Skip to main content

Explaining How Reproductive Laboratories Work

  • Chapter
  • First Online:
Quality Management in ART Clinics

Abstract

In order to perform the procedures under their scope of activity, reproductive laboratories shall have the following (1) written instructions of how procedures are to be carried out, (2) personnel to perform procedures and routines, and (3) resources and facilities to allow procedures to be performed. The development of the laboratory procedure manual defines all aspects of work in a standardized manner. In theory, most procedures performed by RLs are fairly well standardized. These procedures have been designed to either diagnose or treat conditions which impair the reproductive potential of a given couple. In daily practice, however, there is a wide variation in the procedures adopted by different laboratories and even by different personnel working in the same facility.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Boone WR, Higdon III L, Johnson JE. Quality management issues in the assisted reproduction laboratory. J Reprod Stem Cell Biotechnol. 2010;1:30–107.

    Google Scholar 

  2. Clinical and Laboratory Standards Institute (CLSI). Laboratory documents: development and control; approved guidelines. 5th ed. Wayne, PA: CLSI document GP2-A5; 2006:1–80.

    Google Scholar 

  3. The Practice Committee of the American Society for Reproductive Medicine and the Practice Committee of the Society for Assisted Reproductive Technology. Revised guidelines for human embryology and andrology laboratories. Fertil Steril. 2008;90 Suppl 3:S45–59.

    Google Scholar 

  4. Ministry of Health. Brazilian National Agency for Sanitary Surveillance (2006). Resolução no. 33 da Diretoria Colegiada da Agência Nacional de Vigilância Sanitária (amended by RDC23 of 27 May 2011 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells). http://bvsms.saude.gov.br/bvs/saudelegis/anvisa/2011/res0023_27_05_2011.html. Accessed 14 Feb 2012.

  5. Magli MC, Abbeel EV, Lundin K, et al. Revised guidelines for good practice in IVF laboratories. Hum Reprod. 2008;23:1253–62.

    Article  PubMed  Google Scholar 

  6. College of American Pathologists. Standards for reproductive laboratories Accreditation, 2009 edition. http://www.cap.org/apps/docs/laboratory_accreditation/build/pdf/standards_repro.pdf. Accessed 20 Sep 2011.

  7. Centers for Medicare and Medicaid Services (CMS): Clinical Laboratory Improvement Act (CLIA). https://www.cms.gov/CLIA/09_CLIA_Regulations_and_Federal_Register_Documents.asp. Accessed 20 Sep 2011.

  8. Commission of the European Parliament (2006). Directive 2006/86/EC of the European Parliament and of the Council of 24 October 2006 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:294:0032:0050:EN:PDF. Accessed 4 Sep 2012.

  9. Matorras R, Mendoza R, Expósito A, et al. Influence of the time interval between embryo catheter loading and discharging on the success of IVF. Hum Reprod. 2004;19:2027–30.

    Article  PubMed  CAS  Google Scholar 

  10. Fujiwara M, Takahashi K, Izuno M, et al. Effect of micro-environment maintenance on embryo culture after in-vitro fertilization: comparison of top-load mini incubator and conventional front-load incubator. J Assist Reprod Genet. 2007;24:5–9.

    Article  PubMed  Google Scholar 

  11. Little SA, Mirkes PE. Relationship of DNA damage and embryotoxicity induced by 4-hydroperoxydechosphamine in postimplantation rat embryos. Teratology. 1990;41:223–31.

    Article  PubMed  CAS  Google Scholar 

  12. Cohen J, Gilligan A, Esposito W, et al. Ambient air and its potential effects on conception in vitro. Hum Reprod. 1997;12:1742–9.

    Article  PubMed  CAS  Google Scholar 

  13. Schimmel T, Gilligan A, Garrisi GJ, et al. Removal of volatile organic compounds from incubators used for gamete and embryo culture. Fertil Steril. 1997;67 Suppl 1:S165.

    Article  Google Scholar 

  14. Hall J, Gilligan A, Schimmel T, et al. The origin, effects and control of air pollution in laboratories used for human embryo culture. Hum Reprod. 1998;13 Suppl 4:146–55.

    Article  PubMed  Google Scholar 

  15. Mayer JF, Nehchiri F, Weedon VM, et al. Prospective randomized crossover analysis of the impact of an incubator air filtration on IVF outcomes. Fertil Steril. 1999;72 Suppl 1:S42.

    Google Scholar 

  16. Racowsky C, Nureddin A, de los Santos MJ, et al. Carbon-activated air filtration results in reduced spontaneous abortion rates following IVF. Proceedings of the 11th World Congress on In Vitro Fertilization and Human Reproductive Genetics. Sydney, Australia, 1999.

    Google Scholar 

  17. Boone WR, Johnson JE, Locke A-J, et al. Control of air quality in an assisted reproductive technology laboratory. Fertil Steril. 1999;71:150–4.

    Article  PubMed  CAS  Google Scholar 

  18. Worrilow KC, Huynh HT, Bower JB, et al. A retrospective analysis: seasonal decline in implantation rates (IR) and its correlation with increased levels of volatile organic compounds (VOC). Fertil Steril. 2002;78 Suppl 1:S39.

    Article  Google Scholar 

  19. Worrilow KC, Huynh HT, Peters AJ. The innovative marriage between cleanroom and assisted reproductive technologies (ART) – the design, construction and National Environmental Balancing Bureau (NEBB) Certification of a prototype class 100/class 10 IVF laboratory cleanroom. Fertil Steril. 2000;74 Suppl 1:S103.

    Article  Google Scholar 

  20. Esteves SC, Gomes AP, Verza Jr S. Control of air pollution in assisted reproductive technology laboratory and adjacent areas improves embryo formation, cleavage and pregnancy rates and decreases abortion rate: comparison between a class 100 (ISO 5) and a class 1000 (ISO 6) cleanroom for micromanipulation and embryo culture. Fertil Steril. 2004;82 Suppl 2:S259–60.

    Article  Google Scholar 

  21. Von Wyl S, Bersinger NA. Air quality in the IVF laboratory: results and survey. J Assist Reprod Genet. 2004;21:283–4.

    Article  Google Scholar 

  22. Esteves SC, Verza Jr S, Gomes AP. Comparison between international standard organization (ISO) type 5 and type 6 cleanrooms combined with volatile organic compounds filtration system for micromanipulation and embryo culture in severe male factor infertility. Fertil Steril. 2006;86 Suppl 2:S353–4.

    Article  Google Scholar 

  23. Knaggs P, Birch D, Drury S, et al. Full compliance with the EU directive air quality standards does not compromise IVF outcome. Hum Reprod. 2007;22 Suppl 1:i164–5.

    Google Scholar 

  24. Kastrop P. Quality management in the ART laboratory. Reprod Biomed Online. 2003;7:691–4.

    Article  PubMed  Google Scholar 

  25. Mortimer D. A critical assessment of the impact of the European Union Tissues and Cells Directive (2004) on laboratory practices in assisted conception. Reprod Biomed Online. 2005;11:162–76.

    Article  PubMed  Google Scholar 

  26. Hartshorne GM. Challenges of the EU ‘tissues and cells’ directive. Reprod Biomed Online. 2005;11:404–7.

    Article  PubMed  Google Scholar 

  27. Esteves SC. Sala Limpa - Classe 100/ISO 5 - Condição “sine qua non” nos laborátórios de reprodução assistida? Arquivos H Ellis. 2007;3:6–17.

    Google Scholar 

  28. Kao YK, Higdom III HL, Gravis-Herring JE, et al. Where do mouse embryos thrive best? Comparison of mammalian embryo development under varying laboratory environments. J S C Acad Sci. 2009;7:29–30.

    Google Scholar 

  29. United States Food and Drug Administration [homepage on the internet]. Code of Federal regulations title 21, volume 8 (21CFR1271.195) on human cells, tissues, and cellular and tissue-based products. [Revised 1 Apr 2011]. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=1271.195. Accessed 1 Mar 2012.

  30. Commission of the European Union Communities (2000). Communication from the Commission on the precautionary principle. http://eur-lex.europa.eu/smartapi/cgi/sga_doc?smartapi!celexplus!prod!DocNumber&lg=en&type_doc=COMfinal&an_doc=2000&nu_doc=1. Accessed 14 Feb 2012.

  31. International Organization for Standardization (1999). ISO 14644-1:1999 on cleanrooms and associated controlled environments. Institute of Environmental Sciences and Technology (IEST), Arlington Heights, Illinois, USA. http://www.iso.org/iso/iso_catalogue/catalogue_tc/catalogue_detail.htm?csnumber=25052. Accessed 14 Feb 2012.

  32. National Environmental Balancing Bureau. Procedural Standards for Certified Testing of Cleanrooms, Vienna, Virginia. 1998. http://ww.nebb.org. Accessed 2 Mar 2012.

  33. Bernstein JA, Levin L, Crandall MS, et al. A pilot study to investigate the effects of combined dehumidification and HEPA filtration on dew point and airborne mold spore counts in day care centers. Indoor Air. 2005;15:402–7.

    Article  PubMed  CAS  Google Scholar 

  34. Code of Federal Regulations, 40: Chapter 1, Subchapter C, Part 51, Subpart F, 51100. http://cfr.vlex.com/vid/19784887, and EPA’s Terms of Environment: Glossary, Abbreviations, and Acronyms. http://www.epa.gov/OCEPterms/vterms.html. Accessed 27 Sep 2011.

  35. Anderson K, Bakke JV, Bjorseth O, et al. TVOC and health in non-industrial indoor environments. Indoor Air. 1997;7:78–91.

    Article  Google Scholar 

  36. Richardson ME, Bernard RS, Hann BR, et al. Investigation into complaints of in vitro embryo mortality due to toxic embryo culture room conditions. Bull S C Acad Sci. 1996;58:134–5.

    Google Scholar 

  37. Gong Y, Dubin NH. Effect of felt-tip marking pens on mouse embryo growth. Fertil Steril. 1998;70 Suppl 1:S492–3.

    Google Scholar 

  38. Balaban B, Urman B. Embryo culture as a diagnostic tool. Reprod Biomed Online. 2003;9:671–82.

    Article  Google Scholar 

  39. Milholland D. A review of “IES-RP-CCOO6.2 Testing Cleanrooms.” Proceedings of Clean Rooms ’94 East; 1994 Mar 14–17; Philadelphia. Flemington, NJ: Witter Publishing; 1994:203–218.

    Google Scholar 

  40. Martinez-Hurtado JL, Davidson CAB, Blyth J, et al. Holographic detection of hydrocarbon gases and other volatile organic compounds. Langmuir. 2010;26:15694–9.

    Article  PubMed  CAS  Google Scholar 

  41. Esteves SC, Couto M. Classificação ISO 5 em laboratório de fertilização in vitro. Rev Soc Bras Contr Contam. 2005;20:8–10.

    Google Scholar 

  42. Esteves SC, Schneider DT. Male infertility and assisted reproductive technology: lessons from the IVF. Open Reprod Sci J. 2011;3:138–53.

    Article  Google Scholar 

  43. World Health Organization. Laboratory biosafety manual, 3rd ed. Geneva, World Health Organization. http://whqlibdoc.who.int/publications/2004/9241546506.pdf. Accessed 11 Oct 2011.

  44. United States Pharmacopeia [homepage on the internet]. Chapter 85: Bacterial endotoxin test (2005). http://iccvam.niehs.nih.gov/docs/pyrogen/regulatory/28USP85.pdf. Accessed 11 Oct 2011.

  45. Gould M. Bacterial endotoxins in serum. Art to science in tissue culture, vol. 4. Logan, UT: HyClone laboratories Inc.; 1995. p. 3–4.

    Google Scholar 

  46. Clarke RN, Griffin PM, Biggers JD. Screening of maternal sera using a mouse embryo culture assay is not predictive of human embryo development or IVF outcome. J Assist Reprod Genet. 1995;12:20–5.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sandro Esteves M.D., Ph.D. .

Editor information

Editors and Affiliations

Appendix. Equipment, Supplies, and Reagents Commonly Used in Clinical Reproductive Laboratories

Appendix. Equipment, Supplies, and Reagents Commonly Used in Clinical Reproductive Laboratories

 

Andrology lab

Embryology lab

Cryopreservation and storage

Equipment

Phase-contrast microscopes with 10×, 20×, 40× objectives

Optical microscope with 100× objective

Cell counters (single and multiple channel)

Counting chambers

Humidified chamber

Centrifuges (with adjustable speed and time)

Refrigerator and freezer

Vortex mixer

Aliquot mixer

Plate shaker

Automatic pipettors (rechargeable)

Air-displacement micropipettes with different ranges

Analytical balance

Warm and hot plates

Water baths

pH meter

Spectrophotometer

Luminometer

Flow cytometer

Fluorescence microscope

Absorbance microplate reader

Thermometers

Incubator

Laminar flow cabinet

Workstations for micromanipulation and gametes/embryo handling

Inverted phase-contrast microscope with 10×, 20×, 40× objectives

Stereomicroscopes

Warm stages

Tube heaters

CO2 Incubators

Electrohydraulic micromanipulators

Laser system for embryo biopsy/hatching

Refrigerator and freezer

Centrifuge

Thermometers

Automatic pipettors (rechargeable)

Air-displacement micropipettes with different ranges (5–500 μL)

pH meter

Incubator carbon dioxide measurement device

Laminar flow cabinet or cleanroom environment

Software for image capture and recording

Data loggers

Monitoring and alarm notification system

Automated-cryopreservation system

Aliquot mixer

Cryovials barcode identification system and reader

Cryovial sealing device

Liquid nitrogen containers

Liquid nitrogen container alarm system

Oxygen monitor

Thermometers

Supplies

Sterile semen specimen containers (tested against sperm toxicity)

Graduated serological pipettes (1–10 ml)

Test tube racks

Polystyrene graduated centrifuge tubes

Glass microscope slides and coverslips

pH paper

Filter paper

Transfer pipettes (Pasteur pipettes)

Microcentrifuge tubes

Micropipette tips

Marker Pen

Nontoxic powder-free latex gloves

Protective eye glasses

Glassware (beaker, Erlenmeyer flasks, glass funnels)

Catheters for intrauterine insemination

Graduated serological pipettes (1–10 ml)

Culture dishes and flasks

Syringes and syringe filter units

Test tube racks

Polystyrene centrifuge tubes

Transfer pipettes (Pasteur pipettes)

Micropipettes tips

Micromanipulation pipettes

Denuding pipette and tips

Catheters for embryo transfer

Sterile wipes

Laboratory cryomarkers (nontoxic)

Sterile nontoxic powder-free gloves

Plastic cryosleeves

Cryovials

Cryocanes

Laboratory cryomarkers (nontoxic)

Liquid nitrogen

Cryogloves

Protective eye glasses

Reagents

Immersion oil

Tyrode’s salt solution

Modified human tubal fluid medium

Phosphate buffered saline solution 1×

Stain for sperm morphology

Eosin Y and nigrosin stains

Peroxidase staining

Ethanol, 96%

Benzidine

3% H2O2

Sodium citrate

d-fructose

Distilled and deionized water

Resorcinol

Concentrated HCl

Bovine and human serum albumin

Immunobead rabbit anti-human Ig (H & L) reagent

IgA, IgG, IgM immunobeads

Dimethyl sulfoxide (DMSO)

Luminol (5-amino-2,3 dehydro-1,4 phthalazinedione)

Aluminum foil

Oxidative stress assay kit

Commercial kit for DNA integrity testing

Isopropyl alcohol 70%

Sterile wipes

Lower and upper phase colloidal gradient

Sperm wash media

Culture media

Mineral oil

Human serum albumin or synthetic serum substitute

Sperm wash media

Rinsing media

Polyvynilpirrolidone

Hyaluronidase

Embryo biopsy media, microscope slides and fixatives

Sterile distilled water

Isopropyl alcohol 70%

Freezing media

Thawing media

  1. Vary according to the scope of activities, procedures, and protocols

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Esteves, S., Agarwal, A. (2013). Explaining How Reproductive Laboratories Work. In: Bento, F., Esteves, S., Agarwal, A. (eds) Quality Management in ART Clinics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7139-5_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-7139-5_9

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-7138-8

  • Online ISBN: 978-1-4419-7139-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics