Ovarian Hyperstimulation Syndrome

In Vitro Fertilisation (IVF) for the treatment of infertility has become a routine medical procedure in the 21st century. However, women may suffer side effects as a result of the stimulation of the ovaries, including a serious complication known as Ovarian Hyperstimulation Syndrome (OHSS) (Nouri et al, 2014).

IVF treatments use injections of gonadotrophin to increase the number of eggs (oocytes) and embryos available, which in turn increases the success rates of IVF.

OHSS occurs when the ovaries over-respond to the Follicle Stimulating Hormone (FSH) injections producing many egg sacs (follicles). When a large number of follicles are produced the ovaries become enlarged and release chemicals into the bloodstream that make blood vessels leak fluid into the body. The Royal College of Obstetricians and Gynaecologists' (RCOG) Green Top Guidelines (2016) explains OHSS to be “the occurrence of ovarian enlargement with the local and systemic effect of proinflammatory mediators, including increased vascular permeability and prothrombotic effect”. 

Symptoms

• mild OHSS – mild abdominal swelling, discomfort and nausea
• moderate OHSS – symptoms of mild OHSS, but the swelling is worse due to the fluid in the abdomen. This can cause pain, nausea and vomiting
• severe OHSS – symptoms of moderate OHSS with extreme dehydration. Infrequent and small amounts of urine are passed which is dark in colour. Breathing becomes difficult due a build-up of fluid in the chest and a serious, but rare, complication is formation of a blood clot (thrombosis) in the legs or lungs (RCOG, 2016).

Prevalence

Generally prevalence varies from one per cent to ten per cent with severe instances occurring in up to two percent of cases (Balen, 2014).

Risk factors

Prevention is better than cure in this iatrogenic disorder, therefore it is crucial to identify women who may be at high risk high (O'Donovan et al, 2015). Before commencement of gonadotrophin injections, determining a woman’s oocyte reserve by means of testing her Anti –Mullerian Hormone (AMH) via blood serum assessment is essential. The RCOG has recognised that AMH is important in fertility treatment stating that “women with high levels of AMH are at an increased risk of OHSS” (RCOG, 2016).

Research has also found that generally OHSS occurs in younger women compared with older women since these women have a larger number of recruitable follicles thus rendering them more responsive (Whelan and Vlahos 2000). It is further suggested that 40% of women undergoing IVF will have polycystic appearing ovaries which puts them most at risk of developing OHSS (Balen, 2014).

Women with polycystic ovaries (PCO) tend to have a very large pool of follicles residing in the ovaries having the classic “necklace” appearance on ultrasonography, which may suggest a heightened sensitivity to gonadotrophins with the potential to develop into OHSS should all of those follicles be stimulated to excess (Whelan and Vlahos, 2000). Therefore, it is crucial that PCO is recognised prior to the commencement of treatment.

Treatment

Most OHSS symptoms resolve in seven to ten days if treatment does not result in a pregnancy. If a pregnancy is achieved OHSS can become worse and last up to a few weeks or longer. Treatment is to help symptoms and prevent complications and may include:

• analgesia like paracetamol or codeine
• anti emetics to help reduce nausea and vomiting
• an intravenous drip to replace fluids
• support stockings and heparin injections to prevent thrombosis
• paracentesis if the abdomen is tense and swollen with a large build-up of acities (which is an abnormal build-up of fluid in the abdomen).
  (RCOG, 2016).

Prevention measures

The National Institute for Health and Care Excellence (NICE, 2013) supports the use of a GNRH antagonist for its use in PCO in particular. An agonist trigger has been suggested and due to the advances in freezing-thawing techniques, a freeze-all embryos policy to prevent OHSS in high responding patients has been supported by the ROCG.

Recommendations 

The RCOG (2016) emphasises that “information concerning OHSS should be delivered face-to-face to all undergoing fertility treatment, backed up with written information and advice including a 24-hour contact”. The RCOG (2016) recommends that fertility clinics maintain communication at the places where patients may present with symptoms of OHSS and emphasises that “referral pathways and protocols should be agreed with acute units to ensure that specialists provide continuity of care with OHSS particularly when women are admitted to a centre without the required specialist expertise”. 

References 

Balen, A.H. (2014) Infertility in practice, CRC Press.

Human Fertilisation & Embryology Authority (2011) Fertility treatment 2018: trends and figures. 

Nouri, K., Tempfer, C.B., Lenart, C., Windischbauer, L., Walch, K., Promberger, R. and Ott, J. (2014) Predictive factors for recovery time in patients suffering from severe OHSS. Reproductive biology and endocrinology: RB&E, 12(1), pp. 59.

O'Donovan, O., Al Chami, A. and Davies, M. (2015) Ovarian hyperstimulation syndrome. Obstetrics, Gynaecology & Reproductive Medicine, 25(2), pp. 43-48.

Prakash, A. and Mathur, R., (2013) Ovarian hyperstimulation syndrome. The Obstetrician & Gynaecologist, 15(1), pp. 31.

Royal College of Obstetricians and Gynaecologists (2016) The management of Ovarian Hyperstimulation Syndrome Green-top Guideline No.5.

National Institute for Health and Care Excellence (2013). Fertility Problems: assessment and treatment.

Whelan, J.G. and Vlahos, N.F. (2000) The ovarian hyperstimulation syndrome. Fertility and Sterility, 73(5), pp. 883-896.