Ovarian hyperstimulation syndrome (OHSS) is a complication arising from the controlled ovarian stimulation used during in vitro fertilization (IVF). The condition occurs when the ovaries over-respond to fertility medications, leading to ovarian enlargement and a severe shift of fluid from the blood vessels into the abdomen or, in rare cases, into the chest cavity. This fluid shift is driven by the release of chemicals like Vascular Endothelial Growth Factor (VEGF) from the overstimulated ovarian tissue. While OHSS can range from mild discomfort to a potentially serious medical event, modern IVF practices focus heavily on preventative strategies across every stage of the cycle.
Identifying and Managing Patient Risk Factors
The first step in preventing OHSS involves identifying which patients are most likely to experience an over-response to stimulation. Certain patient characteristics are consistently linked to a higher risk profile, and screening for these factors is essential before the cycle begins. These factors include Polycystic Ovary Syndrome (PCOS), a condition characterized by numerous small follicles in the ovaries that are highly sensitive to stimulation.
Baseline screening involves a transvaginal ultrasound for an Antral Follicle Count (AFC) and a blood test to measure Anti-Müllerian Hormone (AMH) levels. A high AFC (typically 24 or more follicles) indicates a large pool of resting follicles ready to respond to medication. Similarly, elevated AMH levels (often above 3.5 ng/mL) predict a robust ovarian response and heightened OHSS risk. Younger patients and those with a lower body mass index (BMI) are also at higher risk. Clinicians use this initial data to tailor the entire treatment protocol, particularly the starting dose of the stimulation drugs, to minimize excessive ovarian growth.
Stimulation Protocols Designed for Safety
Once a patient is identified as being at risk for OHSS, the focus shifts to selecting a stimulation protocol that inherently reduces the chance of an over-response. The Gonadotropin-Releasing Hormone (GnRH) Antagonist Protocol is the preferred choice for high-risk patients because it allows for a safer final trigger shot. This protocol uses a short course of medication, typically starting mid-cycle, to block the pituitary gland from releasing its own Luteinizing Hormone (LH), preventing premature ovulation.
The use of this antagonist co-treatment reduces the overall duration of stimulation and often requires a lower total dose of gonadotropins compared to older agonist protocols. Furthermore, a personalized approach to gonadotropin dosing is implemented, often starting with a lower, individualized dose based on the patient’s AMH level and AFC. If monitoring during the cycle shows the ovaries are responding too vigorously, the strategy of “coasting” can be employed. Coasting involves temporarily stopping the gonadotropin injections while continuing the antagonist until the estrogen levels drop to a safer concentration before the final trigger is administered.
Trigger Shot Optimization for Prevention
The final injection, known as the “trigger shot,” is the most critical moment for preventing severe OHSS, as the standard trigger medication is the primary driver of the syndrome. Traditional triggering involves a high dose of human Chorionic Gonadotropin (hCG), which has a long half-life in the body, continuously stimulating the ovaries for days after retrieval. This sustained stimulation leads to the excessive release of VEGF and the subsequent fluid shift.
For high-risk patients, the standard hCG trigger is replaced entirely with a GnRH Agonist trigger, such as leuprolide or triptorelin. This “OHSS-free trigger” works by causing a rapid, short-lived surge of the body’s own LH and Follicle-Stimulating Hormone (FSH) from the pituitary gland. This surge is sufficient to mature the eggs but does not cause the sustained ovarian stimulation that hCG does. The GnRH Agonist trigger is only effective when used in conjunction with the GnRH Antagonist Protocol. In moderate-risk patients, a “dual trigger” approach may be used, combining a full GnRH Agonist dose with a very low, fractional dose of hCG to balance the need for optimal egg maturity with a lower risk of OHSS.
Post-Retrieval Strategies and Supportive Care
Even after a successful retrieval, preventative measures continue to mitigate the risk of developing late-onset OHSS. The most definitive strategy is the “Freeze-All” approach, where all resulting embryos or eggs are cryopreserved and no fresh transfer is performed. This action prevents the introduction of pregnancy-related hCG, which can exacerbate OHSS symptoms and prolong the condition for weeks. By delaying the embryo transfer to a subsequent cycle, the patient’s hormone levels are allowed to normalize before a potential pregnancy begins.
Immediate post-retrieval care focuses on supportive measures to manage the symptoms of fluid shifts and reduce the progression of the syndrome. Patients are advised to maintain aggressive hydration using electrolyte-rich fluids to help balance the loss of fluid from the blood vessels. Prophylactic medication may also be used, such as Cabergoline, a dopamine agonist that works by inhibiting the action of VEGF, thereby reducing the permeability of the blood vessels. This medication is typically started on the day of the trigger or retrieval and continued for about eight days to minimize the chance of moderate or severe OHSS developing.