News Release

Spanish fertility experts bring hope of avoiding serious complication of assisted reproduction

Peer-Reviewed Publication

European Society of Human Reproduction and Embryology

Madrid, Spain: Research by Spanish fertility experts is bringing new hope to women of avoiding a serious complication of assisted reproduction – ovarian hyperstimulation syndrome (OHSS)[1].

In its severest form, which requires urgent medical treatment, the syndrome affects around 200 women a year in Spain and as many as 2,000 a year in Europe. OHSS occurs when a woman's ovaries go into overdrive and over-produce follicles and eggs in response to hormones given to prepare the ovaries for assisted reproductive techniques (ART).

The researchers, from the Instituto Valenciano de Infertilidad in Madrid and Valencia, have found that levels of a protein called Vascular Endothelial (VE) cadherin and OHSS are associated. VE-cadherin links endothelial (lining) cells together. Its role is to stop fluid leaking from the vessel walls. In some diseases such as cancer, or in OHSS, VE-cadherin links break and fluid builds up and escapes between the endothelial cells. This results in an accumulation of fluid in body cavities, producing conditions such as ascites and oedema.

The research team studied 50 women undergoing controlled ovarian hyperstimulation with hormones at different times in their ART cycle. They found that, compared with a control group, women who developed severe OHSS had a four-fold increase in their serum VE-cadherin levels after they had received human chorionic gonadotrophin (hCG) – a hormone used to stimulate the ovaries. Levels remained much higher in the OHSS group throughout their cycle and persisted through pregnancy until OHSS resolved.

Dr Juan García-Velasco from the Instituto Valenciano de Infertilidad-Madrid, told a news briefing today (Monday 30 June) at the European Society of Human Reproduction and Embryology conference in Madrid: "These results show that VE-cadherin may have a crucial role in controlling the permeability of vascular endothelium in OHSS. We need to do more research to understand the underlying pathology and physiology before we can eradicate the condition. But, if we can use drugs – perhaps blockers or protease inhibitors – to avoid VE-cadherin breaking, we might be able to prevent liquid escaping from the vessels and reduce the incidence of OHSS."

In the meantime, the team have found in another study of 12 patients and 11 controls that moderating the way the ovaries are stimulated significantly reduces the risk of severe OHSS. When a woman is at risk of severe OHSS the only choice up to now has been to press ahead with treatment and risk the patient's health, or to cancel the cycle.

But, by checking serum oestradiol levels and withholding hCG if levels are too high while continuing to give a gonadotrophin releasing hormone (GnRH) analogue, hCG can be resumed once levels drop to a safe point. This novel approach – known as 'coasting' – enables the treatment cycle to continue, but with less risk. Coasting works because the multiple extra unwanted small and medium follicles die without stimulation from hCG, but the key large ones remain.

Said Dr García-Velasco: "We now have excellent pregnancy rates in ART, so we must focus on reducing complications. We have to eradicate OHSS. For now, we have a way of reducing its severity, but the next step is to understand the condition better and develop targeted treatments." (ends)

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Abstract nos: O-097 & O-100 (Tuesday 10.15 & 11.00hrs CET Auditorium A – Europa)

Notes
[1] In ART, hormones called gonodotrophins are given to stimulate the ovaries to produce multiple follicles and therefore multiple numbers of eggs during one cycle. Sometimes, the ovaries overreact and the large number of follicles result in ovarian hyperstimulation syndrome (OHSS). Mild OHSS occurs in about 3% of women undergoing controlled hyperstimulation. But, in about 0.1 to 1% of women it can be a life-threatening condition, putting them at risk of massive ovarian enlargement and fluid accumulation in the abdomen and pleural cavities, serious changes in blood chemistry and thrombosis. Severe OHSS requires urgent hospital admission and intensive treatment.

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