Preparation, characterization and application of long-acting FSH analogs for assisted reproduction

Assisted reproduction technologies are widely used in humans and domestic animals and often include follicle stimulating hormone (FSH) in the protocol. One limitation with most of the available FSH preparations is the relative short half-life in the circulation that dictates multiple daily injections for the desired follicle development and superovulation. The development of bioactive long-acting structurally modified FSH analogs is desirable for human and veterinary use. In addition, optimal preparations and/or formulations are expected to improve the regimen and efficiency of the treatment. This review briefly describes the approaches that have been explored to extend the half-life of FSH in the circulation. These include strategies to increase the mass and/or charge of FSH and to prevent the dissociation of the hormone to inactive subunits components. Most of these strategies, except one that led to a registered drug (Elonva) indicated for controlled ovarian stimulation protocols in humans, are still in experimental stage.