Preventing OHSS — Modern Protocols, Modern Safety

One of the most persistent anxieties associated with IVF treatment, both for patients and clinicians, has historically been the risk of Ovarian Hyperstimulation Syndrome, or OHSS. While mild forms are quite common, severe OHSS can be a serious complication, leading to hospitalisation and, in rare instances, life-threatening outcomes. However, I want to reassure my patients that in 2026, with the advent of modern protocols and a deep understanding of its pathophysiology, severe OHSS is largely a preventable condition.

Understanding OHSS: A Brief Overview

Before we look closely at prevention, it's helpful to understand what OHSS is. It's a systemic disorder that can occur after ovarian stimulation, primarily in women undergoing IVF or other assisted reproductive technologies. It's characterised by enlarged ovaries and a shift of fluid from the blood vessels into the third space, such as the abdominal cavity, leading to symptoms like abdominal distension, discomfort, nausea, and vomiting. In severe cases, it can lead to kidney dysfunction, blood clots, and respiratory distress.

The underlying cause is the body's exaggerated response to hCG, the 'trigger shot' used to mature the eggs before retrieval. While the exact mechanisms are complex, it involves the release of various substances from the ovaries that increase vascular permeability. Women with Polycystic Ovary Syndrome (PCOS), those with a high antral follicle count, or a robust ovarian response to stimulation are typically at a higher risk.

Personalised Stimulation Protocols: Tailoring Treatment to You

The cornerstone of modern OHSS prevention begins even before stimulation starts: personalised treatment planning. Gone are the days of 'one-size-fits-all' protocols. My approach, and that of most leading fertility centres today, is to meticulously assess each patient's risk factors and tailor the stimulation regimen accordingly.

Key elements of this personalised approach include:

• Baseline Assessment. A thorough evaluation of your medical history, ovarian reserve markers (AMH, AFC), and body mass index (BMI). Women with high AMH levels (e.g., >3.5 ng/mL) and a high antral follicle count (e.g., >15 follicles per ovary) are identified as high-risk.

• Gonadotropin Dosing. Starting with lower doses of ovarian stimulating hormones and gradually adjusting based on follicular response. This 'start low, go slow' approach helps prevent overstimulation.

• Monitoring. Regular ultrasound scans and blood tests (especially oestradiol levels) are crucial to track follicular development and predict the risk of OHSS. If oestradiol levels rise very rapidly or reach extremely high thresholds (e.g., >3500-4000 pg/mL), it's a clear warning sign.

The Game-Changer: GnRH Agonist Trigger

Perhaps the most significant advancement in preventing severe OHSS has been the widespread adoption of the GnRH agonist trigger, often referred to as a 'decapeptyl' trigger in India. Traditionally, a recombinant hCG injection was used to trigger final egg maturation. While effective, hCG has a long half-life and is the primary culprit behind the sustained vascular permeability that causes OHSS.

A GnRH agonist trigger, however, stimulates the body's own pituitary gland to release a surge of LH (Luteinising Hormone), mimicking the natural surge but with a much shorter half-life. This means the ovaries are exposed to the 'trigger' effect for a brief period, significantly reducing the risk of developing severe OHSS, especially when used in a GnRH antagonist protocol. It's truly a paradigm shift that has made IVF much safer for high-risk patients. My team here at Apollo Fertility, Banjara Hills, routinely employs this strategy.

'Freeze-All' and Deferred Embryo Transfer Strategy

Another powerful strategy for OHSS prevention, particularly when a patient shows signs of an exaggerated response to stimulation, is the 'freeze-all' approach. In this scenario, all viable embryos created during the IVF cycle are cryopreserved (frozen) instead of being transferred fresh. A fresh embryo transfer can exacerbate OHSS because the natural production of hCG by a nascent pregnancy further prolongs the ovarian stimulation effect.

By freezing all embryos and performing a frozen-thawed embryo transfer in a subsequent cycle, typically a month or two later, the body has ample time to recover from the ovarian stimulation. This completely separates the stimulation phase from the implantation phase, eliminating the risk of pregnancy-related OHSS. While it adds an additional cycle and some cost (typically INR 25,000 - 50,000 for freezing and transfer), the safety benefits for high-risk patients are invaluable.

Proactive Management and Supportive Care

Even with all preventive measures, some patients may still experience mild to moderate OHSS. My team provides proactive advice to manage symptoms and prevent progression. This includes:

• Hydration. Drinking plenty of fluids, ideally electrolyte-rich drinks, is paramount. Plain water might not be sufficient.

• Electrolyte Balance. Monitoring and correcting any electrolyte imbalances.

• Protein Intake. A diet rich in protein can help maintain osmotic pressure in the blood vessels.

• Avoidance of Strenuous Activity. Rest is advisable to minimise discomfort and potential complications.

• Pain Management. Over-the-counter pain relievers can help with abdominal discomfort.

• Medications. In some cases, specific medications like cabergoline can be prescribed to reduce vascular permeability, though its use is debated and not universally applied.

• Close Monitoring. Regular follow-ups to monitor symptoms, ovarian size, and fluid accumulation. For more severe cases, hospitalisation might be needed for intravenous fluids, paracentesis (fluid drainage), and thrombosis prevention.

The Indian Context: Access and Awareness

In India, with the implementation of the Assisted Reproductive Technology (Regulation) Act, 2021, and its subsequent rules, patient safety has gained even greater emphasis. Preventing OHSS aligns perfectly with the ethical guidelines and patient-centric approach mandated by the act. Most reputable clinics, especially in cities like Hyderabad, have robust protocols in place to minimise this risk. However, it's crucial for patients to choose clinics that prioritise safety over aggressive stimulation, even if it promises a higher number of eggs. A smaller number of good quality eggs, retrieved safely, is always preferable to a large cohort with an increased OHSS risk.

Cost considerations are also relevant. While preventive measures might involve slightly different medications or an additional 'freeze-all' cycle, the cost of managing severe OHSS (hospitalisation, medications, potential intensive care) far outweighs these initial expenses. For instance, a hospital stay for severe OHSS in a private hospital in Hyderabad could easily range from INR 75,000 to over INR 2,00,000 depending on the severity and duration.

The Future: Continuous Improvement and Research

The field of reproductive medicine is constantly evolving. Ongoing research continues to refine our understanding of OHSS, identify new biomarkers, and develop even safer stimulation protocols and preventive agents. We are moving towards even more individualised treatment algorithms, potentially incorporating genetic markers to predict risk with greater accuracy. My commitment, and that of my colleagues, is to stay abreast of these developments to ensure my patients receive the safest and most effective care possible.

I hope this comprehensive overview reassures you that modern IVF is far safer than it once was, especially regarding the risk of severe OHSS. Our primary goal is always to achieve a healthy pregnancy while prioritising your well-being throughout the journey.

If you have further questions or wish to discuss your specific fertility journey, please do not hesitate to reach out. You can message me on WhatsApp to schedule a consultation.