Ovarian Hyperstimulation Syndrome (OHSS)

Ovarian Hyperstimulation Syndrome (OHSS) is a side-effect of in vitro fertilisation (IVF) treatment. It occurs due to over-stimulation of the ovaries by the hormone used to prepare the eggs for collection and fertilisation by sperm, in particular the hormone ‘human chorionic gonadotrophin’ (hCG).

What is OHSS?

During IVF treatment, hormones (typically a synthetic form of follicle stimulating hormone; FSH) are used to stimulate the growth of multiple follicles in the ovary (follicles are fluid-filled sacs in the ovaries that contain the eggs).

In order to mature the eggs (enable them to be fertilised by sperm), they require exposure to luteinising hormone (LH). This is most often provided by human chorionic gonadotrophin (hCG), which acts on the same receptors as LH. Unfortunately, hCG has a long duration of action (> 1 week), which can result in overstimulation of the ovaries. This can lead to the release of dangerous chemicals from the ovary (e.g. vascular endothelial growth factor; VEGF) that make the blood vessels in the body leaky. This can cause leakage of fluid from the blood vessels to areas which normally don’t contain fluid, such as the lungs and the abdomen. Therefore, OHSS can be associated with swelling of the abdomen, shortness of breath (due to fluid in the lungs), abnormal kidney function (due to lack of fluid in the blood vessels in the kidney) and swelling of the ovaries (which can then twist called ovarian torsion). Symptoms of OHSS can include feeling sick (nausea), vomiting, abdominal pain, abdominal swelling and breathing difficulties.

What causes OHSS?

The main cause of OHSS is the use of hCG to mature eggs during IVF treatment. Some women with lots of follicles in the ovary are more prone to developing OHSS during IVF treatment, such as those with polycystic ovary syndrome (PCOS).

What are the signs and symptoms of OHSS?

Signs of OHSS include fluid in the abdomen (ascites), fluid on the lungs (pleural effusion), abnormal kidney function and abnormal enlargement of the ovaries.

Symptoms of OHSS include feeling generally unwell, feeling sick, vomiting, abdominal pain, abdominal swelling and breathing difficulties. Women with OHSS are also more prone to clots on the leg or lung, which could lead to shortness of breath.

How common is OHSS? 

The diagnosis of OHSS depends on the specific criteria used, the population studied, and whether they are actually assessed for OHSS (with an ultrasound and blood tests). Typically, a third of women are thought to have mild features, one tenth to have moderate features and 2% to have severe features. OHSS is much more common in women at increased risk such as those with PCOS.

Is OHSS inherited?

It is difficult to say specifically whether OHSS is inherited as it is mostly observed in the context of IVF treatment, which other family members may not have had. However, it is likely that many of the factors that predispose to OHSS are inherited e.g., preponderance towards developing PCOS and differences in the receptors for the stimulating hormones.

How is OHSS diagnosed? 

OHSS is usually diagnosed in an outpatient setting, but if women have severe symptoms like difficulty breathing, admission to hospital may well be required. An ultrasound scan (US scan) of the pelvis is used to assess ovarian size and the presence of fluid in the abdomen (ascites). If there is concern about fluid in the lungs, an ultrasound scan of the lungs or chest X-ray can be used to identify this. If there is concern about a clot on the lungs, then a computed tomography pulmonary angiography (CTPA) can be conducted. Blood tests including for kidney function, protein levels, liver function and clotting factors are also carried out.

How is OHSS treated? 

Treatment of OHSS depends on the specific symptoms and signs present and how severe they are. Most patients with OHSS only need supportive management as an outpatient, e.g. anti-nausea medications, drinking enough fluids, and frequent visits to the IVF unit for monitoring until the signs and symptoms spontaneously resolve. If a patient with OHSS is pregnant, OHSS may take longer to resolve as hCG produced by the embryo could continue to stimulate the ovaries. If there is excess fluid on the lungs or abdomen, these can be drained using a tube placed directly into the lungs or abdomen, as appropriate. If kidney function is abnormal, patients may require admission to receive fluids in the vein. If a clot on the lung or leg is found, then a patient is likely to require blood thinning medications. Rarely, patients require a stay on the intensive care unit to ensure that they get the intensive medical support they need. Although there are some other treatments that have been used, the evidence that these actually work is poor.

Are there any side-effects to the treatment?

Most of the treatment is supportive. Specific treatments such as tubes into the lungs can have specific complication rates, but these are generally small.

What are the longer-term implications of OHSS? 

Generally speaking, most patients do not have any long-term effects after resolution of OHSS. There have been some reports suggesting that OHSS may be associated with pregnancy complications that affect the baby, but this is difficult to prove as such findings could be due to confounding factors that predispose to OHSS, as well as pregnancy complications. Some patients can be affected by psychological trauma as a result of the unpleasant experience of having OHSS, especially if they had a severe or life-threatening forms. The protocol for future IVF treatments in a woman affected by OHSS should be modified to be milder, by using lower doses and safer hormones such as GnRH agonists rather than hCG, in order to try to minimise the risk of OHSS.

Related resources

Human Fertilisation and Embryology Authority: information on IVF Treatment

Last reviewed: Feb 2021