The Effect Of Letrozole On Patients With High Risk Of Ovarian Hyperstimulation Syndrome

Background:With the increase of infertility rate and the development of assisted reproductive technology?ART?,more and more infertile patients successfully get pregnant and give birth by in vitro fertilization-embryo transfer?IVF-ET?,but the incidence of complication also increases accordingly.Ovarian hyperstimulation syndrome?OHSS?is an iatrogenic complication of controlled ovarian hyperstimulation?COH?.OHSS is a self-limited disease characterized by a large number of follicular development,elevated serum estradiol?E₂?levels and ovarian cystic enlargement,with gastrointestinal discomfort,abdominal distention and dyspnea as its main clinical manifestations.Clinical epidemiological studies have shown that the incidence of moderate OHSS is 4%,while the incidence of severe OHSS is 0.5%in all of the IVF cycles.The incidence of moderate and severe OHSS in patients with polycystic ovary syndrome?PCOS?and polycystic ovaries?PCO?after COH is as high as 10%¹6.0%,so the pathogenesis and preventive measures of OHSS are worthy of attention.Elevated serum concentrations of E₂ have been correlated with a higher incidence of OHSS and the serum E₂ level on hCG day can be used as an indicator to predict OHSS.Hyperstimulated ovaries release a number of vasoactive mediators under the influence of hCG.These include vascular endothelial growth factor?VEGF?and several pro-inflammatory cytokines that interact to produce the characteristic pathophysiology of OHSS.The pathogenesis of OHSS is unknown,and now clinically,it mainly focuses on prevention,including reducing the gonadotropin?Gn?duration in IVF/ICSI cycles,the control of exogenous hCG injection,cryopreserving all embryos,etc.None of the current preventive measures can completely avoid OHSS.Letrozole is a third generation,nonsteroidal aromatase inhibitor,and is the limited enzyme in the synthesis process of estrogen.Studies have shown that letrozole could inhibit 90 percent of the conversion of androgens into estrogens potently and specifically by binding the iron atoms of heme in aromatase competitively.Clinically,letrozole combined with Gn can be used to ovulation induction or COH,which can significantly reduce the dosage of Gn and reduce the cost of patients.Recent studies have found that providing letrozole for the high risk patients of OHSS after oocyte retrieval can reduce the level of E₂,VEGF and the incidence of early-onset OHSS.It suggests the potential application in the prevention of early-onset OHSS.However,there are few relevant studies and the results are not consistent,further clinical studies are still needed to verify its effectiveness.Objective:To explore the preventive effect on OHSS of letrozole among the high risk patients of OHSS after oocyte retrieval.Methods:A total of 110 patients who were under the treatment of IVF-ET in the Reproductive Center of the Affiliated Hospital of Qingdao University during Feburary 2017 to March2018,and had to cancel the fresh cycle of embryo transfer due to the OHSS high risk factors,were randomly divided into the experimental group and the control group.The experimental group?n=58?was treated with 5mg/d of letrozole on the date of retrieval for five consecutive days,while the patients in control?n=52?were not treated with letrozole.The proportion of the incidence of OHSS was observed,and the levels of serum estradiol and VEGF were measured on the first day after hCG injection and on the third,fifth day after the oral administration of letrozole.Result:The patients'characteristics of both groups were similar,with no statistically significant difference in age,body mass index?BMI?,basal estradiol?bE₂?,basal follicle stimulating hormone?bFSH?,basal luteinizing hormone?bLH?,basal antral follicle count?bAFC?and the total dosage of gonadotropin?Gn?,the number of retrieved oocytes and the high-quality embryoes?P>0.05?.The levels of E₂ and VEGF in experimental group were significantly lower than control group on the third and fifth day after the oral administration of letrozole?P<0.05?.The incidences of moderate and severe OHSS in experimental group?7.27%?were significantly lower than those in control group?16.37%,P<0.05?.Conclusion:Providing letrozole for the high risk patients of OHSS after oocyte retrieval can reduce the level of estradiol,VEGF and the incidences of moderate and severe OHSS effectively.Whether it can affect the VEGF pathway to change the pathogenesis of OHSS by reducing the serum level of E₂ requires further research in large-scale sample.