|Year : 2022 | Volume
| Issue : 6 | Page : 633-638
Antibiotic usage in surgical sperm retrievals among IVF centers
Le Dang Khoa1, Ngo Dinh Trieu Vy2, Nguyen Minh Tai Loc3, Le Duc Thang4, Dang Tuan Anh5, Nguyen Phuc Hieu6, Giang Huynh Nhu7, Nguyen Dinh Tao8, Le Hoang9, David J Handelsman10
1 IVFTA, Tam Anh General Hospital, Ho Chi Minh 700000, Vietnam
IVFTA, Tam Anh General Hospital, Ha Noi 100000, Vietnam
IVF Center, 16A Ha Dong Hospital, Ha Noi 100000, Vietnam
ANZAC Research Institute, University of Sydney and Concord Repatriation General Hospital, Hospital Road, Concord, NSW 2139, Australia
|Date of Submission||27-Sep-2021|
|Date of Acceptance||20-Dec-2021|
|Date of Web Publication||25-Mar-2022|
Le Dang Khoa
IVFTA, Tam Anh General Hospital, Ho Chi Minh 700000
Source of Support: None, Conflict of Interest: None
Surgical sperm retrieval (SSR) is currently one of the most common procedures in in vitro fertilization (IVF). However, a gap between the guidelines and routine clinical practice regarding antibiotic use in SSR, which might lead to antibiotic resistance, is a challenging problem worldwide. A cross-sectional survey was conducted from May 1, 2021, to July 15, 2021, to investigate antibiotic usage by medical professionals when performing SSR in IVF centers in Vietnam. The confidential questionnaire comprised 12 items, including characteristics of the study population, awareness of antimicrobial resistance, attitude toward prescribing antibiotics, and current practice of prescribing antibiotics when performing SSR. Surveys were completed by 30 of 45 registered IVF centers (66.7%). Among 67 physicians working at those centers, the age and work-experience years (mean ± standard deviation [s.d.]) were 38.6 ± 6.6 years and 11.2 ± 7.0 years, respectively. Over 60% of them held a degree in Obstetrics and Gynecology, and over four-fifths were men. Most respondents “often/very often/always” raised awareness of antimicrobial resistance to their patients (83.3%), but only half of them “often/occasionally” prescribed antibiotics to patients with SSR in cases where the prescription would be optional. About one-tenth of respondents followed the recommendation from the American Urological Association using “prophylaxis only” for SSR patients. For more invasive SSR, physicians tended to prescribe more complicated and sometimes inappropriate regimens. In conclusion, antibiotic usage in SSR was not always appropriate among IVF centers. Further studies may define specific recommendations for regimens, intervention strategies, and programs to promote appropriate antibiotic use for SSR patients among IVF specialists.
Keywords: antibiotic usage; in vitro fertilization; prophylaxis; surgical sperm retrieval; treatment
|How to cite this article:|
Khoa LD, Trieu Vy ND, Tai Loc NM, Thang LD, Anh DT, Hieu NP, Nhu GH, Tao ND, Hoang L, Handelsman DJ. Antibiotic usage in surgical sperm retrievals among IVF centers. Asian J Androl 2022;24:633-8
|How to cite this URL:|
Khoa LD, Trieu Vy ND, Tai Loc NM, Thang LD, Anh DT, Hieu NP, Nhu GH, Tao ND, Hoang L, Handelsman DJ. Antibiotic usage in surgical sperm retrievals among IVF centers. Asian J Androl [serial online] 2022 [cited 2022 Nov 29];24:633-8. Available from: https://www.ajandrology.com/text.asp?2022/24/6/633/341021
| Introduction|| |
The prevalence of azoospermia is about 1.0% of the general population and 10.0%–15.0% of men presenting with infertility. In this scenario, surgical sperm retrieval (SSR) followed by in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) may be appropriate for achieving pregnancy., These procedures (e.g., percutaneous epididymal sperm aspiration [PESA], microsurgical epidydimal sperm aspiration [MESA], testicular sperm aspiration [TESA], testicular sperm extraction [TESE], and microsurgical testicular sperm extraction [micro-TESE]) are classified as “clean” urologic operations,, which are performed in uninfected areas with no involvement of the urinary tract, and primary closure is established after the operation.,, Adequate aseptic, germicide procedures, sterilization operating rooms, and medical instruments are necessary to forestall postoperative infection following clean urologic procedures.
However, there remain differences and controversies between various professional associations or organizations, leading to a gap between the guidelines and clinical practice regarding antibiotic use in SSR. In 2019, according to the American Urology Association (AUA) wound classification, scrotal surgery without entry to the urinary tract was considered a clean wound (Class I), and antibiotic prophylaxis is a highly recommended indication. Meanwhile, the Centers for Disease Control and Prevention (CDC) Guideline showed that additional prophylactic antibiotics should not be prescribed to wounds closed after clean procedures, even if drainage occurred from wounds. In clinical practice, prophylactic antibiotics are still regularly prescribed for preoperative preparation, and some physicians also prescribe empirical oral antibiotics for 3–5 days after the procedures., Excessive, unnecessary antibiotic usage may lead to antibiotic resistance, a challenging problem worldwide, causing higher medical costs, prolonged hospital stays, and higher mortality. This clinical practice is relevant in view of the recent increase in the number of Vietnamese IVF centers performing SSR where the patients have to self-fund infertility treatments.
To our knowledge, there has been no report on antibiotic usage of medical professionals among IVF centers when performing SSR. This study will provide valuable information to formulate appropriate intervention strategies or adjustment programs to enhance the safe use of antibiotics. The survey's primary objectives were to determine (i) the attitude and current practice of prescribing antibiotics for SSR among IVF centers and (ii) the awareness of antimicrobial resistance among physicians utilizing SSR.
| Participants and Methods|| |
Study design, recruitment, and data collection
A confidential cross-sectional survey was conducted from May 1 to July 15, 2021. All heads/directors of IVF centers or team leaders of male infertility groups of 45 IVF centers in Vietnam registered with the Ministry of Health of Vietnam were invited to participate in this survey by email. In order to understand and prepare for the response contents carefully, the questionnaires were emailed to heads/leaders of these IVF centers first. Then, the investigator called them and discussed the study details (i.e., study aims, interview duration, voluntary participation, and freely able to discontinue) with them. The answers would be kept strictly confidential and reported anonymously in aggregated form. The answer sheet will be assigned a code to appear on all questionnaires. Completion of the questionnaire was interpreted as consent to take part in the survey. Some data in questionnaires, which were not readily available in the interview, were collected afterward by phone to enable the heads/leaders to check information and fill the survey out. Partial completion response to any item was classified as a nonresponse when some or all answers were not completed. Completing more than 90.0% of questions was classified as a completed survey.
The survey was piloted in April 2021 with five clinical IVF specialists to validate the questionnaire in terms of length, the order of questions and wording, and the survey logistics. The final questionnaire contains 12 questions, including four questions for characteristics of the study population (Q1, Q2, Q3, and Q12), three questions for awareness toward antimicrobial resistance (Q4, Q9, and Q10), three questions for attitude toward prescribing antibiotics (Q7, Q8, and Q11), and the other two (Q5 and Q6) for current practice of prescribing antibiotics when performing sperm retrieval in IVF centers. The questionnaire form is shown in [Supplementary Information [Additional file 1]]. The data were stored on the computers of the investigators in Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) and password-protected files.
Terms of antibiotics usage
Surgical antibiotic prophylaxis (SAP), called “prophylaxis only”, refers to preventing infectious complications by administering one antimicrobial agent before SSR. According to the recommendation of Ministry of Health of Vietnam, World Health Organization (WHO), AUA, and American Society of Health-system Pharmacists (ASHP), the prophylaxis antibiotics should be administered before the procedure within 60–120 min while considering the half-life of the antibiotic; prophylaxis antibiotics should not be prolonged within 24 h after the procedure.,, Any antibiotics taken beyond this period were considered “prolonged prophylaxis”. The “empirical treatment” was defined as the initial empirical antibiotics for 3–5 days after the SSR., Any combination of two or more antimicrobial agents is called “combination”.
Characteristics and classifications of surgical sperm retrievals
Every procedure has its advantages and disadvantages. From other perspectives, some procedures are “simple and less invasive” than others. “Simple and less invasive” procedures in this study were defined with some characteristics, including fast, repeatable methods with minimal morbidity, no surgical exploration, and few instrument/materials (e.g., PESA). “Complicated and invasive procedures” in this study were defined with some characteristics, including longer operation time, surgical exploration/open surgery, and microsurgical expertise (e.g., micro-TESE).
All analyses were performed using R (version 3.6.2) and R Studio (version 1.3.959) software (Delaware Public Benefit Corporation and Certified B Corporation, Boston, MA, USA). Continuous variables were summarized as mean and standard deviation (s.d.), and frequencies and percentages of categorical variables were calculated. The imputation technique, which replaces any missing value with the mean of that variable in all other cases, was only used on surveys that we designated to be incomplete.
The study was conducted following the ethical standards of the Helsinki Declaration (1975, revised in 2013) and other guidelines/regulations from the Ministry of Health of Vietnam. The study was reviewed, completely approved, and monitored by the local Institutional Review Board (IRB) of Tam Anh General Hospital (protocol IRB No. TAHN.011) in Ha Noi, Vietnam. The key ethical issues were whether the analysis would put the subjects at undue risks and whether the subjects were sufficiently informed about the purpose of the study. The report would not be carried out until the local IRB approval was achieved.
| Results|| |
Of the invited 45 IVF centers, 30 (66.7%) centers completed the surveys [Figure 1]. Among 67 physicians working at the centers, the age and work-experience years (mean ± s.d.) were 38.6 ± 6.6 years and 11.2 ± 7.0 years, respectively. Over 60.0% (42) of them held a degree in Obstetrics and Gynecology, and 82.1% (55) were men. Further demographic characteristics of their clinical practices (e.g., sperm retrievals and most common complications) are given in [Table 1].
|Figure 1: Flowchart of recruitment and interview process. IVF: in vitro fertilization; COVID-19: coronavirus disease 2019.|
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|Table 1: Characteristics of medical professionals among in vitro fertilization centers and their clinical practices|
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When the physicians counseled patients about SSR, 23.3% of patients “never” and 53.3% “sometimes” required antibiotics after procedures. There was also “no impact at all” (43.3%) or “minor impact” (46.7%) of patients' expectations on the prescription of antibiotics for SSR. Furthermore, 83.3% of the physicians often/very often/always raised awareness of antimicrobial resistance to their patients [Table 2]. However, 50.0% of physicians often or occasionally prescribed antibiotics to patients with SSR in cases where the prescription might not be necessary or could be optional. The detailed protocols for each antibiotic and procedure are listed in [Table 3]. Amoxicillin/clavulanic acid, under different dosage regimens, was the most common antibiotic (46.7%) prescribed for sperm retrieval procedures, while cefuroxime showed as a second option by physicians (23.3%). [Figure 2] is built on [Table 2] by looking further at the proportion of respondents choosing antibiotic use strategy when conducting SSR. There are only 8.9% of respondents chose “prophylaxis only” for SSR patients as AUA's recommendation.
|Figure 2: Proportion of respondents choosing antibiotic use strategy when conducting surgical sperm retrievals. PESA: percutaneous epididymal sperm aspiration; MESA: microsurgical epidydimal sperm aspiration; TESA: testicular sperm aspiration; TESE: testicular sperm extraction; micro-TESE: microsurgical testicular sperm extraction.|
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|Table 2: Awareness of antimicrobial resistance and attitude of prescribing antibiotics for surgical sperm retrievals among in vitro fertilization centers|
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|Table 3: Current antibiotic regimen when performing sperm retrieval in in vitro fertilization centers|
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| Discussion|| |
Inappropriate antibiotic use poses a significant challenge to public health through the risks of increasing antimicrobial resistance (AMR), which raises medical costs, prolongs hospital stays, and creates adverse effects and mortality risks. However, gaps remain between the guidelines/recommendations and clinical practice regarding antibiotic use in clean urologic operations (i.e., SSR). The present survey addressed the antibiotic usage of medical professionals among IVF centers when performing SSR. It was found that (i) 83.3% of the respondents often/very often/always raised awareness of antimicrobial resistance to their patients; (ii) 50.0% of respondents often/occasionally prescribed antibiotics to patients with SSR in cases where the prescription might not be necessary or could be optional; and (iii) 8.9% of respondents chose “prophylaxis only” for SSR patients as a recommendation from AUA.
As mentioned above, the physicians faced the dilemma of a “good” attitude/awareness on antibiotic use/resistance or prescribing antibiotics to patients with SSR. Although there was “no impact at all” (43.3%) or “minor impact” (46.7%) of patients' expectations on the prescription of antibiotics for SSR, half of the respondents often/occasionally prescribed antibiotics to patients with SSR in cases where the prescription might not be necessary or could be optional. Moreover, IVF physicians tended to prescribe more complicated and inappropriate regimens (i.e., prolonged prophylaxis, prophylaxis combined with empirical treatment, and combination) when conducting more invasive procedures (from PESA to micro-TESE; [Figure 2]). The reasons might be prophylactic purposes (60.0%) and infection concerns at the second visit (36.7%) of IVF physicians [Table 2]. However, the possible risk of developing antibiotic resistance and increasing medical costs is of great importance rather than the postoperative infection concerns, which might be actively prevented by adequate aseptic, germicide procedures, sterilization operating rooms, and medical instruments.
Only 8.9% of respondents chose the “prophylaxis only” regimen consistent with the AUA's recommendation for clean urologic procedures, while 7.6% of respondents performed SSR without antibiotics which was consistent with a randomized controlled trial (RCT) of Wahyudi et al. The only RCT study, in which the most frequently performed operation was SSR, showed that clean urologic operations could be safely performed without prophylaxis antibiotics. However, this study showed some limitations, especially the small sample size might make it difficult to determine whether a particular outcome is a factual finding. Of note, the rest of the respondents (approximate 83.5%) prescribed more complicated and inappropriate regimens (including prolonged prophylaxis, prophylaxis combined with empirical treatment, and combination) as compared to AUA's recommendation [Figure 2]. This was vastly higher than the CDC's report, which showed that up to 50.0% of antibiotic use in humans is unnecessary or inappropriate.
The potential explanations for this inappropriate antibiotic usage need to be elucidated, but few reasonable hypotheses remain. First, there may be confusion due to differences between guidelines of various professional associations or organizations on antibiotics use when performing SSR.,,,, These guidelines might lead to differing clinical perspectives on antibiotics usage on SSRs among IVF physicians with different backgrounds (62.7% were Obstetrics and Gynecology physicians, 34.3% were Andrologists, and 3.0% were Urologists), as shown in [Table 1]. Second, the crucial principles of antimicrobial therapy might be affected by many variables. Essential considerations when prescribing antimicrobial therapy might include behavior and expectations of local patients, doctor's experience, prior knowledge of bacteria known to affect SSR patients, local bacterial resistance patterns, cost-effective drugs for the shortest duration necessary, and more.
This study highlights the need for further studies to confirm appropriate antimicrobial strategies for SSR (e.g., no treatment versus prophylaxis, prophylaxis versus prolonged prophylaxis, and prophylaxis vs empiric), which leads to consensus guidelines between various associations and organizations and between specialities. Additional data are also needed to make specific recommendations toward dosages, routes, duration of therapy, and timing of presurgical antimicrobials prescribed for SSR patients. Moreover, the behavior and attitudes of IVF specialists in prescribing antibiotics might help policymakers formulate intervention strategies and promotion programs on the appropriate use of antibiotics shortly. Finally, this survey might be recommended to other countries to increase the generalizability of the study with a wider range of population groups. The study question also refers to other common procedures in reproductive medicine (e.g., oocyte collection).
This study also has several limitations. First, the nonresponse bias might occur because the survey measured only 67.0% of registered IVF centers. Second, the respondents were the heads/directors of IVF centers or team leaders of male infertility groups instead of IVF specialists who do the daily prescribing of antibiotics. Although these might not completely represent the opinions of all IVF specialists in their everyday clinical practices, the feedbacks of leaders/heads mostly showed the policy in which IVF centers were officially complying. Third, the study was only based on a quantitative approach. Future studies should include a qualitative aspect to gain a deep understanding of these issues.
| Conclusions|| |
There was inappropriate usage of antibiotics in surgical sperm retrieval among IVF centers. Further studies are needed to make specific recommendations toward regimens, intervention strategies, and promotion programs on the appropriate use of antibiotics for SSR patients among IVF specialists.
| Author Contributions|| |
LDK, NDTV, NPH, GHN, LH, and DJH participated in study design and protocol writing. NDTV, NMTL, LDT, DTA, NPH, GHN, NDT, and LH conducted participants' enrolment, execution, and coordination. LDK, NDTV, NMTL, LDT, DTA, NPH, GHN, NDT, and LH collected the data of the study. LDK, NDTV, and NMTL performed statistical analysis and drafted the manuscript. LDK, NDTV, NMTL, LDT, DTA, NPH, GHN, NDT, and LH revised the article before DJH provided editorial corrections. All authors read and approved the final manuscript.
| Competing Interests|| |
All authors declare no competing interests.
| Acknowledgments|| |
We want to send special thanks to the Center for Training and Scientific Research staff, Tam Anh General Hospital, for their logistics support. We also would like to recognize the academic support of Dr. Le Xuan Nguyen and Dr. Vo Anh Hung (Tam Anh General Hospital, Ho Chi Minh, Vietnam) since the start of this project. We are very grateful to 30 IVF centers (from the North to the South of Vietnam) and Hanoi of Society Assisted Reproduction (HASAR) for their generosity in sharing their information.
Supplementary Information is linked to the online version of the paper on the Asian Journal of Andrology website.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]