The pathophysiology of ovarian hyperstimulation syndrome--views and ideas

Abstract

Ovarian hyperstimulation syndrome (OHSS) is a serious complication affecting ovulation induction. Its most severe manifestation takes the form of massive ovarian enlargement and multiple cysts, haemoconcentration and third-space accumulation of fluid. The full-blown clinical syndrome may be complicated by renal failure and oliguria, hypovolaemic shock, thromboembolic episodes, adult respiratory distress syndrome (ARDS), and death. Although the pathophysiology of this syndrome has not been completely elucidated, it seems likely that the increased capillary permeability triggered by the release of vasoactive substance secreted by the ovaries under human chorionic gonadotrophin (HCG) stimulation plays a key role in this syndrome. Several factors such as histamine, serotonin, prostaglandins, prolactin, and a variety of other substances have been implicated in this process in the past. At present, factors belonging to the renin-angiotensin system, cytokines including the interleukins, tumour necrosis factor alpha, endothelin-1 and vascular endothelial growth factor (VEGF) are thought to be involved in triggering increased vascular permeability after ovulation induction treatment. This manuscript summarizes the current knowledge of the pathophysiology of ovarian hyperstimulation syndrome with emphasis on the correlation of the various factors with the clinical phenomena of this iatrogenic syndrome.

Mini puberty and its interpretation

“…The pathophysiology of this picture which is observed in preterm babies is not known fully. It is thought that lack of maturation of the hypothalamo-pituitary-gonadal axis and lack of complete development of negative feedback mechanisms with discontinuation of placental steroids are involved (42,46). It has been proposed that edema observed in the subjects is related with vascular endothelial growth factor released from the theca and granulosa cells (43,47).…”

Overenthusiastic treatment of infertility by budding gynecologist leading to moderate OHSS

“…8 Certain vasoactive substances such as vascular endothelial growth factor (VEGF), cytokines (IL-2, IL-6, and IL-8), tumor necrosis factoralpha (TNF-alpha), and the ovarian renin-angiotensin system, which are activated by gonadotropin, can lead to increased vascular permeability and extravascular fluid accumulation in OHSS which is responsible for development of ascites, pleural effusions, edema, and hemoconcentration. 9 In spontaneous OHSS extravascular fluid retention may not occur and usually a hemodilution rather than hemoconcentration is seen. 10 Presentation may vary from gastrointestinal upset and abdominal distension in mild cases to dyspnea and hypovolemia in severe cases.…”

Ovarian hyperstimulation syndrome associated with fetal trisomy 21

“…Ovarian hyperstimulation occurs after luteinization of a large number of follicles. 2 OHSS appears to occur because of increased capillary permeability triggered by excessive release of one or more vasoactive substances secreted during maturation and luteinization of multiple follicles. One of the primary vasoactive substances is vascular endothelial growth factor (VEGF) of follicular origin.…”

“…Cardiac, renal, pulmonary and liver function can be impaired. 2 Massive follicular luteinization is usually only observed in exogenous gonadotropin cycles following administration of hCG, or after administration of gonadotropin-releasing hormone agonist. Rarely, it occurs in women treated with clomiphene citrate.…”

“…Clinical symptoms of OHSS usually appear 5 to 10 days following the first dose of the ovulatory trigger. 2 Mild OHSS can rarely develop following an endogenous LH surge. This has been described in case reports, particularly in women with polycystic ovarian syndrome or hypothyroidism.…”