The document discusses the challenges and troubleshooting in IVF clinics, emphasizing the importance of quality control to prevent failures. It outlines various trouble areas such as equipment failures, human resource issues, and environmental factors that can lead to inconsistent success rates. The conclusion highlights the need for well-trained personnel, proper procedures, and systematic corrective actions to maintain high standards in IVF practices.

1. TROUBLE SHOOTING IN ART LAB (BEATING MURPHY’S LAW) Dilip Patil , Biomedical Engineer, CEO, Trivector Scientific International, dilip@ trivectorindia.net www.trivectorindia.net

2. MURPHY’S LAW If anything can go wrong, It will go wrong

3. PRIMARY GOAL OF AN IVF CLINIC Gift Infertile couples with….. The Live birth of healthy child(ren)

4. ALL IS WELL ….. TILL DISASTER STRIKES YOU! Why bother about trouble shooting? We never had any problem in our clinic We are getting one of the best success rates in our clinic, so what is this talk about quality control and improvement? If everything is working fine Why bother spending on maintenance contract and routine calibration (Let’s handle it when problem occurs!) Fear of exposure/ridicule if admitted that there is a ‘problem’ in your clinic REMEMBER : Experienced captain Smith hadn’t hit any iceberg before Titanic’s maiden voyage

5. IVF CLINIC DILEMMA Gradual Reduction in success rates Sudden Reduction in Success rates In consistency in success rates (60% success in one batch while drawing blank in next batch or vice versa!) No single factor can be attributed for a failure or improvement in results (making trouble shooting even worse!)

6. WHAT ARE THE TROUBLE AREAS? Empty follicles (Stimulation Protocols) Person to person variations pH and temperature fluctuations Plastic ware / Disposable Toxicity Equipment failures / calibration Accidents / Mix-ups Air Quality / Contamination / Vibrations Power failure Material logistic issues, Human Resources -Staff

7. HORMONE STIMULATION Patients variation (age, drug response etc.) Use of substandard (un-proven) drugs Sub-optimal stimulation protocols Batch to batch variation in drugs Patient errors : Confusion between HCG and HMG (in case of self administrations)

8. PERSON-TO-PERSON VARIATION For bigger clinics where one task is performed by multiple people: There may be inconsistency in follicle measurements Possibility of inter- and intra-operator variation in ultrasound monitoring Variation in skills for ovum-pick-up / Embryo Transfer and ICSI

9. Important parameters Basic conditions for culturing human cells : Temperature Control pH Control Osmolarity Control Sterility Control

10. CULTURE MEDIA Normally the ‘soft target’ for IVF failures Transportation and handling Problems (Break in Cold chain, Integrity of packages) Home-cooked media (No quality control) Exposure to sun-light pH /Osmolarity changes Batch-to batch variation Overuse of media from opened bottle / Use of Expired media Fungus/ contamination in media (Faulty aliquots) Non-compliance with manufacturer’s instructions for use (equilibration, bench time, centrifugation time etc)

11. DISPOSABLES Embryo Toxicity Material used (PP, PS, Rubber) Packaging size (individually pkd vs pack of many) No proper off-gassing of ETO sterilized material Breakages / particles in the dishes/tubes

12. CO2 INCUBATORS Inadequate number of Incubators Lack of Individual doors/compartment Frequent opening, loss of temperature, gases, humidity Out of sync display and actual parameters Condensation on glass door /side walls Inadequate humidification / water contamination Lack of calibration and preventive maintenance contract

13. WORKSTATIONS (LAF BENCHES) Absence of heat control / Temperature gradients Noisy operations / Vibrations Use of Non-medical grade monitors (radiation) Wooden parts Switching on/off as per convenience Blocked filters, No preventive maintenance

14. ICSI EQUIPMENT Vibrations Incorrect temperature control of sample Oil leakages, air-bubbles and lag in movement Inadequate pipette alignment skills Normally inadequate/ incorrect optical configuration Lack of regular servicing results in gradual reduction in performance

15. CRYOPRESERVATION / VITRIFICATION Shortage of Liquid Nitrogen (LN2) Lower Levels of LN2 in tank (No alarm) Spillage, Cold shocks and sudden burst of vials Depleted Oxygen level in cryo-storage room Losing samples due to improper handling / Lack of labeling and tracking (inventory) Accidental thawing of samples Wrong freezing techniques

16. ACCIDENTS AND MIX-UPS Embryology lab is like air traffic control room (ATC)- Zero tolerance for errors Accidental bump-up of embryo-dish (in busy and crowded lab) Spillage of (possibly contaminated) fluid on work benches, centrifuge and incubators Improper labeling of utensils and absence of witnessing Processing of more than one patients’ gametes at a time leading to accidental mix-ups

17. LAB ENVIRONMENT Dust particles, bacteria and other particulate matters No proper air-differentials in different rooms Excess or lower humidity Chemical Air Contaminants (CACs) and Volatile Organic Compounds (VOCs) generated from : Car fumes and neighborhood Industrial emissions Building materials, flooring adhesives, Plastic casings of equipment, like TV monitors, microscopes Compressed (impure) CO2 gases, de-gassing emissions from plastic ware (petri-dishes, tubes) Anesthetic gases, refrigerants, cleaning agents (isopropyl alcohol) Aromatic agents like after-shave lotion, perfumes, lipsticks Effects of above CACs and VOCs result in fertilization failure and delayed embryonic development to a reduction in viability and pregnancy rates

19. ELECTRICITY Power failures and unclean power is the common occurrence in most part of India Absence of on-line UPS with spike guards (inverter and generators are not appropriate) Improper wiring and earthing (leakage current damages equipment, electrical shocks) Inconvenient location of power points Too many appliances running from single power point

20. LOGISTICS ISSUES Non-availability or Delayed delivery of material when it is needed most Suppliers keeping you in dark about the transportation/delivery of material till the last moment Receipt of products in sub-optimal condition Unexpected shortage of last minute requirements, expired stock (No Inventory) No planning of requirement, underestimating the requirements

21. HUMAN RESOURCES (STAFF) Shortage of skilled man-power Lack of expertise and continual training of technical staff Attitudes, Egos, jealousy and conflicts between staff members (lack of team-work) Unreported absence of key staff member(Back-up) Attrition ( Poaching of staff by rival clinics) Sick and over-stressed staff member may not be able to concentrate on the work (Back-up)

22. BEATING MURPHY’S LAW: SUMMARY Appropriately educated and trained personnel Team work aimed at producing healthy baby Attention to details Documental control and detailed written standard procedures (SOPs, Log Books) Proper air quality, HEPA filtration, VOC Filters, Positive Air Pressure, 15-20 Air changes per hour Correct operation and calibration of all laboratory instruments on regular basis Advance Planning and Control of logistics and vital parameters of disposables and culture media Definite method for Identification and tracking of patients and their biological material Identification and correction of deviations from laboratory procedures TROUBLE SHOOTS BACK

23. ROOT CAUSE ANALYSIS - CHART Understand the problem (Impartial-No Blame game) Identify all possible contributing factors (Why? How? When) Collect data about problem by observation or experimentation Generate an Action Plan by including corrective action(s) Implement the Action Plan by taking corrective action and monitoring the process Follow-up – Assessment of the corrective actions via the monitoring process

24. THANK YOU THANK YOU