< Back to previous page
Project
Optimize clinical in-vitro maturation of oocytes by Translational Molecular Research. (IWTTBM3)
The proposed research is an innovative approach to an existing assisted reproduction technique (named In Vitro Maturation (IVM)) for human. This technique has been pioneered already in the early nineties, but has never penetrated in the clinic.
The fundamental reasons are that the classification of the different maturation stages are still only based on morphological evaluation in the clinics, although we have at our disposal performant and quick molecular techniques to better characterise oocyte maturation stages by biopsying their surrounding cumulus cells. Absence of any more quantitative and sensitive technique to classify immaturity holds up the development of appropriate culture techniques.
A first aim is to validate the potential of a highly select list of genes expressed in cumulus cells generated from own microarray analyses, to determine the oocyte maturity.
Following a more objective classification of oocyte-cumulus complexes, this project will further test an innovative culture technique called "prematuration culture" using a pharmacological compound to better synchronise nuclear and cytoplasmic maturation processes into the oocyte. The rationale for using a pre-maturation phase in the culture practise is that the more immature stage oocytes should benefit longer from the interaction with adequately conditioned cumulus cells. A third investigational accent will evaluate the implementation of chemical factors in medium for which it was previously shown to be enhancing the efficiency of oocyte maturation in large mammalian species and human. The rationale to include previously described factors is that these compounds will probably be even more effective after a prematuration culture phase having induced a better cytoplasmic maturation into the oocyte.
Also economical reasons have been holding up the development of such a promising in vitro technique are that the 3 big pharma players in reproduction are selling gonadotrophins to perform classical in vitro fertilisation techniques. These companies are afraid of losing a very lucrative business by supporting the development of a technique that would use immature oocytes as a source for IVF/ICSI.
Developing IVM means also the investment to test a more prolonged and more complicated culture technique. This development goes hand in hand with media composition, however the profit margins of media companies are (very) small and there are many (5 to 6) players on this market that have to divide the clients. Furthermore there are safety aspects related to prolonged culture that might limit the enthusiasm of the developers.
At the Center for Reproductive Medicine (VUB) we are equipped to make safety testing an integral part of our project. Before the eventual transfer of embryos developed after prematuration culture to the patient we plan to evaluate frequency of aneuploidy in oocytes and embryos using fluorescent In Situ Hybridisation techniques. Gene expression in the early embryo and unfertilised oocytes, embryos and conception tissue for methylation errors at the representative imprinted genes.
The current IVM techniques have only seldom reported more than 10% implantation rate per embryo transferred, which is 2 to 3 times lower than embryos from IVF/ICSI and the abortion rate is higher (up to 30%). The pre-treatment methods for IVM will try to limit the intake of fertility hormones, avoid a whole range of minor and major complications, and will reduce the total cost of fertility treatment for the social security. The minimal invasiveness of this procedure will also benefit cancer patients in an urgent need to store their germ cells before undergoing germ cell devastating oncological treatment.
A first group to benefit of the new IVM are the PCOS patients that frequently (5% of PCOS patients) develop severe ovarian hyperstimulation, a life threatening condition. If this technique is established practically all patients would be willing doing IVM instead of IVF due to its cost-saving and gentle procedure.
The final objective of this work is to prove that by designing a differential culture system take home baby rates after IVM can approach those of conventional IVF, but with a significant cost-saving and less invasive treatment.
The fundamental reasons are that the classification of the different maturation stages are still only based on morphological evaluation in the clinics, although we have at our disposal performant and quick molecular techniques to better characterise oocyte maturation stages by biopsying their surrounding cumulus cells. Absence of any more quantitative and sensitive technique to classify immaturity holds up the development of appropriate culture techniques.
A first aim is to validate the potential of a highly select list of genes expressed in cumulus cells generated from own microarray analyses, to determine the oocyte maturity.
Following a more objective classification of oocyte-cumulus complexes, this project will further test an innovative culture technique called "prematuration culture" using a pharmacological compound to better synchronise nuclear and cytoplasmic maturation processes into the oocyte. The rationale for using a pre-maturation phase in the culture practise is that the more immature stage oocytes should benefit longer from the interaction with adequately conditioned cumulus cells. A third investigational accent will evaluate the implementation of chemical factors in medium for which it was previously shown to be enhancing the efficiency of oocyte maturation in large mammalian species and human. The rationale to include previously described factors is that these compounds will probably be even more effective after a prematuration culture phase having induced a better cytoplasmic maturation into the oocyte.
Also economical reasons have been holding up the development of such a promising in vitro technique are that the 3 big pharma players in reproduction are selling gonadotrophins to perform classical in vitro fertilisation techniques. These companies are afraid of losing a very lucrative business by supporting the development of a technique that would use immature oocytes as a source for IVF/ICSI.
Developing IVM means also the investment to test a more prolonged and more complicated culture technique. This development goes hand in hand with media composition, however the profit margins of media companies are (very) small and there are many (5 to 6) players on this market that have to divide the clients. Furthermore there are safety aspects related to prolonged culture that might limit the enthusiasm of the developers.
At the Center for Reproductive Medicine (VUB) we are equipped to make safety testing an integral part of our project. Before the eventual transfer of embryos developed after prematuration culture to the patient we plan to evaluate frequency of aneuploidy in oocytes and embryos using fluorescent In Situ Hybridisation techniques. Gene expression in the early embryo and unfertilised oocytes, embryos and conception tissue for methylation errors at the representative imprinted genes.
The current IVM techniques have only seldom reported more than 10% implantation rate per embryo transferred, which is 2 to 3 times lower than embryos from IVF/ICSI and the abortion rate is higher (up to 30%). The pre-treatment methods for IVM will try to limit the intake of fertility hormones, avoid a whole range of minor and major complications, and will reduce the total cost of fertility treatment for the social security. The minimal invasiveness of this procedure will also benefit cancer patients in an urgent need to store their germ cells before undergoing germ cell devastating oncological treatment.
A first group to benefit of the new IVM are the PCOS patients that frequently (5% of PCOS patients) develop severe ovarian hyperstimulation, a life threatening condition. If this technique is established practically all patients would be willing doing IVM instead of IVF due to its cost-saving and gentle procedure.
The final objective of this work is to prove that by designing a differential culture system take home baby rates after IVM can approach those of conventional IVF, but with a significant cost-saving and less invasive treatment.
Date:1 Jul 2008 → 31 Aug 2011
Keywords:ICSI, fertilisation, IVM, IVF, Oocytes
Disciplines:Basic sciences, Biological sciences