Balancing Post-Vasectomy Adequate Sperm Clearance with Patient Compliance: Time to Rethink?

Abstract

Background/Objectives: The American Urological Association (AUA) vasectomy guidelines’ current recommendation to obtain the first post-vasectomy semen analysis (PVSA) from 8 weeks to 16 weeks post-vasectomy is based predominantly on azoospermia rates. However, non-compliance with semen analysis after vasectomy is a known problem in this patient population. An approach that optimizes clearance and compliance is essential when adopting appropriate post-vasectomy care guidelines, specifically the scheduling of the first PVSA. We aimed to conduct a systematic review and meta-analysis of studies assessing compliance and clearance to determine the optimal time of first PVSA. Methods: Databases (MEDLINE, EMBASE, POPLINE) were searched for studies that contained the following: rate of azoospermia and rare nonmotile sperm (RNMS), compliance, recanalization, persistent RNMS, pregnancies, and incidence of repeat vasectomy. Results: A total of 28 studies were included in this review. The patient compliance was 47–100% and trended downward with increasing time to first PVSA. There was a positive trend in azoospermia rate as post-vasectomy time increased, but this plateaued at 8 weeks. Compliance and post-vasectomy semen analysis clearance (PVSAC) converged at 5.7 weeks, with rates of 74.5% and 74.6%, respectively. A proportion of 1.5% of patients exhibited persistent RNMS. Recanalization events had an incidence rate of 1.5%. Repeat vasectomies were performed in 1.6% of patients. Conclusions: Based on our study optimizing post-vasectomy semen clearance with follow-up compliance, we recommend initial PVSA between 6 to 18 weeks post-vasectomy, as this offers improved compliance over current AUA guidelines which recommend PVSA at 8 to 16 weeks and allows for the identification of instances of “subclinical recanalization” that may be missed at later time points.

1. Introduction

Vasectomy is a popular method of male contraception that is utilized across many countries as a safe, effective, and economical choice for patients who desire permanent contraception. Approximately 11% of men between the ages of 15 and 44 in the USA have had a vasectomy, a rate that has been stable since the 1980s [1,2]. Current US census data of men in the same age range amounts to 65.5 million men, which translates to approximately 7 million US men who have had a vasectomy.

The effectiveness of vasectomies for permanent contraception is excellent, with most studies reporting success rates of close to 99% [3,4,5,6,7]. However, post-vasectomy care guidelines for practitioners have been historically ambiguous, with a wide range of time intervals for post-vasectomy semen analysis (PVSA) [8]. This has led to ongoing post-procedure obstacles such as differing recommendations by practitioners, patients that are unaware of the post-vasectomy interval requiring continued contraception, and low patient compliance in PVSA, which grants ‘clearance’ of patient sterility. The current AUA guidelines, established in 2015, provided the first attempt at standardized post-vasectomy care. These guidelines recommend patients refrain from ejaculation for 1 week and continue contraception until a negative semen sample is obtained. The time interval for the first semen analysis is currently between 8 and 16 weeks post-vasectomy, with substantial discretion left to the performing surgeon. Ultimately, a definitive, evidence-based time point for scheduling the first PVSA is lacking.

The decision to establish robust post-vasectomy guidelines and schedule the first PVSA can essentially be broken down into two main criteria of clearance and compliance. Sperm clearance, or post-vasectomy semen analysis clearance (PVSAC), based on the original 2012 AUA guidelines [9], which were amended in 2015, is established by achieving either azoospermia or <100,000/mL nonmotile sperm, with a high variability in time to clearance post-vasectomy. Patient compliance is understood as the completion of PVSA for clearance post-vasectomy. This has been shown to be consistently poor across previous studies and varies by time from vasectomy to PVSA appointment. Proper standardization of post-vasectomy care is nuanced by these three factors.

The objective of this study is to review the current literature and determine optimal post-vasectomy care guidelines, specifically the scheduling of the first PVSA, based on criteria of clearance and compliance to maximize patient outcomes and satisfaction. To our knowledge, this is the first systematic review to investigate and suggest alterations to optimize post-vasectomy care guidelines.

2. Methods

This systematic review was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [10]. This study was not registered prior to being conducted. The purpose of this search strategy was to find all articles related to the primary outcome measure of azoospermia (a lack of detectable sperm when using the semen-analysis method outlined in the relevant study). Articles were included that either measured the percentage of successful cases in post-vasectomy follow-up visits or examined the time taken to reach azoospermia. Secondary outcome measures included compliance, incidence of recanalization, persistent RNMS, number of pregnancies, and incidence of repeat vasectomy. Secondary outcome measures were not a requirement for a study to be included in this review, but data from secondary outcome measures were gathered and analyzed (there is no registration number for this research).

This review adapted a search strategy that investigated four databases. The original search strategy surveyed MEDLINE and was adapted to search POPLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The range in publication dates was from 1 January 2002 to 1 March 2022. The search strategy used for PubMed was (1) vasectomy, AND (2) sperm OR azoospermia OR semen analysis OR nonmotile sperm OR follow-up OR success OR failure, NOT (3) IVF-ICSI. This search strategy was adjusted to meet the technical search criteria for POPLINE, EMBASE, and CENTRAL. The complete search method is outlined and represented visually in Figure 1 and Figure 2.

After the completion of the search, duplicate studies and irrelevant studies were removed. One reviewer screened titles and abstracts of search results for relevant studies to be included. Both the primary and secondary reviewers independently examined the full text of any studies deemed to meet the selection criteria. Exclusion criteria included duplicate studies, studies that were irrelevant to the manuscript, studies that were not original research, and those that did not have full texts available (including conference abstracts). If both reviewers determined that the study met the criteria for inclusion, the study data were extracted and added to an Excel spreadsheet, and identifying information and pertinent data points were recorded. Microsoft Excel version 2406 was used to collect all data and complete all data analyses. Figures were created using Microsoft Excel functionalities, including scatter functions fit with log linear trend lines for figures. A brief discussion between reviewers resolved any discrepancies in study inclusion. There were several scenarios in which groups published several reports regarding their experiences with post-vasectomy follow-up. Therefore, there was the possibility of an overlap in data sampling due to a shared pool of patients. The study with the largest sample size was identified and utilized to resolve this issue.

Due to variability in study methodologies and reporting, it was not possible to combine the clinical data from the different studies for a meta-analysis.

Table 1. List of included studies organized by date, number of patients included in study, and follow-up length.

Reference	Date	Number of Patients	Follow-Up Length
Mason et al. [11]	October 2001	163	Up to 34 Weeks
Pearce et al. [12]	August 2002	72	Up to 3 Months
Labrecque et al. [5]	December 2002	5460	Up to 16 Weeks
Barone et al. [13]	September 2003	217	Up to 24 Weeks
Sokal et al. [14]	March 2004	813	Up to 14 Weeks
Eisner et al. [15]	May 2004	106	Up to 3 Months
Chawla et al. [16]	July 2004	295	Up to 1 Year
Barone et al. [17]	July 2004	364	Up to 24 Weeks
Katsoulis et al. [18]	March 2005	263	Up to 30 Weeks
Song et al. [19]	December 2005	144	Up to 1 Year
Dhar et al. [20]	April 2006	327	Up to 12 Weeks
Labrecque et al. [21]	September 2006	2618	Up to 4 Months
Dilbaz et al. [22]	March 2007	279	Up to 2 Months
Dhar et al. [23]	May 2007	170	Up to 12 Weeks
Roushani et al. [24]	January 2008	142	Up to 4 Months
Trollip et al. [25]	April 2009	479	Up to 1 Year
Munro et al. [26]	August 2009	427	Up to 16 Weeks
Amory et al. [27]	May 2010	11	Up to 24 Weeks
Korthorst et al. [28]	June 2010	1073	Up to 12 Weeks
Singh et al. [29]	August 2010	741	Up to 3 Months
Senanayake et al. [30]	May 2011	685	Up to 20 Weeks
Farrokh-Eslamlou et al. [31]	June 2011	334	Up to 24 Weeks
Duplisea et al. [32]	June 2013	493	Up to 4 Months
Coward et al. [33]	July 2013	972	Up to 20 Weeks
DeRosa et al. [34]	November 2014	895	Up to 18 Weeks
Bieniek et al. [35]	May 2015	111	Up to 18 Weeks
Altok et al. [36]	November 2015	200	Up to 4 Months
Oliveira et al. [37]	March 2018	29	Up to 25th Ejaculation

shows which studies were included in each review phase. As the study data extracted for this review were heterogeneous and not normally distributed, the median value, and thus box and whisker plots, were used to assess trends.

3. Results

Using the outlined methodology, a total of 843 articles were identified from the 4 databases. MEDLINE produced 574 potential studies, EMBASE produced 64 potential studies, CENTRAL produced 70 potential studies, and POPLINE produced 135 potential studies. After full screening, 28 articles were included in the study.

3.1. Compliance

All 28 studies included in this review provide data regarding patient follow-up. Compliance was defined as at least one completed follow-up PVSA. Due to variations in the reporting of compliance and accounting for patients lost to follow-up, full compliance was difficult to assess. Compliance rates ranged from 47% to 100% across studies, with a median of 73%. Figure 3 presents the compliance rate versus time after vasectomy for the first PVSA sample provided. As time to first PVSA increases, compliance decreases, demonstrating a negative relationship. Of note, the first data point at one week was from a clinical trial [15] of 106 patients.

3.2. Azoospermia

In total, 21 studies reported the percentage of patients achieving azoospermia as a function of post-vasectomy time interval. Azoospermia was defined as the absence of sperm in a post-vasectomy semen specimen that was analyzed within 2 h, well mixed, and uncentrifuged, except in the case of three studies [11,12,36], which defined successful vasectomy as azoospermia in two consecutive PVSAs. Outcome measures from these studies were extracted to reflect the AUA guidelines, requiring only one azoospermic sample. Figure 4 also demonstrates a positive trend in the percentage of patients achieving azoospermia as post-vasectomy time increases. After week 6, the median number of patients achieving azoospermia does not fall below 65%. The three data points in Figure 4 measuring 100% azoospermia represented in weeks 26, 28, and 30 all originate from [18], a retrospective case series of 216 patients. There was only one study [19] that measured outcomes up to 52 weeks post-vasectomy. It is important to note that this figure does not include patients exhibiting RNMS, which is considered a successful vasectomy outcome under AUA guidelines. Median percentage of patients achieving azoospermia based on number of ejaculations were calculated in two studies, as seen in Figure 5.

3.3. Rare Nonmotile Sperm

Twelve studies reported the percentage of patients achieving vasectomy success via the presence of ≤100,000 nonmotile sperm, also known as RNMS. As stated previously, AUA guidelines specify that semen samples be analyzed within 2 h, be well mixed, and uncentrifuged. They also state that the presence of RNMS in a sample under these conditions is sufficient to demonstrate its sterility, therefore classifying the patient as having achieved a successful vasectomy. Figure 6 presents the overall trend for the percentage of patients with RNMS on PVSA against post-vasectomy time without apparent time trends. Figure 7 shows the percentage of patients exhibiting RNMS in the first PVSA versus the time at first PVSA. Three studies had the first PVSA scheduled 12 weeks post-vasectomy [19,28,33], with the next most common time interval being 4 weeks post-vasectomy, which was utilized by two studies [25,26]. Figure 8 shows the percentage of patients with RNMS in the first PVSA based on the time the first PVSA was taken. No apparent time trends were present across studies, and one study [27] was an outlier at 4 weeks, most likely due to the small sample size. Due to wide variability across studies, it is difficult to conclude overall trends.

3.4. Persistent RNMS

A total of 14 studies included the percentage of patients exhibiting persistent RNMS as an outcome measure. Persistence of RNMS is defined in this review as a sample exhibiting RNMS six months after vasectomy. The AUA guidelines recommend stoppage of contraception after patients demonstrate persistent RNMS. However, some surgeons performing vasectomies may offer patients the option for a repeat vasectomy. Across the 14 studies, 157 patients exhibited PVSA samples demonstrating persistent RNMS. Of 10,329 total patients, this equates to approximately 1.5% of patients exhibiting persistent RNMS, with the understanding that some patients could have been lost to follow-up or may have decided not to undergo repeat vasectomy. Of 57 patients demonstrating persistent RNMS there was one reported pregnancy, resulting in a pregnancy rate of 0.64% in the RNMS patient population.

3.5. Recanalization and Vasectomy Failure

Vasectomy failure was determined by a patient exhibiting persistent high sperm counts on multiple PVSAs or via partner pregnancy. The etiologies of a vasectomy failure are multiple, and may include recanalization, rare cases of duplication of vas deferens, inadequate procedural quality by the practitioner/clinic, and failure to follow instructions regarding contraception prior to sterility confirmation. We studied published data on vasectomy failures due to recanalization. A total of 17 studies measured the percentage of patients deemed to have experienced recanalization. Although the definition of recanalization differs slightly among practitioners, the following general guideline was used in this review: a patient was deemed to have undergone recanalization if initial PVSA showed azoospermia or RNMS and any subsequent PVSA showed a substantial increase in the number of motile sperm. Given the time variability for patients to achieve azoospermia, there are no current strict time guidelines to define recanalization. Across studies, there were 204 vasectomy failures due to recanalization in approximately 13,475 patients, equating to 1.5% of patients. Vasectomy failure was diagnosed as early as 1 month to 3 years post-vasectomy. Identification of patients who never achieved azoospermia/RNMS versus patients demonstrating semen analysis patterns of recanalization was difficult due to lack of reporting from initial testing of semen samples in several studies. Persistent RNMS is not classified as vasectomy failure or recanalization and therefore was not included in the aggregation and analysis for this portion of the data.

3.6. Repeat Vasectomies

Across the included studies, repeat vasectomies were performed (1) if a vasectomy failure was diagnosed and (2) if patients with persistent RNMS elected for repeat vasectomy as offered in several studies. A total of 186 repeat vasectomies were performed across 17 studies including 11,659 patients, equating to approximately 1.6% of patients, although this may not accurately reflect the true number due to patients with PVSA samples with inadequate sterility or recanalization being lost to follow-up or deciding to forgo any further procedures.

3.7. Pregnancies

In total, there were eleven pregnancies across four studies post-vasectomy. None of the pregnancies were confirmed by paternal DNA analysis; however, subsequent semen analysis was performed in seven out of the eleven patients with confirmed pregnancy reported. Of these seven patients, four were found to have a positive PVSA sample demonstrating viable motile or nonmotile sperm.

4. Discussion

4.1. Appropriate Time Interval or Ejaculation Count for First PVSA

According to AUA guidelines, the appropriate time range for the first PVSA is eight to sixteen weeks, ultimately leaving the decision of when to perform the first PVSA to the judgment of the surgeon. In this study, we demonstrate a negative time trend for percent compliance as time to first PVSA increases (Figure 3). We found a median percent compliance greater than 80% up to four weeks post-vasectomy, which is substantially higher than the historically poor 50–60% of patients completing a PVSA in previous studies [15,20,28,36,38]. This is likely in part due to most of the data within this time range originating from clinical trials and prospective case series, both situations in which the importance of semen sampling was likely more heavily stressed in comparison with retrospective studies. Given the benefits of shorter PVSA times regarding compliance, a shorter time to PVSA may prove beneficial. However, this must be balanced with the goal of reducing unnecessary subsequent appointments due to premature PVSAs. Premature PVSAs themselves should be considered when selecting a proper timeline for first PVSA in the context of patient satisfaction, anxiety, and confidence in their choice of contraception. Conducting the first PVSA at an earlier time post-vasectomy would improve compliance, but this must be balanced with the risk of a first PVSA showing non-clearance and causing inadvertent patient anxiety and dissatisfaction.

After a successful vasectomy, motile sperm disappear within a few weeks [21]. Evidence shows that, at week 6, there is a median percent of azoospermia at 65%. From weeks 10 to 16, the median percent ranges from 70% to 73%. With the inclusion of RNMS as an appropriate endpoint for vasectomy in the AUA guidelines, it is important to consider the median percentage of patients achieving RNMS, which ranges from 12% to 34% from week 6 to week 16, into the vasectomy success rate.

Identifying the appropriate interval for initial post-vasectomy testing has historically been based on azoospermia rates. However, we propose the addition of PVSA compliance as an appropriate endpoint and the effect of post-vasectomy interval on compliance rate. By plotting both PVASC and compliance concurrently, we see in Figure 9 that the trend lines, with coefficients of determination of 0.44 and 0.93, respectively, intersect at approximately week 5.7 and not at week 8, which is the current earliest recommendation for PVSA. The rates for PVASC and compliance at the convergence point are 74.5% and 74.6%, respectively. This indicates the AUA recommendation for post-vasectomy interval testing may be optimally adjusted two weeks earlier. For patients who are unaware of this post-vasectomy interval requiring continued contraception, the ability for physicians to verify vasectomy success as early as possible is crucial for patient satisfaction.

The use of ejaculation count on scheduling PVSA is not included in current AUA guidelines, which is supported by one study [21] which shows high variability in the effect of ejaculation count on the rate of azoospermia. Figure 7 represents findings indicating positive relationships when measuring percent azoospermia against ejaculation count in two studies, but the rate of patients achieving azoospermia in one study [29] is approximately twice that of the second [37]. A previous study [21] found that 30 ejaculations were needed before 50% of patients achieved azoospermia. Furthermore, one study [37] found that patients were highly unreliable in accurately counting the number of ejaculations.

For these reasons, we propose that the guidelines for scheduling the first PVSA, 8 to 16 weeks, can be adjusted to 6 to 16 weeks, and we support the idea of avoiding the use of ejaculation counts as reliable markers for scheduling PVSA.

4.2. Appropriate Criterion for Vasectomy Success

Prior to publication of the current AUA guidelines, two consecutive azoospermic PVSAs one month apart were generally required before patients were advised to stop contraception use. The origin of this prudent approach was largely due to fear of legal action and the considerable financial implications associated with a pregnancy after vasectomy, i.e., a failed vasectomy. However, almost all large-scale case series studies to date show the percent of vasectomy patients ultimately achieving azoospermia never reaches 100% and two studies [21,33] suggest that the percent of men who fully achieve azoospermia varies between 70% to 85%. One study [19] suggests that approximately 10% of patients exhibit RNMS up to one-year post-vasectomy, categorizing these patients as showing persistent RNMS. Evidence from this review also suggests that the percent of patients achieving RNMS status demonstrates no clear time trend and does not reach 0%, even up to 1-year post-vasectomy. In addition, there is no evidence-based consensus that requiring two consecutive samples, as opposed to one, decreases the risk of future pregnancies.

With respect to RNMS, the exact cause is not known. It has been hypothesized that RNMS can be due to incomplete emptying of seminal vesicles in some patients. Conditions such as diabetes can decrease the force of ejaculation and hence lead to prolonged rare non motile sperms to persist in the ejaculation. Some medications or neuropathies, which can decrease the pelvic musculature force of contraction, and the condition of megalocystis (pathological dilation of seminal vesicles), which can decrease ejaculatory force, have also been implicated as a cause of RNMS. Rare cases of delayed recanalization can sometimes lead to RNMS. In the case of vasectomy, RNMS is not considered a technical failure. Technical failure is defined as the presence of motile sperms in the post vasectomy semen. This can be due to the same vas being occluded twice, the presence of vas duplication or spontaneous canalization.

One study [28] suggests that most instances of recanalization happen between two to six weeks, thus two consecutive samples after eight weeks would not be able to identify these “subclinical recanalizations”. Spontaneous recanalization as a possible cause for vasectomy failure was first investigated in patients who achieved pregnancy with their partners several years after a successful vasectomy had been determined. Late failures due to recanalization are usually revealed with unsuspecting pregnancies; however, there is no consensus on the frequency or pattern of recanalization in this time range. With regards to vasectomy technique leading to recanalization, it has been hypothesized that ligating the ends of vasa is more unpredictable in achieving consistent occlusion as compared with metallic clips. Some ligatures may dissolute sooner than expected, whether due to suture quality or increased lytic enzyme activity in the host, especially in the presence of infection. This can potentially increase the chances of vasectomy failure with resultant RNMS or failure.

Finally, three recent studies [20,28,33] all suggest that a nonmotile sperm count of <100,000/mL is sufficient to consider a vasectomy a success, with no statistically significant difference in outcomes when compared with that of true azoospermia. In addition, three studies [33,34,35] demonstrate evidence of significant cost-saving and timesaving measures for utilizing RNMS without compromise in clinical outcomes. In this review we found current AUA guidelines, which recommend the stoppage of contraception after “one well-mixed, uncentrifuged fresh post-vasectomy semen specimen shows azoospermia or only rare nonmotile sperm (≤100,000 nonmotile sperm/mL)”, to be appropriate.

4.3. Major Limitations and Research Perspectives

A major limitation of this review is the dearth of high-quality evidence. Most studies in this review were retrospective case series, which carries an evidence level of IV. Another limitation is the lack of comparability of included studies due to variations in guidelines for the testing of post-vasectomy samples and the reporting of outcomes.

Future research perspectives should be focused on the standardization of a time interval and methodology for checking post-vasectomy semen analysis. Causes of RNMS need to be further studied. Additionally, future randomized clinical trials of different timepoints correlating compliance and PVASC are needed to provide higher power evidence to corroborate our findings.

5. Conclusions

In this review and analysis of the literature we found an optimal PVSA timepoint for compliance and PVASC at 5.7 weeks, which corresponds with PVASC and compliance rates of 74.5% and 74.6%, respectively. Therefore, we recommend initial PVSA between 6 weeks to 18 weeks post-vasectomy, as this offers improved compliance over current AUA guidelines, which recommend PVSA at 8 weeks to 16 weeks, and allows for the identification of instances of “subclinical recanalization” that may be missed at later timepoints. An approach that optimizes clearance and compliance is essential in order to adopt appropriate post-vasectomy care guidelines. Further studies utilizing randomized controlled trials of different time points are necessary to corroborate our findings.