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Giles ivf


1.1 Improving air quality in ART Laboratories

Giles Palmer-ESHRE Senior Clinical Embryologist,
Director of Assisted Conception Unit,
Mitera Hospital, Athens, Greece

Air in urban areas can contain high levels of pollutants such as carbon monoxide, nitrous oxide, sulphur dioxide and heavy metals.
Indoors, construction materials, MDF, PVC flooring, paints and adhesives constitute the major source of volatile organic compounds (VOCs) leading to the phenomenon called “sick building syndrome”.
Other sources of indoor chemical hazards are cleaning fluids, floor waxes, cosmetics and cigarette smoke.

National Health and Safety Authorities recommend safe limits of VOC exposure for humans and give guidelines for building ventilation-but there is little evidence in the IVF literature of the toxicological effect of these embryos in vitro.

Pollutants can settle on work surfaces and dissolve in aqueous solutions of embryo culture medium. Embryos, lacking an immune system, cannot protect themselves against these environmental contaminants.

Cohen et al (1997) illustrated that not only high levels of aldehydes and other noxious compounds are present in the IVF laboratory (higher than outside air and the average house) but also in the incubators.
Controlling air quality in an ART laboratory has shown beneficial effects regarding fertilization and embryo development (Boone et al., 1999).

In Europe the EU directive 2004/23/EC which stipulates quality requirements when Human tissue and cell are handled (a critical point being clean air) has lead to most centers making -at the very least- slight structural changes to their IVF units.

The implementation has created problems in the IVF industry –some measures being contradictory to temperature control associated with in vitro conception procedures but do not mention reduction of damaging compounds in the air such as VOCs.

Laboratory design
If one if fortunate and can design an IVF facility from the beginning then the most important consideration should be location.  Challenges of reducing air pollution must factor into your initial design phase.

Control of the air quality may be hindered in an urban area, or units close to busy roads and car parks. Within a hospital difficulties may be encountered with working in an area adjacent to the Laundry, Sterilizing or Histology departments.

If embryo development and implantation depends so highly on its culture environment, the IVF laboratory should do well to follow the stringent regulatory standards of the food and pharmaceutical industry.

Clean room technology creates a carefully controlled sealed environment in which the number of particles and contamination is significantly minimized-achieved by highly filtered air under positive pressure being flushed through High Efficiency Particle Air (HEPA) filters.
All furniture, cleaning methods and clothing are clean room approved-orientated by the level of air quality required.

The laboratory should have smooth, non-porous walls, impervious unbroken surfaces with no difficult to clean corners and ledges, no sliding doors, sinks and drains. The lighting should be within sealed lighting units.
Partition Wall systems specially designed for clean rooms or from a non-porous material such as Corian® panels made from aluminium tri-hydrate are expensive but provide an inert, hypoallergenic, easy to clean wall surface.

Ducts and pipes can be hidden between wall panels or covered within an alcove to prevent dust accumulation.

Traditionally copper pipes have been used to transport the gas from cylinder to incubator. Copper, however is prone to oxidation and therefore inert stainless steel tubing certified for the use with medical gasses is now recommended.

The egg collection and embryo transfer when cooperation with operating theatre is required creates a challenge for maintaining clean air conditions-hermetically sealed doors and pass through windows may help these critical steps.

Changing rooms should be as clean as possible, flushed with filtered air and adjacent to the laboratory. Positive pressure in the laboratory will be easier to maintain and not require such a high velocity output if the adjoining operating theater also has sealed doors and ceiling.

Provision should be given to how bulky ART equipment will access the unit after the construction phase. A removable sealed section of wall allows not only ventilation in the final stages of building but an easy way to bring large equipment such as incubators and laminar flow cabinets into the completed laboratory space.

New equipment.
When at all possible new incubators should be “run in” in a room other than the laboratory for a certain time period to dissipate latent VOCs produced in their manufacture.
This may make the difference between a poor initial pregnancy rate or triumphant start to a new IVF unit!

How can an existing laboratory improve its air quality?
Other than install a central air handling system that includes activated carbon pre-filters and HEPA filters, several commercial mobile filter units exists which clean air quite efficiently- purifying the air of damaging volatile compounds, bacteria and moulds (Forman et al. 2004). Air is force through the device and either passed through carbon filters and/or ultra violet light for photo catalytic purification.

Compressed gas can contain harmful compounds such as benzene, isopropanol and pentane (Cohen.1997). Medical grade O2 and CO2 can be filtered before entering the incubators by gas line filters.
As high levels of VOCs have been shown to be present incubators, internal air filtering systems may be added to decrease VOC levels inside incubators themselves. (Hall et al 1998., Mayer et al 1999).

Also as anesthetic gasses use in oocytes retrieval may linger in the air a suitable extraction system may be installed in the operation theatre

Removal of wooden furniture:
To reduce VOC emissions from laboratory shelves, cupboards and tables can be replace with stainless furniture and workbenches used in pharmaceutical electronic and food industry.

Unauthorized Personnel, packaging and other materials into the laboratory should be restricted .
An air lock chamber before entering the laboratory offers both a physical barrier and acts as an “air shower” if flushed with filtered air.

Laboratory dress code
Staff can be one of the biggest contaminants in a clean environment
Clean room clothing provide maximum control against microbial and particle contamination.
Cotton hospital “greens” should be replaced by pocket-less trouser suits or two piece suits with covered wrists and neck. Made specifically for clean rooms these polyester garments act as a particle barriers which shred no fibers into the environment.

Renovation and building work
Renovating an existing laboratory can introduce a variety of compounds into the work place and emission of harmful compounds used in finishing can have an adverse effect on embryo development and pregnancy rate either temporarily or long term!

Traditionally, paints, adhesives and sealants can contain alkanes, aromatics, alcohols, aldehydes and ketones amongst others. Epoxy paints emit VOCs and take several weeks to cure and thus their use should be avoided.

When renovating an older laboratory, there are materials that can be used with less harmful chemicals: Adhesives used for floor covering are available solvent free with low VOC emissions as well as “ecological” water based paints that contain non volatile chemicals.

On site supervision is essential to assure no materials or methods are used that could jeopardize later IVF success.

Enough time to purge the room of harmful chemicals should be allocated before laboratory start up.
At least for one week room Temperature and positive air pressure should be increased dramatically aiding removal of VOCs introduced in the construction processes.

Following the above measures we renovated our Laboratory in Athens in August 2009. The laboratory premises were already fitted with Activated Carbon pre filters and HEPA and in-line filters but an upgrade to a Clean room GMP Class C (ISO class 7) was sanctified.
Completion took one month and VOC measurements of the environment using ACS badges were measured during each critical phase of reconstruction and two weeks following.
Highest VOC levels were observed in the adhesion of Corian © wall panels where acetone reached a level of 15.5 ppm.
Vinyl Glue used in the final stages of floor surfacing also indicated emissions of hazardous VOCs.
One week of purging was performed after completion. Two weeks after completion no detectable chemicals were present.

Figure 1 illustrates the VOC emissions in various phases before and after renovation

Although not statistically significant, an improvement of IVF outcome was observed after renovation of our clinic in Athens (Table 1., Fig 2).This reassures us that the reconstruction of the laboratory did not have a detrimental effect on our Assisted Conception  program and an adequate air filtration system was possibly already in place.
We are pleased, however, with our new working environment and are satisfied that we have created a better environment for the culture of oocytes and embryos.
It is up to every IVF facility to access the clean air requirements and determine if changes need to be made.


Maintaining good air quality

To maintain the clean air environment good laboratory practice must be continued. Frequent measurements air flow parameters and servicing of equipment safeguards against drop in air quality due to exhausted HEPA filters.

Positive pressure between the laboratory and adjacent rooms can be monitored by the pressure differential recorded daily to indicate filter efficiency.
Validation of air quality can be measured periodically by particle counters and VOC levels should be monitored either electronically or inexpensively with Organic chemical sensors that analyze absorbs ion levels on chromatography paper which can measure workplace exposure of toxic vapors

Agar contact plates or commercially available kits count microbial load on surfaces. The practice of bench marking for parameters such as conventional in vitro fertilization rate, embryo quality and pregnancy rates adds to your total quality management.



W.R Boone, J.E. Johnson, A. Locke, M.M. Crane, T.M. Price (1997). Control of air quality in an assisted reproductive technology laboratory.
Fertil. Steril. Vol 71 (1) pp150-154.

J. Cohen, A. Gilligan, W. Esposito, T. Schimmel, B. Dale (1997). Ambient air and its potential effects on conception in vitro.
Hum. Reprod. Vol 12 (8) pp 1742-1749.

M. Forman, V. Polanski, A. Gilligan, D. Reiger. (2004) Reduction in volatile organic compounds, adehydes, and particulate air contaminants in an IVF laboratory  by centralized
and stand alone air filtration systems
Fertil Steril Vol. 82, Suppl.2. P-535 (Abstract).

J.Hall, A. Gilligan, T. Scchimmel, M. Cecchi, J. Cohen (1998). The origin, effects and control of air pollution in laboratories for human embryo culture.
Hum. Reprod. Vol 13 (4) pp 146-155.

J.F.Mayer, F. Nehchiri, V.M Weedon et al . (1999) Prospective randomized crossover
analysis of the impact of an IVF incubator air filtration system ( Coda. Gen X) on Clinical pregnancy rates. Fertil Steril Vol. 72,  Suppl. 1. S42.