understanding Ovarian Hyperstimulation Syndrome

Ovarian Hyperstimulation Syndrome: What is OHSS?

Dr. Jolene BrightenPublished: Last Reviewed: Fertility

Ovarian hyperstimulation syndrome (OHSS) is a rare but potentially life-threatening complication associated with assisted reproductive therapy (ART). It most often occurs in women who take hormone medications to stimulate egg development in their ovaries.

OHSS (ovarian hyperstimulation syndrome) can cause the ovaries to swell and become painful. It's diagnosed based on a range of symptoms, from mild to severe. While these extreme cases are less common (occurring in only 0.1%–2% of cycles), mild OHSS is estimated1 to occur in 20 to 33% of all IVF cycles.

While discussed in some reproductive health circles, ovarian hyperstimulation syndrome isn't well known, and it is important for people to understand this risk and the steps they can take to prevent it. This article will discuss what exactly OHSS is and how it can affect women undergoing fertility treatments.

In this article

What Is Ovarian Hyperstimulation Syndrome?

Ovarian hyperstimulation syndrome2 is called an iatrogenic condition, which means it's caused by medical treatment—in this case, the drugs used to stimulate the ovaries to make more eggs. During a natural cycle, the body is regulated in the number of eggs that will develop and subsequently be ovulated. With OHSS, ovarian stimulation during in vitro fertilization (IVF) or other assisted reproductive therapies can lead to a large number of egg containing follicles to develop. The ovaries may then swell and cause discomfort, along with other symptoms.

OHSS3 can occur when the blood vessels become leaky in response to the hormone shifts associated with the fertility medication. These substances cause fluid to accumulate in the intravascular space—where it shouldn't be. In severe cases, when fluid leaks from the blood vessels to the spaces between cells in the body, it can cause fluid build-up in the abdomen or lungs, low blood pressure, or worse health outcomes.

Symptoms of Ovarian Hyperstimulation Syndrome

Understanding the signs of OHSS, from mild to severe symptoms, can help you recognize the condition and seek treatment quickly. OHSS is diagnosed and treated based on severity—let's take a look at each in more detail.

What is The First Sign of OHSS?

One of the first signs4 of OHSS is mild abdominal swelling, bloating—like you need to loosen your clothing—or even nausea. The swelling is due to the accumulation of excess fluid.

Mild OHSS

Symptoms of mild OHSS5 can include:

  • Abdominal distention or discomfort
  • Nausea and/or vomiting
  • Mild shortness of breath
  • Diarrhea
  • Enlarged ovaries

Moderate OHSS

Symptoms of moderate OHSS6 can include:

  • Any of the above mild symptoms, including ovarian enlargement
  • Evidence of ascites on ultrasound scan
  • Increase in blood cells due to fluid loss from the bloodstream (hemoconcentration)
  • Elevated white blood cells

Severe Forms of OHSS

Symptoms of severe OHSS7 can include:

  • Any of the above mild and moderate symptoms
  • Ascites (fluid buildup in the abdomen)
  • Fluid in the lungs
  • Severe shortness of breath
  • Hard to control nausea and vomiting
  • Unusually low or no urine production
  • Abnormal kidney and liver labs
  • Low blood pressure
  • Rapid weight gain (greater than 1 kg or 2.2 pounds in 24 hours)
  • Dizziness
  • Severe abdominal pain
  • Blood clots

Critical OHSS

Critical OHSS8 means life-threatening. All of the above symptoms can occur, but additional include:

  • Impaired Kidney Function and Kidney failure
  • Worsening of lab values
  • Heart arrhythmia
  • Fluid around the heart
  • Life-threatening blood clots
  • Respiratory distress
  • Sepsis (organ impairment or failure due to the body’s infection-fighting process)

Who Is At Risk for OHSS?

While rare, those undergoing fertility treatments, being younger than 35 years old, having high estrogen during treatments, and having polycystic ovary syndrome are all risk factors for developing OHSS.

The above can feel scary, but remember that more severe cases of OHSS are rare. That said, knowing if you have any risk factors can help you keep an eye out for symptoms and talk to your doctor if you feel like something is off.

Anyone receiving treatment for ovarian stimulation technically is at risk, but certain situations increase the risk. These include:

Polycystic Ovarian Syndrome (PCOS)

Studies9 suggest that those with polycystic ovarian syndrome (PCOS) are at increased risk of OHSS. This may be because women with PCOS10 already have some of the other risk factors, like higher antral follicle counts (AFCs), anti-müllerian hormone (AMH) levels, and serum estradiol (E2) levels (discussed below).

PCOS is a complex metabolic and endocrine disorder that leads to hormone imbalance and infertility. There are special considerations for women wanting to become pregnant with PCOS and in some cases ART or IVF procedures are a necessary part of the treatment.

Low Body Mass Index (BMI)

A low body mass index (BMI) means you have a lower body weight for your height. Several studies11 link BMI and a higher risk of OHSS (although several other studies showed no connection).

High Antral Follicle Count (AFC)

Antral follicle count (AFC) measures how many follicles, or potential eggs, are on your ovaries. This is assessed via trans vaginal ultrasound as part of evaluating a patient's fertility and prior to beginning an IVF cycle. Studies12 suggest that women with a higher AFC have a significantly increased risk of OHSS, with some suggesting13 developing more than 24 follicles increases the risk of OHSS from 2.2 to 8.6 percent. 

In general, having 20 or more follicles measuring at least 10 mm can increase the risk of OHSS.

Increased Anti-Mullerian Hormone Levels (AMH)

Anti-mullerian hormone levels are another measure of egg count. Elevated AMH levels appear to be a significant indicator for OHSS. In fact, one study14 demonstrated that individuals with high AMH levels were six times more likely to develop OHSS than those with normal levels of the same age.

An elevated AMH can also be found in those who have PCOS.

Elevated Serum Estradiol Concentrations (E2)

Significantly higher estradiol15 (E2) is also associated with OHSS in multiple studies16. In patients who developed OHSS, the mean mean estradiol has been found to be greater than 3,500 pg/mL, which is why monitoring this hormone is an important part of the egg retrieval treatment. In another study17, it as concluded that a serum E2 level of 12,315 pmol/L (3,354 pg/mL) on day 11 of ovarian stimulation gives a sensitivity and specificity of 85% for the detection of women at risk for OHSS.

As the ovarian follicles make more E2, vascular endothelial growth factors (VEGF) can stimulate the growth of new blood vessels and inflammatory mediators that influence vascular permeability rise, which allows for the leakage of fluid. Both contribute to the fluid shift seen in OHSS, and some research18 suggests that high E2 may even be a precipitating factor in triggering OHSS.

Can You Predict OHSS?

During the IVF process, monitoring the above indicators, like AMH, AFC, and estradiol levels (along with ongoing follicle count), can be used to predict19 and hopefully prevent the occurrence of OHSS.

AMH is generally measured at the start of fertility evaluation and not an ongoing measurement, like estradiol. E2 is monitored during the administration of fertility drugs through blood testing, while AFC and ongoing follicle count can be assessed through ultrasound imaging. By keeping a close eye on these markers, your care team can tailor medication doses and adjust protocols accordingly to minimize the risk of OHSS. This individualized approach is especially crucial for individuals considered high-risk for OHSS.

What Causes Ovarian Hyperstimulation Syndrome?

I've touched on this a bit already, and the cause of OHSS is still not entirely understood. However, it likely involves a combination20 of growth factors and inflammatory molecules that influence vascular permeability.

When the ovaries over-respond to treatment, they can enlarge and cause mild symptoms like bloating and nausea. As the blood vessels become more permeable, fluid shifts can lead to decreased blood volume and worsening symptoms.

In Vitro Fertilization (IVF)

Human Chorionic Gonadotropin (hCG) is a hormone that plays a crucial role in the IVF process21. It's the same hormone secreted by the placenta during pregnancy, but for IVF, it's used as the final stage of egg maturation because it has similar effects as luteinizing hormone (LH). It also plays a role in enabling the egg to be released from the ovary so that it can be collected as part of the egg retrieval.

Research22 suggests that OHSS can be triggered by the administration of HCG. It may influence the release of vascular endothelial growth factor23, increasing follicular growth, vascular permeability, and fluid shifts.

Spontaneous Occurrence in Pregnancy

Spontaneous OHSS, without using exogenous fertility medicine and hormones like HCG, is extremely rare. If you scan the science, several case studies24 link spontaneous OHSS with conditions like PCOS or hypothyroidism. Still, there really isn't enough research for any actual connection.

ways to prevent ohss

Does OHSS Affect Egg Quality?

There isn't a lot of research to suggest OHSS can impact egg quality. An older study25 found no relationship between egg quality and OHSS, and more recent guidance26 suggests the same.

OHSS and Pregnancy

It is possible to be pregnant with OHSS, but pregnancy can worsen the condition. As your body naturally starts making the pregnancy hormone hCG, it can continue to influence vascular permeability and exacerbate symptoms.

Can You Have a Successful Pregnancy with OHSS?

If you become pregnant and have OHSS, you can still have a successful pregnancy. A study27 comparing 190 women with OHSS and 197 women without found no significant differences between the two groups in rates of live birth, preterm delivery and birth, c-section, or low birth weight.

A more recent study28 did find an increased risk of preterm birth and small-for-gestational-age birth to mothers with OHSS, but no other risk factors were noted. It is difficult to know if pregnancy complications are related to OHSS are are do to other factors that may also be present and may have necessitated the need for reproductive technologies.

How Long Does OHSS Last When Pregnant?

Since the rising hCG can worsen OHSS, it can last several weeks into pregnancy (and you'll be closely followed by your doctor to prevent complications).

Can OHSS Cause Miscarriage

While some older studies29 suggested an increased risk of miscarriage for those with severe OHSS, more recent studies30 on moderate to critical OHSS suggest that OHSS does not increase the risk of miscarriage. The severity, need for hospitalization, and interventions can likely impact each pregnancy differently.

How to Prevent OHSS

With more knowledge about OHSS, your care team will likely be taking steps to prevent it. With a better understanding of how to identify people at risk combined with prevention and treatment strategies, there are steps you and your doctor can take. There are many different medical options available for the prevention and treatment of OHSS. We'll focus on a few of the more common approaches this article, but working with your doctor to determine the best treatment options for you is vital to effectively managing this condition.

Communicating with your provider of any concerning changes during the ovarian stimulation phase and in the days after oocyte retrieval or egg retrieval is important.

Individualized Fertility Treatment Plans

Close monitoring of your treatment cycle is fundamental in preventing OHSS. Your doctor will carefully monitor the development of your follicles via vaginal ultrasound and potentially adjust your medication dosage based on your body's response. Blood tests are also utilized to monitor hormone levels throughout the IVF cycle, including estradiol.

Your doctor may also decide to withhold hCG, known as cycle cancellation since hCG can trigger OHSS. Or, they may lower the amount of hCG, which has been found to reduce the risk of OHSS in some research31.

Even if you know the reason for cycle cancellation is to protect you and your health, it can be distressing and disappointing. I always encourage patients who have struggled with infertility or are going through fertility treatments to work with a mental health provider. 

Coasting

Coasting involves withholding gonadotropin therapy and continuing pituitary suppression with a GnRH agonist or antagonist. Leveraging an agonist protocol in this approach is continued until serum E2 levels fall into a range in which hCG can be administered.

The intention of coasting32 is used to reduce the risk of OHSS, although studies are mixed as to how well it works. While early studies suggested coasting could reduce the risk of OHSS, more recent33 and more extensive trials haven't found strong evidence to support its effectiveness compared to other treatments. However, your doctor may decide that it's still an appropriate option for your treatment plan.

HCG Alternative: GnRH Agonist Trigger (Leuprolide or Lupron Trigger)

Lupron is a gonadotropin releasing hormone agonist (GnRH agonist) that is used in place of hCG to stimulate a rise in both luteinizing hormone (LH) and follicle stimulating hormones (FSH). In an antagonist cycle, Lupron has been shown to effectively trigger oocyte maturation and may help reduce the risk of OHSS. GnRH stands for gonadotropin-releasing hormone, which is naturally produced in the body and helps regulate ovulation. This approach is generally reserved for those at high risk or for individuals who are undergoing egg preservation or donation.

  • GnRH Agonist: a medication that stimulates the pituitary GnRH receptors to release FSH and LH hormones.
  • GnRH Antagonist: a medication that bings the GnRH receptors in the pituitary and decreases the effect of gonadotropin releasing hormone. 

Studies34 using GnRH antagonists have found that they may significantly lower OHSS risk by reducing estrogen levels associated with hCG injections, with no differences in the ability to become pregnant or have a healthy baby. That being said, there is always new data emerging, which is why it is best to discuss the best treatment approach for you with your doctor.

how long ohss lasts

What is the Best Diet to Prevent OHSS

While lifestyle can't completely prevent OHSS, it can help. There are several diet strategies you can use to reduce the risk (or use to support) OHSS, including:

High protein diet 

Protein is essential for OHSS prevention (and during any fertility treatment). Conditions impacting fluid overload, as seen with moderate to severe OHSS, reduce protein stores in the body, so higher intakes are needed. Aim for at least 1 gram per kilogram of body weight per day from protein-rich sources like lean meat, fish, eggs, and protein powders. In many cases, 1.2-1.6 grams per kg of body weight will be necessary in order to support fluid balance.

While nuts, seeds, and beans do contain some protein, they may not be enough compared to the amount of carbohydrates or fat they contain in preventing OHSS. 

I have a collection of free recipes if you're looking for nutrition support to increase your protein and support optimal hormone balance.

Adding protein powder or collagen to beverages, smoothies, sauces, and breakfast items like pancake batter can be one way to boost protein intake. For more breakfast ideas, I invite you to read this article.

When I personally went through IVF, I began my Paleo Detox Kit and continued it for 14 days. This is something that has been helpful for patients going through the procedure as well since it provides an additional 18 grams of protein and supports the liver in processing the excess levels of estrogen, plus the medication used during IVF.

Hydrate and Increase Electrolytes

Research35 has shown that women with OHSS have a severe electrolyte imbalance, namely low sodium and potassium. Daily intake of electrolyte rich beverages is necessary during ovarian stimulation and following egg retrieval

In general, it is advised to drink about 6 cups or 48 ounces of electrolyte beverages in a day. Overall fluid intake should be in the 2-3 liter range for most women. IVF patients are often advised to drink electrolyte beverages like Gatorade, which are high in sugar. One 20 ounce serving of gatorade can contain 36 grams of sugar. When you consider that it is best to limit added sugar to 25 grams or less in a day and that you may need at least two Gatorades, that's a lot of sugar to be consuming. Additionally, as those undergoing IVF understand, weight gain can be an issue and some clinics have limits on BMI—meaning they may not move forward with a procedure if you read the upper limit.

The alternative I recommend is the electrolyte blend by LMNT. It has no added sugar and contains sodium, potassium, and magnesium. Magnesium has the added benefit of supporting estrogen metabolism.

Avoid Alcohol

Alcohol can lead to dehydration and often times, the consumption of these beverages replace the fluid intake necessary to prevent OHSS. Dehydration can contribute to electrolyte imbalances and further complicate fluid balance. Alcohol can negatively impact liver function, which can impact your hormones. 

Lifestyle Changes

In addition to nutrition, consider the following during and after treatment:

  • Get enough rest: The process of ovarian stimulation and an egg retrieval is a strain on the body. Prioritize getting enough sleep and take breaks when needed.
  • Reduce stress: Stress can negatively impact almost all health outcomes and during fertility treatments, it can feel like it is at an all time high. Find ways to manage stress and incorporate relaxation techniques such as meditation, walking, journaling, or yoga into your routine.
  • Gentle exercise: Light movement can help improve circulation, reduce inflammation, and support overall well-being. In addition, it can reduce the risk of blood clots associated with OHSS. Your doctor may advise avoiding exercise due to the risk of ovarian torsion, but in most cases, very gentle movements are ok. When in doubt, discuss with your doctor what is best for your body.  
  • Daily measurement and monitoring: Your doctor may suggest measuring your abdominal girth with a tape measurer, tracking urine output, and weighing yourself daily to monitor for any rapid weight gain. These measurements will be especially important if you are at high risk for developing OHSS.

If you develop breathing difficulties, decreased amounts of urine, rapid weight gain, or any symptoms of concern, please contact your provider.

How Long Does OHSS Last?

The length of time OHSS lasts will depend on whether or not you’re moving forward with an embryo transfer and if you become pregnant.

If Fertility Treatment Does Not Result in Pregnancy

If the fertility treatment doesn't result in a pregnancy, symptoms36 should resolve by your next period or usually within 10 days.

If Fertility Treatment Results in Pregnancy

If you become pregnant with OHSS, symptoms37 can worsen and last longer, weeks to months. As hCG levels continue to rise and stimulate the ovaries, symptoms can last even until the end of the first trimester.

OHSS Treatments

OHSS treatment38 depends on severity and usually focuses on supportive care and preventing further complications. I'll share some treatments used to support OHSS below, but these are not a replacement for medical advice.

Always call your doctor if symptoms progress, especially if you’re experiencing vomiting, urinary problems, chest pain, or trouble breathing.

Mild Cases of OHSS

Treatment for mild cases of OHSS may include:

  • Regular hydration: Drinking electrolyte-rich water throughout the day using supplemental electrolytes like LMNT, coconut water, or use the recipe below. 
  • Avoid anti-inflammatory pain reliever: Anti-inflammatory drugs like ibuprofen should be avoided because they can negatively impact the kidneys and may interfere with the release of the eggs from the ovary following the trigger injection.
  • Frequent medical exams or ultrasounds: Monitoring of the ovaries and fluid accumulation may be necessary to assess the progression of OHSS.
  • Dopamine agonists (DA): This medication39 helps decrease VEGF production.

Moderate & Severe Cases

Once OHSS progresses to moderate or severe, continuous care under a physician becomes necessary. This may mean treatments like:

  • Draining of fluid around the abdomen
  • Medications to reduce the risk of blood clots
  • IV fluid rehydration

Pain Management Options

Safe pain-relief options include:

  • Paracetamol, or acetaminophen (also known as Tylenol)
  • Codeine
  • Heating pad

Ovarian Hyperstimulation Syndrome Conclusion

Ovarian Hyperstimulation Syndrome (OHSS) is an exaggerated response to hormone medications used in advanced reproductive technologies (ART). When the ovaries are overstimulated, they can enlarge and release chemicals that can cause fluid to leak into the abdomen or even the heart and lungs.

Severe cases of OHSS are rare. You can safely navigate your fertility treatments with proper monitoring and medical intervention. Awareness of the symptoms and seeking prompt medical attention are crucial for a positive outcome. By staying informed and working closely with your care team, you can have a safe and successful journey towards parenthood.

Homemade Electrolyte Beverage Recipe

Electrolyte beverages are essential for maintaining proper hydration and replacing lost minerals during physical activity, when you're feeling dehydrated, or while undergoing fertility treatments. This homemade recipe combines sodium and potassium to help replenish these important electrolytes. Here's how to make a simple and effective homemade electrolyte beverage:

Ingredients:

  1. 4 cups of filtered water
  2. 1/4 teaspoon of salt (for sodium)
  3. 1/4 teaspoon of potassium chloride (often sold as “lite” salt or potassium salt substitute, available in most grocery stores)
  4. 1/4 cup of fresh orange juice (for flavor and additional potassium)
  5. 1 tablespoon of honey or maple syrup (for sweetness)
  6. Optional: 1/4 cup of coconut water for added potassium and natural electrolytes
  7. Optional: A few drops of lemon or lime juice for flavor

Instructions:

  1. Measure out the 4 cups of filtered water and pour it into your container.
  2. Add the 1/4 teaspoon of salt (for sodium) to the water. Stir well to ensure it dissolves completely.
  3. Next, add the 1/4 teaspoon of potassium chloride (lite salt) to the mixture. This will provide the potassium content. Be cautious not to use too much, as excessive potassium can be harmful. Follow the recommended dosage on the salt substitute container.
  4. Squeeze the 1/4 cup of fresh orange juice into the mixture. This not only adds a pleasant citrus flavor but also contributes extra potassium and vitamin C.
  5. For sweetness, add 1 tablespoon of honey or maple syrup to taste. Adjust the amount according to your preference.
  6. If you have coconut water on hand, you can add 1/4 cup to the mixture. Coconut water is naturally rich in potassium and contains essential electrolytes.
  7. If you'd like to enhance the flavor, add a few drops of lemon or lime juice.
  8. Shake the container or stir vigorously to ensure all the ingredients are well combined.
  9. Place your homemade electrolyte beverage in the refrigerator for a few hours to chill. It's best when served cold.
  10. Before consuming, shake the bottle again or stir to ensure everything is evenly mixed.
  11. Pour your homemade electrolyte beverage into a glass, and enjoy! This beverage can help rehydrate and replenish essential electrolytes after exercise or during periods of dehydration.

Remember to consume this homemade electrolyte beverage in moderation, and consult with a healthcare professional if you have any medical conditions that may affect your electrolyte balance.

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About The Author

Dr. Jolene Brighten

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Dr. Jolene Brighten, NMD, is a women’s hormone expert and prominent leader in women’s medicine. As a licensed naturopathic physician who is board certified in naturopathic endocrinology, she takes an integrative approach in her clinical practice. A fierce patient advocate and completely dedicated to uncovering the root cause of hormonal imbalances, Dr. Brighten empowers women worldwide to take control of their health and their hormones. She is the best selling author of Beyond the Pill and Healing Your Body Naturally After Childbirth. Dr. Brighten is an international speaker, clinical educator, medical advisor within the tech community, and considered a leading authority on women’s health. She is a member of the MindBodyGreen Collective and a faculty member for the American Academy of Anti Aging Medicine. Her work has been featured in the New York Post, Forbes, Cosmopolitan, Huffington Post, Bustle, The Guardian, Sports Illustrated, Elle, and ABC News. Read more about me here.