» Articles » PMID: 19443574

A Unique Human Chorionic Gonadotropin Antagonist Suppresses Ovarian Hyperstimulation Syndrome in Rats

Overview
Journal Endocrinology
Specialty Endocrinology
Date 2009 May 16
PMID 19443574
Citations 2
Authors
Affiliations
Soon will be listed here.
Abstract

Ovarian hyperstimulation syndrome (OHSS) is a complication of in vitro fertilization associated with physiological changes after hCG administration to induce final oocyte maturation. It presents as widespread increases in vascular permeability and, in rare cases, results in cycle cancellation, multi-organ dysfunction, and pregnancy termination. These physiological changes are due primarily to activation of the vascular endothelial growth factor (VEGF) system in response to exogenous human chorionic gonadotropin (hCG). An hCG antagonist (hCG-Ant) could attenuate these effects by competitively binding to the LH/CG receptor, thereby blocking LH activity in vivo. We expressed a form of hCG that lacks three of its four N-linked glycosylation sites and tested its efficacy as an antagonist. The hCG-Ant binds the LH receptor with an affinity similar to native hCG and inhibits cAMP response in vitro. In a rat model for ovarian stimulation, hCG-Ant dramatically reduces ovulation and steroid hormone production. In a well-established rat OHSS model, vascular permeability and vascular endothelial growth factor (VEGF) expression are dramatically reduced after hCG-Ant treatment. Finally, hCG-Ant does not appear to alter blastocyst development when given after hCG in mice. These studies demonstrate that removing specific glycosylation sites on native hCG can produce an hCG-Ant that is capable of binding without activating the LH receptor and blocking the actions of hCG. Thus hCG-Ant will be investigated as a potential therapy for OHSS.

Citing Articles

Revisiting ovarian hyper stimulation syndrome: Towards OHSS free clinic.

Banker M, Garcia-Velasco J J Hum Reprod Sci. 2015; 8(1):13-7.

PMID: 25838743 PMC: 4381376. DOI: 10.4103/0974-1208.153120.


Association between the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) rs4073366 polymorphism and ovarian hyperstimulation syndrome during controlled ovarian hyperstimulation.

OBrien T, Kalmin M, Harralson A, Clark A, Gindoff I, Simmens S Reprod Biol Endocrinol. 2013; 11:71.

PMID: 23883350 PMC: 3727944. DOI: 10.1186/1477-7827-11-71.

References
1.
Alvarez C, Alonso-Muriel I, Garcia G, Crespo J, Bellver J, Simon C . Implantation is apparently unaffected by the dopamine agonist Cabergoline when administered to prevent ovarian hyperstimulation syndrome in women undergoing assisted reproduction treatment: a pilot study. Hum Reprod. 2007; 22(12):3210-4. DOI: 10.1093/humrep/dem315. View

2.
Doldi N, Bassan M, Messa A, Ferrari A . Expression of vascular endothelial growth factor in human luteinizing granulosa cells and its correlation with the response to controlled ovarian hyperstimulation. Gynecol Endocrinol. 1997; 11(4):263-7. DOI: 10.3109/09513599709152544. View

3.
Lee K, Kim S, Jee B, Kim Y, Suh C, Kim K . Comparison of clinical characteristics between early and late patterns in hospitalized patients with ovarian hyperstimulation syndrome. Fertil Steril. 2009; 93(7):2274-80. DOI: 10.1016/j.fertnstert.2009.01.057. View

4.
Orvieto R, Zohav E, Scharf S, Rabinson J, Meltcer S, Anteby E . The influence of estradiol/follicle and estradiol/oocyte ratios on the outcome of controlled ovarian stimulation for in vitro fertilization. Gynecol Endocrinol. 2007; 23(2):72-5. DOI: 10.1080/09513590601137137. View

5.
Owj M, Tehrani Nejad E, Amirchaghmaghi E, Ezabadi Z, Baghestani A . The effect of withholding gonadotropin (a coasting period) on the outcome of in vitro fertilization cycles. Eur J Obstet Gynecol Reprod Biol. 2007; 133(1):81-5. DOI: 10.1016/j.ejogrb.2006.10.035. View