ASPIRE Guidelines for Assisted Reproductive Technology (ART) Laboratory Practice in Low and Medium Resource Settings

INTRODUCTION

Gaps in access to fertility care exist in nearly all health care settings but are particularly present in many countries of the Asia Pacific region. A crude measure of this access gap may be obtained from analysis of the number of IVF cycles per head of population (Chambers et al., 2021). Countries with high access gap are often called low or low medium resource settings. The prevalence of infertility appears similar across all regions though data are not available from some countries of the Asia Pacific region. (Mascarenhas et al., 2012) Healthcare resources are often referred to as the means available in a health system to deliver services to the population and when the health system does not meet the accepted norms of other global settings the system can be called a low-resource setting for health care (Lahariya, 2013). Access gap may be present when fully stimulated IVF cycles per million of population are below the global average, and where the measure is very much lower than global average high, access gap may exist. Factors which contribute to access gap in health care include financial shortage, paucity of knowledge, underdeveloped infrastructure, restricted social resources (tangible and intangible), influence of cultural and religious beliefs and practices, human resource limitations, suboptimal healthcare service delivery, geographical and environmental factors and research challenges. (Van et al., 2021). Use of telehealth will play a useful part in reducing access gaps (Mikhael et al., 2021).

Enabling access to fertility treatments in areas of reduced provision of care is complex and will take years of sustained effort in many cases. Expectations of care should legitimately be set at the same level as seen in high resource settings and this should be the ultimate goal. However, in the rehabilitative phase compromise may be acceptable in some settings and the goal of these guidelines, a collaboration of experts in the various disciplines and with wider consultation of the ASPIRE membership, is to set the minimum standards of an ART unit in a low resource setting.

The purpose of these guidelines is also to give easy access to existing guidelines within ASPIRE member countries and those of other regions for example, ASRM, ESHRE, RTAC, Alpha Scientists in Reproduction (Istanbul, Vienna, ALPHA, ISAR and Cairo Consensus) and these are provided in the Further Reading section at the end of this document. Underpinning this document are several guidelines on universal precautions, patient confidentiality, and good laboratory practice and these are also provided.

ASPIRE has developed these guidelines to provide clinical recommendations to improve the Standards of care within the APAC region. These guidelines represent the views of ASPIRE, which were achieved after careful consideration of available scientific evidence at the time of preparation (2022–2023). The aim of clinical practice guidelines is to aid healthcare professionals in everyday clinical decisions about appropriate and effective care of their patients. However, adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not override the healthcare professional’s clinical judgment in diagnosis and treatment of particular patients. Ultimately, healthcare professionals must make their own clinical decisions on a case-by-case basis, using their clinical judgment, evidence available, and expertise, and considering the condition, circumstances, and wishes of the individual patient, in consultation with that patient and/or the guardian. ASPIRE makes no warranty, expressed or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. ASPIRE shall not be liable for direct, indirect, special, incidental, or consequential damages related to the use of the information contained herein. While ASPIRE makes every effort to compile accurate information and to keep it up-to-date, it cannot, however, guarantee the correctness, completeness, and accuracy of the guidelines in every respect. In any event, these clinical practice guidelines do not necessarily represent the views of all clinicians that are members of ASPIRE. The information provided in this document does not constitute business, medical or other professional advice, and is subject to change from time to time with the availability of newer evidence.

FACILITIES AND EQUIPMENT REQUIREMENTS FOR ESTABLISHING AN ASSISTED REPRODUCTION UNIT

Quick summary/at a glance

Objectives

An ART clinic should be designed to facilitate workflow of the Centre and consider both laboratory and clinical perspectives. Compliance with national or regulatory guidelines is required. A basic ART lab design should provide a safe and clean environment for biomaterials and for laboratory personnel.

Recommendations in regular practice for minimum standard of care

Facility

Floor plan design

The ART clinic and laboratory should be in a safe structure that complies to local building regulations.

Equipment

Consumables

Consumables should be sterile and tested for human culture purpose. If not tested for human grade, bioassay such as sperm survival test should be applied to minimize cytotoxicity to human gametes.

IVF laboratory basic design

Building materials

Gas delivery system for CO₂, N₂ and Tri-Gas incubators

Power supply

Sockets should be sufficient for all the essential electronic equipment present in the laboratory. A back up UPS or generator is strongly suggested to ensure undisrupted power supply for all the critical equipment in the embryology lab such as ICSI machine for an appropriate amount of time. For areas with unstable power supply, a generator for backup power supply (diesel) is essential be isolated for the ART lab (Bai et al., 2020).

Environmental control (air quality, temperature, humidity, and light)

ART laboratory should be equipped with independent heating, gas phase filtration, ventilation, and air conditioning (HVAC) to control the air changes (∼15 times/hour, 20% fresh air), temperature (20–24^∘C) and humidity (40–60%). Air handling unit with HEPA filtration system should be installed to maintain positive pressure ($>+30$$$Pa) in the laboratory and control the particle counts (preferably less than $<10,000$ particles larger than 0.5$$$\mu$m to 10$$$\mu$m per cubic foot of air) and micro-organisms in the air less than 5 colony-forming units/90$$mm petri dish in passive sampling method to control. The light source in ART lab should be dimmable to minimize light exposure to oocytes and embryos (ESHRE, 2015).

Ideally, HVAC system should have potassium permanganate/alumina filter in addition carbon filter to control VOC.

Equipment for gamete/embryo manipulation and culture

General Requirements

The type and number of devices should be appropriate to the workload and backup units of mission-critical equipment should be considered (e.g., micromanipulators, microscopes, laminar flow cabinets, incubators, refrigerators, freezers, LN₂ tanks, etc.).

The availability of backup equipment in case one particular unit fails should be taken into account.

Equipment location

For optimal efficiency of laboratory operations, equipment location must be carefully planned for safety and ideal workflow in each working area.

Equipment

Refer to section 1.3.b

Maintenance

Systems

Medical records system

Witnessing system

Alarm systems

STAFFING IN THE IVF LABORATORY

Quick summary/at-a-glance

Objectives

Complex Techniques including ICSI and PGT, requirements in risk management e.g., patient consent, double witnessing, as well as frequent communications with the clinical team and patients generate a high amount of workload to the laboratory staff. At the time of writing these guidelines, there is no established guidance with an overview on staffing in the embryology laboratory in ASPIRE membership countries.

In this section, we have established recommendations on staffing suitable for various laboratory settings.

Recommendations for minimum standard of care

Staff educational and experience requirements

Table 2 Lists a description of an embryologist and the appropriate minimum educational and skill levels to be adopted universally in the APAC region. Each ASPIRE member association or organization shall determine the eligible relevant majors for each category of laboratory profession. This may be influenced by each country’s government regulations and requirements.

Role and responsibilities of laboratory leadership and staff

The laboratory is directed and supervised by an experienced scientist or medical doctor who has sufficient knowledge in IVF laboratory techniques and management, and complies with national legislation or regulation applicable to the location of the laboratory. The director ensures an adequate number of staff to safely undertake the laboratory workload. All new staff are given comprehensive initial training, and staff are evaluated for competency annually. Continuing professional education in interactive settings is recommended for all laboratory personnel, even if not mandated by the national rules. Besides the duties and responsibilities outlined in this section, the laboratory should have an organizational chart, and written procedure describing the responsibility of each individual laboratory staff, and line of responsibilities and reporting, with sections including but not limited to hands-on techniques, administration, training, quality management including start-up and shutdown checklists, negative outcome handling and basic troubleshooting, and communication.

Recommended minimum number of embryologists based on workload

Each lab should factor in the workload of all lab procedures, paperwork and other areas contributing to the complexity of IVF laboratory, to determine an adequate number of staff. To avoid work burnout, key considerations should include sufficient staffing for witnessing procedures, individual performance, teamwork, leave cover, and staff wellness. Staff numbers are often calculated in full-time equivalent (FTE). Part-time and managerial staff should be calculated by their actual hands-on percentage, e.g., a lab director/supervisor with 50% hands-on duties should only count as 0.5 FTE.

While it is difficult to precisely estimate each laboratory’s FTE needs, we propose a simplified “cycle point” system, taking into consideration the major IVF laboratory procedures, for a recommended minimum number of embryologists. Each fresh conventional insemination IVF cycle or oocyte cryopreservation equals 1.0 cycle point. Each FET is 0.5 point. For fresh cycles, each ICSI case adds 0.1 point and PGT case adds 0.5 point of weight to the cycle. Note: Andrology and endocrine testing tasks are not included in this calculation.

The recommended minimum numbers of embryologist in the IVF laboratory are listed as below, with clinics having regular settings with sufficient resources, and with low resources setting performing treatment cycles in batches or utilizing part time external sources. (Table 3) (Yamada et al., 2022).

QUALITY MANAGEMENT IN THE IVF LABORATORY

Quick summary/at-a-glance

Background and specific objectives

Successful ART programs depend on the controlled conditions in every aspect of the treatment. The QMS involves a system whereby all levels of an organization are committed to ongoing quality improvement. This includes administration, patient management, laboratory procedures and reporting.

Although there are several documents providing guidance on QMS for the embryology laboratory in some ASPIRE membership countries, the guidance does not exist in some countries. There are needs of uniformed guidance to be utilized by clinics in the APAC region.

Recommendations minimum standard of care

Quality manual

The QMS must be documented in a quality manual. The manual should at least include the organizational structure, management, personnel, equipment, and consumables, buildings and facilities, traceability of all samples, documentation under document control, records, and review of outcomes and should be systematically reviewed annually. QMS should include the format and process of audit, e.g., frequency and schedule, audit team consisting of clinicians, embryologists, and administrators. (ASRM and SRBT, 2022; ESHRE, 2015; Mortimer et al., 2015)

Written, authorized, signed, and up-to-date SOPs should exist to optimize outcomes. SOPs should include daily quality control methods for all procedures performed in the lab. All new protocols should be validated by parallel testing prior to clinical implementation.

Organizational structure

A clear organizational structure showing lines of accountability and reporting should be presented. It is not necessary to have a separate individual for each position. In a small organization, an individual can have multiple roles. (Elder et al., 2015; ESHRE, 2015; Mortimer et al., 2015)

Management

The responsibility of management is to measure the effectiveness of the ART programs. Good management optimizes the provision of services according to the available resources. (ASRM and SRBT, 2022)

Personnel

The transparent procedures for the staff recruitment should be established. Each position should have a clear description on duties and authorization of tasks to be performed. There should be annual evaluation of performance, maintenance of record of competencies, achievements, and continuous education (ASRM and SRBT, 2022; ESHRE, 2015).

Equipment and consumables

All details of the equipment and consumables were listed in a separate section of this guideline (refer to 1.3.b) and this equipment should be fit for this purpose. It is preferred the all equipment is externally validated through third party service providers. After clinical use for a specified period, each piece of equipment should be monitored for performance, interval service maintenance, and calibration. All equipment should have a back-up plan in the event of failure, and critical equipment be supported with either an UPS or emergency generator. All consumables should be accompanied by a Certificate of Analysis, expiration dates and lot numbers of all reagents and media and should also be MEA tested by the manufacturer.

Buildings and facilities

Maintenance of buildings and facilities are important to avoid introduction of contaminants and to provide a safe environment for both embryos and staff. Annual maintenance of the HVAC system and any controlled environmental chambers as well as annual testing of air quality, is required. Annual general maintenance is also required to prevent natural wear and tear, mould, and insect infestation prevention. All facilities should have emergency evacuation plans under extreme conditions such as earthquakes, fire, flooding, volcanic activity, and war. (ASRM and SRBT, 2022; ESHRE, 2015)

Samples traceability

All samples entering the ART process must have maintenance of traceability. The following three strategies address the requirements :

Documentation

Within the organization, there will be well over a hundred documents involving information given to patients, quality manual, clinical, nursing, counselling, administration, laboratory procedures and consent forms. These documents are continually updated to reflect the quality management cycle.

The document control system with a hierarchy of authorization needs to be established to update and re-issued the documents with a serial number. A simple protocol such as only printing a document as required and no ‘stock’ of copies could help to ensure that the correct version of the document is handled. Document control with time-stamp on revision and/or locked for editing is recommended (ASRM, 2021; ASRM and SRBT, 2022).

Records

The QMS requires the storage of procedure records. Medical records have defined retention period depending on national legislation. All records must have traceability on the outcomes, and the procedure down to a particular batch or lot number for critical equipment and consumables. Records can be stored electronically provided there is a appropriate on-site and off-site backup of the data (ASRM, 2021).

Data should include :

Review

All aspects of a QMS should be reviewed regularly, preferably using a quantitative system such as KPI regularly. The ESHRE and Alpha scientists in Reproductive Medicine published the Vienna consensus that provide the competency and benchmark value for KPIs which the laboratory can used as external benchmarks.

However, the organization itself is responsible for the KPIs they choose to use in the various important areas of the clinics such as :

DOCUMENT CONTROL AND CONSENT

Quick summary/at a glance

Background and specific objectives

QMS and associated processes require an institution to “maintain a set of procedures, policies, and rules that are essential to support the functioning of processes and also to ensure confidence that the processes are being executed as intended” (ESHRE, 2017).

Document control is a system that ensures only relevant policies, forms, and procedures are being used and ensure that records of approval and review by the laboratory director are being maintained. This is usually achieved using a control log containing all procedures, forms, and policies with the respective location. A defined process is necessary to make sure that all personnel have proper knowledge about the respective procedures and policies.

The safety aspect and success in an ART program are highly important and only a well-executed TQMS can help in achieving this.

Recommendations for minimum standard of care

Standard operating procedures (SOPs)

The first step in TQMS is to have SOPs in place. SOP is a document that enables uniformity in practice. Errors and risks are minimized when operating procedures are standardized. The SOPs must be developed in a standardized format. SOPs must be modeled, based on scientific evidence and must be updated regularly. A printed copy of SOPs should be accessible to the authorized staff of the IVF center. An electronic copy should be maintained with password protection which ensures the safeguarding of the organization’s intellectual property.

Procedures and process maps

Every process must be mapped using the flowchart method. The process map lists the descriptions of procedures, how they should be undertaken and indicates the expected outcome (performance indicators). Documenting every step as described in the process map is essential and this is the first step in troubleshooting in any clinic.

Documentation/data capturing

Documented information must be maintained by the organization in order to provide evidence of the results achieved (records). Documentation is essential to gain confidence that all processes are being executed as planned. Several documents are part of the IVF cycle and this segment specifically deals with the laboratory-related documents that are necessary to implement TQMS.

At the start of each day, as a routine practice, a checklist must be verified before the lab starts functioning. This will include verifying appropriate environmental conditions (room temperature and humidity), equipment function, and appropriate levels in gas cylinders and LN₂ tanks. A list of essential checklists for an IVF lab is mentioned below (ASRM, 2022).

Essential laboratory related documents for andrology laboratory and embryology laboratory

The proper functioning of a lab can be ensured by a timely audit of the data captured during daily QC. Laboratory daily QC values must be compared with a peer group, when possible, to confirm accuracy on a regular basis (often monthly).

Records or data management must be compliant with local statutory and regulatory authorities. Document control systems that indicate evidence of implementation, approval, and review of internal and external documents should be done at timed intervals.

The Organization/ART Unit should undertake regular reviews of treatment outcomes. It should provide evidence of implementation and review of policies and procedures to :

Data reporting

The organizations/ART Unit should report the captured data of every IVF cycle to the national registry of their country in the stipulated time frame (if applicable). Nevertheless, patient confidentiality should not be breached. Apart from IVF cycle data, (patient demographics, gamete, and embryo information), it is very important to report pregnancy outcomes of all ART interventions.

Key points:

The data captured has to reported to the regulatory body as per the respective country’s national norms at specific time intervals.

Confidentiality with documentation

Data capture is necessary but it should be compliant with any legislation pertaining to patient privacy. Patient information should not be used anywhere outside the IVF unit once the audit is complete. The information that is shared as a result of a clinical relationship is considered confidential and must be protected. The information can take various forms (including identification data, diagnoses, treatment and progress notes, and laboratory results) and can be stored in multiple media (e.g., paper, video, electronic files).

Report generation

Labs should have an adequate manual or electronic system to ensure test results are sent precisely and reliably from the point of data entry to the final report destination in a timely manner. All test reports must include the following items: results; patient name and unique identifier; name and address of the testing laboratory; test report date; date of performance; units of measurements; and reference intervals or normal values. Test reports should include signed and verified by the person performing the test. In case of any error in a patient’s laboratory report, the authorized person ordering the test or the individual using the test results must be immediately notified.

Reports must be issued promptly after corrections. The original as well as the corrected report must be maintained. All test reports of patients should be easily accessible for surveys or audits.

Key points:

Labs should have an adequate manual or electronic system to ensure that the test results are sent precisely and reliably from the point of data entry to the final report destination in a timely manner.

Incident reporting, corrective and preventive action

Incident Reporting (IR) is a reactive tool and is well-accepted in all critical industries such as ART that has minimal tolerance for errors. A system to report the incident and near misses create corrective/preventive measures helps in minimizing errors in an IVF cycle.

Patient information documents

This must include but not be limited to :

Consents

The Organizations/ART Unit must :

Record keeping

The embryology laboratory must retain records of all its policies and procedures as well as personnel employment, training, evaluations, and continuing education activities. In addition to this, documentation of the proper identification, outcome, and disposition of all gametes, gonadal tissue, and embryos is important (Olofsson et al., 2013).

The laboratory must maintain these records for a period according to local legislative requirements or for 10 years beyond the final disposition of all data obtained during each patient’s ART cycle, whichever is later.

All paper records must be maintained on-site or in a secure, audited off site facility, and electronic records must have appropriate safeguards against data loss. In the event that the laboratory ceases operation, provisions must be made for these records to be maintained according to the time frame required.

DISASTER MANAGEMENT

Quick summary/at a glance

Background and specific objectives

Disasters are serious disruptions to the functioning of a community that exceed its capacity to cope using its own resources. Disasters can be caused by natural, man-made and technological hazards, as well as various factors that influence the exposure and vulnerability of a community (ref www.ifrc.org accessed 1/3/23). The impact of disasters is magnified in low resource settings. (WHO document). Perceived threats and disasters will vary according to the environment, population, political and other factors. All clinics in LRS need to have considered disaster mitigation unique to their location and resources. Disaster mitigation includes risk assessment, prevention of disaster and preparedness for disaster and the document prepared by the WHO is a useful framework for the clinic to use. The immediate intervention of response to disaster should also be considered. Rehabilitation and reconstruction as part of the disaster response can be developed after the immediate response. Disasters can occur beyond the control of the ART units that require action to be taken to limit damage or loss. Such disasters can affect ART units in several ways including the interruption of clinical procedures, damage to critical equipment resulting in disruption of the culture and storage of gametes and embryos, medications, and reagents. Safety and protection of personnel and patients from disasters or imminent threats is of paramount importance.

Contingency and scenario analysis is the key to disaster management. To minimize risks, ART units should implement an emergency action plan that include a risk assessment programme and risk management strategies appropriate for their geographic locations to protect patients, personnel, and specimens (embryos, oocytes, and sperm) in the case of an emergency, natural disaster, pandemic, or other potentially devastating event.

The objectives of an emergency action plan should be to provide for (in descending order of importance) the safety of personnel and patients, fresh and cryopreserved embryos, oocytes and sperm, and critical equipment and records.

Recommendations in regular practice for minimum standard of care

Implementation, monitoring and quality assurance

SOP for an emergency action plan should be developed by ART units. The emergency plan should include (1) providing for the safety and protection of personnel and patients; (2) the safety and preservation of fresh and cryopreserved oocytes, sperm, and embryos; and (3) the protection and security of important materials, such as patient records, laboratory records, financial and operational documents, and facility equipment.

Outline of the emergency plan

SAFETY AND INFECTION CONTROL

Quick summary

Background and specific objectives

Reduction of risk of transmission of infection between clinic personnel and patients

Policy and procedures for the safety of personnel from infectious diseases and contamination within the ART unit should also be provided (European Council, 2019). Human body fluids, such as semen and follicular aspirate, are potentially infectious and shall be handled and disposed using standard universal precautions.

The main diseases potentially transmitted to staff by patient samples in the ART laboratory are hepatitis B, hepatitis C and HIV (Junk et al., 2009).

All patients shall be screened for HIV, hepatitis B and C, syphilis, and other sexually transmitted diseases according to disease prevalence in the community and other infectious diseases prior to treatment commencement and at regular intervals thereafter. Pipetting by mouth is not recommended when handling oocytes and embryos (Jindal et al., 2016).

Universal precautions should be applied when handling all potentially infected samples.

This includes: (Elder et al., 2005)

Prevention of aerosol transmission of infection between staff and patients

Prevention of cross contamination between patient samples

Whilst samples are being handled precautions need to be taken. See section 6.3.a While risks of cross-contamination in storage tanks are more perceived than real, IVF laboratories should make an informed decision on their risk mitigation strategy. Though there are no reports of cross-contamination of oocytes or embryos in LN₂, the following points provide evidence for theoretical risk.

ESHRE guidelines state: Safety issues have been raised regarding direct contact of the biological material with the LN₂; however, at this point closed devices cannot be favored over open devices. Laboratories should make decisions based upon their results, risk analysis and regulations in place. Specimens from sero-positive patients should be stored in high-security closed devices.

Guideline: Potentially infectious oocytes and embryos may be stored in separate cryotanks if available, but it is recommended that semen samples from potentially infectious individuals be stored in dedicated cryotanks.

In a LRS the decision to not offer storage of infected semen may be taken because of the requirement to have a separate cryostorage tank.

Safe handling of liquid nitrogen

Laboratory personnel should wear protective safety goggles, insulated gloves, and closed shoes when handling LN₂. Liquid nitrogen is a colorless, odorless liquid with a boiling point of −196^∘C and is a hazardous liquid. At low temperatures nitrogen (in gaseous and vapour states) N₂ is heavier than air. One liter of LN₂ produces ∼700 liters of gas when LN₂ vaporizes at room temperature. In the event of a leakage in a cryogenic storage tank or during handling of LN₂, oxygen within the confined space will be quickly displaced by nitrogen without warning. Nitrogen gas is invisible – the cloudy vapour which appears when liquid nitrogen is exposed to air is condensed moisture, not the gas itself. Some of the main hazards associated with liquid nitrogen are asphyxiation, cryogenic burns, frostbite, and hypothermia (Tomlinson et al., 2012). Low oxygen tension alarms with supportive contingency plans are required in areas where refilling of cryostorage tanks with LN₂ occur.

Risk of high CO₂ in laboratories

High CO₂ tension alarms with supportive contingency plans are required where CO₂ is piped into the laboratory.

Recommendations for minimum standard of care

TRACEABILITY (PATIENTS AND GAMETES)

Quick summary

Background and specific objectives

Each stage of ART should consider the potential for errors in the following steps, which are the most critical: (1) incorrect identification of the patient, (2) improper specimen labeling, (3) oocyte retrieval, (4) sperm collection and preparation, (5) incorrect mixing of sperm and oocytes or incorrect sperm injection into the oocyte, (6) improper transfer of gametes or embryos between tubes/dishes, and (7) improper embryo transfer. Additionally, the following procedures should be considered as potential sources of errors:

(1) Cryopreserving the wrong gamete or embryo, (2) removing the wrong gamete or embryo from cryotanks (3) discarding the wrong gamete or embryo, and (4) transferring the wrong gamete or embryo.

Identification and traceability of each patient and biomaterial derived from the patient are critical in ART. The laboratories for ART should establish an accurate tracking system to identify each step uniquely and characteristically according to established protocols (Malhotra et al., 2021).

Evidence

This guideline is based on established international guidelines and regulations from professional organizations such as ASRM, ESHRE, HFEA, and India-ISAR, as well as related publications and the ASPIRE expert consensus.

Recommendations for minimum standard of care

Identification and traceability of each patient and biomaterials from the patient, such as gametes, are critical in the ART procedure. The laboratories for ART should establish an accurate traceability system to uniquely identify and characterize each step according to established protocols.

Establishment of procedures

The laboratory director is responsible for determining the proper tracking system, and appropriate identification systems must ensure that the patient (or donor) and information about biological materials from the patient or donor are constantly identified. The use of 3 unique identification markers is advised.

Identification training

It is strongly recommended that specific identification of patients and/or biological materials be verified by at least two trained and qualified staff. The handling of specimens should be conducted by staff who are trained in proper laboratory procedures for specimen (Malhotra et al., 2021).

Code assignment

Patient/Couple-specific unique identification code must be provided to the laboratory prior to the start of the ART procedure. This code should be easily and clearly accessible for patient consent forms, clinical data, serological results for patient ART procedures, and any revisions from the attending doctor. A patient-specific unique identification code must be assigned to each treatment cycle. For gamete or embryo collection from non-partner donors, specific coding may be required in certain countries (Rebecca et al., 2021).

Treatment steps

Patient identification must be verified at all critical steps of the ART procedure using the patient’s photo, name, date of birth and unique patient identification code. The patient is responsible for providing the necessary documented proofs (Rienzi et al., 2017).

Recommendations in regular practice

The introduction of a barcode label system or a Radio-Frequency Identification (RFID) based technology system could be an alternative to prevent potential errors and would be appropriate to verify every step in ART. However, these systems are expensive and may not be used in LRS.

Genetic testing

All cells and embryos for genetic testing must be handled individually, carefully identified, labeled, and tracked throughout the entire procedure. Double-checking of patient and embryo identification should be performed at every step (Rebecca et al., 2021).

Overseas transfer

The transport of reproductive cells and tissues requires confirmation of the biological material and its suitability for clinical application. Wherever applicable, the identity of the sending and receiving organizations must be confirmed and verified. Each organization must verify the identity and attached specimen documentation, and match the patient’s records.

Overall recommended traceability steps (Rienzi et al., 2017)

Retention of documentation

The date and time of each procedure, the identity of personnel and second staff (or observer) should be documented throughout the ART procedure, and should be retained for a period specified by national legislation or governing, licensing and accrediting bodies. The identity of all clinicians and staff handling specimens at each step-in procedure should be documented and traceable.

TRACEABILITY (CONSUMABLES AND MEDIA)

Quick summary

Background and specific objectives

Traceability of consumables and media in an IVF laboratory refers to the ability to track and document the use, movement, and storage of the materials and supplies used in the laboratory. The implementation of traceability systems in an IVF laboratory can have both advantages and disadvantages. On the one hand, traceability systems can improve patient safety by reducing the risk of contamination, misidentification, mix-ups, and other errors. They can also help to ensure quality control and regulatory compliance and improve the efficiency of the IVF procedure by streamlining processes. On the other hand, setting up and maintaining traceability systems can be time-consuming and costly, and may require additional staff training and infrastructure. In addition, the use of electronic systems may pose security and privacy risks, such as the possibility of data breaches or unauthorized access to patient information. It is important for IVF laboratories to carefully weigh the pros and cons of implementing traceability systems and to design a system that meets their specific needs and constraints.

Although the latest traceability technologies should be taken into consideration when establishing a modern IVF laboratory, minimum standards are necessary for low-volume clinics or resource-limited settings. This section aims to review various techniques for managing consumables and media and establish a minimum standard for their management in resource-constrained environments.

Evidence

The evidence for the recommendations in this guideline is based on established international guidelines and directives from professional organizations (ASRM, ESHRE, RTAC, ISAR and HFEA), and ASPIRE expert consensus.

Recommendations for minimum standard of care

In regulated IVF labs, traceability and accurate documentation of inventory items is crucial for regulatory compliance reporting and efficiency in laboratory operations. Two categories of solutions for inventory management in IVF labs exist: manual and digital. Manual entry into paper or spreadsheets is the oldest and most common method of tracking consumables, but it is time-consuming and prone to human error. Digital systems such as barcode labels and RFID offer superior accuracy and several benefits compared to cumbersome manual systems.

In low resource settings, implementing a traceability system for consumables and media can be challenging due to limited financial and technical resources. However, there are several recommendations that can help IVF labs in low resource settings to establish effective traceability systems :

BENCHMARKING

Quick summary/at a glance

Background and specific objectives

In the context of in vitro fertilization (IVF), benchmarking refers to the process of comparing the performance of a fertility clinic with the performance of other clinics, in terms of their success rates in treating infertility. This comparison is typically made using standard metrics, such as the clinical pregnancy rate per embryo transfer or the live birth rate per cycle started. The purpose of benchmarking is to provide patients with information about the relative success of different clinics, which can help them make informed decisions about where to seek treatment. Competency values provide a set of defined standards for embryologists to ensure the quality of their work and patient safety. Defining competency values helps to :

Evidence

The Vienna Consensus Report is a set of guidelines for in vitro fertilization (IVF) laboratories that were developed by a group of experts in the field of reproductive medicine. The report is intended to promote consistent and high standards of care in IVF laboratories and to support the ongoing development of the field. The American Society for Reproductive Medicine (ASRM) also provides recommendations for benchmarking in vitro fertilization (IVF) laboratories (ASRM, 2022) these recommendations are intended to provide a standard of care for IVF clinics and laboratories, and to help improve the quality and consistency of IVF services. They recommend that IVF laboratories adopt best practices for benchmarking, including accreditation, quality control, laboratory design and organization, personnel qualifications, and access to the latest equipment and supplies. These recommendations are intended to support the ongoing development of the field and to improve the quality and consistency of IVF services.

The consensus provides recommendations on various aspects of IVF, including :

The Vienna Consensus aims to promote evidence-based, patient-centred, and safe IVF practices. The guidelines also emphasize the importance of considering individual patient factors and balancing the benefits and risks of treatment (ESHRE, 2017).

The ASRM recommends that IVF laboratories implement the following best practices for benchmarking :

Recommendations for benchmarking in minimum standard of care

Defining a reference population is crucial while calculating these KPIs.

The suggested reference population is a female patients $<40$ years old, with own fresh eggs, ejaculated sperm (fresh or frozen), any insemination method and no preimplantation genetic diagnosis (PGT). If applicable: stratified by ovarian response [poor (PR), normal (NR), and High response (HR)]. Competency and Benchmark values are generally used for Normal to High responders. Competency values are minimum expected outcomes whereas benchmark values are the best practice goals to achieve the KPIs (Maribor Consensus, 2021). Several factors can compromise these rates and segregating a pool of patients that the clinic believes have a good prognosis can be a good starting point to calculate these benchmarks.

Andrology laboratory:

Embryology laboratory: (ESHRE, 2017)

Clinical recommendations (ESHRE, 2017; Maribor Consensus, 2021)

Recommendations for benchmarking for low volume clinic or low resource setting

Owing to the differences in staffing and infrastructure it is recommended that a Low resource or low volume centre document the following benchmarks. A low volume clinic should at least document these benchmarks in order to ensure standards of care are maintained.

Implementation, Monitoring and Quality Assurance (Fabozzi, Gemma, et al., 2020)

The control chart is one of the most popular tools employed in this process. The Shewhart chart or Levey-Jennings quality control chart is the most often used diagram. In a nutshell, a control chart should show the “control mean” for the previous six months, upper and lower “warning limits” set at 2 and 3 standard deviations, respectively. An indicator should, in theory, oscillate between the lower and higher control limits according to physiological fluctuation brought on by patient variability. There are four possible outcomes, though :

FURTHER READINGS

Listing other available guidelines/guidance, e.g., ASRM, ESHRE, RTAC, HFEA, ISAR, ALPHA, Istanbul, Vienna Consensus, Cairo Consensus.

UPDATING THE GUIDELINES

Proposed revision frequency and timeline- 5 Years

ACKNOWLEDGEMENT

ASPIRE Guidelines Steering Committee would like to acknowledge the Key Opinion Leaders (KOLs), Stakeholders, and ASPIRE board for their invaluable contribution in drafting these guidelines.

AUTHOR CONFLICT OF INTEREST DISCLAIMERS

The initial meeting of the core members of the guideline group was sponsored by Merck. The authors express their thanks for their contribution.

General/universal guidance for all ART laboratories

Overall, this document gives the concept of good laboratory practice. It provides a list of currently available local guidelines. It is worth noting that these are general guidelines and this document does not intend to replace or override any regulations governed by individual country/region.

TABLE OF ABBREVIATIONS AND ACRONYMS

The members of the working party and their relative roles.