Female Reproductive System ORGAN SYSTEMS

Ovarian hyperstimulation syndrome (OHSS)

Iatrogenic complication of assisted reproduction technology characterized by cystic enlargement of the ovaries and a fluid shift from the intravascular to the third space due to increased capillary permeability and ovarian neoangiogenesis.


Iatrogenic complication of assisted reproduction technology characterized by cystic enlargement of the ovaries and a fluid shift from the intravascular to the third space due to increased capillary permeability and ovarian neoangiogenesis.

  • M/serious iatrogenic complication of ovulation induction


Human chorionic gonadotrophin (hCG) administration

OHSS is almost always associated with exogenous gonadotropin stimulation, followed by hCG administration, for triggering final oocyte maturation.

Risk factors:

Existing factors likely to amplify the response to ovarian stimulation
  • Young age
  • History of elevated response to gonadotrophins
  • Previous OHSS
  • Polycystic ovary syndrome (PCOS)


Vascular endothelial growth factor (VEGF)

Hallmark of OHSS is an increase in the permeability of the capillaries due to hCG mediated VEGF, resulting in a fluid shift form the intravascular space to the extravascular compartments.

OHSS is secondary to vasoactive products released by the ovaries after being exposed to human chorionic gonadotropin (HCG). This results in increased capillary permeability which in turn leads to leakage of fluid from the vascular compartment causing third space fluid accumulation and intravascular dehydration

Intraovarian renin angiotensin system (RAS):

The ovarian RAS is involved in regulating vascular permeability, angiogenesis, endothelial proliferation, and prostaglandin release.

hCG causes a strong activation of the RAS, evidenced by high renin activity in the follicular fluid of women with OHSS. Overstimulation of this cascade, together with increasing VEGF levels, is postulated to synergistically potentiate OHSS

Graphical representation of the pathophysiology of ovarian hyperstimulation syndrome (OHSS). | Smith, V., Osianlis, T., & Vollenhoven, B. (2015). Prevention of Ovarian Hyperstimulation Syndrome: A Review. Obstetrics and gynecology international, 2015, 514159.

Early OHSS:

Occurs within 9 days of hCG administration as an ovulatory trigger and reflects the effect of exogenous hCG on ovaries that have already been hyperstimulated by gonadotrophins.

Late OHSS:

Occurs after 10 days since use of hCG as an ovulatory trigger (in the absence of luteal hCG support) and demonstrates the ovarian response to endogenous (placental) hCG produced by the trophoblas

Clinical freatures

  • Abdominal pain, nausea and vomiting: Enlargement of the ovaries (up to 25 cm) causes abdominal pain, nausea and vomiting. The enlargement is sometimes as much as 25 cm. Another consequence is discomfort resulting from increased intra-abdominal pressure due to ascites.
  • Dyspnea: Pulmonary function compromised as enlarged ovaries and ascites restrict diaphragmatic movement.

Clinical classification:

OHSS is classified 3 categories based on the severity of symptoms, signs, and laboratory findings.
Classification of ovarian hyperstimulation syndrome (OHSS). | Pharmacotherapy of ovarian hyperstimulation syndrome – Scientific Figure on ResearchGate. Available from: [accessed 6 Nov, 2020]


Hypotension and/or hypovolemia:

Leakage of fluid through the impaired blood vessels both within and outside the ovary there is massive fluid-shift from the intravesicular bed to the third compartment results in intravascular hypovolemia
  • Oedema
  • Hydrothorax
  • Hydropericardium
  • Ascites and tense distention: Leakage of fluid from follicles, increased capillary permeability leading to third spacing (due to the release of vasoactive substances), or frank rupture of follicles can all cause ascites.

Localized/generalized peritonitis:

Caused by peritoneal irritation secondary to blood from ruptured cysts, protein rich fluid, and inflammatory mediators.

Acute abdominal pain:

  • Ovarian torsion
  • Intraperitoneal hemorrhage or rupture of cysts

Pulmonary manifestations of OHSS:

  • Pleural effusion
  • Pulmonary edema
  • Atelectasis
  • Pulmonary embolism
  • Acute respiratory distress syndrome (ARDS)
  • Pericardial effusion

Hypercoagulable state:

Due to hemoconcentration and hypovolemia resulting from fluid to third space shift.
  • Deep venous thromboses (DVT) (60-80%)
  • Pulmonary embolism (4-12%)

Electrolyte imbalance:

Extravasation of fluid and resultant renal dysfunction resulting from decreased perfusion leads to oliguria. Increased reabsorption of sodium and water which occurs in the proximal tubule, leads to low urinary sodium excretion.The exchange of hydrogen and potassium for sodium in the distal tubule is reduced causing, hyperkalemia and a tendency to develop acidosis.

Acute renal failure:

Hypovolemia of OHSS leads to hemoconcentration and creates a hypercoagulable state. Microthrombi tubules lead to decreased renal perfusion. Acute renal failure may result.


Predictive factors:

Surveillance for OHSS is vital for monitoring potential OHSS complication
  • Serum anti-Müllerian hormone (AMH) >3.36 ng/mL
  • Ultrasound markers: Antral follicle count (AFC) ≥24
  • Serum E2 (rapid rise in estradiol levels and serum estradiol concentrations >2500 pg/mL)


Primary prevention:

In women who are identified as being at a high risk of OHSS, treatment regimens need to be modified in view of curtailing an overexcessive ovarian response.
Sindhu, V., & Prakash, A. (2011). Prevention and management of ovarian hyperstimulation syndrome. Obstetrics, Gynaecology & Reproductive Medicine, 21, 20-23.


OHSS is a self-limiting disease. Therefore, treatment should be conservative and directed at symptoms. Medical therapy suffices for most patients. Women with severe symptoms often require intensive medical care. Surgery is necessary only in extreme cases, such as in the case of a ruptured cyst, ovarian torsion or internal hemorrhage.
Treatment of Ovarian Hyperstimulation Syndrome | Rizk, B., Holliday, C., Albasha, S., & Antonious, D. (2017). Treatment of Ovarian Hyperstimulation Syndrome. In B. Rizk & J. Gerris (Eds.), Complications and Outcomes of Assisted Reproduction (pp. 141-148). Cambridge: Cambridge University Press. doi:10.1017/9781107295391.014

Leave a Reply