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Benefits of Recombinant Technology
Figure 3: Preparation of Recombinant Human Follicle-stimulating Hormone Production in Bioreactor
Roller bottles
Ampoule TC flask
Seeding
36 days
Pump Pump
Clarification
Media
Harvest feed
collection
Purification
4ºC
34 days
Crude
FSH
Bulk kg
kg
Filtration
Harvest
Feed
(0.2 micron)
Bulk FSH
QC test
released
7 weeks
An aliquot from the selected clone of Chinese hamster ovary cells is first grown in T-flasks, then subcultured into roller bottles and allowed to expand for up to 36 days. The cells are then mixed with
a suspension of microcarrier beads and transferred to a bioreactor vessel with continuous culture media infusion for an average duration of 34 days. The harvested ‘crude FSH’ is stored at 4ºC until
purification. The final product is released after extensive quality control testing over a period of seven weeks.
Source: Lunenfeld B, Historical perspectives in gonadotrophin therapy, 2004.
2
With permission of Oxford University Press.
contamination with rFSH.
23
Conversely, even urine-derived gonadotropin Future Applications of Genetic Technologies in
preparations indicated to be highly purified contain significant amounts of Treatments for Infertility
urinary protein impurities, some of which are beginning to be identified.
24,25
Improvements in Recombinant Gonadotropins
Recombinant technology offers an important treatment modality for
expanding the range of gonadotropins available to treat infertility. New
Recombinant technology offers an
recombinant products are being developed that are geared toward a
patient-centered approach of administration. Ease of use, improved
important treatment modality for convenience, and fewer monitoring parameters will be the focus of
expanding the range of gonadotropins
future developments in the treatment of infertility.
available to treat infertility. Use of Genotyping to Personalize Infertility Treatment
The advent of pharmacogenomics brings hope that drug treatment
can be optimized according to an individual’s genetic profile.
Pharmacogenomics in infertility treatment may be able to optimize
As ART has advanced, the number of couples seeking treatment has outcomes of controlled ovarian stimulation (COS) in women
increased. It takes on average two liters of urine to prepare one 75IU vial, undergoing ART. Much of the pharmacogenetics research in COS has
which means that approximately 100 liters of urine are needed to focused on the FSH receptor (FSHR) gene.
27
Researchers have
complete an average ovarian cycle.
26
To consider this on a larger scale, in determined that in normal ovulatory women undergoing ART, basal FSH
2000 120 million liters of urine were necessary to satisfy the need levels were significantly different between FSHR genotypes, suggesting
worldwide, requiring 600,000 donors.
12
This has led to growing concern that women have differences in FSH hormone sensitivity related to
over the impossibility of absolute source control. different FSHR genotypes.
28
FERTILITY TREATMENT REVIEW 15
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