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Ovarian Hyperstimulation Syndrome(OHSS)  


Ovarian hyperstimulation syndrome (OHSS) is a rare but serious iatrogenic complication of ovarian stimulation occurring as a part of assisted reproductive technologies (ART). While the safety and efficacy of ART is well established, we should always be aware of the risk of OHSS in patients undergoing ovarian stimulation , as it can be fatal.


OHSS is an exaggerated response to controlled ovarian stimulation(COS) characterized by the shift of protein-rich fluid from the intravascular space to the third space, mainly the abdominal cavity that occurs when the ovaries become enlarged due to follicular stimulation . This shift in fluid is due to increased vascular permeability in response to stimulation with human chorionic gonadotropin (hCG). Prostaglandins, inhibin, the renin-angiotensin-aldosterone system and inflammatory mediators have all been implicated in the aetiology of OHSS .However, vascular endothelial growth factor (VEGF) has been identified as the major mediator. The clinical manifestations of OHSS reflect the extent of the shift of fluid into the third space and the resulting hemoconcentration due to intravascular volume depletion. Symptoms range from mild abdominal distention due to enlarged ovaries alone or with an accompanying fluid shift into the abdomen, to renal failure and death as a result of hemoconcentration and reduced perfusion of organs such as the kidneys, heart and brain. Indeed, as the severity of OHSS increases, so does the number of organs affected .

Classification of OHSS :

OHSS can be “early” or “late” based on the source of hCG. It also can be classified as mild moderate or severe according to the severity of symptoms. Early OHSS occurs in the luteal phase of COS after the administration of exogenous hCG to induce oocyte maturation. Late OHSS occurs when ART results in pregnancy and is the consequence of an increase in endogenous hCG levels following conception. In most cases, OHSS is self-limiting and resolves spontaneously within several days. However, OHSS may persist, particularly late OHSS due to pregnancy.


Prevention of OHSS is a multi-stage process. The key to the primary prevention of OHSS during Ovarian stimulation is recognizing risk factors and individualizing the ovarian stimulation protocol appropriately. There are a number of well-established primary risk factors for the development of OHSS, including young age, polycystic ovary syndrome (PCOS) – characterized by ultrasound and the ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH) – and a history of an elevated response to gonadotropins, i.e. prior H/O OHSS. In the very early follicular phase of the cycle, a number of antral follicles (2–10 mm in size) is related to age and may reflect the ovarian reserve . Basal Anti-Müllerian hormone (AMH) levels prior to COS have also been shown to be predictive for OHSS. Basal AMH levels ~ ≥3.5 ng/mL were predictive of hyper-response with high sensitivity and specificity by some randomised studies. Moreover, AMH may be a better predictive marker of excessive ovarian response to COS than age, basal FSH, and estradiol (E2) on the day of hCG administration and has been shown to be at least as good as AFC . Furthermore, AMH predicts ovarian response independently of age and PCOS . The number of follicles in combination with serum E2 levels predicts OHSS with high sensitivity and specificity.

Prevention of OHSS

Primary prevention is achieved before starting ovarian stimulation and secondary prevention achieved after starting ovarian stimulation. The key to the primary prevention of OHSS during COS is recognizing risk factors and individualizing the ovarian stimulation protocol appropriately using individualized controlled ovarian stimulation. Secondary preventative measures are normally applied. Various preventative protocols have been proposed such as coasting, cancelling the cycle, stop or delay the hCG trigger dose, and using a gonadotropin-releasing hormone agonist (GnRHa) trigger, Cryopreservation of oocytes and embryos. However, despite the widespread use of these preventative techniques, supporting evidence is limited.