Ovarian hyperstimulation syndrome: Wikis


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Ovarian hyperstimulation syndrome
Classification and external resources
ICD-10 N98.1
ICD-9 xxx
DiseasesDB 32038

Ovarian hyperstimulation syndrome (OHSS) is a complication from some forms of fertility medication. Most cases are mild, but a small proportion is severe.



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 (weight gain of greater than 2 pounds per day), increased 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, urination significantly darker or has ceased, calf and chest pains, marked abdominal bloating or distention, and lower abdominal pains (in addition to mild and moderate symptoms).


In mild forms of OHSS the ovaries are enlarged, in moderate forms there is additional accumulation of ascites with mild abdominal distension, while in severe forms of OHSS there may be hemoconcentration, thrombosis, abdominal pain and distension, oliguria (decreased urine production), pleural effusion, and respiratory distress. Early OHSS develops before pregnancy testing, and late OHSS is seen in early pregnancy.


OHSS may be complicated with ovarian torsion, ovarian rupture, thrombophlebitis and renal insufficiency. Symptoms generally resolve in 1 to 2 weeks, but will be more severe and persist longer if pregnancy occurs. This is due to hCG from the pregnancy acting on the corpus luteum in the ovaries in sustaining the pregnancy before the placenta has fully developed. Typically, even in severe OHSS with a developing pregnancy, the duration does not exceed the first trimester.


OHSS has been characterized by the presence of multiple luteinized cysts within the ovaries leading to ovarian enlargement and secondary complications, but that definition includes almost all patients undergoing ovarian stimulation. The central feature of clinically significant OHSS is the development of vascular hyperpermeability and the resulting shift of fluids into the third space.

As hCG causes the ovary to undergo extensive luteinization, large amounts of estrogens, progesterone, and local cytokines are released. It is almost certain that vascular endothelial growth factor (VEGF) is a key substance that induces vascular hypermeability, making local capillaries "leaky", leading to a shift of fluids from the intravascular system to the abdominal and pleural cavity. Supraphysiologic production of VEGF from many follicles under the prolonged effect of hCG appears to be the specific key process underlying OHSS. Thus, while the patient accumulates fluid in the third space, primarily in the form of ascites, she actually becomes hypovolemic and is at risk for respiratory, circulatory, and renal problems. Patients who are pregnant sustain the ovarian luteinization process through the production of hCG.

Avoiding OHSS typically requires interrupting the pathological sequence, such as avoiding the use of hCG. One alternative is to use a GnRH agonist instead of hCG. While this has been repeatedly shown to "virtually eliminate" OHSS risk, there is some controversy regarding the effect on pregnancy rates if a fresh non-donor embryo transfer is attempted, almost certainly due to a luteal phase defect. There is no dispute that the GnRH agonist trigger is effective for oocyte donors and for embryo banking (cryopreservation) cycles.


Sporadic OHSS is very rare, and may have a genetic component. Clomifene citrate therapy can occasionally lead to OHSS, but the vast majority of cases develop after use of gonadotropin therapy (with administration of FSH), such as Pergonal, and administration of hCG to trigger ovulation, often in conjunction with IVF. The frequency varies and depends on patient factors, management, and methods of surveillance. About 5% of treated patients may encounter moderate to severe OHSS. Risk factors include young age, the development of many ovarian follicles under stimulation, extreme elevated serum estradiol concentrations, the use of hCG as the "trigger" agent, the continued use of hCG for luteal support, and the occurrence of a pregnancy (resulting in hCG production).

Mortality is low, but several fatal cases have been reported.


Physicians can reduce the risk of OHSS by monitoring of FSH therapy to use this medication judiciously, and by withholding hCG medication. Once OHSS develops, reduction in physical activity, closely monitoring fluid and electrolyte balance, and aspiration of accumulated fluid (ascites) from the abdominal/pleural cavity may be necessary, as well as opioids for the pain. If the OHSS develops within an IVF protocol, it can be prudent to postpone transfer of the pre-embryos since establishment of pregnancy can lengthen the recovery time or contribute to a more severe course. Over time, if carefully monitored, the condition will naturally reverse to normal - so treatment is typically supportive, although patient may need to be treated or hospitalized for pain, paracentesis, and/or intravenous hydration.

Emotional Issues

The couple who is already facing stress due to infertility, the OHSS as a complication of treatment is major issue for them. Such couples need to be provided with adequate counselling and patient hearing. They must be explained with optimistic outcome of OHSS. In most cases, symptoms do subside and condition reverts back to normal. So much so, that the patient will forget the symptoms when pregnancy is carried over successfully. An optimistic attitude is very necessary in the treatment.


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