IVF laboratory Design

kosmogonia hellas

“ Your IVF program is only as good as the lab which supports it “

1. Air Quality in ART laboratory

2. Laboratory design

3. Quality Control in ART laboratory

Kosmogonia IVF services:

Consultation and SupportDesign and Operation of IVF laboratoriesFully Trained Staff

Giles Palmer www.kosmogonia.gr

1. Air Quality in ART laboratory

• 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.

• 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.

Products used in Home and work

Possible VOCs

Petroleum distillates: Paint thinner, oil-based paints, liquid insect pest products, furniture polishes

BTEX (benzene, toluene, ethylbenzene), hexane, cyclohexane, 1,2,4-trimeyhylbenzene

Personal care products: nail polish & remover, colognes, hair spray

Acetone, ethyl alcohol, isopropyl alcohol, methacrylates, ethyl acetate

Fabric cleaners: Dry cleaned clothes, stain removers, leather cleaners

Tetrachloroethene, perchloroethene, trichloroethene

Adhesives: PVC cement, contact cement, model cement

Tetrahydrofuran, cyclohexane, methyl ethyl ketone, toluene, acetone, hexane, 1,1,1-trichloroethane

Refrigerant: air conditioners, freezers, dehumidifiers

Freons (trichlorofluoromethane, dichlorodimethane)

Air fresheners: Moth balls, deoderizers, 1,4-dichlorobenzene, naphthalene

Furniture: Upholstered furniture, carpets,plywood, pressed wood products

Formaldehyde

• National Health and Safety Authorities -safe limits of VOC exposure for humans/ 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.

• Laboratory design -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.

Regulations

• EU Directive 2004/23/EC: Setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells-

-to be implemented in all member countries.

• Greek law 2008: ΠΔ 26/2008 εναρμόνιση προς την οδηγίας 2004/23/ΕΚ.

• Greek National Authority:Terms and Conditions of licensing Assisted Reproduction Units.

• -awaiting final approval.

Air quality effect on embryos

• Ambient air and its potential effects on conception in vivo.

Cohen Hum. Repro 12.8. (1997)

Scientific Publications

• Revised Guidelines for Human Embryology and Andrology Laboratories.Fertil.Steril 82.6. (2004)

• Revised Guidelines for good practice in IVF laboratories.

Hum. Repro 23.6.(2008)

Air Quality and Regulations

Max. permitted number of particles per m3 equal to or greater than the tabulated size

At rest In operation

Grade 0.5μm 5 μm 0.5μm 5 μm

A 3 520(5)

20 3 520(5)

20

B 3 520(5)

29 352 000(7)

2 900

C 352 000 (7) 2 900 3 520 000(8)

29 000

D 3 520 000 29 000 Not defined

Updated 2008, EU GMP Annex 1-Manufacture of Sterile Medical Products

Cleanroom classification

ISO classification

Clean Room

• Construction with non-volatile chemicals

• Class C clothing• Microbial counts

Clean Room

• HEPA filters• Airlock, secure entry• Positive pressure• Stainless steel furniture,

smooth, non-porous walls

• Constant temperature• Constant UPS

Laboratory dress code

• Bunny suit • Class C • Scrubs

Paints & Adhesives• Water based paint: formulated

with low VOC potential.

• NO EPOXY PAINTS

• No paints containing: formaldehyde, acetaldehyde,

isocynates, reactive amines, phenols and other water soluble volatile organics.

• Purge room: ↑ ْ C by 10-20 ْ C + ↑ Ventilation = aids removal of VOC

• Lights turned on 10 days.

Paints & Adhesives

• Benjamin Moore Paints

• Thomsit Adhesives

• Corian

• Lindner

• Knauf Tiles

Renovation of 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! ”

• Removal of wooden furniture: replace with stainless furniture and workbenches used in pharmaceutical electronic and food industry.

• Avoid: alkanes, aromatics, alcohols, aldehydes and ketones.

• Adhesives/Vinyl Glue used for floor covering are available solvent free with low VOC emissions.

Renovation of Laboratory

• No difficult to clean corners and ledges, no sliding doors, sinks and drains. Lighting should be within sealed lighting units.

• Partition Wall systems/ non-porous material such as Corian® panels -expensive but provide inert, hypoallergenic,

• Ducts/ pipes can be hidden between wall panels or covered. Sealed doors and pass through windows may help these critical steps.

• Avoid copper-inert stainless steel tubing certified for the use with medical gasses is now recommended.

• Changing rooms-clean as possible,flushed with filtered air/ adjacent to lab.

• Positive pressure- easier to maintain and not less velocity if the adjoining operating theater also has sealed doors and ceiling.

• New equipment-should be “run in” 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!

Unseen Dangers• Compressed gas can contain

harmful compounds such as benzene, isopropanol and pentane (Cohen.1997).

• As high levels of VOCs have been shown to be present incubators, (Hall et al 1998., Mayer et al 1999).

• Anesthetic gasses use in oocytes retrieval- linger in the air.

• Mobile units Coda/ Zander.

On site supervision is essential

Chemicals detected in laboratory renovation (Athens 2009)

*

*

00,5

11,5

22,5

33,5

4

* >4 ppm(15,5ppm)

ppm

Chemicals detected in laboratory renovation

ethyl alcoholacetonemethyl metacrylichexanetoluene

IVF Outcome• Improvement of IVF outcome-

after renovation of our clinic in Athens.

• Reassurance -reconstruction of did not have a detrimental effect!

• Adequate air filtration system was possibly already in place?

• New working environment -satisfaction / better environment for the culture of oocytes and embryos.

• Every IVF facility- access the clean air requirements/determine if changes need to be made.

IVF Outcome before and after renovation of laboratory

0%

10%

20%

30%

40%

50%

60%

70%

Positive βHCGClinical Pregnancy rateImplantation rate

Maintaining good air quality good laboratory practice

• measurement of air flow parameters, servicing of equipment, exhaustion HEPA filters.

• Positive pressure between the laboratory/adjacent rooms monitored by the pressure differential recorded daily to indicate filter efficiency.

• Bench marking for parameters such as conventional in vitro fertilization rate, embryo quality and pregnancy rates: total quality management.

1AB

2BB

4BB

Maintaining good air quality Particle Monitors & VOC counters

1AB

2BB

4BB

Maintaining good air quality Environmental Monitoring

Monitoring techniques

A - Air Sampling:, • Settle Plates • Air Sampler

B - Surface Sampling: • Contact Plates• Glove Prints

1AB

2BB

4BB

Embryologists

Εμβρυολόγοι του ΜΗΤΕΡΑ IVF

Palmer Giles Κουρή Aγγιολίνα

Mαζοκοπάκη KατερίναΜποτζάκη ΜητροδώραΠαπανίκου Χαρά

Παπαδοπουλος ΔημητριοςΣιαλακούμα Aφροδίτη

Bibliography

• 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