How can modern technology help IVF succeed?
Scientific institutes, universities and in vitro industry leaders worldwide have attempted to optimize in vitro culture conditions by simulating conditions in the oviduct (Fallopian tube) and uterus. All these attempts to improve in vitro culture systems have focused primarily on modifying the components of media, energy or nitrogen sources and growth factors/hormone supplements. However, this type of standard static microfluidic culture system has led to only limited pregnancy success rates.
The underlying idea
In order to simulate conditions in the oviduct, mechanical stimulating factors are crucially important. They play a role that has not been a focus of previous investigations. It is known that an embryo developing naturally in vivo is exposed to constant vibrations of around 6 Hz increasing to 20 Hz when the oviductal fluid is mechanically agitated by the cilia (Paltieli et al., 1995).
Our aim was therefore to develop and design an autonomous device to imitate the natural complex movements and vibrations in the oviduct dynamically. Thus, after a long research and development phase in IVF centers, we developed Viboviduct at SimSoTec GmbH. Viboviduct’s advanced technology and high efficiency allow dynamic execution of defined vibration protocols. The device is designed and developed for use in an incubator. It withstands extreme conditions (moisture and temperatures, foreign bodies and dust, contamination with bacteria and viruses).
Natural Fertilization Steps with Viboviduct
Free calcium (CA2+) plays a crucial role in oocyte fertilisation and development. The mechanical stimulation of ciliated epithelial cells in culture induces a wave of increasing Ca2+ that spreads from the stimulated cells to neighbouring ones. In the absence of extracellular Ca2+ these mechanically stimulated cells show no change or a decrease in Ca2+, whereas Ca2+ increases in neighbouring cells. The in vitro culture of human embryos in a medium subjected to regular short intervals of mechanical agitation leads to increased development rates. This type of treatment mimics conditions in nature whereby oviductal fluid is mechanically agitated by the epithelial cilia.
Viboviduct uses microvibration with defined strength, frequency and time intervals to simulate the mechanical stimulation of the ovum in the oviduct. Use of Viboviduct can reduce or inhibit toxic substances such as free oxygen radicals and ammonia without removing useful autocrine growth factors. This is not the case when the culture medium is statically or dynamically refreshed and renewed.
The advantages of using Viboviduct 1500
Stimulates
Mechanical stimulation of embryos in surrounding culture fluid.
Amplifies
Induces and amplifies the cell to cell communication leading to a significantly better blastocyst count.
Refreshes
Reduces toxic substances in culture fluid without removing beneficial autocrine substances.
High quality embryos
Leads to a positive effect on embryo development and quality at all maturity stages.
Results
The use of Viboviduct 1500 increases live birth rate (LBR) by up to 59%. In vitro culture of embryos under microvibration conditions significantly increases live birth rates for patients aged 30 years and older. This has been shown in a recently-published article presenting data on 4303 patients treated between August 2010 and December 2014 (E. Isachenko et al. 2015).
Written informed consent was obtained from all the participating couples for the culture of pronuclear oocytes and embryos. The patients were divided into four age-groups: <29 years, 30-34 years, 35-39 years and >40 years.
Participants/materials, setting, methods: Patients with unexplained infertility underwent stimulated IVF- or ICSI-cycles.
Informed consent was obtained from 4303 patients (median age 34±4.6) for the culture of pronuclear oocytes (two per patient) under two different conditions: with mechanical agitation (20 Hz delivered over 5 seconds once every hour) (2152 patients, n = 4304) and without mechanical agitation of the culture medium (2151 patients, n = 4302). Embryo transfer (two embryos per patient) was performed on Day 3 or Day 5 after oocyte collection.
Live birth rates (LBR) were analysed by ANOVA for categorical variables using the CATMOD procedure (SAS Institute Inc., 2011).
The terms included in the model were: type of culture (vibration vs. static), age of patient donor and their interaction. Comparisons between age-groups were performed by pairwise contrasts and Bonferroni-Holm adjustment for multiple comparisons using the SAS MULTTEST procedures.
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