How Doctors Minimize OHSS Risk During Egg Freezing Cycles

If you're considering egg freezing, you've likely come across information about ovarian hyperstimulation syndrome (OHSS). While OHSS is a potential complication of the egg retrieval process, its occurrence has decreased significantly in recent years, thanks to improved protocols and preventive strategies.

This article will explore how fertility doctors work to minimize your risk of OHSS during egg freezing cycles, ensuring a safer and more comfortable experience.

What is OHSS?

Before diving into prevention strategies, let's first understand what OHSS is and why it occurs.

Ovarian hyperstimulation syndrome (OHSS) is an exaggerated response to the hormonal medications used to stimulate egg production. In OHSS, the ovaries become swollen and fluid can leak into the abdomen and sometimes the chest. This can cause a range of symptoms from mild bloating and discomfort to, in rare severe cases, more serious complications.

OHSS is typically classified into three categories:

1. Mild OHSS: Characterized by abdominal bloating and mild pain. This form is common and generally resolves on its own.
2. Moderate OHSS: Involves more noticeable abdominal pain, nausea, and sometimes vomiting. Ultrasound may show fluid in the abdominal cavity.
3. Severe OHSS: A rare but serious condition that can involve severe abdominal pain, rapid weight gain, severe nausea/vomiting, decreased urination, and shortness of breath. This form requires immediate medical attention.

Data suggest the incidence of mild OHSS is 20%–33%, moderate OHSS is 3%–6%, and severe OHSS occurs in 0.1%–2% of cycles. In rare cases, OHSS can be life-threatening, so it's important to be aware of the potential risks and to inform your doctor of any symptoms (severe abdominal pain, bloating, and nausea). 

Read more in What is OHSS and What Are My Risks?

Seven ways doctors try to minimize OHSS risk

Fertility doctors have several strategies to reduce your risk of OHSS if they believe you are at a high-risk. The body of evidence and research is constantly evolving, and new approaches are continually being studied and refined. What's considered the best practice today may be updated in the future as we learn more about ovarian stimulation and OHSS prevention.

While these strategies may reduce the risk of OHSS, they can't eliminate it entirely. Every patient responds differently to fertility treatments, and what works well for one person may not be as effective for another. This is why personalized care and close monitoring throughout your treatment cycle are so important.

Personalizing your treatment

Gone are the days of "one-size-fits-all" approaches to ovarian stimulation. Modern fertility clinics use personalized protocols based on each patient's individual characteristics. This process typically involves:

• Thorough pre-treatment assessment: Your doctor will consider your age, BMI, ovarian reserve tests (AMH and AFC), and any history of PCOS or previous OHSS.
• Tailored medication doses: Based on your risk profile, your doctor will choose an appropriate starting dose of gonadotropins (the hormones used to stimulate egg production). Women at higher risk of OHSS often start with lower doses.
• Dose adjustments: Throughout your stimulation, your doctor will monitor your response through blood tests and ultrasounds, adjusting medication doses as needed.

Picking the right protocol

During IVF, your fertility doctor will prescribe medications to stimulate your ovaries to produce multiple eggs. This process helps to control the egg development so they can retrieve a safe number of mature eggs at the best time. There are a few ways (stimulation protocols) to do this:

• "GnRH agonist protocol or "long protocol": This involves taking medications for several weeks to essentially rest your ovaries before stimulating them.
• GnRH antagonist protocol: This approach has a shorter duration of injections, and uses an “antagonist to prevent your body from releasing eggs too early.
• Flare protocol: Also known as the microdose flare or low dose Lupron protocol, uses a low dose of Lupron to trigger the pituitary gland to release follicle stimulating hormone (FSH).

Research has shown that the newer method (GnRH antagonist protocol) is safer and reduces the risk of ovarian hyperstimulation syndrome (OHSS).  A very large review and meta-analysis, including 73 RCTs with 12,212 participants, demonstrated a statistically significant reduction in all types of OHSS in cycles using GnRH antagonists, due to the Lupron trigger shot. 

Most clinics prefer the GnRH antagonist protocol because it's easier for patients and gives clinics more flexibility to adjust your treatment if needed. However, there may be cases where a doctor will choose the best protocol for you based on your individual situation. You can always ask your doctor which protocol they have chosen and why!

Lower starting doses plus oral medication

To reduce OHSS risk, your fertility doctor may start with lower doses of gonadotropins (the injectable hormones used to stimulate egg production), especially if you have risk factors for OHSS. This "low and slow" approach allows your body to respond more gradually, reducing the risk of over-stimulation.

Your doctor might also add oral fertility medications (pills) to your protocol, such as:

• Clomiphene citrate (Clomid): This medication helps stimulate egg production and can allow for lower doses of injectable hormones.
• Letrozole (Femara): Originally a breast cancer drug, letrozole is now commonly used in fertility treatments. It can help stimulate egg production while potentially reducing OHSS risk. It also lowers estradiol levels which can aid in reducing OHSS risk and lower side effects.

By combining lower doses of injectable hormones with these oral medications, doctors may be able to minimize the risk of overstimulation while still achieving good outcomes. This approach is especially beneficial for women with PCOS or other risk factors for OHSS.

Alternative trigger medications

The trigger shot, also known as the "ovulation trigger" or simply "the trigger," is a hormonal medication given near the end of your egg freezing cycle. Its primary purpose is to mimic the natural surge of luteinizing hormone (LH) that occurs in your body just before ovulation. This surge signals your ovaries to complete the final maturation of the eggs and prepare them for retrieval.

Traditionally, the trigger shot has been human chorionic gonadotropin (hCG), which mimics the natural LH surge. However, hCG has a long half-life and can increase the risk of OHSS. To mitigate this risk, doctors now have alternative options:

• GnRH agonist trigger (eg. Leuprolide, Lupron): For cycles using a GnRH antagonist protocol, a GnRH agonist can be used to trigger ovulation. This causes a short, self-limited LH surge. Research has found this can dramatically reduce OHSS risk.
• Dual trigger: Some doctors use a combination of a low dose of hCG along with a GnRH agonist. This approach aims to balance OHSS risk reduction with optimal egg maturation.
• Low-dose hCG: If a GnRH agonist trigger isn't possible, some doctors might use a lower dose of hCG. However, research has not found a consistent or statistically significant differences in the rate of OHSS when comparing hCG-only triggers of 4,000 IU compared with 6,000 IU or 10,000 IU.

Medications called dopamine agonists, particularly cabergoline, have been shown to reduce the risk of OHSS when given around the time of the trigger shot. These medications work by reducing VEGF activity, which is thought to play a key role in OHSS development.‍

Metformin for PCOS patients

For women with PCOS who are at higher risk of OHSS, some doctors prescribe metformin during the stimulation phase. While the evidence is mixed, some studies suggest it may help reduce OHSS risk in this population.

Monitoring: The key to OHSS prevention

Perhaps the most important aspect of OHSS prevention is careful monitoring throughout the stimulation process. This typically involves:

• Frequent ultrasounds: To track the number and size of developing follicles.
• Blood tests: To monitor estradiol and other hormone levels.
• Symptom tracking: Your doctor will ask about any symptoms you're experiencing.

This close monitoring allows your fertility team to adjust your treatment plan quickly if you show signs of over-responding to the medications.

What about other strategies?

You may hear about other OHSS prevention methods, such as taking aspirin, certain supplements, eating a high-protein diet, or drinking lots of electrolyte solutions. While some of these may have anecdotal support, current scientific evidence doesn't strongly back their use for OHSS prevention. 

Always consult with your doctor before taking any additional medications or supplements during your egg freezing cycle.

What to expect after egg retrieval

Even with all these preventive measures, it's normal to experience some mild OHSS symptoms after egg retrieval, such as bloating, mild abdominal pain, and feeling full quickly when eating. These symptoms usually resolve within a week.

However, it's crucial to contact your doctor if you experience:

• Severe abdominal pain
• Significant abdominal swelling
• Nausea or vomiting
• Decreased urination
• Shortness of breath
• Rapid weight gain (more than 2-3 pounds per day)

These could be signs of more severe OHSS and require prompt medical attention.

The bottom line

While OHSS remains a concern in ovarian stimulation cycles, modern protocols, and preventive strategies have dramatically reduced its occurrence and severity. By working closely with your fertility doctor, asking questions, carefully following their instructions, and promptly reporting any concerning symptoms, you can minimize your risk and focus on a successful egg freezing cycle.

Remember, everybody responds differently to fertility medications. What works best for one person may not be ideal for another. That's why individualized care and open communication with your medical team are so important throughout the egg freezing process.

If you have any questions or concerns about OHSS or any other aspect of egg freezing, don't hesitate to discuss them with your doctor. They're there to support you and ensure the safest possible experience as you take this important step toward preserving your fertility options.