Background and facts about Recombinant Human Albumin and the use of protein supplementation in media.

The role of protein in IVF culture media
Albumin functions as a carrier of small molecules such as water, salts, free fatty acids, vitamins, hormones and growth factors. The binding capacity of albumin makes it an effective scavanger. Other putative roles of albumin include: buffer, regulator of osmotic pressure and as a stabilisation agent for cell membranes.

The role of albumin as a direct source of nutrients for the embryo has been debated, especially at the early cleavage stages. However, at the blastocyst stage of development, albumin has been shown be endocytosed into the embryo from the medium.

On a practical level, albumin has an important role in facilitating the handling of gametes and embryos in vitro.

Protein supplementation of media
Up until the early 1990´s, the most commonly used protein source in human IVF and embryo culture was human serum, obtained either from donors or from female IVF patients (maternal donors).

It has been generally believed that the positive effect of adding serum to culture media was due to its carrier functions. The problem is that the identification, concentration and embryotrophic effects of the carried agents, is difficult to elucidate, particularly with the LOT-to-LOT variation that exists.

HSA is purified from serum and the most important criticism raised against the use of human or animal (BSA) blood products is the risk of transmitting possible viral/prion contaminations.

HSA is the most well defined additive to culture media that is available on the market today. Even so, variation between both manufacturers and batches still exists and makes complete control in media composition impossible . The concerns of LOT-to-LOT variability and incomplete purity of HSA (see electrophoresis pattern) have fuelled a search for alternative macromolecules, but many leading scientists still believe that a completely pure albumin source would be the most desirable option.

Safety of recombinant human albumin
The safety and tolerability of the r-HA, supplied by Delta Biotechnology Limited, has been demonstrated in an extensive and comprehensive range of studies which included toxicology and mutagenicity studies conducted with potential process contaminants.

These studies include:

Acute toxicity studies
Multiple dose toxicity studies
Mutagenicity studies
Pharmacokinetic studies
Antigenicity
Phase 1 clinical studies in human volunteers

The result of the clinical study demonstrated the safety and tolerability of r-HA up to a dose of 65 mg.

All of these studies, where appropriate, have been carried out in accordance with FDA Good Laboratory Practice (GLP) or FDA Good Clinical Practice (GCP) guidelines.

Recombinant human albumin r-HA
r-HA has proven to be structurally identical to plasma-derived HSA and possesses several advantages including LOT-to-LOT consistency, greater homogeneity (see electrophoresis pattern), free from viral/prion contamination concerns, lower endotoxin levels and the absence of plasma-derived impurities.

A new definition of safety and consistency
The new Vitrolife ready-to-use culture media r-S1™/r-S2™ containing recombinant human albumin will provide state of the art efficacy with high rate blastocyst formation, biochemical pregnancy rate exceeding 55 % (two embryos per transfer), uncompromised safety for mother and child and minimised LOT-to-LOT variation.

Comparison of HSA and r-HA