Factors affecting patency time and semen quality in a single-armed microsurgical vasoepididymostomy

Abstract

Although microsurgical vasoepididymostomy (MVE) is an effective treatment for epididymal obstructive azoospermia, some patients may experience delayed patency or suboptimal semen parameters after patency. However, research into patency time, semen quality postpatency, and associated influencing factors remains limited. This study aimed to address these issues by evaluating 181 patients who underwent at least one-sided MVE employing asingle-armed longitudinal intussusception vasoepididymostomy technique, with a follow-up period of over 12 months for 150 patients. The overall patency rate was 75.3%, with 86.0% of patients achieving patency within 6 months following MVE. Unexpectedly, factors such as age, history of epididymitis, duration of surgery, side of anastomosis, sperm motility in epididymal fluid, and the site of anastomosis showed no correlation with patency time. Nonetheless, our univariate and multivariate linear regression analysis indicated that only the site of anastomosis was positively correlated with and could independently predict postoperative total motile sperm count. Therefore, the site of anastomosis might serve as a predictor for optimal postoperative semen quality following the MVE procedure.

INTRODUCTION

Epididymal obstructive azoospermia (EOA) refers to a condition where the testes produce sperm normally, but the sperm cannot be ejaculated because of a blockage in the epididymal ducts, resulting in azoospermia and accounting for 30%–77% of azoospermic nonvasectomized men.1 Microsurgical vasoepididymostomy (MVE) is an effective surgical method for treating EOA and is considered the most challenging surgical procedure of all male microsurgeries.2

MVE techniques have gradually developed and improved over the past few decades.3,5,6,7,8 The two-suture double-armed longitudinal intussusception vasoepididymostomy (DA-LIVE) procedure has demonstrated superior outcomes and has now become the established standard of care.8 However, Monoski et al.9 showed comparable patency rates to the DA-LIVE procedure using the single-armed MVE method in animal experiments. Zhao et al.10 first performed a two-suture single-armed longitudinal intussusception vasoepididymostomy (SA-LIVE) for EOA in humans. They believed that this approach offered the advantage of using an easily accessible and cost-effective single-armed suture.

Several studies have reported that the patency rates of SA-LIVE range from 55.2% to 83.1%.11,12,13,14,15,16 Despite the established efficacy of SA-LIVE in EOA management, uncertainties remain, particularly in the patency time and semen quality postsurgery. The length of time required for postoperative patency of SA-LIVE, sperm parameters, and related influencing factors are critical issues for both patients and surgeons. Extended patency time and potential suboptimal sperm quality postpatency may not fulfill patients’ and their partners’ desires for early conception. Hence, further studies are essential to elucidate the factors impacting patency time and semen quality after MVE employing SA-LIVE technique.

Therefore, this study aimed to investigate the patency time and semen parameters after SA-LIVE. Simultaneously, relevant influencing factors were analyzed to provide effective information for treatment and decision-making in patients with EOA.

PATIENTS AND METHODS

Study population and participants

We retrospectively collected data from 181 patients diagnosed with EOA who underwent the SA-LIVE procedure at the First Affiliated Hospital of Fujian Medical University (Fuzhou, China) from October 2019 to February 2023. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Fujian Medical University [MRCTA, ECFAH of FMU (2019) 213] and was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients.

The diagnostic criteria for EOA included azoospermia confirmed by at least two centrifuged semen analyses,17 and normal serum levels of total testosterone, follicle-stimulating hormone, and inhibin B. No significant genetic abnormalities were detected through chromosome analysis of peripheral blood lymphocytes and Y chromosome microdeletion testing. Color Doppler ultrasound examination (GE LOGIQ Fortis; GE Healthcare, Chicago, IL, USA) showed at least one normal testicular volume and the presence of vas deferens. Magnetic resonance imaging (MRI; Magnetom Prisma; Siemens, Munich, Germany) showed no abnormalities in the seminal vesicles and prostate. This study exclusively included cases of obstructive azoospermia due to epididymal obstruction, excluding cases of intratesticular obstructive azoospermia and those with ejaculatory duct obstruction.

SA-LIVE surgical approach

The patients were positioned supine and given combined lumbar and epidural or general anesthesia. A surgical microscope with a maximum magnification of 20× (Zeiss S88; Carl Zeiss, Oberkochen, Germany), an inverted microscope (CKX31; Olympus, Tokyo, Japan), a microbipolar electrocautery, and standard microscopic instruments were prepared for the procedure.

All surgeries were performed by the same surgeon (SXT). We confirmed the presence of epididymal obstruction by observing the absence of sperm in fluid collected from the testicular end of the vas deferens following its partial transection under a microscope. To ensure the patency of the distal vas deferens, we injected a diluted solution of methylene blue into the vas deferens lumen toward the seminal vesicles and verified the presence of methylene blue in urine. By examining the epididymis microscopically, we determined the locations of blockages within the epididymis and pinpointed an appropriately dilated epididymal duct proximal to the obstruction. This segment typically exhibited dilation, indicating its suitability for anastomosis. The chosen longitudinal epididymal tubule was located as close as possible to the blockage for anastomosis. A precise incision was made into the epididymal tunic, ensuring alignment with the vas deferens’ diameter. The identified epididymal tubule was then carefully dissected under microscopic guidance, preparing for subsequent anastomosis (Figure 1a).

Figure 1.

The two-suture single-armed longitudinal intussusception microsurgical vasoepididymostomy surgical approach. (a) A micro-marking pen was used to mark four micropoints A2, A1, B1, and B2 at 1-o’clock, 5-o’clock, 7-o’clock, and 11-o’clock in the muscular layer of the vas deferens as the insertion points. The vas deferens and epididymal epididymis were fixed with an 8-0 prolene thread at 6-o’clock in the direction of the vas deferens. Two 10-0 single-armed prolene threads penetrated the vas deferens lumen from the outside to the inside from the mucosal layer of the vas deferens at marked points at the (b) 5-o’clock and (c) 7-o’clock positions. (d) A sharp knife gently cut the wall of the epididymal duct longitudinally between the two single-armed prolene threads, and a thin tube was used to suck out spilled epididymal fluid. (e) The opening on the longitudinal epididymal ducts are clearly visible. Two single-armed prolene threads penetrated the vas deferens cavity from the inside to the outside at (f) 11-o’clock and (g) 1-o’clock, through the muscular layer. Two 10-0 Prolene threads were gently tightened, first tying (h) one thread and then (i) the other, and then fully dragging the open epididymal duct into an intussusception within the vas deferens lumen. (j) Schematic diagram of single-armed two-suture microsurgical longitudinal intussusception vasoepididymostomy.

Subsequently, the vas deferens was completely transected under a microscope, the proximal vas deferens was ligated, and the distal vas deferens was freed to reduce anastomotic tension. A micro-marking pen was used to make four micropoints at the 1-o’clock, 5-o’clock, 7-o’clock, and 11-o’clock positions in the muscular layer of the vas deferens as insertion points (Figure 1a). One 8-0 prolene thread (W2777; 6.5 mm, 3/8C; Ethicon, Somerville, MA, USA.) was used to fix the outer membrane of the vas deferens and epididymis in the 6-o’clock position. Two 10-0 single-armed prolene threads (W2790; 3.8 mm, 3/8C; Ethicon.) were used to penetrate the vas deferens lumen from the outside to the inside of the mucosal layer at the marked points at 5-o’clock and 7-o’clock positions (Figure 1b and 1c). Two parallel stitches were sewn into the preanastomosed epididymal tube without temporarily pulling it out. A sharp knife was used to gently cut the wall of the epididymal tube longitudinally between the two single-armed prolene threads (Figure 1d and 1e). After the epididymal fluid overflowed, a thin tube was used to draw and dilute the fluid, and the presence of sperm was immediately observed under an inverted microscope. After microscopically identifying the presence of sperm, two single-armed 10-0 prolene threads (Ethicon) were delicately pulled out and threaded through the vas deferens lumen from the inside out, precisely at the 1-o’clock and 11-o’clock positions (Figure 1f and 1g).

The surgical steps described above are similar to those previously reported by Hong et al.11 However, we made minor adjustments to our operating procedure. We also utilized an 8-0 prolene thread (Ethicon) to suture the vas deferens and epididymal tunic in the 12-o’clock direction. Before proceeding to tie the knot, we chose to first gently tighten and separately tie the two 10-0 prolene threads (Ethicon; Figure 1h and 1i). This modification had an advantage in that the epididymal tubules were precisely intussuscepted into the lumen of the vas deferens under direct visualization through the microscope. The schematic diagram of the procedure was shown in Figure 1j.

Finally, the vas deferens and epididymal tunic were intermittently sutured with 12–14 stitches using 8-0 prolene threads (Ethicon), serving to secure and reduce tension.

Postoperative care and follow-up

After the surgery, patients were instructed to wear a scrotal support for 6 weeks and refrain from strenuous exercise. Masturbation and sexual intercourse were not allowed for 4 weeks, after that sexual activity was resumed 1–2 times per week. The first two semen analyses were conducted at 1.5 months and 3 months after surgery, followed by subsequent analyses at 4–6 months, 7–9 months, and 10–12 months or later after the procedure. The semen analysis timing, semen parameters, and the spouse’s pregnancy status were recorded either through outpatient consultations or over the phone. The 5^th edition of the World Health Organization standards17 was employed for semen analysis, with our laboratory’s sperm analysis corresponding with the standardization described in the inspection table published by Björndahl et al.18

Patency was defined as a sperm concentration ≥1 × 104 ml⁻¹ in the postoperative semen sample.19 The patency time was defined as the months between surgery and the first semen analysis that confirmed patency. If sperm was initially detected and then not detected again more than two times, re-obstruction was considered. Clinical pregnancy in the patient’s partner indicated successful natural pregnancy. If no sperm was found in the semen examination after more than 12 months postoperatively, assisted reproductive technology was recommended.

Statistical analyses

SPSS 26.0 software (IBM Corp., Armonk, NY, USA) was used for statistical data processing, and the measurement data were expressed as mean ± standard deviation (s.d.) or median (interquartile range [IQR]). Count data were described using examples or percentages. Data distribution was assessed using the Shapiro–Wilk test, and homogeneity of variance was examined using Levene’s test. Pearson’s Chi-square test was used to compare the rates. The Mann–Whitney U test was employed to compare data that did not conform to the normal distribution. Univariate linear regression analysis was conducted to ascertain the determinants of patency time. Additionally, both univariate and multivariate linear regression analyses were conducted to identify the factors influencing total motile sperm count (TMSC) among patients who achieved patency following MVE. All statistical tests were two-tailed, with statistical significance set at P < 0.05.

RESULTS

In our study, 181 patients successfully underwent at least a one-sided MVE. Of these, 42.0% (76/181) had a history of epididymitis, and 58.0% (105/181) had idiopathic causes for their condition; none were related to vasectomy. We successfully followed up 150 of these patients over 12 months. The follow-up duration (mean ± s.d.) was 15.2 ± 2.5 months, ranging from 12 months to 29 months. Patients’ ages ranged from 20 years to 49 years (mean ± s.d.: 30.2 ± 5.0 years). Of the 150 patients, 122 patients underwent bilateral MVE, while the remaining 28 patients had unilateral MVE. Thirty-five patients underwent anastomosis solely at the caput, while 115 patients underwent anastomosis on at least one side to the corpus or cauda.

The patency rate was 75.3% (113/150). However, three initial patent cases later developed re-obstruction, as evidenced by the absence of sperm in subsequent evaluations, resulting in a re-obstruction rate of 2.7% (3/113). We investigated factors associated with successful patency versus nonpatency after the MVE procedure. Our analysis indicated that a significantly higher proportion of patients with successful patency had motile sperm in the intraoperative epididymal fluid compared with those without patency (P < 0.001; Table 1).

Table 1.

Characteristics of patients with patency vs nonpatency after microsurgical vasoepididymostomy

Characteristic	Patency (n=113)	Nonpatency (n=37)	P
Age (year)	30.0 (27.0–32.0)	30.0 (27.0–34.5)	0.406
History of epididymitis, n (%)	62 (54.9)	14 (37.8)	0.072
Duration of surgery, n (%)			0.830
<3 h	68 (60.2)	23 (62.2)
≥3 h	45 (39.8)	14 (37.8)
Side of anastomosis, n (%)			0.769
Bilateral	94 (83.2)	30 (81.1)
Unilateral	19 (16.8)	7 (18.9)
Sperm motility in epididymal fluid, n (%)			<0.001
Motile	88 (77.9)	16 (43.2)
Nonmotile	25 (22.1)	21 (56.8)
Site of anastomosis, n (%)			0.541
Caput	25 (21.8)	10 (27.5)
Corpus or caudal	88 (78.2)	27 (72.5)

We determined the initial patency time across 100 cases, with observed time ranging from 1.5 months to 12 months (mean ± s.d.: 4.9 ± 2.7 months). Analysis revealed that 18 patients achieved patency within 1.5 months, 27 patients between 1.5 months and 3 months, and 41 patients between 4 months and 6 months. A smaller group achieved patency after 6 months; 10 patients between 7 months and 9 months, and four patients between 10 months and 12 months. Notably, 86.0% (86/100) of the patients achieved patency within the 6 months after MVE. Through univariate linear regression analysis, it was found that age, history of epididymitis, surgical duration, side of anastomosis, sperm motility of epididymal fluid, and site of anastomosis were not correlated with the patency time (all P > 0.05; Table 2).

Table 2.

Univariate linear regression analysis of influencing factors of patency time (n=100)

Characteristic	Univariate regression
	β (95% CI)	P
Age	0.07 (−0.04–0.18)	0.206
History of epididymitis	0.33 (−0.75–1.41)	0.549
Duration of surgery	0.16 (−0.94–1.25)	0.778
Side of anastomosis	1.04 (−0.38–2.46)	0.151
Sperm motility in epididymal fluid	−0.13 (−0.88–0.62)	0.731
Site of anastomosis	−0.20 (−0.64–0.25)	0.380

CI: confidence interval

Among the 113 patients who underwent MVE and achieved successful patency, the median TMSC was 6.05 × 10⁶ (range from 0 to 150.42 × 10⁶). Through both univariate and multivariate linear regression analyses, the site of anastomosis was identified as a significant independent predictor of TMSC after MVE. Notably, patients who had anastomosis at the epididymal corpus or cauda exhibited a significantly higher TMSC compared with those with anastomosis solely at the caput (Table 3).

Table 3.

Analysis of influencing factors on total motile sperm count in patients with patency following microsurgical vasoepididymostomy (n=113)

Characteristic	Univariate regression		Multivariate regression
	β (95% CI)	P	β (95% CI)	P
Age	−0.42 (−1.37–0.53)	0.380	−0.37 (−1.30–0.56)	0.430
History of epididymitis	−6.39 (−15.69–2.91)	0.176	−5.25 (−14.60–4.10)	0.268
Duration of surgery	−4.21 (−13.71–5.29)	0.382	−1.70 (−11.25–7.85)	0.725
Side of anastomosis	−2.08 (−14.55–10.39)	0.741	−3.75 (−16.31–8.82)	0.556
Sperm motility of epididymal fluid	−1.75 (−12.98–9.49)	0.759	−6.24 (−17.60–5.12)	0.278
Site of anastomosis	19.24 (5.07–33.41)	0.008	20.12 (5.09–35.16)	0.009

CI: confidence interval

The natural pregnancy rate was 37.3% (56/150). Among the subset of 113 patients who demonstrated successful patency postprocedure, three experienced re-obstruction and nine were unmarried, leaving 101 married patients for our analysis. The age of the spouses (mean ± s.d.) in this group was 28.1 ± 3.7 years (range from 22 years to 38 years). The TMSC of patients who had a natural pregnancy postpatency were significantly higher than those of who did not (median [IQR]: 24.85 [6.43, 39.72] vs 0.95 [0.11, 5.55]; P < 0.001).

DISCUSSION

Our review of 181 cases performed by the same surgeon revealed a patency rate of 75.3% and a natural pregnancy rate of 37.3%. These results, derived from a significant caseload, further substantiate the efficacy of the SA-LIVE technique for patients with EOA.

We also noted postoperative delays in patency time.20 In the preliminary semen analysis at 1.5 months, only 18.0% showed first-time patency. However, this figure rose to 45.0% at 3-month and climbed to 86.0% within 6 months. This finding indicates that most of the patency for SA-LIVE occurs within 6 months, in line with past findings on patency time after DA-LIVE.21 The causes of this delay remain unclear but may be due to several factors, such as resolution of local tissue inflammation, edema, and blood clots, changes in epididymal physiology, or recovery of spermatogenic efficiency in testes following long-term epididymal obstruction.22

To explore the factors influencing patency time following SA-LIVE, we conducted linear regression analysis on several variables, including age, history of epididymitis, duration of surgery, side of anastomosis, sperm motility in epididymal fluid, and site of anastomosis. However, no significant associations were observed between these factors and patency time following SA-LIVE, contrasting with previously reported findings associated with patency rates. Prior studies indicated that the presence of motile sperm in the epididymal fluid, as well as bilateral or distal anastomoses, were associated with higher patency rates.23,24,25 These findings indicate that the mechanisms affecting patency time postsurgery could be more complex and multifaceted than considered in our study. To the best of our knowledge, few studies have analyzed these specific variables in relation to patency time after SA-LIVE. Future research is warranted to explore potential factors and to further our understanding of the determinants of patency time postsurgery.

To comprehensively assess sperm motility and counts following patency, we employed the TMSC as the postoperative evaluation metric. Univariate and multivariate linear regression analysis revealed that exclusively the site of anastomosis was positively correlated with and independently predictive of the postoperative TMSC. This suggests that the site of anastomosis, especially in the corpus or caudal region of the epididymis during SA-LIVE, is an effective predictor of postpatency TMSC. One possible explanation is the relatively poor sperm motility in the caput region compared with the cauda, as noted in the assessment during MVE by Pal et al.26 Additionally, MVE surgery may compromise the functional length of the epididymis. This could lead to partial epididymal transit and subsequently reduced semen quality.27 As a result, we propose that the site of anastomosis may predict optimal postoperative semen quality after the MVE procedure.

Although pregnancy post-MVE involves partner-related factors, Peng et al.28 maintained that sperm concentration and motility could effectively predict natural pregnancy outcomes after patency. Our study also revealed higher levels of TMSC in patients who successfully achieved a natural pregnancy postpatency, compared with those who did not. Hence, the aim of EOA treatment should extend beyond improving patency rates to include enhancing sperm quality postpatency, thereby improving the partner’s conception likelihood. Consequently, it is essential to identify patients who have the potential for favorable sperm quality after MVE.

Our study has certain limitations. First, we had to exclude some patients from the study because of inadequate postoperative semen analysis data and could potentially limit the generalizability of our findings. For instance, patients with pregnant spouses may not have completed the semen analysis at each interval. Second, there was a lack of data on sperm morphology, attributed to the low sperm count observed in some patients following the procedures, which may limit the understanding of the procedures’ full impact of sperm quality.

In conclusion, our results showed that after SA-LIVE, most patients with EOA experienced patency within 6 months. Furthermore, factors such as patient age, history of epididymitis, duration of surgery, side of anastomosis, sperm motility in epididymal fluid, as well as the site of anastomosis, did not predict patency time. The site of anastomosis was found to be a positively correlated independent factor affecting sperm quality. By incorporating these findings, clinicians can provide patients with EOA more detailed information about expected outcomes, in terms of patency time and sperm quality following SA-LIVE, thus refining fertility planning.

AUTHOR CONTRIBUTIONS

SXT, HX, HXZ, and HLZ made significant contributions to the concept and design. SXT, HX, YLD, PY, HLH, XC, and SZ conducted those clinical studies. SXT, HX, HXZ, and QC took part in the collection, analysis, and interpretation of the data and made crucial changes to the primary knowledge content of the article. SXT, HX, HLZ, and HXZ provided major revisions to critical knowledge content. All authors were involved in revising the manuscript, and read and approved the final manuscript.

COMPETING INTERESTS

All authors declare no competing interests.