|Year : 2011 | Volume
| Issue : 2 | Page : 92-95
Severe ovarian hyperstimulation syndrome: Intensive care management of two cases
Praveen Talawar, Vimi Rewari, Renu Sinha, Anjan Trikha
Department of Anaesthesiology, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||17-Mar-2012|
Department of Anaesthesiology, Room No. 5020, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Severe ovarian hyperstimulation syndrome (OHSS) is characterized by increased capillary permeability and fluid retention in the third space. It is generally a complication of assisted reproduction therapy (ART) with exogenous gonadotropins, but cases with natural onset of OHSS have been reported. The massive extravascular exudation can cause tense ascites, pleural and pericardial effusion, hypovolemic shock, oliguria, electrolyte imbalance (hyponatremia and hyperkalemia), and hemoconcentration, with a tendency for hypercoagulability and risk of life-threatening thromboembolic complications. The patient can rarely develop multi-organ failure (adult respiratory distress syndrome, renal failure) and death. With increasing use of ART, this syndrome may be seen more frequently in the intensive care unit (ICU), requiring multidisciplinary care. We report the management of two cases of severe OHSS, which required admission to the ICU in our hospital.
Keywords: Intensive care, multi-organ failure, ovarian hyperstimulation syndrome
|How to cite this article:|
Talawar P, Rewari V, Sinha R, Trikha A. Severe ovarian hyperstimulation syndrome: Intensive care management of two cases. J Obstet Anaesth Crit Care 2011;1:92-5
|How to cite this URL:|
Talawar P, Rewari V, Sinha R, Trikha A. Severe ovarian hyperstimulation syndrome: Intensive care management of two cases. J Obstet Anaesth Crit Care [serial online] 2011 [cited 2018 May 26];1:92-5. Available from: http://www.joacc.com/text.asp?2011/1/2/92/93995
| Introduction|| |
Severe ovarian hyperstimulation syndrome (OHSS), occurring as a complication of assisted reproduction therapy (ART), is a rare cause of admission to the intensive care unit (ICU). The syndrome is characterized by increased capillary permeability and fluid retention in the third space. , The onset of this syndrome is marked by abdominal distension, nausea and vomiting following therapy with gonadotrophins or antiestrogens.  OHSS is classified as mild (8-23%), moderate (1-7%), severe (0.5-5%) and critical, depending upon clinical and laboratory investigations. ,
With the increasing number of patients opting for ART, physicians involved in the care of these patients must be conscious of this rare clinical condition and its presentations, which can cause multi-organ dysfunction and, potentially, death.
We report the management of two cases of severe OHSS, which required admission to ICU in our hospital.
| Case Reports|| |
A 30-year-old female with no previous co-morbidities was undergoing in vitro fertilization (IVF) in our hospital for primary infertility. As a part of the IVF protocol, she was administered gonadotropin releasing hormone. She was subsequently given human chorionic gonadotropin (HCG) after confirming presence of multiple follicles on ultrasonography (USG), followed by oocyte aspiration under conscious sedation. The patient complained of nausea, vomiting, abdominal distension and decreased urine output after 2 days of oocyte aspiration. Provisional diagnosis of severe OHSS was made and the patient was transferred to the ICU for monitoring. In the ICU, the patient remained conscious, oriented and was hemodynamically stable. However, she required oxygen supplementation and continuous positive airway pressure (CPAP) support for 2 days for respiratory distress, and diuretic therapy (furosemide) for decreased urine output during her ICU stay. An ultrasound examination of her chest and abdomen revealed bilateral mild pleural effusion and bilateral bulky ovaries with moderate ascites. She also received prophylactic broad-spectrum antibiotics, albumin and low molecular weight heparin (LMWH) during her ICU admission. She responded to therapy, did not require any removal of pleural or ascetic fluid, was shifted to the ward and was discharged after 2 days.
A 31-year-old female with no known previous co-morbidities was on IVF protocol for secondary infertility in our hospital. The patient had previous uneventful history of laparoscopic ovarian drilling for polycystic ovarian disease (PCOD) under general anesthesia and history of abortion at 5 months for previous twin pregnancy after intrauterine insemination (IUI).
The patient developed abdominal distension with discomfort a day after ovum pickup. The provisional diagnosis of severe OHSS was made; supportive treatment with colloids was started. Two days later, the patient developed nausea, vomiting and decreased urine output. She underwent therapeutic ascitic tap thrice for tense ascites. The patient also developed slowly worsening respiratory distress, which required endotracheal intubation, and she was transferred to the ICU for further management.
On admission, the patient was conscious, obeying commands; her heart rate was 130/min and blood pressure was 85/50 mmHg. Systemic examination revealed decreased air entry in bilateral basal areas of the chest and abdominal distension. The USG abdomen revealed enlarged multiple follicles with size of the ovaries 13 cm x 7 cm, moderate-to-massive ascites and bilateral mild pleural effusion. She required inotropic support with noradrenaline and furosemide infusion for decreased urine output, and received broad-spectrum antibiotics, albumin, LMWH and total parenteral nutrition.
She developed multiple episodes of pulmonary edema on her 3 rd and 4 th day of ICU stay. The transthoracic echocardiography revealed rheumatic heart disease with moderate-to-severe mitral stenosis (MS) (mitral valve area 1.1-1.2 cm 2 ) and mitral regurgitation, mitral valve gradient of 33/19 mmHg, with normal left ventricular ejection fraction (LVEF 65%). The patient was shifted to the coronary care unit for emergency percutaneous balloon mitral commissurotomy because of her repeated pulmonary edema episodes and worsening general condition. The procedure was, however, deferred and conservative management was continued with furosemide and nitroglycerine infusion. She was weaned from the ventilator subsequently and her trachea was extubated. The patient was advised to repeat echocardiography at a later date and she was discharged from the hospital with a prescription of beta blocker and diuretics.
| Discussion|| |
OHSS is a self-limiting condition; subsides on its own, but it possibly will continue longer if the patient conceives. The resolution correlates with fall in HCG levels.  The syndrome is generally a complication of ART with exogenous gonadotropins, but cases with natural onset of OHSS have been reported.  Both of our cases developed OHSS following IVF.
The exact etiopathogenesis is not completely understood, but there are certain risk factors known to predispose for the development of OHSS: younger age, PCOD, multiple follicles, retrieval of more than 20 oocytes, higher doses of exogenous gonadotropins, high serum E 2 levels, conception and previous history of OHSS. ,,, Both of our patients had multiple follicles on USG and the second patient had history of PCOD.
Recognizing the risk factors and individualizing the management regimen are the key factors in the prevention of this syndrome. One should exercise vigilance when there are a great number of intermediate-size follicles and early symptoms like abdominal distension and discomfort. Monitoring ovarian response to gonadotrophins by USG and serum E 2 levels is considered as the gold standard in predicting the patients at risk of OHSS.  When signs of impending OHSS appear even before administration of HCG, cycle cancellation and less aggressive stimulation in the subsequent cycle should be considered. The luteal phase support with HCG (ovulatory trigger injection) should be avoided (cancelling cycle) in women at risk;  progesterone rather than HCG for luteal phase support may further decrease the danger of OHSS.  Prophylactic albumin and hydroxy ethyl starch solution infusion have been reported to reduce the incidence of early OHSS. ,
The increase in capillary permeability and fluid shift to third space is the distinguishing feature of OHSS. Vascular endothelial growth factor (VEGF) is blamed for increase in vascular permeability and its levels correlate with severity of OHSS.  Increased exudation of protein-rich fluid mainly occurs around the enlarged ovaries and other endothelial surfaces. Distension and abdominal discomfort due to ascites is the first indication of the fluid shift; the massive extravascular exudation can cause tense ascites, pleural and pericardial effusion, hypovolemic shock, oliguria, electrolyte imbalance (hyponatremia and hyperkalemia) and hemoconcentration. ,,
The patient may have tendency for hypercoagulability and is at risk of life-threatening thromboembolic complications.  The patient can rarely develop adult respiratory distress syndrome (ARDS),  renal failure and multiorgan failure, leading to death.
The patient can have increased lower abdominal discomfort, bloating, nausea and vomiting in the mild form of OHSS. Progression of illness is recognized when symptoms persist, worsen or include ascites. Serious illness is said to exist when abdominal pain is accompanied by vomiting, rapid weight gain, ascites, pleural effusion, oliguria, hypoalbuminemia, hemoconcentration and electrolyte abnormalities. The onset of symptoms takes 3-10 days to develop after HCG administration.
Respiratory distress in a patient with OHSS can arise from pulmonary embolism, pleural effusion and ARDS; pulmonary edema is an uncommon but grave complication of OHSS. There are reports of pulmonary edema (both low and high pressure) in patients with OHSS, attributed to excessive capillary permeability. 
In the present series, the first patient had mild disease, and just required intensive monitoring and supplementary oxygen with CPAP. However, the second patient had severe OHSS, had repeated episodes of pulmonary edema on the 3 rd and 4 th day of her ICU stay and was found to have moderate-to-severe mitral stenosis.
The patient did not have symptoms suggestive of mitral stenosis in the past; she had uneventful anesthesia exposure for laparoscopic ovarian drilling 1 year back in a peripheral hospital, and there was no history of breathlessness in the previous pregnancy. It is possible that her disease had progressed over the past year.
ART in a patient with any known severe medical disease carries high morbidity and mortality. Severe mitral stenosis is an absolute contraindication, as the resulting conception is a potential threat to maternal life. Issues relating to complications should be explained to the patient before initiating therapy.  As our patient was asymptomatic, diagnosis of MS was missed; she had a critical course of OHSS and, fortunately, recovered uneventfully.
Patients with severe OHSS require hospital admission; those with critical OHSS (ARDS, renal failure and thromboembolism with tense ascites or massive pleural effusion) require multidisciplinary care in ICU. The laboratory workup required are: complete blood count, liver function tests, renal function tests, baseline clotting studies, pelvic ultrasound, chest X-ray (CXR, for respiratory symptoms), electrocardiogram and echocardiogram in suspected pericardial effusion. Strict intake and output chart, abdominal girth, hematocrit, electrolytes and weight recordings should be maintained daily; serial abdominal USG and CXR may be done as needed.
The management is usually supportive until the condition resolves spontaneously; nausea and vomiting should be treated symptomatically. Correction of fluid deficit, hypotension and oliguria due to increased capillary permeability should be done; fluids should be administered judiciously to maintain adequate urine output and reverse hemoconcentration. Central venous pressure monitoring is needed in patients with pulmonary edema and renal impairment. Evidence to support specific regimen of fluid replacement in women with OHSS are lacking, 20% albumin (50-100 g) is an effective plasma expander when crystalloids fail to achieve hemodynamic stability and satisfactory urine output; fresh frozen plasma may be used alternatively. Diuretics should be used carefully as these patients may have intravascular volume depletion. Low-dose dopamine has also been used in an attempt to improve urine output when other measures fail.
Ultrasound-guided paracentesis can be considered in patients with tense ascites that causes respiratory distress, oliguria and abdominal pain. The optimal quantity to be removed and time interval is not well known. Thoracentesis can be considered in a patient with respiratory distress due to bilateral or severe pleural effusion; endotracheal intubation and mechanical ventilation can be considered if needed. Cabergoline (dopamine agonist) may be beneficial as it decreases VEGF-mediated capillary permeability.  Thromboembolism is a serious complication due to hypercoagulable condition; prophylactic measures like intermittent pneumatic compression device and anticoagulation with heparin may be necessary. Therapeutic anticoagulation should be initiated in case of pulmonary embolism. 
To conclude, OHSS is rare obstetric cause for ICU admission. However, with increasing use of ART, this syndrome may be seen more frequently in the ICU. Early diagnosis, intensive monitoring and institution of supportive therapy may help in preventing complications.
| References|| |
|1.||Tollan A, Holst N, Forsdahl F, Fadnes HO, Oian P, Maltau JM. Transcapillary fluid dynamics during ovarian stimulation for in vitro fertilization. Am J Obstet Gynecol 1990;162:554-8. |
|2.||Goldsman MP, Pedram A, Dominguez CE, Ciuffardi I, Levin E, Asch RH. Increased capillary permeability induced by human follicular fluid: A hypothesis for an ovarian origin of the hyperstimulation syndrome. Fertil Steril 1995;63:268-72. |
|3.||Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): A review. Hum Reprod Update 2002;8:559-77. |
|4.||Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: An update review. Obstet Gynecol Surv 1989;44:430-40. |
|5.||Navot D, Bergh PA, Laufer N. Ovarian hyperstimulation syndrome in novel reproductive technologies: Prevention and treatment. Fertil Steril 1992;58:249-61. |
|6.||Singh RK, Singhal S, Azim A, Baronia AK. Severe ovarian hyperstimulation syndrome leading to ICU admission. Saudi J Anaesth 2010;4:35-7. |
|7.||Smits G, Olatunbosun O, Delbaere A, Pierson R, Vassart G, Costagliola S. Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor. N Engl J Med 2003;349:760-6. |
|8.||Golan A, Ron-El R, Herman A, Weinraub Z, Soffer Y, Caspi E. Ovarian hyperstimulation syndrome following D-Trp-6 luteinizing hormone-releasing hormone microcapsules and menotropin for in vitro fertilization. Fertil Steril 1988;50:912-6. |
|9.||Navot D, Relou A, Birkenfeld A, Rabinowitz R, Brzezinski A, Margalioth EJ. Risk factors and prognostic variables in the ovarian hyperstimulation syndrome. Am J Obstet Gynecol 1988;159:210-5. |
|10.||Tal J, Paz B, Samberg I, Lazaroun N, Scharf, M. Ultrasonographic and clinical correlates of metropin versus sequential clomiphene citrate: Menotropin for induction of ovulation. Fertil Steril 1985;44:342. |
|11.||Delvigne A, Dubois M, Battheu B, Bassil S, Meuleman C, De Sutter P, et al. The ovarian hyperstimulation syndrome in in-vitro fertilization: a Belgian multicentric study. II. Multiple discriminant analysis for risk prediction. Hum Reprod 1993;8:1361-6. |
|12.||Karam KS, Taymor ML, Berger MJ. Estrogen monitoring and the prevention of ovarian overstimulation during gonadotropin therapy. Am J Obstet Gynecol 1973;115:972-7. |
|13.||Hancock KW, Stitch SR, Oakey RE, Scott JS, Levell MJ, Ellis FR. Ovulation stimulation. Problems of prediction of response to gonadotrophins. Lancet 1970;2:482-5. |
|14.||Penzias AS. Luteal phase support. Fertil Steril 2002;77:318-23. |
|15.||Shaker A, Zosmer A, Dean N, Bekir JS, Jacobs HS, Tan SL. Comparison of intravenous albumin and transfer of fresh embryos with cryopreservation of all embryos for subsequent transfer in prevention of ovarian hyperstimulation syndrome. Fertil Steril 1996;65:992-6. |
|16.||Graf MA, Fischer R, Naether OG, Baukloh V, Tafel J, Nuckel M. Reduced incidence of ovarian hyperstimulation syndrome by prophylactic infusion of hydroxyaethyl starch solution in an in-vitro fertilization programme. Hum Reprod 1997;12:2599-602. |
|17.||Geva E, Jaffe RB. Role of vascular endothelial growth factor in ovarian physiology and pathology. Fertil Steril 2000;74:429-38. |
|18.||Schenker JG, Weinstein D. Ovarian hyperstimulation syndrome: A current survey. Fertil Steril 1978;30:255-68. |
|19.||Shanbhag S, Bhattacharya S. Current management of ovarian hyperstimulation syndrome. Hosp Med 2002;63:528-32. |
|20.||Balasch J, Fábregues F, Arroyo V, Jiménez W, Creus M, Vanrell JA. Treatment of severe ovarian hyperstimulation syndrome by a conservative medical approach. Acta Obstet Gynecol Scand 1996;75:662-7. |
|21.||Zimmerman C. Ovarian hyperstimulation syndrome and development of pulmonary embolism in pregnancy: Case report. Proc Obstet Gynecol 2010;1:11. |
|22.||Zosmer A, Katz Z, Lancet M, Konichezky S, Schwartz-Shoham Z. Adult respiratory distress syndrome complicating ovarian hyperstimulation syndrome. Fertil Steril 1987;47:524-6. |
|23.||BaHammam AS. Pulmonary edema complicating ovarian hyperstimulation syndrome: Low-pressure edema, high-pressure edema, or mixed edema? Ann Saudi Med 2005;25:335-8. |
|24.||Neill AM, Nelson-Piercy C. Hazards of assisted conception in women with severe medical disease. Hum Fertil (Camb) 2001;4:239-45. |
|25.||Garcia-Velasco JA. How to avoid ovarian hyperstimulation syndrome: A new indication for dopamine agonists. Reprod Biomed Online 2009;18:71-5. |
|26.||Practice committee of the American society for reproductive medicine. Ovarian hyperstimulation syndrome. Fertil Steril 2004;82:S81-6. |