Ovarian hyperstimulation syndrome
The ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation treatment (ovarian induction therapy) for in vitro fertilisation. Rarely, it may also occur as a spontaneous event in pregnancy (see spontaneous ovarian hyperstimulation later in the article).
The clinical syndrome consists of ovarian enlargement with extra-vascular accumulation of exudates leading to varying degrees of
- weight gain
- increase in abdominal circumference
- pleural effusions
- intravascular volume depletion with haemoconcentration
The syndrome is relatively common, occurring in ~5% of patients undergoing in vitro fertilisation (IVF).
The clinical picture may vary from abdominal distension and discomfort to potentially life-threatening capillary leak with fluid sequestration in a third space, and massive ovarian enlargement. Pain, abdominal distention, nausea, and vomiting are frequently seen as symptoms.
It is characterised by massive cystic ovarian enlargement and fluid shift from the intravascular compartment into the peritoneal, pleural or pericardial cavities. The vascular fluid leakage is thought to result from an increased capillary permeability of mesothelial surfaces under the action of one or several vasoactive ovarian factors produced by multiple corpora lutea. Acute pelvic pain can result from stretching of the ovarian capsule or hemorrhage/rupture of a follicle.
- baseline ovarian volume 8
- background polycystic ovaries 9
- low body weight 8
- long ovulation induction cycle duration 8
- serum oestradiol (E2) levels are elevated
Spontaneous ovarian hyper-stimulation
This sub type occurs in the absence of any external stimulation. This form can occur in pregnancy 15.
There are also very rare sporadic forms which carry a genetic components. These have an association with early pubertal development and primary hypothyroidism. Ovarian stimulation in the hypothyroid child may result in oestrogen production, breast development, endometrial proliferation, and vaginal bleeding. It is likely that raised TSH concentrations bind and stimulate the FSH receptor, although a similar overlap phenomenon might occur at the level of the pituitary, with enhanced TRH production stimulating the GnRH receptor with subsequent ovarian enlargement. The cystic ovarian enlargement resolves with thyroid hormone replacement. A hyperstimulation phenomenon in patients with an abnormal FSH receptor has been described.
Based upon the clinical manifestation and imaging findings, OHSS can be classified into 12
mild OHSS: characterised by bilateral multicystic ovarian enlargement
- grade 1: abdominal distention and discomfort
- grade 2: plus nausea, vomiting and/or diarrhoea plus ovarian enlargement from 5 to 12 cm
moderate OHSS: if there is associated ascites and abdominal distension
- grade 3: features of mild OHSS plus ultrasonographic evidence of ascites
severe OHSS: characterised by hypovolemia, haemoconcentration, thrombosis, oliguria, pleural and pericardial effusion
- grade 4: moderate OHSS plus clinical evidence of ascites and/or hydrothorax and dyspnea
- grade 5: grade 4 plus change in the blood volume, hemoconcentration, coagulation abnormalities and diminished kidney perfusion and function
Imaging findings can be similar on ultrasound, CT and MR imaging.
- typically shows bilateral symmetric enlargement of ovaries (often >12 cm in size)
- multiple cysts of varying sizes, giving the classic spoke-wheel appearance
- associated ascites and pleural +/- pericardial effusion (which is due to capillary leak) may also be present
Treatment and prognosis
The syndrome is usually self limiting on most cases and management is mainly supportive, however cases with fatal outcome have been reported 14. Severe cases usually require hospitalization and a close monitoring of the haematocrit, liver function, renal function, serum electrolytes and oxygen saturation.
The profoundly altered maternal environment of OHSS is a significant risk factor for miscarriage, especially when occurring in the early phase after IVF (defined as <10 days after oocyte retrieval) 16.
- hypo-volaemic shock with resultant
- increased risk of ovarian torsion 6
For ultrasound appearances in mild cases consider
- cysts are typically small
- no ascites or pleural effusions
- theca lutein cysts associated with gestational trophoblastic disease: some also considered a part of OHSS
- mucinous ovarian malignancy
Role of the radiologist
Familiarity with ovarian hyperstimulation syndrome and the appropriate clinical setting should help avoid the incorrect diagnosis of an ovarian cystic neoplasm. On encountering severe forms not suspected by the clinician suggesting the diagnosis may reduce both morbidity and mortality.
- 1. Smits G, Olatunbosun O, Delbaere A et-al. Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor. N. Engl. J. Med. 2003;349 (8): 760-6. doi:10.1056/NEJMoa030064 - Pubmed citation
- 2. Sultan A, Velaga MR, Fleet M et-al. Cullen's sign and massive ovarian enlargement secondary to primary hypothyroidism in a patient with a normal FSH receptor. Arch. Dis. Child. 2006;91 (6): 509-10. doi:10.1136/adc.2005.088443 - Free text at pubmed - Pubmed citation
- 3. Jung BG, Kim H. Severe spontaneous ovarian hyperstimulation syndrome with MR findings. J Comput Assist Tomogr. 25 (2): 215-7. J Comput Assist Tomogr (link) - Pubmed citation
- 4. Bennett GL, Slywotzky CM, Giovanniello G. Gynecologic causes of acute pelvic pain: spectrum of CT findings. Radiographics. 22 (4): 785-801. Radiographics (full text) - Pubmed citation
- 5. Jung SE, Byun JY, Lee JM et-al. MR imaging of maternal diseases in pregnancy. AJR Am J Roentgenol. 2001;177 (6): 1293-300. AJR Am J Roentgenol (full text) - Pubmed citation
- 6. Pedrosa I, Zeikus EA, Levine D et-al. MR imaging of acute right lower quadrant pain in pregnant and nonpregnant patients. Radiographics. 27 (3): 721-43. doi:10.1148/rg.273065116 - Pubmed citation
- 7. Delbaere A, Smits G, De leener A et-al. Understanding ovarian hyperstimulation syndrome. Endocrine. 2005;26 (3): 285-90. doi:10.1385/ENDO:26:3:285 - Pubmed citation
- 8. Danninger B, Brunner M, Obruca A et-al. Prediction of ovarian hyperstimulation syndrome by ultrasound volumetric assessment [corrected] of baseline ovarian volume prior to stimulation. Hum. Reprod. 1996;11 (8): 1597-9. Hum. Reprod. (link) - Pubmed citation
- 9. Rizk B, Smitz J. Ovarian hyperstimulation syndrome after superovulation using GnRH agonists for IVF and related procedures. Hum. Reprod. 1992;7 (3): 320-7. Hum. Reprod. (link) - Pubmed citation
- 10. Papanikolaou EG, Pozzobon C, Kolibianakis EM et-al. Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles. Fertil. Steril. 2006;85 (1): 112-20. doi:10.1016/j.fertnstert.2005.07.1292 - Pubmed citation
- 11. Kim IY, Lee BH. Ovarian hyperstimulation syndrome. US and CT appearances. Clin Imaging. 21 (4): 284-6. Clin Imaging (link) - Pubmed citation
- 12. Golan A, Ron-el R, Herman A et-al. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv. 1989;44 (6): 430-40. Pubmed citation
- 13. Kasum M. New insights in mechanisms for development of ovarian hyperstimulation syndrome. Coll Antropol. 2010;34 (3): 1139-43. Pubmed citation
- 14. Semba S, Moriya T, Youssef EM et-al. An autopsy case of ovarian hyperstimulation syndrome with massive pulmonary edema and pleural effusion. Pathol. Int. 2000;50 (7): 549-52. Pubmed citation
- 15. Lovgren TR, Tomich PG, Smith CV et-al. Spontaneous severe ovarian hyperstimulation syndrome in successive pregnancies with successful outcomes. Obstet Gynecol. 2009;113 (2, Part 2): 493-5. doi:10.1097/AOG.0b013e318184182b - Pubmed citation
- 16. Papanikolaou EG, Tournaye H, Verpoest W et-al. Early and late ovarian hyperstimulation syndrome: early pregnancy outcome and profile. Hum. Reprod. 2005;20 (3): 636-41. doi:10.1093/humrep/deh638 - Pubmed citation
Ultrasound - gynaecology
- ultrasound (introduction)
- acute pelvic pain
- chronic pelvic pain
- Mullerian duct anomalies
- ovarian follicle
- ovarian torsion
- pelvic inflammatory disease
- ovarian cysts and masses
- ovarian cyst
- corpus luteum
- haemorrhagic ovarian cyst
- ruptured ovarian cyst
- ovarian epithelial tumours
- granulosa cell tumours of the ovary
- paraovarian cyst
- polycystic ovaries
- ovarian hyperstimulation syndrome
- post-hysterectomy ovary
- fallopian tube