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 the present, 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.

Trials under consideration were evaluated for methodological quality and appropriateness for inclusion without consideration of their results. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomization, 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 three included trials demonstrated significant reduction in severe ovarian hyperstimulation syndrome on administration of human albumin (common odds ratio 0.1, 95% confidence interval 0.03 to 0.39). There was no evidence of an increase in the pregnancy rate (common odds ratio 1.69, 95% confidence interval 0.7 to 4.07).

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. However, the results of this review can not be regarded as conclusive as they are based on only three small trials. Further trials are urgently needed.