Page 21 - Focus on reproduction january 2016

ovaries (PCO-like ovaries and women with PCOS) are the best candidates for IVM. They yield sufficiently high numbers of immature oocytes to compensate for the inherently lower efficiency of IVM compared to standard IVF.5 Serum concentration of AMH, a biomarker which correlates well with the severity of the PCOS phenotype, is a strong predictor of the number of immature oocytes retrieved by follicle aspiration, and, by proxy of oocyte number, AMH correlates with the probability of pregnancy after IVM.5
There may be a learning curve for egg collections from small antral follicles, and closed-circuit needle flushing systems have been developed to avoid blood clots in the aspirated follicular fluid, although the optimal technique of immature oocyte collection from antral follicles requires further study.6
What’s driving IVM today?
However, despite its lower efficiency than standard IVF, a number of fertility clinics have continued to use IVM for several years, for a variety of reasons - to avoid OHSS, to circumvent local regulations on the number of oocytes that could be fertilised in vitro, and to reduce costs related to gonadotrophins. And even though OHSS has almost become extinct after the introduction of GnRH agonist triggering and elective embryo cryopreservation, interest in IVM as a minimal-burden alternative has not disappeared. A number of key developments can be identified as major drivers of this interest:
1. Favourable clinical outcomes
Athough the patient series are small, live birth rates of 40% and higher in patients with polycystic ovaries have been reported from Western Australia.7 Key elements contributing to the success of this non-hCG triggered IVM protocol include FSH priming and blastocyst culture. However, in comparison with conventional IVF, IVM has not been able to generate an equal amount of blastocysts, although the implantation rate per embryo appears similar in both approaches. One could therefore state that IVM is a less wasteful system in terms of embryo production
MICHEL DE VOS: ‘A LACK OF INCENTIVE TO DEVELOP ALTERNATIVE METHODS TO ART HAS BEEN ONE MAJOR IMPEDIMENT TO THE PROGRESS OF IVM.
than conventional ART.
We launched an IVM programmme at our centre in
Brussels in 2010. It was embedded within a research project aimed at improving IVM outcomes through modification of the clinical approach and culture system. Our initial results in patients with polycystic ovaries were disappointing, but, contrary to what happened in a number of pioneering IVM centres, we did not abandon the programme. First, we learnt that transfer of warmed IVM embryos after vitrification three days after ICSI performed better than fresh embryo transfer. Second, we reduced the IVM incubation period from 40 to 30 hours and applied extended embryo culture to the blastocyst stage in a subset of patients. By doing so, consistently good clinical outcomes were obtained, comparable with those published by the Australian group. Nevertheless, sufficiently powered clinical trials investigating the true potential of current IVM systems compared with conventional IVF are still lacking.
2. Reassuring safety scores of IVM systems
At both a cytogenetic and epigenetic level, in vitro matured oocytes and embryos generated after IVM do not carry more chromosomal or methylation defects.8 Data from these studies mitigate concerns with efficiency and safety of IVM technology (as proposed by the ASRM and SART), although follow-up of children born after IVM remains mandatory.9 Previous studies had shown abnormal methylation in oocytes after IVM, but the immature oocytes used in these studies were derived from conventional IVF cycles and had failed to complete meiosis after an ovulation trigger. There is now compelling evidence that attempts to ‘rescue’ these immature oocytes are not recommended, as they have a high prevalence of DNA damage, and embryonic development is grossly compromised.10
3. In fertility preservation for cancer patients
Immature oocytes can be obtained from antral follicles in the follicular and luteal phase of the cycle when there is not enough time to stimulate the ovaries and harvest mature oocytes. Oocytes can even be retrieved from extracorporeal ovarian tissue, matured in vitro,
Current clinical protocol of IVM in Brussels.
JANUARY 2016 // Focus on Reproduction 21