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Ovarian Hyperstimulation Syndrome (OHSS)

Introduction

Ovarian hyperstimulation syndrome (OHSS), usually occurs as a result of taking hormonal medications that stimulate the development of eggs in a women ovaries (ovulation induction), which may cause serious impact on the patient’s health. Around 0.1 % – 2% of the patients develop severe forms of the syndrome. This low prevalence is increasing worldwide through the expansion of assisted reproductive tachniques.

What is OHSS

In general terms, OHSS is a consequence of injection hormone gonadotropin for ovulation induction used in assisted reproductive techniques. This potentially life threatening disorder characterized by the presence of multiple luteinized cysts within the ovaries leading to ovarian enlargement. The central feature of clinically significant OHSS is the development of vascular hyperpermeability and the resulting shift of fluids from the intravascular system to the abdominal and pleural cavity. Thus, while the patient accumulates fluid , primarily in the form of ascites, she actually becomes hypovolemic and is at risk for respritory, circulatory( such as arterial thromboembolism), and renal problems.

Causes

The hormonal drugs most likely to be involved with developing OHSS are:

  • Follicle stimulating hormone (FSH), which stimulates the formation of multiple fluid-filled cysts (follicles) on the ovaries.
  • Luteinizing hormone(LH), which supports egg maturation and triggers ovulation
  • Human menopausal gonadotropin (hMG), which has both LH and FSH
  • Human chorionic gonadotopin  (HCG), a stand-in for the LH surge that, in natural cycles, causes the follicle to release the egg.
  • Oral clomiphene citrate, which use for ovulation induction, very occasionally seen to be involved in OHSS.

Incidence

About 5 percent of women undergoing ovarian stimulation develop a moderate to severe form of ovarian hyper stimulation syndrome.

Risk Factors

  • Polycystic ovarian syndrome – a common reproductive disorder that causes irregular menstrual cycle, excess hair growth and unusual appearance of the ovaries on ultrasound examination
  • Large number of follicles
  • Young age- younger than 35
  • Low body weight
  • High level of estradiol
  • Previous episode of OHSS
  • GnRH- agonist down regulatory protocol
  • The use of hCG for final oocyte maturation
  • High serum anti-Mullerian hormone

Symptoms and Tests

Symptoms are set into 3 categories: mild, moderate, and severe.

Mild symptoms include abdominal bloating and feeling of fullness, nausea, diarrhea, and slight weight gain. Moderate symptoms include excessive weight gain, increase abdominal girth, vomiting, diarrhea, darker urine and less in amount, excessive thirst, and skin and/or hair feeling dry ( in addition to mild symptoms). Severe symptoms are fullness/bloating above the waist, shortness of breath, pleural effusion, urination significantly darker or has ceased, calf and chest pains, marked abdominal bloating or distention, rapid weight gain and lower abdominal pains ( in addition to mild and moderate symptoms).

Clinical classification of ovarian hyperstimulation syndrome.

Classification

Ovary

Clinical

Blood

Mild

5 – 10 cm

Abdominal distension and discomfort, nausea, vomiting, and/or diarrhea

Hematocrit < 45%
WBC < 15,000

Moderate

>10 cm

Features of mild OHSS plus evidence of ascites

Hematocrit < 45%
WBC < 15,000
Normal renal function

Severe

>12 cm

Marked  abdominal distension with ascites,dyspneoa, hypovolemia  and/or hydrothorax and pericardial effusion, oligoanuria

Hematocrit > 45%
WBC > 15,000
Renal failure deteriorating

Prognosis

The prognosis in mild or moderate cases of ovarian hyperstimulation syndrome (OHSS) is excellent. However, morbidity may be clinically significant in cases of severe OHSS, and fatalities do occur. However, the prognosis is optimistic in severe OHSS if proper (or adequate) treatment given.

Death from OHSS is largely due to hypovolemic shock and electrolyte imbalance, hemorrhage, and thromboemboli (hypercoagulability may endanger the patient). Estimated fatality rates are 1 per 400,000 – 500,000 stimulated cycles.

Complications

OHSS may be complicated with Thrombo-embolic, ovarian torsion, ovarian rupture, renal failure, intra-abdominal bleeding, gastrointestinal symptoms, acute respiratory distress syndrome (ARDS) and liver dysfunction. Symptoms generally resolve in 1 to 2 weeks, but will more severe and persists longer if pregnancy occurs.

Prevention

  • GnRH- Antagonists 

    GnRH antagonists protocol, seem to be associated with a decreased risk of OHSS compared with the GnRH agonists long protocol in patients undergoing IVF.
     
  • Adjusting medication dosage

    To use the lowest possible dose of gonadotropins to achieve the goals of stimulating the ovaries.
     

  • Coasting

    If the estradiol levels are high or a large number of follicles have developed, the gonadotropins injections may stop and wait a few days before given HCG, which triggers ovulation.

  • Avoiding use of HCG

    Because OHSS develops only after HCG is given , alternative to HCG for triggering are used for example GnRH agonist.
     

  • Follicles aspiration and freezing all embryos.

    For women undergoing IVF, all the follicles may be removed (aspirated) to reduce the chance of OHSS. The mature follicles are fertilized and frozen, and the ovaries are allowed to rest for one or two cycles. Then the desired number of embryos are thawed and transferred back to uterus.

 

Last Reviewed : 1 September 2014
Writer : Dr. Mohd. Nasir Tak b. Abdullah
Accreditor : Dr. Wan Abu Bakar b. Yusof