By Álvaro Díez Álvarez (Gynecologist – License No. 282865580).
Ovarian hyperstimulation syndrome is a complication that can occur following ovarian stimulation. However, it is important to distinguish it from a high ovarian response, as a patient may develop many follicles or have a large number of oocytes retrieved without developing the syndrome. For OHSS to be diagnosed, certain symptoms and clinical changes must also be present.
In OHSS, the ovaries become enlarged and the permeability of the blood vessels increases. One of the molecules involved in this process is vascular endothelial growth factor (VEGF). Its activity increases in response to factors such as the hormone hCG and causes some of the fluid normally contained within the blood vessels to move into other areas of the body, particularly the abdominal cavity.
It is this shift in fluid that causes the symptoms of the syndrome. Although OHSS can potentially become a serious complication, current ovarian stimulation strategies allow us to identify patients at greater risk and tailor treatment to considerably reduce the likelihood of severe OHSS. In fact, both ESHRE (European Society of Human Reproduction and Embryology) and ASRM (American Society for Reproductive Medicine) include specific measures for preventing OHSS in their recommendations.
Ovarian hyperstimulation syndrome does not usually develop while the first doses of ovarian stimulation medication are being administered. Instead, it tends to occur in the days following final oocyte maturation and often after egg retrieval has taken place. Depending on when symptoms develop, OHSS is generally classified as either early- or late-onset:
For patients at high risk, preventive strategies such as embryo freezing and deferred embryo transfer can be used. By avoiding pregnancy during the same cycle, the risk of late-onset OHSS can be reduced.
Symptoms depend on the severity of the syndrome. In mild cases, patients may experience some abdominal bloating, discomfort or nausea. As fluid accumulation increases, more pronounced abdominal pain and even vomiting may occur.
However, it is important to remember that some abdominal discomfort following egg retrieval does not necessarily mean that OHSS is present. Symptoms therefore need to be assessed in terms of their severity and progression, together with other clinical findings.
Severity | Common manifestations |
Mild | Abdominal bloating, discomfort or mild abdominal pain, and nausea. |
Moderate | Increased abdominal distension, pain, nausea or vomiting, and fluid accumulation in the abdomen. |
Severe | Significant ascites, reduced urine output, dehydration, blood or kidney abnormalities and, in some cases, breathing difficulties. |
Although severe OHSS can occur, most cases do not progress to a severe form. However, when a substantial amount of fluid moves out of the blood vessels, considerable fluid can accumulate in the abdomen — a condition known as ascites — while the effective circulating blood volume decreases.
When this happens, the blood can become more concentrated, urine output from the kidneys may decrease and electrolyte imbalances may develop. If fluid also accumulates around the lungs, the patient may experience difficulty breathing.
In more severe cases, there is also an increased risk of thromboembolism, in which a blood clot forms and may affect the veins in the legs or the lungs.
Treatment depends on the severity of the condition. There is no medication that can make OHSS disappear immediately once it has developed, so treatment focuses on managing symptoms, maintaining an appropriate fluid balance and preventing potential complications while the body recovers.
In mild cases, outpatient monitoring is usually sufficient, with appropriate hydration according to the medical team's advice and monitoring of how symptoms progress. In moderate cases, ultrasound scans and blood tests may be required to assess the amount of fluid that has accumulated, the degree of haemoconcentration, electrolyte levels and kidney function.
Severe cases may require hospital admission. Treatment may include intravenous fluids, medication to control nausea or pain, and measures to reduce the risk of thrombosis.
When pregnancy has not occurred, symptoms generally improve gradually as ovarian hormonal activity decreases. However, if pregnancy has occurred, the hCG produced during the first few weeks of pregnancy can cause the syndrome to take longer to resolve.
Many assisted reproduction treatments involve ovarian stimulation as part of the process. The aim is to encourage several follicles to develop at the same time so that as many oocytes as possible can be retrieved. This requires the administration of hormonal medication and ultrasound monitoring to assess how the ovaries are responding.
In some patients, however, the ovarian response may be greater than expected. When this response leads to a series of changes in the body, it can result in what is known as ovarian hyperstimulation syndrome (OHSS).
Prevention is a key part of managing the risk of ovarian hyperstimulation syndrome. To reduce this risk, it is important to identify patients who may have a high ovarian response and tailor treatment to their individual characteristics. The main preventive measures include:
A high ovarian response therefore does not necessarily mean that OHSS will develop or that treatment will need to be cancelled. Individualised treatment and appropriate monitoring can substantially reduce the risk while prioritising patient safety.
Ata B, Bosch E, Broer S.
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Actualización de la guía de ESHRE sobre estimulación ovárica para tratamientos de fecundación in vitro e ICSI:
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Practice Committee of the American Society for Reproductive Medicine.
Prevention of moderate and severe ovarian hyperstimulation syndrome: a guideline.
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Recomendaciones basadas en la evidencia para prevenir el síndrome de hiperestimulación ovárica moderado y grave:
https://doi.org/10.1016/j.fertnstert.2023.12.024
Royal College of Obstetricians and Gynaecologists.
The Management of Ovarian Hyperstimulation Syndrome. Green-top Guideline No. 5.
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Guía sobre la prevención, diagnóstico y tratamiento del síndrome de hiperestimulación ovárica:
https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guidelines/the-management-of-ovarian-hyperstimulation-syndrome-green-top-guideline-no-5/
Palomba S, Costanzi F, Nelson SM, Caserta D, Humaidan P.
Interventions to prevent or reduce the incidence and severity of ovarian hyperstimulation syndrome: a systematic umbrella review of the best clinical evidence.
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Revisión paraguas de la evidencia clínica disponible sobre las intervenciones destinadas a prevenir o reducir la incidencia y gravedad del síndrome de hiperestimulación ovárica:
https://doi.org/10.1186/s12958-023-01113-6
Humaidan P, Nelson SM, Devroey P.
Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials.
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Revisión del síndrome de hiperestimulación ovárica que propone nuevos criterios de clasificación para su descripción y notificación en ensayos clínicos:
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