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Review Article
Clinical research nurses are closely involved in assisted reproductive drug trials. This review discusses how their role can be better defined and supported through clearer position management, specialty training, quality-control awareness, and career-development pathways in reproductive medicine.
Assisted reproductive drug clinical trials require close coordination between reproductive medicine, nursing, embryology, pharmacy, laboratory, data management, and regulatory teams. Their implementation is complicated by cycle-dependent treatment schedules, frequent endocrine and ultrasound monitoring, strict medication timing, reproductive specimen handling, pregnancy follow-up, and safety reporting. These features create specific demands for clinical research nurses (CRNs), whose responsibilities extend beyond routine nursing care. This review summarizes the roles and functions of CRNs in assisted reproductive drug clinical trials in China, focusing on position management, subject management, investigational product management, material and specimen traceability, data documentation, quality control, and inspection readiness. Existing literature suggests that CRNs can support protocol implementation, subject protection, visit coordination, adverse-event reporting, and data integrity when their responsibilities are clearly defined. However, CRN practice in this field remains insufficiently standardized, particularly regarding admission criteria, specialty training, competency evaluation, workload allocation, and career development. Thus, establishing reproductive-medicine-specific CRN training systems and position-management frameworks may improve trial quality and support the professional development of clinical research nursing in assisted reproductive medicine.
In China, declining fertility rates and adjustments to national fertility policies have increased attention to infertility diagnosis and treatment1. Infertility is commonly defined as the failure to achieve pregnancy after 12 months of regular unprotected intercourse and affects many reproductive-age couples worldwide2. Accordingly, assisted reproductive treatment has become an important component of reproductive medicine, particularly for couples with ovulatory dysfunction, tubal disease, diminished ovarian reserve, male-factor infertility, or unexplained infertility.
Assisted reproductive treatment involves repeated visits, ovarian stimulation, medication adjustment, endocrine and ultrasound monitoring, gamete or embryo handling, embryo transfer, luteal support, pregnancy confirmation, and follow-up3. Patients may also experience psychological distress, uncertainty, treatment fatigue, sexual or relationship concerns, and reduced quality of life, which can affect adherence and communication during care4. These features distinguish assisted reproductive drug trials from many conventional drug trials, as trial procedures must be aligned with menstrual-cycle timing, reproductive laboratory workflows, and patient-centered counseling5.
The development of assisted reproductive drugs remains important for improving infertility care, but their evaluation requires strict trial procedures to confirm safety, efficacy, and protocol feasibility6. Even minor deviations in medication timing, dose adjustment, specimen handling, visit scheduling, or outcome documentation may affect reproductive endpoints and trial reliability7. Therefore, these trials require continuous coordination among investigators, reproductive physicians, nurses, embryologists, pharmacists, clinical trial coordinators, monitors, data managers, and sponsors.
Clinical research nurses (CRNs) support assisted reproductive drug trials through screening and recruitment support, health education, protocol-based medication guidance, adverse-event observation, follow-up coordination, investigational product and specimen-related assistance, source-data documentation, and communication among trial team members8. These responsibilities are particularly important because participants often require time-sensitive interventions, frequent monitoring, clear explanation of protocol restrictions, and careful expectation management9. Although CRNs are increasingly involved in clinical trials in China10, their role in assisted reproductive drug trials requires further clarification, particularly in position management, qualifications, training, responsibility boundaries, workload allocation, competency evaluation, and career development. Therefore, this review discusses the current context of clinical trials of assisted reproductive drugs in China and summarizes the role of CRNs in position management, subject management, investigational product and specimen management, quality control, and professional development in this specialized field. The review development process is provided in Supplementary File 1.
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Roles and functions of research nurses in assisted reproductive drug clinical trials
Existing studies in China describe CRNs as important members of clinical trial teams, with responsibilities involving clinical care, subject management, nursing coordination, quality control, and subject education. Their work is closely linked to subject safety, protocol implementation, and trial quality11. However, large-scale CRN surveys and training studies have shown that further professional education and competency-based training are still needed12,13. In assisted reproductive drug trials, this training should also emphasize multidisciplinary communication, protocol awareness, and reproductive-medicine-specific nursing knowledge, as these trials involve reproductive medicine, nursing, embryology, pharmacy, laboratory testing, data management, and sponsor-related procedures14. Figure 1 summarizes the main domains of CRN responsibilities in assisted reproductive drug clinical 101 trials.
In assisted reproductive drug trials, CRNs and CRCs (clinical research coordinators) support different aspects of trial implementation. CRNs are registered nurses within the hospital nursing system and provide nursing-based clinical and safety support, including participant care, health education, medication guidance, safety observation, emergency response, nursing documentation, and communication of clinical problems to investigators. In contrast, CRCs may not be registered nurses, and their work primarily focuses on project coordination, visit arrangements, CRF(case report form) completion, data entry or verification, document preparation, and communication with monitors or sponsors. The Chinese Expert Consensus on Clinical Research Nurse Management provides a framework for CRN qualifications, responsibilities, training, evaluation, workload management, staffing, performance appraisal, and career development14. Therefore, clear role boundaries should be established before trial initiation, particularly for nursing operations, adverse-event observation, source documentation, investigational product procedures, specimen handling, data entry, and sponsor-related communication, so that CRNs and CRCs can work within their authorized responsibilities without inappropriate role substitution.
Training and evaluation system
CRN training systems are relatively well established in Western countries, particularly in the United States and the United Kingdom. For example, the Oncology Nursing Society competency framework emphasizes scientific knowledge, patient care coordination, protocol adherence, and regulatory compliance15. Similarly, competency-based education frameworks 124 for clinical research professionals emphasize research ethics, scientific concepts, participant 125 safety, protocol implementation, regulatory compliance, and continuous professional development16,17. However, differences in healthcare systems and clinical trial environments mean these models may not be directly applicable to China. CRNs in China often have to balance clinical nursing with research duties, resulting in heavier workloads, greater pressure, and a need for flexible, structured training with appropriate support18. In addition, frequent regulatory updates require CRNs to adapt to evolving trial requirements despite limited standardized training resources. Therefore, CRNs should complete NMPA (National Medical Products Administration) recognized GCP (Good Clinical Practice) training, training at hospital drug clinical trial centers, internal assessments, sponsor-organized site initiation training, and protocol-specific evaluation before trial implementation. These steps help ensure familiarity with trial procedures, investigational product management, adverse-event handling, and specimen collection and preservation.
Defining the scope of responsibilities
According to the 2020 revised GCP for Drug Clinical Trials issued by the National Medical Products Administration and the National Health Commission19, establishing CRN positions requires clear responsibilities and workflows to standardize nursing work in drug clinical trials. CRN responsibilities focus on protocol implementation, subject safety, data integrity, and compliance with ethical and scientific requirements14. In practice, CRNs participate in protocol, procedure, and emergency-skills training; evaluate trial preparation before initiation; provide clinical care and follow-up support; assist with informed-consent and safety management; observe and report adverse events; maintain trial documents and source data; manage investigational products, equipment, and consumables; assist with specimen collection, processing, and preservation; and coordinate communication among investigators, subjects, sponsors, monitors, and related departments.
Subject screening and cycle-based trial coordination
Subject management is a central component of CRN work in assisted reproductive drug trials, encompassing pre-trial preparation, recruitment and screening support, medication guidance, health education, adherence monitoring, reproductive procedure coordination, pregnancy follow-up, psychological support, adverse event surveillance, and management of scheduled or unscheduled visits. Unlike many conventional drug trials, these studies are closely linked to menstrual-cycle timing, ovarian response, laboratory procedures, and reproductive outcomes. Before enrollment, CRNs assist investigators in reviewing eligibility criteria, screening workflows, visit schedules, required examinations, informed-consent procedures, and subject education materials8. During recruitment and screening, they help identify eligible subjects, coordinate baseline assessments, and ensure accurate documentation of infertility-related information, including menstrual history, infertility duration, prior assisted reproductive treatment, ovarian reserve indicators, (polycystic ovary syndrome )PCOS or insulin-resistance status, semen-related findings, pregnancy history, concomitant medication or supplement use, and relevant gynecological or surgical history. Accurate screening is therefore essential because eligibility, treatment timing, and outcome assessment often depend on cycle-specific clinical findings.
Patient education, adherence support, and psychological care
After enrollment, CRNs provide protocol-consistent education on trial procedures, medication use, prohibited medications or supplements, visit windows, sample collection, diary completion, questionnaire requirements, and symptom-reporting criteria. Since assisted reproductive treatment often involves frequent visits, complex medication schedules, and emotionally demanding waiting periods, this education is reinforced during follow-up, with attention to medication timing, route, dose, storage, diary completion, and follow-up records. CRNs also help identify emotional distress, treatment fatigue, unrealistic expectations, and communication difficulties, as infertility-related conditions may be associated with anxiety, depressive symptoms, reduced quality of life, and decreased treatment adherence4. Through health education, communication support between subjects and clinicians, and referral for psychological assessment when clinically indicated or required by the protocol, CRNs help maintain adherence, subject safety, and continuity of trial participation.
Medication guidance and protocol-specific monitoring
Medication guidance in assisted reproductive drug trials requires careful attention to timing, adherence, and documentation. CRNs explain protocol-defined medication schedules, verify adherence during follow-up, and document the indication, dose, duration, concomitant medications or supplements, endocrine monitoring results, intolerance, and adverse events. When trials involve adjunctive or nutraceutical agents, such as myo-inositol or D-chiro-inositol, CRNs present these interventions according to the protocol and available evidence, as some adjunctive approaches remain preliminary or apply only to selected patient groups20,21. In ovarian stimulation trials, even small deviations in medication timing or dose adjustments may affect follicular development, oocyte retrieval scheduling, OHSS (ovarian hyperstimulation syndrome) risk, and reproductive outcomes. Evidence from high-risk IVF(in vitro fertilization )/ICSI (intracytoplasmic sperm injection) antagonist cycles suggests that individualized GnRH (gonadotropin-releasing hormone ) antagonist and gonadotropin adjustment may reduce early moderate or severe OHSS without compromising clinical pregnancy outcomes22. Accordingly, CRNs assist in identifying OHSS risk indicators, confirming medication timing and administration requirements, communicating abnormal symptoms to physicians, and documenting the hCG (human chorionic gonadotropin )trigger window, ovarian response, and follow-up findings in accordance with the protocol.
Coordination of reproductive procedures and follow-up
CRNs coordinate key reproductive procedures and follow-up in assisted reproductive drug trials, including oocyte retrieval, vitrification, warming, fertilization, embryo transfer, luteal support, pregnancy testing, and pregnancy outcome assessment. In trials involving fertility preservation or oocyte donation, they provide protocol-specific education on the purpose, timing, follow-up requirements, and investigational nature of trial-related procedures. Evidence showing comparable outcomes between closed and open oocyte vitrification systems supports careful counseling and documentation rather than treating vitrification as a uniform procedure23. Similarly, adjunctive embryo-transfer procedures require cautious explanation when evidence remains inconsistent, as intrauterine injection of embryo culture supernatant before embryo transfer has not clearly improved pregnancy or implantation outcomes24. CRNs also help coordinate communication among reproductive physicians, embryologists, and subjects when unexpected fertilization failure occurs, particularly because routine semen parameters may not fully predict fertilization ability and cryptic sperm defects may contribute to total fertilization failure25. In these situations, CRNs support counseling, rescue-procedure coordination, follow-up planning, and outcome documentation in accordance with trial requirements.
Pregnancy, neonatal, and offspring follow-up
For trials that include pregnancy follow-up, CRNs coordinate protocol-defined assessments of maternal, delivery, and neonatal outcomes, including biochemical and clinical pregnancy, miscarriage, ectopic pregnancy, gestational age at delivery, mode of delivery, live birth, birth weight, neonatal sex, Apgar score, congenital anomalies, neonatal complications, and neonatal intensive care unit admission. This is particularly important in trials involving embryo cryopreservation or frozen embryo transfer, as recent studies have reported differences in several perinatal outcomes, including birth weight, large-for-gestational-age infants, macrosomia, low birth weight, and small-for-gestational-age infants, while findings for congenital anomalies and neonatal mortality remain less consistent26,27. Therefore, CRN involvement mainly supports complete and traceable documentation of pregnancy, delivery, and neonatal outcomes rather than independent interpretation of the relative safety of fresh and frozen embryo transfer. When diagnostic examinations are required during pregnancy for maternal or fetal indications, CRNs also assist in confirming counseling on the indication, alternatives, expected benefit, potential maternal-fetal risks, allergy history, renal risk factors, and post-exposure follow-up. If iodinated contrast is used, neonatal thyroid assessment may be considered according to clinical indication and local practice28.
For trials involving frozen embryo transfer, offspring follow-up after birth requires attention beyond routine pregnancy and neonatal assessment. Recent studies have evaluated child growth, body mass index, blood pressure, lipid profiles, glucose metabolism, hospitalization, and neurodevelopmental outcomes after assisted reproduction or frozen embryo transfer, but available evidence varies in follow-up duration, transfer protocol, population characteristics, and adjustment for parental infertility and obstetric factors29,30,31. For instance, in a Finnish register study evaluating the health of singletons born after frozen embryo transfer until early adulthood, Terho et al.32 reported that the overall long-term health of children born after frozen embryo transfer did not differ from that of children born after fresh embryo transfer. In another study focusing on growth until early adulthood, the same research group reported that adolescent boys born after frozen embryo transfer had a higher mean proportion and increased odds of overweight compared with boys born after fresh embryo transfer, whereas the findings among girls were different and less consistent33. These findings indicate that live birth and neonatal outcomes cannot fully replace postnatal child follow-up in assisted reproductive drug trials involving frozen embryo transfer. In this context, CRNs help maintain family contact information, remind families about postnatal or childhood follow-up visits, assist with parent-reported questionnaires, coordinate pediatric or developmental assessments when required by the protocol, and verify that child outcome data are complete, traceable, and consistent with the case report form.
Adverse-event monitoring and emergency management
Safety monitoring is an important responsibility of CRNs during subject management. CRNs are needed to monitor, record, and report post-medication symptoms and adverse events, including abdominal distension, nausea, vomiting, ascites, dyspnea, reduced urine output, allergic symptoms, endocrine abnormalities, renal-related abnormalities, menstrual changes, psychological distress, and other protocol-defined safety signals. When serious adverse events occur, CRNs should follow emergency procedures, promptly notify investigators, assist in clinical management, and ensure complete documentation in source records and case report forms. This process helps integrate clinical care with trial requirements while protecting subject safety and data integrity34.
Blinding, visit management, and communication
Subject management also varies according to trial design. In double-blind or double-dummy trials, maintenance of blinding is essential for scientific validity35. When separate blinded and unblinded CRN responsibilities are required, clear role boundaries help prevent unintended disclosure of treatment allocation. In this model, unblinded CRNs have no direct subject-facing role and do not share allocation-related information with blinded CRNs, investigators, subjects, or data managers36. Such separation supports allocation concealment, reduces performance and assessment bias, and preserves data credibility.
Effective visit management is also important in assisted reproductive drug trials, particularly when treatment requires repeated assessments within narrow cycle-dependent time windows. Since assisted reproductive drug therapy is cyclical, the timing of initial medication dispensing often determines subsequent monitoring and follow-up schedules. Therefore, careful planning of this initial visit facilitates orderly follow-up, improves coordination among the research and clinical teams, and reduces the likelihood of protocol deviations15. In addition, CRNs play an important role in managing unscheduled visits and urgent subject contacts, especially when adverse symptoms, medication concerns, or reproductive-procedure-related complications occur. Continuous communication between CRNs and subjects can improve adherence, strengthen nurse-patient cooperation, and support trial completion.
Investigational product, material, specimen, and data management
Investigational product management
Investigational product management is a key component of quality control in assisted reproductive drug trials, which may involve gonadotropins, GnRH agonists or antagonists, ovulation triggers, luteal-support agents, placebo preparations, or adjunctive therapeutic products. These products may differ in storage requirements, preparation procedures, routes of administration, accountability rules, and blinding arrangements. Therefore, standardized management according to Good Clinical Practice and institutional drug-management procedures is essential for subject safety, protocol compliance, and data reliability37,38. In many institutions, CRNs assist the central pharmacy or trial drug management team with receipt, verification, storage, dispensing, return, and documentation. Before trial initiation, they confirm key product information, including name, specification, dosage form, batch number, quantity, storage conditions, temperature-monitoring requirements, preparation method, allocation procedure, emergency unblinding process, and disposal plan, which is particularly important because medication use in assisted reproductive trials is often linked to cycle-dependent procedures and narrow visit windows.
During trial implementation, CRNs help ensure that investigational products are stored in designated areas, monitored under required temperature conditions, and fully traceable through receipt, inventory, dispensing, return, and destruction records. They assist in managing temperature excursions, packaging damage, dispensing errors, or accountability discrepancies through product isolation, documentation, and communication with the sponsor or trial management team. Before administration or dispensing, CRNs verify subject identification, randomization number, product code, dose, route, administration time, and relevant medical order, while maintaining blinding according to the protocol. For injectable or prepared products, they confirm preparation, labeling, administration, and double-checking procedures. When adjunctive or nutraceutical agents, such as inositol preparations, are included, CRNs document product source, batch information, dose, duration, adherence, intolerance, concomitant medication or supplement use, discontinuation criteria, and adverse events, without presenting such agents as established therapies when evidence remains preliminary20,21. Through these activities, CRNs help reduce medication-related deviations and support the reliability of safety and efficacy data in assisted reproductive drug trials.
Specimen and data management
Specimen and data management are essential in assisted reproductive drug trials because reproductive endpoints depend on accurate collection, processing, storage, transfer, and documentation of biological materials7. Compared with conventional drug trials, these studies may involve serum samples, follicular fluid specimens, semen samples, oocytes, embryos, cryopreserved reproductive materials, and pregnancy-related follow-up data, thereby creating greater demands for traceability across clinical, laboratory, and research workflows. For reproductive specimens, CRNs assist with protocol-defined collection and documentation, including specimen source, collection time, processing method, storage condition, transfer route, receiving personnel, laboratory result, deviation record, and linkage with subject identification and visit number. In trials involving oocyte vitrification or fertility preservation, documentation further includes oocyte source, maturation status, cryopreservation method, storage tank identification, warming protocol, fertilization outcome, embryo development, transfer outcome, and pregnancy follow-up. Evidence showing comparable outcomes between closed and open vitrification systems when procedures are standardized, together with possible safety advantages of closed systems in long-term cryostorage, highlights the need to document the cryopreservation method, labeling, storage location, transfer logs, warming records, and chain-of-custody procedures rather than treating vitrification as a uniform event23,39.
Semen-related and trial data documentation also require careful management. Conventional semen parameters may not fully reflect functional fertilization capacity, and unexpected total fertilization failure may occur even when routine semen analysis appears normal40. Therefore, assisted reproductive trials require accurate records of semen collection and processing, insemination method, fertilization assessment, rescue ICSI decisions when applicable, embryo quality assessment, cryopreservation and warming procedures, protocol deviations, and reproductive outcomes. Data management needs to be planned alongside specimen management, with clear source-data requirements, case report form fields, subject diary content, questionnaire procedures, laboratory data transfer, and data-verification responsibilities41. During the trial, CRNs assist in collecting, preserving, checking, and transmitting subject diaries, questionnaires, laboratory reports, imaging or reproductive-procedure records, adverse-event records, and follow-up data according to the protocol42. Through these activities, CRNs help ensure the authenticity, accuracy, completeness, timeliness, and traceability of research data while reducing avoidable deviations in assisted reproductive drug trials.
Supporting quality control and inspection
Quality control and inspection support are essential throughout assisted reproductive drug trials. Under Good Clinical Practice requirements and National Medical Products Administration supervision, trial implementation must follow the approved protocol, standard operating procedures, ethical requirements, and source-documentation standards38. Risk identification studies have shown that common quality risks are often related to investigational product management, biological specimen handling, and protocol design43. Therefore, quality control in assisted reproductive drug trials needs to function as a continuous process rather than an end-stage inspection activity. In this process, CRNs contribute to routine self-inspection and risk prevention by reviewing protocol adherence, visit-window compliance, informed-consent completeness, investigational product traceability, and consistency between source documents and case report forms11. They also help identify missing records, delayed entries, laboratory or procedural inconsistencies, incomplete adverse-event documentation, and unreported protocol deviations, allowing timely correction before these issues affect subject safety or endpoint reliability.
For trials involving reproductive specimens, quality control focuses on traceability, procedural consistency, and inspection readiness. When gametes, embryos, follicular fluid specimens, semen samples, or cryopreserved reproductive materials are involved, CRNs help verify that labeling, storage records, transfer logs, warming records, deviation reports, and chain-of-custody documents comply with protocol requirements. In vitrification-related studies, quality review may also include the cryopreservation method and storage pathway, particularly when closed systems are used to reduce direct contact between reproductive materials and liquid nitrogen in fertility preservation, oocyte banking, or long-term cryostorage39. Quality control also extends to protocol-defined follow-up and safety records, including pregnancy outcomes, maternal-fetal safety documentation, clinically indicated examinations, and, when contrast agents are used, records of indication, gestational age, contrast type, renal function, allergy assessment, informed consent, breastfeeding counseling when relevant, and fetal or neonatal follow-up28. During monitoring visits, audits, or regulatory inspections, CRNs assist in preparing source documents, investigational product records, specimen logs, informed consent forms, adverse event reports, deviation records, training files, and communication records, and support responses to queries and corrective and preventive actions. These activities strengthen protocol compliance, reduce preventable deviations, and improve the credibility of safety and efficacy data in assisted reproductive drug trials.
CRN advantages in assisted reproductive drug clinical trials
CRNs provide distinct value in assisted reproductive drug trials through their combined understanding of clinical nursing and research implementation8. As hospital-based professionals, they are familiar with departmental workflows, patient care routines, documentation requirements, and interdepartmental communication, enabling the integration of research procedures into routine clinical care. Their continuous contact with subjects and multidisciplinary teams also supports repeated visits, cycle-dependent interventions, laboratory coordination, follow-up, and protocol adherence9. Early CRN involvement can help identify practical risks, such as visit burden, unclear responsibilities, specimen transfer issues, medication management risks, or inadequate emergency planning42. Overall, CRNs strengthen trial feasibility, subject protection, workflow efficiency, and standardized clinical research nursing practice11.
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CRNs play an important role in assisted reproductive drug clinical trials by supporting protocol implementation, subject management, follow-up coordination, data quality, and regulatory compliance. Further development of reproductive-medicine-specific training, competency evaluation, workload management, and career pathways may clarify the CRN role and support more standardized trial implementation. As assisted reproductive drug research continues to expand in China, the systematic development of CRN positions may improv...
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All authors declare that they have no conflicts of interest related to this study.
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