John Libbey Eurotext

Médecine thérapeutique / Médecine de la reproduction, gynécologie et endocrinologie

Evolution of commercial preparations with FSH activity Volume 19, issue 3, Juillet-Août-Septembre 2017

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Author
Médecine et biologie du développement et de la reproduction, université Paris 13, France
* Tirés à part
  • Key words: follitropin, recombinant technology, calibration
  • DOI : 10.1684/mte.2017.0661
  • Page(s) : 174-80
  • Published in: 2017

While both FSH and LH molecules present in the gonadotropin preparations manufactured from the urines proved to be efficient, the critical role of FSH in the process of follicular growth is likely to explain why products with FSH activity only were subsequently developed. For that reason, molecules with FSH only activity were manufactured with a progressive improvement in the process of purification allowing an increase in the specific activity of the products. However, several drawbacks in the urine collection emerged when a dramatic increase in the need of products was evident further to the development of In Vitro Fertilization in the late 80s: involvement of countries where the quality control was poos regarding the sources of donors, the ways of urine storage and transportation and the risk of virus contamination. In addition, the possible advantage of the LH activity supplementation suggested by some scientists led to the production of urinary products where LH molecules were extracted and substituted with hCG in a FSH/LH ratio of 1 as done in the 60s. However, whatever the manufacture of urinary products, their low specific activity related to urinary contaminants and their poor batch to batch consistency can easily explain why they could not satisfy clinicians in their daily practice. Meanwhile, identification of FSH genes simultaneously with the emergence of DNA recombinant technologies allowed the production of recombinant FSH molecules. This was actually a major step forward in the process of gonadotropin supply: no limitation in production, an improved safety due to the traceability of the process, higher purity and bio-activity as compared to urinary products. However, the final step in the manufacture process was still dependent on the Steelman & Pohley bioassay consisting in the measurement of the rat ovarian weight. The major drawback of the bioassay was actually its imprecision. Because Follitropin alpha can be produced with a highly constant isoform profile, it can be eventually calibrated through a simple and highly precise measurement of the mass (Filled by mass process). This step was absolutely critical to improve the batch to batch consistency of the final product and, eventually, the reproducibility of the ovarian response. The technics of recombinant technology, eventually applied to gonadotropins, are clearly a new step forward at the benefit of couples.