with chest tightness and abdominal distension pain, it is the quickest and most effective treatment method to improve symptoms. For severe OHSS with more follicles, puncture and aspiration of follicles can achieve good results.
In this case, the risk factors of OHSS included age < 35 years old, polycystic ovary syndrome, hCG triggering ovulation and pregnancy. Age < 35 years old is an independent risk factor for OHSS. There are more antral follicles in the ovaries of young patients, and the number of follicles collected during COH cycle is also increased. In addition, there are a large number of Gn receptors in the ovaries of young patients, and they are prone to overreaction to Gn. PCOS is an ovulation disorder and endocrine disease, which affects about 26% of women of childbearing age. It significantly increases the risk of OHSS during COH cycle. The gonadotropin required for follicular development is quite different during COH cycle, and the follicular development is difficult to control.HCG is widely used in ART cycles for COH cycle and luteal support. Exogenous hCG can increase the content of the internal hCG, activate renin angiotensin system, and enhance the activities of renin, angiotensin and their invertase, thus producing angiotensin II, the ultimate active substance, resulting in the increase of vascular permeability and the occurrence of OHSS.
In this case, the patient developed moderate OHSS 4 days after oocyte retrieval, and was not hospitalized in time. 8 days after oocyte retrieval, the patient developed into severe OHSS and was hospitalized. After 13 days of volume expansion, supportive symptomatic treatment and four times of peritoneal puncture fluid extraction treatment, the patient's condition was still delayed. Finally, the patient was discharged because she refused to continue treatment. Two weeks after discharge, urine HCG was tested positive and blood HCG gradually decreased, and biochemical pregnancy was considered. The patient did not undergo fresh embryo transplantation due to the consideration of moderate OHSS 4 days after oocyte retrieval. Then, when was the embryo implanted?
After make a detailed inquiry of the patient's medical history, we learned that the patient had no history of coitus during the luteal phase ovulation induction period, but had a history of coitus during letrozole ovulation induction period. Therefore, it was inferred that the patient had ovulation during letrozole ovulation induction period, and normal fertilization and implantation occurred. It is considered that the placenta trophoblast secretes a large amount of endogenous hCG due to pregnancy, which increases the risk of severe OHSS and prolongs the course of disease. Other studies have found that hCG plays a key role in promoting the release of VEGF, which can increase the activity of VEGF, thus aggravating the patient's condition.