Abstract
PurposeControlled ovarian stimulation significantly amplifies the number of maturing and ovulated follicles as well as ovarian steroid production. The ovarian hyperstimulation syndrome (OHSS) increases capillary permeability and fluid extravasation. Vascular integrity intensely is regulated by an endothelial glycocalyx (EGX) and we have shown that ovulatory cycles are associated with shedding of EGX components. This study investigates if controlled ovarian stimulation impacts on the integrity of the endothelial glycocalyx as this might explain key pathomechanisms of the OHSS.MethodsSerum levels of endothelial glycocalyx components of infertility patients (n=18) undergoing controlled ovarian stimulation were compared to a control group of healthy women with regular ovulatory cycles (n=17).ResultsPatients during luteal phases of controlled ovarian stimulation cycles as compared to normal ovulatory cycles showed significantly increased Syndecan-1 serum concentrations (12.6 ng/ml 6.1125th–19.1375th to 13.9 ng/ml 9.625th–28.975th; p=0.026), indicating shedding and degradation of the EGX.ConclusionA shedding of EGX components during ovarian stimulation has not yet been described. Our study suggests that ovarian stimulation may affect the integrity of the endothelial surface layer and increasing vascular permeability. This could explain key features of the OHSS and provide new ways of prevention of this serious condition of assisted reproduction.
Highlights
We have shown that ovulatory cycles influence release of endothelial glycocalyx (EGX) components and highest concentrations of Syndecan-1 were demonstrated in luteal phases, suggesting products of the corpus luteum are involved in destabilizing the EGX and increasing vascular permeability [13]
Assuming luteal phase components to be the damaging noxae to the EGX, it was questionable whether comparable EGX component levels could be expected in the current trial
We were able to demonstrate in a translational approach both the negative influence of progesterone on EGX components measurable in serum and, in an experimental setting, that progesterone leads to the degradation of the EGX
Summary
Controlled ovarian stimulation (COS) is an important element of many assisted reproductive treatment modalities as it provides increased metaphase II oocyte numbers and significantly improves pregnancy rates. It is generally accompanied by amplified ovarian steroidogenesis. Both estradiol and progesterone concentrations during COS significantly exceed the levels measured during monofollicular cycles [1, 2]. A rare, but serious complication of COS is ovarian hyperstimulation syndrome (OHSS) that is characterized by increased capillary permeability, fluid extravasation, augmented coagulation, and hemoconcentration. OHSS may become life-threatening secondary to thromboembolism or compromised pulmonary or cardiovascular function [1,2,3,4,5]
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