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Understanding & Preventing Ovarian Hyperstimulation Syndrome (OHSS) with the Lupron Trigger Protocol

Authored and medically reviewed by Dr. Eli Reshef

Dr. Eli Reshef is a reproductive endocrinologist and fertility specialist who sees patients in Chicago and the greater Chicagoland area.

Ovarian Hyperstimulation Syndrome (OHSS) is a potential complication of fertility treatment, particularly during IVF cycles that involve injectable hormone medications to stimulate the ovaries. At Advanced Fertility Center of Chicago (AFCC), we use a range of personalized protocols—including the Lupron trigger—to reduce the risk of OHSS, especially in patients more likely to be affected.

What Is OHSS?

OHSS occurs when the ovaries become enlarged and begin leaking fluid into the abdomen, or producing chemicals that can increase leaking of fluid from small blood vessels, often due to an exaggerated response to fertility medications. While mild symptoms are common after egg retrieval, true OHSS involves more serious symptoms that may require medical management—or in rare cases, hospitalization.

Common Symptoms of OHSS:

• Abdominal bloating and distention

• Pelvic or abdominal pain

• Nausea and vomiting

• Rapid weight gain

• Shortness of breath due to pressure on the diaphragm

• Low urine output

OHSS usually develops a few days after egg retrieval and may worsen in early pregnancy if not monitored closely.

What Causes OHSS?

The underlying cause of OHSS is increased vascular permeability—the blood vessels become “leaky,” allowing fluid to shift from the bloodstream into the abdomen. This process is largely driven by a hormone-like substance called vascular endothelial growth factor (VEGF), which is elevated after ovulation triggers like human chorionic gonadotropin (hCG).

Certain patients are more likely to experience OHSS, including those with:

• Polycystic ovary syndrome (PCOS)

• High antral follicle counts

• High anti-Müllerian hormone (AMH) levels

• A strong response to ovarian stimulation

The Role of the Trigger Shot

At the end of the ovarian stimulation phase, a “trigger shot” is given to mature the eggs before retrieval. Traditionally, this has been hCG, but hCG can remain in the body for up to 10 days—prolonging hormonal stimulation and increasing the risk of OHSS.

The Lupron Trigger Protocol: A Safer Alternative

For patients at higher risk of OHSS, we often recommend the Lupron trigger protocol, which replaces hCG with a dose of Lupron (leuprolide acetate). Lupron triggers an ovulation-like surge of luteinizing hormone (LH) from the pituitary gland, without the extended hormone exposure caused by hCG.

Benefits of the Lupron Trigger:

• Eliminates or greatly reduces OHSS risk

• Allows for safe egg retrieval in high responders

• Results in smaller post-retrieval ovarian size and less fluid buildup

How It Works:

• Lupron is administered in place of hCG approximately 34–36 hours before egg retrieval

• Bloodwork the next day confirms the LH surge and hormone levels

• Patients begin intensive luteal-phase support (estrogen and progesterone) the day after retrieval to support the uterine lining and early pregnancy

Luteal Phase Support: What’s Changed?

In early versions of the Lupron trigger protocol, pregnancy rates were lower due to inadequate hormonal support following retrieval. However, modern protocols include aggressive supplementation with:

• Estradiol (oral or patch)

• Progesterone (injections or suppositories)
  

• Frequent hormone monitoring to ensure proper uterine conditions

With these improvements, success rates are comparable to hCG-triggered cycles—without the risk of OHSS.

Monitoring and Managing OHSS

Most mild or moderate cases of OHSS resolve on their own with observation and supportive care. Severe cases, though rare, may require:

• Daily weight checks and urine output monitoring

• Blood tests for electrolytes, complete blood count (CBC), and kidney function

• Ultrasounds to monitor ovarian size and fluid levels

• Hospitalization in cases of low blood pressure, severe pain, or dehydration

• Paracentesis, a procedure to drain excess fluid from the abdomen, guided by ultrasound

Is the Lupron Trigger Right for You?

This protocol is often recommended for:

• Patients with PCOS or polycystic-appearing ovaries

• Women with high AMH or high antral follicle counts

• Egg donors or those with prior high ovarian response

• Anyone with a history of OHSS

In rare cases, a Lupron trigger alone may not produce a strong enough LH surge. In these situations, your physician may prescribe a “dual trigger” (Lupron + low-dose hCG), balancing fertilization rates with a lower OHSS risk.

The Bottom Line

OHSS is a manageable risk of fertility treatment, and our team at AFCC is committed to tailoring your protocol to reduce that risk as much as possible. For patients at higher risk, the Lupron trigger offers a safer alternative to traditional methods—without compromising your chance of success.

Questions about your IVF protocol or OHSS prevention strategy? Contact us to speak with your care team or schedule a consultation!

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