Published on November 9, 2021

Ovarian hyperstimulation syndrome

Overview

Ovarian hyperstimulation syndrome is an exaggerated response to excess hormones. It usually occurs in women taking injectable hormone medications to stimulate the development of eggs in the ovaries. Ovarian hyperstimulation syndrome (OHSS) causes the ovaries to swell and become painful.

OHSS may occur in women undergoing in vitro fertilization (IVF) or ovulation induction with injectable medications. Less often, OHSS happens during fertility treatments using medications you take by mouth, such as clomiphene.

Treatment depends on the severity of the condition. OHSS may improve on its own in mild cases, while severe cases may require hospitalization and additional treatment.

In vitro fertilization
During in vitro fertilization, eggs are removed from mature follicles within an ovary (A). An egg is fertilized by injecting a single sperm into the egg or mixing the egg with sperm in a petri dish (B). The fertilized egg (embryo) is transferred into the uterus (C).

Symptoms

Symptoms of ovarian hyperstimulation syndrome often begin within a week after using injectable medications to stimulate ovulation, though sometimes it can take two weeks or longer for symptoms to appear. Symptoms can range from mild to severe and may worsen or improve over time.

Mild to moderate OHSS

With mild to moderate ovarian hyperstimulation syndrome, symptoms can include:

  • Mild to moderate abdominal pain
  • Abdominal bloating or increased waist size
  • Nausea
  • Vomiting
  • Diarrhea
  • Tenderness in the area of your ovaries

Some women who use injectable fertility drugs get a mild form of OHSS. This usually goes away after about a week. But, if pregnancy occurs, symptoms of OHSS may worsen and last several days to weeks.

Severe OHSS

With severe ovarian hyperstimulation syndrome, you might have:

  • Rapid weight gain — more than 2.2 pounds (1 kilogram) in 24 hours
  • Severe abdominal pain
  • Severe, persistent nausea and vomiting
  • Blood clots
  • Decreased urination
  • Shortness of breath
  • Tight or enlarged abdomen

When to see a doctor

If you're having fertility treatments and you experience symptoms of ovarian hyperstimulation syndrome, tell your health care provider. Even if you have a mild case of OHSS, your provider will want to observe you for sudden weight gain or worsening symptoms.

Contact your provider right away if you develop breathing problems or pain in your legs during your fertility treatment. This may indicate an urgent situation that needs prompt medical attention.

Causes

The cause of ovarian hyperstimulation syndrome isn't fully understood. Having a high level of human chorionic gonadotropin (HCG) — a hormone usually produced during pregnancy — introduced into your system plays a role. Ovarian blood vessels react abnormally to HCG and begin to leak fluid. This fluid swells the ovaries, and sometimes large amounts move into the abdomen.

During fertility treatments, HCG may be given as a "trigger" so that a mature follicle will release its egg. OHSS usually happens within a week after you receive an HCG injection. If you become pregnant during a treatment cycle, OHSS may worsen as your body begins producing its own HCG in response to the pregnancy.

Injectable fertility medications are more likely to cause OHSS than is treatment with clomiphene, a medication given as a pill you take by mouth. Occasionally OHSS occurs spontaneously, not related to fertility treatments.

Risk factors

Sometimes, OHSS happens in women with no risk factors at all. But factors that are known to increase your risk of OHSS include:

  • Polycystic ovary syndrome — a common reproductive disorder that causes irregular menstrual periods, excess hair growth and unusual appearance of the ovaries on ultrasound examination
  • Large number of follicles
  • Age under 35
  • Low body weight
  • High or steeply increasing level of estradiol (estrogen) before an HCG trigger shot
  • Previous episodes of OHSS

Complications

Severe ovarian hyperstimulation syndrome is uncommon, but can be life-threatening. Complications may include:

  • Fluid collection in the abdomen and sometimes the chest
  • Electrolyte disturbances (sodium, potassium, others)
  • Blood clots in large vessels, usually in the legs
  • Kidney failure
  • Twisting of an ovary (ovarian torsion)
  • Rupture of a cyst in an ovary, which can lead to serious bleeding
  • Breathing problems
  • Pregnancy loss from miscarriage or termination because of complications
  • Rarely, death

Prevention

To decrease your chances of developing ovarian hyperstimulation syndrome, you'll need an individualized plan for your fertility medications. Expect your health care provider to carefully monitor each treatment cycle, including frequent ultrasounds to check the development of follicles and blood tests to check your hormone levels.

Strategies to help prevent OHSS include:

  • Adjusting medication. Your provider uses the lowest possible dose of gonadotropins to stimulate your ovaries and trigger ovulation.
  • Adding medication. Some medications seem to reduce the risk of OHSS without affecting the odds of pregnancy. These include low-dose aspirin; dopamine agonists such as carbergoline or quinogloide; and calcium infusions. Giving women who have polycystic ovary syndrome the drug metformin (Glumetza) during ovarian stimulation may help prevent hyperstimulation.
  • Coasting. If your estrogen level is high or you have a large number of developed follicles, your provider may have you stop injectable medications and wait a few days before giving HCG, which triggers ovulation. This is known as coasting.
  • Avoiding use of an HCG trigger shot. Because OHSS often develops after an HCG trigger shot is given, alternatives to HCG for triggering have been developed using Gn-RH agonists, such as leuprolide (Lupron), as a way to prevent or limit OHSS.
  • Freezing embryos. If you're undergoing IVF, all the follicles (mature and immature) may be removed from your ovaries to reduce the chance of OHSS. Mature follicles are fertilized and frozen, and your ovaries are allowed to rest. You can resume the IVF process at a later date, when your body is ready.

Diagnosis

Ovarian hyperstimulation syndrome diagnosis may be based on:

  • A physical exam. Your provider will look for any weight gain, increases in your waist size and abdominal pain you may have.
  • An ultrasound. If you have OHSS, an ultrasound may show that your ovaries are bigger than usual, with large fluid-filled cysts where follicles developed. During treatment with fertility drugs, your provider regularly evaluates your ovaries with a vaginal ultrasound.
  • A blood test. Certain blood tests allow your provider to check for abnormalities in your blood and whether your kidney function is being impaired because of OHSS.

Treatment

Ovarian hyperstimulation syndrome generally resolves on its own within a week or two or somewhat longer if you're pregnant. Treatment is aimed at keeping you comfortable, decreasing ovarian activity and avoiding complications.

Mild to moderate OHSS

Mild OHSS typically resolves on its own. Treatment for moderate OHSS may involve:

  • Increased fluid intake
  • Frequent physical exams and ultrasounds
  • Daily weigh-ins and waist measurements to check for drastic changes
  • Measurements of how much urine you produce each day
  • Blood tests to monitor for dehydration, electrolyte imbalance and other problems
  • Drainage of excess abdominal fluid using a needle inserted in your abdominal cavity
  • Medications to prevent blood clots (anticoagulants)

Severe OHSS

With severe OHSS, you may need to be admitted to the hospital for monitoring and aggressive treatment, including IV fluids. Your provider may give you a medication called cabergoline to lessen your symptoms. Sometimes, your provider may also give you other medications, such as gonadotropin-releasing hormone (Gn-RH) antagonist or letrozole (Femara) — to help suppress ovarian activity.

Serious complications may require additional treatments, such as surgery for a ruptured ovarian cyst or intensive care for liver or lung complications. You may also need anticoagulant medications to decrease the risk of blood clots in your legs.

Self care

If you develop mild ovarian hyperstimulation syndrome, you'll probably be able to continue your day-to-day routine. Follow your provider's advice, which may include these recommendations:

  • Try an over-the-counter painkiller such as acetaminophen (Tylenol, others) for abdominal discomfort, but avoid ibuprofen (Advil, Motrin IB, others) or naproxen sodium (Aleve, others) if you have recently had an embryo transfer, as these drugs can interfere with implantation of the embryo.
  • Avoid sex, as it may be painful and can cause a cyst in your ovary to rupture.
  • Maintain a light physical activity level, avoiding strenuous or high-impact activities.
  • Weigh yourself on the same scale and measure around your abdomen each day, reporting unusual increases to your provider.
  • Call your provider if your signs and symptoms get worse.

Preparing for your appointment

Depending on how severe your ovarian hyperstimulation syndrome is, your first appointment may be with your primary care provider, your gynecologist or infertility specialist, or possibly with a treating doctor in the emergency room.

If you have time, it's a good idea to prepare in advance of your appointment.

What you can do

  • Write down any symptoms you're experiencing. Include all of your symptoms, even if you don't think they're related.
  • Make a list of any medications and vitamin supplements you take. Write down doses and how often you take them.
  • Have a family member or close friend accompany you, if possible. You may be given a lot of information at your visit, and it can be difficult to remember everything.
  • Take a notebook or notepad with you. Use it to write down important information during your visit.
  • Prepare a list of questions to ask your provider. List your most important questions first.

Some basic questions to ask include:

  • What's the most likely cause of my symptoms?
  • What kind of tests do I need?
  • Does ovarian hyperstimulation syndrome usually go away on its own, or will I need treatment?
  • Do you have any printed material or brochures I can take home with me? What websites do you recommend?

Make sure that you completely understand everything that your provider tells you. Don't hesitate to ask your provider to repeat information or to ask follow-up questions for clarification.

What to expect from your provider

Some potential questions your provider might ask include:

  • When did your symptoms begin?
  • How severe are your symptoms?
  • Does anything make your symptoms better?
  • Does anything seem to make your symptoms worse?