Intra-venous albumin for preventing severe ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition that occurs after the administration of human menopausal gonadotrophin (hMG) with or without gonadotrophin releasing hormone (GnRH) agonists. OHSS is a threat to every woman undergoing ovulation induction and is potentially lethal in its severest form. Severe OHSS is characterised by growth of multiple large follicles with massive extravascular protein rich fluid shift. This may lead to hypovolaemia, haemoconcentration, oliguria, and electrolyte disturbance. Human albumin solutions are now used in the management of shock and other conditions in which restoration of blood volume is urgent, the acute management of burns, and clinical situations associated with hypoproteinaemia. Recently, a number of clinical trials with conflicting results have been reported in which albumin has been tested as a possible way for preventing the severe form of OHSS.

To review the effectiveness of human albumin administration in prevention of severe ovarian hyperstimulation syndrome.

The Menstrual Disorders and Subfertility Group literature search strategy was used to identify randomised trials that had compared the use of human albumin with placebo or no treatment in the prevention of severe ovarian hyperstimulation syndrome. A diverse search strategy was employed, including handsearching of core journals from 1966 to November 2001, searching bibliographies of relevant trials, MEDLINE, EMBASE, PsychLIT and CINAHL databases, the MDSG specialised register, abstracts from North American and European meetings and contact with authors of relevant papers.

Trials were included if they compared the effect of human albumin with placebo or no treatment on relevant outcomes. Only randomised controlled studies were included in this review.

Seven randomised controlled trials were identified, five of which met our inclusion criteria and enrolled 378 women (193 in the albumin treated group and 185 in the control group). Trials under consideration were evaluated for methodological quality and appropriateness for inclusion without consideration of their results.The five included trials were single-centre parallel randomised controlled studies. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention.

2x2 tables were generated for all relevant outcomes. Odds ratios were calculated using the Peto modified Mantel-Haenszel technique.

Meta-analysis of the five included trials demonstrated significant reduction in severe ovarian hyperstimulation syndrome on administration of human albumin (odds ratio was 0.28 (95% CI 0.11 to 0.73). Relative risk was 0.35 (0.14 - 0.87) and absolute risk reduction was 5.5. For every 18 women at risk of severe OHSS, albumin infusion will save one more case. There was no evidence of an increase in the pregnancy rate (odds ratio was 1.09, (95% CI 0.65 to 1.83) REVIEWER'S CONCLUSIONS: This review shows a clear benefit from administration of intra-venous albumin at the time of oocyte retrieval in prevention of severe OHSS in high-risk cases. Whether the NNT would justify the routine use of albumin infusion in cases at risk of severe OHSS needs to be judged by clinical decision makers.