Ovarian Hyperstimulation Syndrome (OHSS)

Southern Ontario
Fertility Technologies
Introduction
All IVF and some IUI involve controlled ovarian
hyperstimulation, which is the simulation of the ovaries to make more than one egg per cycle. It is one
step higher than ovulation induction (IE – just pills like clomiphene or femara) and adds injectable
fertility medicines. Ovarian hyperstimulation
syndrome (OHSS) is a serious, life-
threatening complication resulting from this
process where the ovaries become more
stimulated than planned. The ovaries become
leaky, allowing fluid which is usually confined
within the blood vessels to pass out into the
abdominal cavity and other parts of the body.
Ovarian hyperstimulation syndrome, by
definition, is composed of a combination of
ovarian enlargement and an acute fluid shift out
of the blood vessels. The ovarian enlargement
is caused by ovarian cyst formation (follicles)
and the fluid shift may result in fluid in the
abdominal cavity (ascites), or in the space
between the lungs and the chest wall
Ultrasound of a severely enlarged ovary in a
(hydrothorax or pleural effusions), or in the fat
patient with OHSS
and other body tissues (generalized edema). This
results in the accumulation of large amounts of
fluid in the body and relatively too little fluid in the blood vessels.

Incidence
Despite careful monitoring, a small number of women (about 3-5% of the treatment cycles) may
develop OHSS. Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of
exogenous gonadotropin administration (injectable fertility medicines). Clinically significant OHSS
occurs in 1% to 10% of IVF-ET cycles and up to 4% of ovulation induction cycles. At S.O.F.T. we
have completed over 1500 IVF cycles in 10 years of operation and had to hospitalize 4 patients with
severe OHSS (0.3%) and perform out-patient paracentesis on 7 (0.5%).

Predisposing Factors or Risk Factors

OHSS is an unexpected over response to fertility drugs. In IVF we try to make 10 to 15 follicles or
eggs. OHSS occurs if we make 40 by mistake. There are some predisposing factor which include:
 Younger women
 Polycystic ovary syndrome
 Hypothalamic amenorrhea
 Previous OHSS
 Use of injectable fertility medications
 High estrogen hormone levels and a large number of follicles or eggs.
 Administration of GnRH agonist.
 The use of HCG for luteal phase support.
 Pregnancy increases the likelihood, duration, and severity of OHSS symptoms.

Symptoms and Clinical Features

Almost all women undergoing IVF have mild OHSS. Symptoms of this include transient lower
abdominal discomfort and bloating. About 30% of women undergoing IVF will have significant
abdominal distension. Usually symptoms will begin about the time of ovulation in IUI cycles or after
oocyte retrieval in an IVF cycle. We don’t consider this significant or necessary to treat and refer to it
as mild OHSS.
If OHSS progresses to moderate it will often cause more severe abdominal distension; one
example would be that your usual pants don’t fit. At this point, ultrasound usually demonstrates ovaries
with a maximum diameter of 10 cm or greater and some abdominal free fluid (ascites).
As OHSS progresses there may be some mild nausea, vomiting and diarrhea. Abdominal
distension often becomes worse and an increased weight due to fluid retention can be demonstrated. At
this point the ovaries usually measure larger and more ascites can be measured in the abdominal cavity.
Severe OHSS is characterized by fluid in the pleural spaces (around the lungs). When this is
mild it will present as a dry cough but as more fluid accumulates it causes shortness of breath. At this
point we can often document increasing abdominal girth. Sometimes edema of the legs and arms will
be experienced.
The most severe OHSS (requiring hospitalization) leads to an increased heart rate and
decreased blood pressure. The patient may experience orthostatic hypotension (dizziness when getting
up because of a drop of blood pressure and decreased blood supply to the brain). Often there is not
enough blood pressure to adequately supply the kidneys and this leads to decreased urine production.
Generalized edema can occur which includes the skin of the abdomen and back. Sometimes there will
be abnormalities in blood tests at this stage. Often your hemoglobin level rises and abnormalities in
coagulation can be seen. At this point we worry about an increased risk of clot formation.

What Is Happening?
OHSS is fluid leaking out of the vascular system causing it to not be full enough and leaking
into the tissues of the body. This results in accumulation of fluid in the wrong places. First this is likely
to occur in the abdominal cavity (ascites). Usually next around the lungs in the pleural spaces
(hydrothorax or pleural effusions) and then in the general body tissues (edema). However as the fluid
leaks out of the blood vessels, they don’t have enough volume. This first is expressed as decreased
urine volume and perhaps some mild changes in blood pressure.
Life-threatening complications of OHSS include renal failure, adult respiratory distress
syndrome (ARDS), hemorrhage from ovarian rupture, and thromboembolism (blood clots). These have
never occurred at S.O.F.T.

Treatment
No treatment is necessary for the milder forms of OHSS, which occur in almost all IVF patients
and occasionally in IUI patients. It will simply resolve on its own. This usually takes only a few days if
a pregnancy does not occur; up to several weeks if a pregnancy had occurred. Our clinical impression
at S.O.F.T. is that a twin pregnancy further prolongs recovery.
 Patients at high risk for OHSS are usually recognized during their cycle because of greater
than usual number of follicles and higher estradiol. Usually as soon as this is recognized, the dose of
injectable fertility medicine is decreased. Some clinics have decreased the dose of HCG to 5,000 units
from 10,000 units but we have not done this for fear it might affect the final egg maturity and therefore
egg quality.
In very high-risk cycles, clinics have cancelled the cycle. Fortunately, we have not needed to do
this yet with any patients. Another strategy is to complete the IVF and retrieve the eggs but freeze all
the embryos. This is because a pregnancy aggravates the OHSS. If no embryo transfer is done, no
pregnancy results. Frozen embryos can then be transferred at a safer time. We are reluctant to do this
but have had to do it twice in the history of S.O.F.T. Termination of a pregnancy had been reported in
the literature but has not been considered or necessary at S.O.F.T.
Weight should be recorded daily by the patient or if you prefer at the clinic, as well as the
frequency and/or volume of urine output. We also ask you to measure your abdominal girth at the
umbilicus. Weight gain of >2 pounds per day, decreasing urinary frequency or > 2 inch increase in
abdominal girth should be reported to us. Patients who we feel are at risk of OHSS will be asked to
come in for an ultrasound in the week after egg retrieval (or insemination). Most patients at risk for
OHSS will be predicted as they monitor their cycles. Significant OHSS seldom occurs with less than
20 follicles or an estradiol of less than 15,000 pmol/l. However, we have an “open door policy” if you
have any concerns.
If any fluid accumulates outside of the ovaries or the ovaries are
greater than 10 cm in maximum diameter, you will be asked to follow
conservative management of your OHSS. Most patients will respond
to conservative management. This consists of maintaining mild activity
but allowing for time during the day to lie down and put your feet up.
Strenuous physical activity should be avoided as it is uncomfortable and may increase
the risk of ovarian torsion when the ovaries are significantly enlarged. Light physical
activity should be maintained to the best extent possible. Strict bed rest is unwarranted
and may increase risk of blood clots ©. It also consists of mild fluid management. This involves
measuring urine output. We often recommend a large measuring cup to collect the urine and measure
it. We then ask you to replace your urine output with an equal amount of electrolyte drink (Gatorade©,
PowerAde©). If you urine output drops below one liter / day, we still like you to replace a full liter.
Uncomfortable abdominal distention can safely be treated with Tylenol or Tylenol with
codeine. Codeine can aggravate constipation, which is already likely in these circumstances so some
mild laxative or bulk agent can be used before this occurs. Gravol is safe if mild nausea occurs.
Other fluids are not eliminated but minimized. There is a tendency to feel very thirsty as the
volume of fluid in the blood vessels is decreased. We ask you to resist drinking large volumes of fluid
because the leaky ovaries will allow a large % of this to end up outside the blood vessels in the form of
ascites, pleural effusions and edema. Solid foods are not restricted but most patients with OHSS feel
easily filled and not very hungry. A protein bar or shake can be an effective meal substitute
Very occasionally, enough fluid will leak into the abdominal cavity to cause dramatic decreases
in urine output or into the chest cavity to cause significant shortness of breath. Under these
circumstances, we will advise patients to have outpatient drainage of the fluid (a paracentesis). This
is done almost like the egg retrieval. Instead of the needle being passed into each follicle to drain the
fluid, it is places in the ascitic fluid. It is done at ISIS just like the egg retrieval. Dr. Martin or Dr.
Frank will try to arrange to do this personally for you. But if that is not possible one of our colleges at
ISIS will do this. Outpatient paracentesis often results in a dramatic improvement. It can be repeated if
necessary.
Drainage of the fluid from the lungs has been reported in the literature but has never been
necessary at S.O.F.T. When I was at University Hospital we would admit patients for continuous
drainage of their ascites and this has been reported in the literature but has not been necessary at
S.O.F.T. The few patients who have required hospitalization have been managed with periodic
paracentesis.

Summary of Management
Moderate or severe OHSS will be avoided if possible but unfortunately will occur from time-
to-time. When it occurs, it almost always resolves with careful conservative management.
Occasionally, outpatient paracentesis is required and rarely admission to hospital is required.
We encourage you to maintain very close contact and communications with S.O.F.T. To
facilitate the outpatient management of OHSS or potential OHSS we have prepared the following a
chart for you to document your condition which is presented below. This will facilitate our care of you
and help in the efficient resolution of this complication.
The chart allows documentation of 7 days and additional copies are available at the clinic or on
our web page. We ask you to document the amount of discomfort or pain you are having on a scale of
one to 10. One is almost no pain and ten is extremely severe pain. By using the numbers, the clinic
staff can be aware of any trend in your pain level (getting worse or getting better). Nausea can be
reported as mild, moderate or severe and it is important to report any vomiting as this affects your
fluid balance. Shortness of breath (SOB) can be reported as mild, moderate or severe. Mild SOB
usually means with exercise (going up a flight of stairs or running a short distance); moderate SOB
means with mild activity (walking to the bathroom, getting dressed) and severe SOB occurs at rest
(lying in bed). We also ask you to document any cough. A dry none productive cough often predicts
the beginning of fluid accumulation in the pleural cavity (pleural effusion).
The next box is left for any other symptoms you may be experiencing. Even if something is
occurring that seems to be unrelated to the OHSS, do not hesitate to report it to us.
Next, we ask you to document some measurements for us. If you feel uncomfortable
documenting these, we will be happy to do it at the clinic. However, if you live some distance, this
documentation may allow us to decrease the number of visits you need and car travel can sometimes
be uncomfortable with OHSS.
The first one is your weight. The trend in your weight will often indicate whether the OHSS is
getting better or worse. Most households have a simple scale. If you don’t they are usually very
inexpensive. Abdominal circumference can be difficult to monitor. To measure your waist size, use a
standard tape measure to do the following steps: (1) Put one end
of the measuring tape against your stomach right over your belly
button and hold it in place. (2) Use your other hand to wrap the
measuring tape around your waist until it meets the end you're
holding over your belly button. (3) Take note of the
measurement where the two ends meet. The tape should be kept
parallel to the floor. When you pull the other end of the tape
around, you should keep it close to your skin, but it should not
compress it at all. Despite your best attempts at doing this measurement the same way each day, it will
vary but it is the general trend we are most interested in documenting.
 Urine output refers to the amount you urinate in a day (24 hours). We find the best way to measure
it is to urinate in a large measuring cup. Plastic, 4-litre ones are usually available. Again, day-to-day
volumes can vary a great deal and it is the general trend we are looking at analyzing. Other findings
can include swelling of the feet or hands. Sometimes, fluid can accumulate in the skin of the abdominal
wall. You can tell this by pressing your finger into the skin of your stomach for 15 to 30 seconds and
observing whether it makes a dint.
We have left a space for you to document your ultrasound. This is our responsibility not yours and
we will fully document it at the clinic. However, we are very willing to share the important information
with you if you would like to keep a record for yourself. The main things we look for are the largest
measurement of each ovary, the presence of and size of any abdominal fluid collections and the
presence and size of any fluid around the lungs.
The last row is for documentation of any special instructions. This can include none prescription
medications, follow-up ultrasounds, diet instructions, fluid intake instructions or any other advice.

In Conclusion
OHSS will occur in infertility treatment despite all attempts to eliminate it. However, careful
conservative treatment as outlined in this information sheet is usually very effective. By monitoring
closely, the clinic staff will be able to tell if any other intervention is indicated. Occasionally, we will
perform an outpatient paracentesis (drainage of the excess fluid in the abdomen). As stated before, this
is done at ISIS and is very similar to the IVF retrieval. Rarely, hospitalization is required.
Remember. S.O.F.T. has an open door policy. We would much rather you consult us “too”
often rather than not often enough. OHSS is common in infertility practices but very rare in general
medicine. Because of this non-infertility doctors have very little experience with it. It is far better for
you to consult us about any OHSS. However, should something happen when we are not available and
you have to consult an emergency department, we would be happy to consult with them as soon as
possible. Pelvic examinations are discouraged with OHSS. We prefer to follow OHSS with
ultrasound; it provides much more information and eliminates the risk of an internal examination
damaging the fragile ovaries. Surgery should be considered only in extreme emergencies. OHSS can
often masquerade as surgical indications for laparoscopy or laparotomy but these are very dangerous
procedures with enlarged ovaries. Surgery should only be considered in extreme circumstances.
 Chart for Monitoring OHSS

Parameter Date

Pain (1 to 10)
Nausea
Vomiting
Short of Breath
Cough
Others
Weight
Abdominal
Circumference
Urine Output
Other Findings
Ultrasound
Instructions

James Martin MD ©
Southern Ontario Fertility Technologies (S.O.F.T.)
555 Southdale Rd E., Suite 107
London, Ontario, Canada, N6E 1A2
Tel: 519-685-5559
Check out our web page at soft-infertility.com