WHAT DO YOU KNOW ABOUT: OVARIAN HYPERSTIMULATION SYNDROME

Introduction

Ovarian hyperstimulation syndrome (OHSS) occurs in the luteal phase of the cycle after multifollicular stimulation and hCG administration.  It is characterised by multiple corpus luteum cysts and transudation of plasma from blood across serosa, particularly the peritoneum.  OHSS most frequently occurs following ovulation induction therapy and superovulation for assisted conception treatments, but occasionally in naturally occurring multiple pregnancy, hydatidiform mole and choriocarcinoma.  It is the commonest serious side effect of ovarian stimulation using gonadotrophins but is very uncommon with clomiphene.

 Classification:  (Modified after Schenker and Weinstein, 1978 and Navot et al., 1992).

Mild:  ovaries <8 cm diameter.  Abdominal "bloating".

Moderate:  ovaries 8-12 cm diameter.  Abdominal distension.  May also have nausea, vomiting, breathlessness and ultrasound evidence of ascites.

Severe:  ovaries >12 cms.  Clinical ascites and possibly hydrothorax.  Increased blood viscosity, electrolyte disturbance, hypoproteinaemia, hypovolaemia.  Decreased renal perfusion, anuria, renal failure.

Critical: Tense ascites or large hydrothorax with haematocrit >55%, WCC ³25,000/ml, oliguria, thrombo-embolism or Adult Respiratory Distress Syndrome (ARDS).

Incidence

Severe OHSS occurs in about 2% of gonadotrophin-stimulated cycles.  More frequent in conception cycles (4-fold increased risk), in thin, young women with a large number of follicles and also in patients with polycystic ovarian syndrome.

Prevention

Individualised treatment for ovulation induction with adequate monitoring by ultrasonography and serum oestradiol levels.  If large number of follicles and high serum oestradiol levels, consider coasting or abandoning cycle by withholding hCG injection and advise avoidance of intercourse (if LH surge possible).  Use of progesterone rather than HCG for luteal phase support may reduce the risk or severity of OHSS.

Clinical Presentation

·                    Tense, painful and distended abdomen

·                    GI symptoms: nausea/vomiting/diarrhoea

·                    Ascites, pleural effusion, vulval oedema

·                    Respiratory difficulty

·                    Oliguria

·                    Haemoconcentration/electrolyte imbalance

·                    Hypercoagulability and thrombo-embolism

 MANAGEMENT

       Empirical Treatment

·                    Analgesia/anti-emetics PRN. Avoid non-steroidal analgesics, such as Voltarol, as they may precipitate renal failure by inhibiting vasodilator renal prostaglandins. If cocodamol is not sufficient, use opiates for pain relief.

·                    Full length TED stockings (venous thrombosis risk).

·                    Consider Fragmin prophylaxis if:
 severely dehydrated and reduced mobility for long period of time,
 or abnormal clotting results at initial screening,
 or family history of venous thrombo-embolism under the age of 45 years (suggestive of an hereditary thrombophilia).

·                    Encourage oral fluid intake if not vomiting or significant hypovolaemia

·                    Discontinue hCG support (if being given).  Instead give progesterone:  Cyclogest 400 mg vaginal suppositories 12-hourly or Gestone I/M 50 mg twice weekly.

     Discuss management with consultant/senior registrar for Reproductive Medicine Unit when results of initial investigations available and before commencing IV therapy.

       Intravascular fluid replacement

Although in moderate or severe OHSS, fluids will usually have to be given intravenously encourage normal fluid intake.  Fluids given will depend on the type and extent of the intravascular disturbance.  Below is a rough guide, to be modified according to clinical state.

            i)          Serum albumin >34 g/l, Hb<14 g/dl:
IV crystalloid, approx 3L/24 hrs.

            ii)         Serum albumin £ 34 g/l, Hb>16 g/dl, Hct> 55% or serum urea >6.0 mmol/l:
2 x 100 mls - 20% albumin followed by 2L crystalloid over 18-24 hrs.  Future fluid replacement will depend on response to rehydration and the results of daily investigation.

Management of the "grey area" between (i) and (ii) will depend on the clinical situation and the stage of the syndrome.

Diuretics are generally avoided and should NOT be used without colloid especially if the serum albumin concentration is low (ie the active phase of OHSS), as this will aggravate intravascular dehydration and can lead to multi-organ failure.

             Abdominal paracentesis. (Only following discussion with the Reproductive Medicine Unit consultant)

            Indications:       Massive ascites

                             Respiratory distress

                             Oliguria unresponsive to correction of haemoconcentration with
albumin.

Should be done under ultrasound control to avoid damage to the bowel. Some believe that ascites rapidly re-accumulates and paracentesis will accelerate protein loss, others favour it to get rid of vasoactive substances from the peritoneal cavity and claim quicker recovery.  If abdominal paracentesis is undertaken particular care should be taken to monitor serum albumin afterwards as it may fall precipitously.