Increased Follicle-Stimulating Hormone is Associated With Higher Assisted Reproduction Use After Vasectomy Reversal

Sexual Function/Infertility

Increased Follicle-Stimulating Hormone is Associated With Higher Assisted Reproduction Use After Vasectomy Reversal Wayland Hsiao, Raymond Sultan, Richard Lee and Marc Goldstein* From the Center for Male Reproductive Medicine, Department of Urology (WH, RL, MG) and Institute for Reproductive Medicine, Weill Cornell Medical College and The Population Council Center for Biomedical Research, New York (WH, MG), New York, and Robert Wood Johnson Medical School (RS), New Brunswick, New Jersey

Abbreviations and Acronyms ART ⫽ assisted reproductive technique FSH ⫽ follicle-stimulating hormone ICSI ⫽ intracytoplasmic sperm injection IUI ⫽ intrauterine insemination IVF ⫽ in vitro fertilization LH ⫽ luteinizing hormone VE ⫽ vasoepididymostomy Submitted for publication October 12, 2010. Study received institutional review board approval. Supported by a grant from The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust (WH). * Correspondence: 525 East 68th St., Starr 900, New York, New York 10065 (telephone: 212746-5470; FAX: 212-746-0977; e-mail: mgoldst@ med.cornell.edu).

Purpose: Of men with vasectomy 6% elect to have more children. When considering vasectomy reversal vs in vitro fertilization/intracytoplasmic sperm injection, an elucidation of preoperative factors that predict surgical success would help determine appropriate management. We tested the hypothesis that preoperative follicle-stimulating hormone 10 U/l or greater predict a lower paternity rate after vasectomy reversal. Materials and Methods: Using preoperative follicle-stimulating hormone levels we retrospectively reviewed the records of patients who underwent vasectomy reversal. Follicle-stimulating hormone was measured in cases suspicious for impaired spermatogenesis. The final analysis included 206 men, who were divided by follicle-stimulating hormone less than 10 U/l (normal in 155) and 10 U/l or greater (high in 51). Nominal logistic regression was performed to evaluate assisted reproduction predictors. Results: Mean ⫾ SD follicle-stimulating hormone in the normal and high groups was 5.1 ⫾ 2.2 and 16.2 ⫾ 6.2 U/l, respectively. Postoperative semen parameters were similar. However, in the high hormone group there was greater use of any type of assisted reproduction (78.4% vs 54.8%, p ⫽ 0.0028). On multivariate analysis follicle-stimulating hormone 10 U/l or greater (OR 3.02, 95% CI 1.34 – 6.83) and vasoepididymostomy that was bilateral or to a solitary testis (OR 3.26, 95% CI 1.09 –9.69) was associated with greater assisted reproduction use. Conclusions: We evaluated preoperative follicle-stimulating hormone as a predictor of reproductive outcome in men with suspected subfertility who underwent vasectomy reversal. Increased follicle-stimulating hormone was associated with a higher rate of assisted reproduction even after controlling for confounding covariates. Thus, men with increased follicle-stimulating hormone should be counseled on the increased likelihood of needing assisted reproduction to achieve pregnancy after vasectomy reversal. Key Words: testis; follicle stimulating hormone; reproductive techniques, assisted; vasovasostomy; infertility, male

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VASECTOMY is the most common urological procedure with more than 500,000 performed annually in the United States.1 While vasectomy should be considered a permanent form of contraception, approximately 6% of men who undergo vasectomy elect to

have more children.2 Options for these men include vasectomy reversal, surgical sperm retrieval coupled with IVF/ICSI or using previously cryopreserved or donor sperm. The Practice Committee of the American Society for Reproductive

0022-5347/11/1856-2266/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION

Vol. 185, 2266-2271, June 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.02.011

AND

RESEARCH, INC.

INCREASED FOLLICLE-STIMULATING HORMONE AFTER VASECTOMY REVERSAL

Medicine guidelines for vasectomy reversal state that no specific preoperative laboratory evaluation is indicated before vasectomy reversal beyond routine preoperative tests.3 However, in the IVF/ICSI era it has become increasingly important to elucidate preoperative factors that predict surgical success to adequately counsel patients on the likelihood of success of surgical vasectomy reversal. Factors that predict the success of microsurgical vasectomy reversal include the obstructive interval, surgeon skill, sperm granuloma, prior fertility, prior inguinal surgery, prior vas reversal, same partner, partner age and antisperm antibodies.4 – 6 To our knowledge no laboratory findings predict reproductive outcomes after vasectomy reversal. Testing antisperm antibodies before or after vasectomy reversal remains controversial.7,8 DNA fragmentation measured by sperm chromatin structure assay also does not predict the postreversal spontaneous or assisted reproductive pregnancy rate.9 A laboratory test commonly used for infertility evaluation is FSH. FSH, which is made in the anterior pituitary in response to gonadotropin-releasing hormone, is essential for complete spermatogenesis. Serum FSH levels inversely correlate with fertility potential in men and women. We tested the hypothesis that preoperative FSH 10 U/l or greater predicts a lower paternity rate in men in whom impaired spermatogenesis is suspected.

METHODS AND MATERIALS Patients and Evaluation After receiving institutional review board approval we reviewed the records of 927 men who underwent vasovasostomy or VE at a tertiary referral center, as done by a single reproductive surgeon (MG). Of these patients only those with previous vasectomy, known FSH levels before surgery and known reproductive outcomes (birth outcomes and data on assisted reproduction use) were included in our study. Those with primary infertility or nonvasectomy related azoospermia were excluded. A total of 206 men (22.2%) met study criteria and were included in the final analysis. We reviewed demographics, operative notes, clinical charts, and laboratory and semen analyses. A full history was obtained and physical examination was done by the primary surgeon (MG) in all cases. Physical examination included a full general and urological examination with emphasis on testicular volume, varicocele and sperm granuloma. Our surgical technique of microsurgical vasovasostomy and VE was previously described.10,11 We do not routinely determine serum FSH in men before vasectomy reversal. However, preoperative FSH was measured in cases suspicious for impaired sperm production due to any of certain factors, including no prior proven fertility, a history of infertility, a long obstructive interval or physical examination findings suggesting sub-

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fertility, including a large varicocele or a smaller volume testis. Since we did not require that all patients undergo laboratory testing at a central laboratory, the normal range may have differed across laboratory tests. We chose a cutoff of 10 U/l because generally FSH 10 U/l or higher is considered high or at least in the high normal range. Results were stratified by FSH levels. The normal FSH group (less than 10 U/l) comprised 155 men while the high FSH group (10 U/l or greater) comprised 51. All semen analysis data available in the clinical record were reviewed. Early semen analysis was considered analysis done after the immediate postoperative period and before 6 months. Late semen analysis was considered the next semen analysis obtained after 6 months postoperatively. Vasectomy reversal failure was defined as persistent azoospermia on 2 postoperative semen analyses.

Analysis Statistical. Statistical analysis was performed using JMP® and SPSS® 16.0. To calculate the natural clinical pregnancy and natural live birth rates patients who proceeded to ART were recorded as no for statistical purposes regardless of ART outcome. The 25 men who did not undergo ART and had an unknown pregnancy outcome were excluded from pregnancy subanalysis. Results are shown as the mean ⫾ SD. The Student t test was used to compare continuous variables and the Pearson chi-square test was used to compare categorical variables. The Kruskal-Wallis test was used to compare categorical variables with 3 levels. For semen analysis total sperm count and concentration we used cube root transformation to achieve normal distribution.12 Statistical significance was considered at p ⬍0.05. Multivariate. Multiple logistic regression was done for any ART. Included in this model were serum FSH (less than 10 vs 10 U/l or greater), previous proven fertility, clinical varicocele (none, unilateral or bilateral), obstruction duration (15 years or less, or greater than 15), partner age (35 years or less vs greater than 35), need for bilateral VE or VE in a solitary testicle, anastomotic failure and testicular hypotrophy (none, unilateral or bilateral). A cutoff of 15 years was used for obstruction duration since our previous data showed a decrease in the pregnancy rate only after 15 years of obstruction.6 A total of 192 patients had complete information available and were included in the multivariate model. All variables were assessed for pairwise interaction.

RESULTS Baseline Characteristics A total of 206 patients met study criteria and were included in the final analysis. The normal and high FSH groups had similar age at surgery, obstruction duration and partner age (table 1). There were similar numbers of children before vasectomy and a similar percent of couples with no proven fertility (p ⫽ 0.49). Intercourse frequency was similar in the 2 groups, as was the percent of men with a history of reversal surgery. Mean followup was similar in the

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INCREASED FOLLICLE-STIMULATING HORMONE AFTER VASECTOMY REVERSAL

Table 1. Baseline demographics, hormonal profile and physical examination findings Normal FSH Mean ⫾ SD age: Vasectomy Reversal Mean ⫾ SD yrs of obstruction Mean ⫾ SD partner age at surgery Mean ⫾ SD No. children before vasectomy No. couples with no children (%) No. previous vasovasostomy or VE elsewhere (%) Mean ⫾ SD No. sexual episodes/wk Mean ⫾ SD followup (years) Mean ⫾ SD hormonal profile: FSH (U/l) LH (U/l) Testosterone (ng/dl) Mean ⫾ SD testicular vol (cc): Rt Lt No. sperm granuloma on examination (%) No. grade 1–3 clinical varicocele (%): None Unilat Bilat

33.1 ⫾ 44.1 ⫾ 12.6 ⫾ 33.6 ⫾ 2.0 ⫾ 24 (15.7) 25 (16.1) 3.0 ⫾ 2.5 ⫾

High FSH 32.6 ⫾ 44.9 ⫾ 11.0 ⫾ 34.1 ⫾ 1.9 ⫾ 6 (11.8) 14 (27.5) 3.2 ⫾ 2.7 ⫾

5.9 6.5 5.5 4.7 1.2

1.7 2.9

p Value

6.0 7.1 5.5 5.0 1.1

2.8 2.5

0.58 0.47 0.08 0.54 0.88 0.49 0.07 0.66 0.73

5.1 ⫾ 2.2 4.2 ⫾ 2.7 460 ⫾ 183

16.2 ⫾ 6.2 7.7 ⫾ 5.0 452 ⫾ 171

⬍0.0001 ⬍0.0001 0.77

23.2 ⫾ 4.6 21.6 ⫾ 4.6 51 (33.3)

21.1 ⫾ 5.1 20.4 ⫾ 4.2 20 (40.8)

0.01 0.08 0.34

32 (65.3) 11 (22.5) 6 (12.3)

0.13 (Kruskal-Wallis test)

116 (76.8) 21 (13.9) 14 (9.3)

normal and high FSH groups (2.5 ⫾ 2.9 vs 2.7 ⫾ 2.5 years, p ⫽ 0.73). Mean FSH in the normal and high groups was 5.1 ⫾ 2.2 (range 1.3 to 9.9) and 16.2 ⫾ 6.2 U/l (range 10.0 to 33.0), respectively. Hormonal evaluation revealed similar testosterone levels in the 2 groups but higher serum LH in the high FSH group (table 1). On physical examination patients with high FSH had lower right testis volume (p ⫽ 0.01) while the left testis trended toward lower volume (p ⫽ 0.08). However, with a mean difference of only 2.1 and 1.2 cc on the right and left sides, respectively, the clinical significance of this mean difference is

questionable. There was a similar incidence of sperm granuloma and varicoceles in the 2 groups. Postoperative Semen Analysis Early semen analysis was done at a mean of 2.6 ⫾ 1.4 months in 176 patients and late semen analysis was done at 10.8 ⫾ 6.0 months in 133 with similar followup in the 2 groups. On early semen analysis volume, total sperm count, sperm concentration and motility, and the percent of patients with azoospermia were similar. There was a higher percent of sperm with normal forms in the high FSH group (table 2). On late semen analysis all measured vari-

Table 2. Postoperative semen analysis of patients by initial preoperative FSH Semen Analysis Early: No. pts No. azoospermia (%) Mean ⫾ SD mos postop Mean ⫾ SD vol (ml) Mean ⫾ SD total sperm count (millions) Mean ⫾ SD concentration (millions/ml) Mean ⫾ SD % motility Mean ⫾ SD % normal forms Late: No. pts No. azoospermia (%) Mean ⫾ SD mos postop Mean ⫾ SD vol (ml) Mean ⫾ SD total sperm count (millions) Mean ⫾ SD concentration (millions/ml) Mean ⫾ SD % motility Mean ⫾ SD % normal forms * Student t test results applied to cube root transformation.

Normal FSH

High FSH

p Value

135 19 (14.1) 2.6 ⫾ 1.4 2.9 ⫾ 1.7 78.2 ⫾ 124.2 29.0 ⫾ 46.7 21.8 ⫾ 21.4 23.8 ⫾ 20.1

41 10 (24.4) 2.6 ⫾ 1.4 2.8 ⫾ 1.5 77.8 ⫾ 141.4 29.0 ⫾ 48.7 25.5 ⫾ 20.0 33.8 ⫾ 23.8

0.12 0.89 0.71 0.51* 0.59* 0.38 0.04

97 19 (19.6) 10.3 ⫾ 6.0 2.9 ⫾ 1.4 80.8 ⫾ 103.4 33.1 ⫾ 45.9 32.8 ⫾ 22.9 30.2 ⫾ 19.9

36 7 (19.4) 12.1 ⫾ 6.0 2.7 ⫾ 1.3 67.8 ⫾ 115.2 29.1 ⫾ 45.6 26.7 ⫾ 22.1 35.9 ⫾ 23.5

0.98 0.14 0.40 0.39* 0.68* 0.22 0.26

INCREASED FOLLICLE-STIMULATING HORMONE AFTER VASECTOMY REVERSAL

ables were similar in the 2 groups. On early and late analysis there were no significant differences in concentration, total count or the percent of patients with azoospermia. Operative and Reproductive Outcomes The percent of patients requiring bilateral VE or VE in a solitary testis was similar in the normal and high FSH groups (11.8% vs 11.6%, p ⫽ 0.98), as were the anastomotic failure rate (15.7% vs 16.1%, p ⫽ 0.94) and the number of years to failure (mean 29.9 ⫾ 25.2 vs 27.7 ⫾ 12.5 months, p ⫽ 0.83). The high FSH group showed much higher use of any ART (78.4% vs 54.8%, p ⫽ 0.0028) and of IVF (56.9% vs 40.7%, p ⫽ 0.04). A total of 33 men required IUI with IUI in a similar percent in the 2 groups (14.2% vs 21.6%, p ⫽ 0.21). The natural clinical pregnancy rate was lower in the high FSH group (14.9% vs 33.6%, p ⫽ 0.01) and there was a trend toward a lower natural live birth rate (9.8% vs 20.6%, p ⫽ 0.07). The assisted reproduction live birth rate was similar in the 2 groups (25.0% vs 28.2%, p ⫽ 0.70, table 3). The high FSH group had a longer time to natural clinical pregnancy (mean 1.9 ⫾ 1.0 vs 0.9 ⫾ 1.0 years, p ⫽ 0.02) and to natural live birth (2.5 ⫾ 1.3 vs 1.5 ⫾ 0.8 years, p ⫽ 0.04). However, in patients who used ART the time to live birth was similar in the 2 groups (mean 3.4 ⫾ 1.9 vs 3.6 ⫾ 1.6 years, p ⫽ 0.73). In the IUI subgroup the live birth rate was 36.4% (4 of 11 patients) in the high FSH group and 22.7% (5 of 22) in the normal FSH group (p ⫽ 0.41). Table 3. Operative and reproductive outcomes in 206 patients with known birth outcomes and assisted reproduction information

Bilat or solitary testis VE Late anastomotic failure Any assisted reproduction: Yes No IVF: Yes No Intrauterine insemination: Yes No Natural clinical pregnancy:* Yes No Natural live birth: Yes No Assisted reproduction live birth:† Yes No

No. Normal FSH (%)

No. High FSH (%)

18 (11.6) 25 (16.1)

6 (11.8) 8 (15.7)

85 (54.8) 70 (45.2)

40 (78.4) 11 (21.6)

0.0028

63 (40.7) 92 (59.4)

29 (56.9) 22 (43.1)

0.0438

22 (14.2) 133 (85.8)

11 (21.6) 40 (78.4)

0.214

45 (33.6) 89 (66.4)

7 (14.9) 40 (85.1)

0.01

32 (20.6) 123 (79.4)

5 (9.8) 46 (90.2)

0.07

24 (28.2) 61 (71.8)

10 (25.0) 30 (75.0)

0.70

* Excluding 25 patients with unknown pregnancy outcome. † In patients who proceeded to ART (IUI or IVF).

p Value 0.98 0.94

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When patients were stratified by ART, couples who eventually underwent ART included men with a lower mean sperm concentration (25.0 ⫾ 47.4 vs 49.2 ⫾ 77.2 million per ml, p ⫽ 0.009), total sperm count (61.6 ⫾ 107.5 vs 106.3 ⫾ 153.0 million, p ⫽ 0.003) and percent of motile sperm (19.4 ⫾ 18.6 vs 27.8 ⫾ 23.7, p ⫽ 0.01). Also, 23 of the 111 patients (20.7%) who used ART had azoospermia on early analysis, which was significantly higher than the 6 of 66 (9.1%) in the nonART group (p ⫽ 0.04). Multivariate Analysis Nominal logistic regression analysis was performed for assisted reproduction use. Of 206 patients 192 (93.2%) had complete data available and were included in the model. Prior fertility, varicocele, obstruction duration, partner age, need for VE, anastomotic failure and low testicular volume did not predict the need for assisted reproduction. Only FSH 10 U/l or greater (OR 3.02, 95% CI 1.34 – 6.83) and bilateral VE or VE to a solitary testicle (OR 3.26, CI 1.09 –9.69) were associated with a higher rate of assisted reproduction on multivariate analysis (table 4).

DISCUSSION There remains a need for predictors of vasectomy reversal outcomes, especially in the IVF/ICSI age. While obstruction duration, granuloma, prior fertility, prior surgery, partner age and antisperm antibodies correlate with vasectomy reversal outcomes,6,13 to our knowledge the value of serum FSH as a prognostic marker before vasectomy reversal has not been studied. We reviewed the experience of a high volume, tertiary referral reproductive surgeon. In patients with a history of vasectomy and suspicion of subfertility FSH 10 U/l or greater was associated with higher IVF use. Multivariate modeling indicated that increased FSH and bilateral VE or single VE to a solitary testicle were associated with an increased rate of assisted reproduction. However, due to the relatively small number of patients in the increased FSH group (51) this multivariate analysis should be considered explorative. Our study suggests that FSH is a useful prognosticator in men suspected of having subfertility even if they previously fathered children. FSH increases are associated with a higher rate of assisted reproduction. Thus, patients with FSH 10 U/l or greater should be counseled on the higher use of assisted reproduction. FSH is easy to measure before vasectomy reversal and it is routinely used in infertility practices. Given the slightly lower testicular volume, higher LH and higher FSH, a picture emerges that is con-

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INCREASED FOLLICLE-STIMULATING HORMONE AFTER VASECTOMY REVERSAL

Table 4. Multivariate model of associations with any assisted reproduction

Proven fertility: Yes No Varicocele: No Unilat Bilat Obstruction duration (yrs): 15 or Less Greater than 15 Partner age: 35 or Less Greater than 35 FSH (U/l): Less than 10 10 or Greater Procedure: Vasovasostomy Bilat or solitary testis VE Sperm on semen analysis: Yes Azoospermic on 2 consecutive analyses Testicular size: Bilat normal Unilat less than 16 cc Bilat less than 16 cc

OR (95% CI)

p Value

1.0 1.03 (0.43–2.43)

0.951

1.0 0.73 (0.31–1.74) 2.17 (0.69–6.86)

0.48 0.19

1.0 0.78 (0.36–1.71)

0.54

1.0 1.15 (0.60–2.20)

0.68

1.0 3.02 (1.34–6.83)

0.008

1.0 3.26 (1.09–9.69)

0.034

1.0 1.83 (0.77–4.38)

0.17

1.0 0.67 (0.24–1.84) 6.16 (0.72–52.82)

0.43 0.10

sistent with poorer baseline testicular function in men with increased FSH. This study further supports the need for a good history and physical examination before vasectomy reversal to evaluate testicular quality and size. In our practice the attending reproductive surgeon personally takes the history and performs a full physical examination of each patient who undergoes vasectomy reversal. We cannot underestimate the importance of putting fertility in the context of overall patient health, given the link between infertility and other disease states.14,15 Notably in this study our clinical pregnancy rate was lower and our ART rate was higher, even in the normal FSH group, than in our overall series.6 We believe that this was due to the selection of men with suspected impaired fertility potential for this study. Thus, even patients in our normal FSH group should not be considered normal men undergoing vasectomy reversal but rather men with suspicion of impaired spermatogenesis who have normal FSH. Also, this was a complex group from a surgical perspective since 39 of the 206 patients (18.9%) in our study population underwent previous vasectomy reversal elsewhere while 33 (16.0%) required bilateral VE or VE to a solitary testicle at surgery. However, even after controlling for all of these factors increased FSH was still an independent predictor of increased assisted reproduction use. As with any retrospective study, we can only speculate on the mechanism of this association. We believe that in-

creased FSH is a marker of impaired spermatogenesis. Men with impaired spermatogenesis have a lower fertility rate even with adequate anastomotic patency and, thus, they show a higher rate of ART. Patients who proceed to ART have a lower sperm concentration, a lower total sperm count and a lower percent of motile sperm than those who do not. However, the timing of the recommendation to proceed to ART is a complex issue that must consider female partner age, the number of children desired and the degree to which the couple is adverse to more demanding female therapy, ie IVF stimulation. The recommendation to proceed to IVF must be individualized to each couple. However, we generally recommend IVF to patients only after at least 1 year of attempting natural conception without any pregnancy. In couples in which the female partner is older (generally age 37 years or greater) we may recommend that they proceed to IVF sooner. One of the most significant limitations of our study is that it was limited to a subgroup of men (22% of our overall population) with vasectomy reversal in which we suspected impaired spermatogenesis due to history or physical examination. Since we only measure FSH in men in whom we suspect impaired spermatogenesis, we do not know the FSH levels in our remaining patients with vasectomy reversal. Thus, while we believe that FSH is prognostic in patients in whom the surgeon suspects impaired spermatogenesis, it remains uncertain whether this finding can be generalized to all men who undergo vasectomy reversal, which is certainly most men who undergo vasectomy reversal. Notably we previously reported that patients lost to followup had a pregnancy rate similar to that in those who were followed regularly after vasectomy reversal.16 Another study weakness is the limited followup. While this represents a large review of patients during a 20-year period, many of our patients are referred from elsewhere and, thus, we often have limited followup information. IVF is not done at our institution in all patients and so we have limited information on those outcomes. However, we believe that the mean 2.6-year followup is reasonable followup for a vasectomy reversal study since one would consider pregnancy likely by 2½ years. Mean time to pregnancy in this study was 1.3 years.

CONCLUSIONS We evaluated FSH as a preoperative parameter in the assessment of men with suspected subfertility undergoing vasectomy reversal. Increased FSH was associated with a higher assisted reproduction rate even after controlling for confounding covariates. Although surgical outcomes were similar, men with

INCREASED FOLLICLE-STIMULATING HORMONE AFTER VASECTOMY REVERSAL

increased FSH should be counseled on the increased likelihood of needing assisted reproduction to achieve pregnancy. Finally, our data stress the importance

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of a complete history and physical examination in the preoperative evaluation of men seeking vasectomy reversal.

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7. Meinertz H, Linnet L, Fogh-Andersen P et al: Antisperm antibodies and fertility after vasovasostomy: a follow-up study of 216 men. Fertil Steril 1990; 54: 315. 8. Carbone DJ Jr, Shah A, Thomas AJ Jr et al: Partial obstruction, not antisperm antibodies, causing infertility after vasovasostomy. J Urol 1998; 159: 827. 9. Smit M, Wissenburg OG, Romijn JC et al: Increased sperm DNA fragmentation in patients with vasectomy reversal has no prognostic value for pregnancy rate. J Urol 183: 662. 10. Goldstein M, Li PS and Matthews GJ: Microsurgical vasovasostomy: the microdot technique of precision suture placement. J Urol 1998; 159: 188. 11. Schlegel PN and Goldstein M: Microsurgical vasoepididymostomy: refinements and results. J Urol 1993; 150: 1165.

12. Handelsman DJ: Optimal power transformations for analysis of sperm concentration and other semen variables. J Androl 2002; 23: 629. 13. Belker AM, Thomas AJ Jr, Fuchs EF et al: Results of 1,469 microsurgical vasectomy reversals by the Vasovasostomy Study Group. J Urol 1991; 145: 505. 14. Salonia A, Matloob R, Gallina A et al: Are infertile men less healthy than fertile men? Results of a prospective case-control survey. Eur Urol 2009; 56: 1032. 15. Walsh TJ, Croughan MS, Schembri M et al: Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med 2009; 169: 351. 16. Fazeli-Matin S, Morrison G and Goldstein M: What is the pregnancy rate in vasovasostomy and varicocelectomy patients who are “lost to follow-up.” Presented at annual meeting of American Urological Association, San Francisco, California, May 14 –19, 1994.