by Daniel Potter, M.D.
Ovarian hyperstimulation syndrome or OHSS is a common complication in vitro fertilization (IVF). In its mild form consisting of bloating and mild abdominal distension, OHSS can be identified up to 33% of IVF patients. Fortunately, the severe form of OHSS, which requires alteration of lifestyle and medical intervention, affects less than 5% of IVF patients.
OHSS, at its root, is a cluster of symptoms that result from leaky capillaries in the ovarian follicles. After ovulation, even in natural cycles, new and temporary capillaries are made in response to LH/hCG. These capillaries invade the granulosa cells of the follicles, delivering cholesterol to these cells so that the granulosa cells can produce progesterone (which is made from cholesterol). These capillaries, made in haste, are leaky. The fluid portion of the blood leaks through the capillary wall but the cellular part of the blood stays in the capillary. This is not a big deal in a spontaneous cycle as there is only a single follicle in most cases.
In typical cases of OHSS, there are many, many follicles and therefore a lot of leaky capillaries. The fluid that exudes from the capillaries accumulates in the abdominal cavity as ascites. In an IVF cycle this can occur at two different points. The first point is after hCG administration (early onset) and the second point is when hCG levels start to rise after pregnancy has been established (late onset). In severe OHSS, the ascites can accumulate to the point that the abdominal cavity is so full of fluid that it interferes with the diaphragm’s ability to move and makes breathing labored (‘respiratory embarrassment’ in medical jargon). The pressure from the ascetic fluid also puts pressure on the stomach causing a sense of fullness and decreased appetite as well as pressure on the vessels perfusing the kidneys. It is important to remember that OHSS is a self-limiting condition and will get better on its own with time in nearly every case. Please understand that only in very unusual cases do these things result serious threat to the patient’s health. OHSS treatment is always a matter of buying time while the OHSS resolves on its own.
There are many signs and symptoms of OHSS. We will briefly review the four most serious and their causes. They are decreased urine output, increased blood viscosity, low sodium and ovarian enlargement. Decreased urine output is one of the most concerning symptoms of severe OHSS. This is defined as less than 30 mL of urine per hour. It is caused by a combination of factors that lead to decreased renal perfusion. These factors include: decreased blood volume due to the leaking of fluid from the capillaries in the follicles to the abdominal space as ascites; increased intra-abdominal pressure due to tense ascites causing a.) decreased blood flow to the kidneys. b.) decreased fluid intake because the patient feels full; alterations in the renin-angiotensin system that controls salt balance. This is poorly understood and may be genetic.
Increased blood viscosity is a sign of severe OHSS indicated by an elevated hematocrit. Increased blood viscosity is the result of the fluid portion of the blood leaking through the poorly made follicular capillaries, leaving the cellular portion of the blood highly concentrated within the vascular system. This can put patient at risk for thrombus formation (blood clot).
Decreased sodium or hyponatremia is a sign of severe OHSS and often results in the patient feeling sick and lethargic. This sign is found when your physician performs a blood test measuring serum sodium. The combination of low sodium and low intravascular volume is somewhat of a paradox and is also accompanied by low potassium (hypokalemia). This is due possibly to the follicles functioning as faulty glomerulii (the glomerulus is the filtering apparatus of the kidney and usually retains sodium and potassium) as well as the alterations in the renin-angiotensin system which I alluded to above.
The most common symptom of severe OHSS is lower abdominal discomfort due to ovarian enlargement. This is due to the stretching of the capsule of the ovaries. This occurs as the ovaries increase in size due to the ‘lutienization’ that occurs in response to hCG. This common symptom occurs in moderate as well as severe OHSS.
Many regimens have been concocted to prevent or, more likely, reduce OHSS symptoms. Here is what I have found helpful in my patients:
1. Drink at least two protein supplements per day each containing 30 grams of protein. Try to eat protein rich foods like meats and legumes. Rationale: the protein will serve two purposes. It will possibly help provide substrate so that the capillaries formed are more substantial and less leaky. Protein will also provide substrate for the production of albumin. Albumin is a component of blood that is integral in keeping the fluid part of the blood from leaking out of the vascular system. The albumin is too large to leak out of the capillaries and will (hopefully) provide oncotic pressure and keep more of the liquid part of the blood in the vascular system, thereby reducing ascites. Failure to get adequate nutrients will quickly lead to a reduction of albumin production and is part of the reason that patients often rapidly deteriorate with OHSS when they get tense ascites and lose their appetites.
2. Drink electrolyte balanced fluids rather than water. Gatorade or like electrolyte drinks will provide sodium and potassium, which is being lost in the ascitic fluid. Maintaining adequate hydration is key to maintaining adequate renal perfusion. When you are thirsty or notice dry mouth and lips, chug Gatorade. If you have concentrated urine or dry mucus membranes, you are not getting enough fluid, drink Gatorade until it improves. Coconut water is another popular electrolyte rich fluid but is not as good as Gatorade in my opinion.
3. Put extra salt on your food and eat salty snacks. See number 2 above. You need sodium and potassium. Low sodium and potassium contribute to the feeling of lethargy and decreased appetite that often accompany severe OHSS. You are losing sodium through the capillaries and need to replace it.
4. Stay off your feet as much as possible. Walking excessively results in increased ovarian pain and may also increase leaking from the new capillaries. Often the pain is most noticeable at night. Staying off your feet may also aid in the reabsorption of the ascitic fluid.
5. Take a baby aspirin per day. The 81 mg of aspirin helps to prevent clotting of the concentrated blood. In certain severe cases, lovinox may be added to prevent thrombus formation.
6. Take narcotic pain medication as needed for pain. We usually prescribe Vicodin or a similar agent. Do not be afraid to take pain medication if needed, you do not get extra credit for being a hero.
Your doctors may also recommend that you have IV hydration and drainage of tense ascites (abdominal fluid) in certain circumstances.
In conclusion, severe OHSS is a condition that occurs in less than 5% of IVF cases but can cause significant discomfort for the affected patient. OHSS can be adequately managed in most cases with temporizing symptomatic relief and occasional medical intervention in the form of IV hydration and drainage of excess ascites. OHSS is a self-limiting condition that will spontaneous resolved over time.
Daniel Potter, M.D. is a reproductive endocrinologist at HRC Fertility