1. Induction of Spermatogenesis in Azoospermic Men after Varicocele Repair
Hasan Farsi
K.A. University Hospital
King Faisal Specialist Hospital
Jeddah

3. Case Report 26y male with 1ry infertility of 3y.
Examination: Bilateral normal testes, Bilateral grade II varicocele.
Semen x2 Azooepermia, Volume 2-3cc, normal semen fructose
FSH was normal.
Bilateral inguinal varicocelectomy, testicular biopsy:
Hypospermatogenisis

4. 18 months later one child Semen: Volume: 1.5 cc Conc.: 3 m/cc
Motility: 25%

5. Varicocele 10-15% general population 40% 1ry infertility

6. Ambroïse Paré (1500–1590): a clinical problem
Barfield, late 19th century: Relationship to infertility
Lipshultz, 1979: Relationship to testicular atrophy that is progressive with age
Kass and Belman, 1987:significant increase in testicular volume after varicocele repair in adolescents

7. Clinical study of varicocele: the results of long-term follow-up.
Sixty-four infertile male patients with varicocele :
Varicocelectomy 31 cases
No surgery 30 cases
The mean follow-up duration was 76.2 months
The pregnancy rate: (60%) VS (28%)
Int J Urol Aug;9(8):

8. Surgery Vs Observation
146 men left varicocelectomy
62 men refused surgery treated with tamoxiphene
Followed up for at least 1 year
Improvement in semen parameters:
83.2% VS 32.3%
Pregnancy within 1 year:
62(46.6%) VS 8 (12.9%) (p<0.001).
Eur Urol Mar;39(3):322-5.

9. Is varicocelectomy really beneficial in the treatment of male factor infertility?

10. Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach.
A meta-analysis was performed to evaluate both randomized controlled trials and observational studies using a new scoring system.
Adjust and quantify for various potential sources of bias, including selection bias, follow-up bias, confounding bias, information or detection bias, and other types of bias, such as misclassification
Of 136 studies identified through the electronic and hand search of references, only 17 studies met our inclusion criteria

11. Statistically significant improvement in:
…..continue
Statistically significant improvement in:
Concentration
Motility
Morphology
CONCLUSIONS: Surgical varicocelectomy significantly improves semen parameters in infertile men with palpable varicocele and abnormal semen parameters.
Agarwal A, Department of Obstetrics Gynecology, Cleveland Clinic Urology Sep;70(3):532-8

12. Daitch JA. J Urol. 2001 May;165(5):1510-3
Varicocelectomy Improves Intrauterine Insemination Success Rates in Men with Varicocele.
24 pts intrauterine insemination cycles without varicocele treatment.
34 pts intrauterine insemination cycles following varicocelectomy.
No statistically significant difference was noted in the mean post-wash total motile sperm count in the treated and untreated groups.
The pregnancy rate per cycle = 6.3 VS 11.8, p = 0.04
Live birth rate per cycle =1.6 VS 11.8, p = 0.007
Conclusion: A functional factor not measured on routine semen analysis may affect pregnancy rates in this setting
Daitch JA. J Urol May;165(5):1510-3

13. Why Does Varicocelectomy Improve the Abnormal Semen Parameters?
68 infertile men
Seminal plasma levels of two ROS and six antioxidants on the day prior to varicocelectomy
Same parameters were measured again 3 and 6 months post-operatively.
concluded that varicocelectomy reduces ROS levels and increases antioxidant activity of seminal plasma from infertile men with varicocele.
Conclusion: Varicocelectomy reduces ROS levels and increases antioxidant activity of seminal plasma from infertile men with varicocele.
Mostafa T, Department of Andrology, Faculty of Medicine, Cairo University Int J Androl Oct;24(5):261-5.

14. Varicocele: a bilateral disease
286 infertile men
Physical examination, contact thermography, Doppler sonography, and venography of both testes.
88.8% bilateral
Mean sperm concentration increased from / to / million/mL
mean sperm motility from / to /- 1.41%
mean sperm morphology from / to /- 1.17%.
Pregnancy rate was 43.5%
This may suggest that we should consider varicocele a bilateral disease
Gat Y. Fertil Steril Feb;81(2):424-9.

15. Is assisted reproduction the optimal treatment for varicocele-associated male infertility? A cost-effectiveness analysis.
The cost per delivery with ICSI was found to be $89,091
The cost per delivery after varicocelectomy was only $26,268
The average published U.S. delivery rate after one attempt of ICSI was only 28%. whereas a 30% delivery rate was obtained after varicocelectomy.
CONCLUSIONS: Specific treatment of varicocele-associated male factor infertility with surgical varicocelectomy is more cost-effective than primary treatment with assisted reproduction.
Schlegel PN. Urology Jan;49(1):83-90

17. Varicocele & Azoospermia%

18. Consideration of sterility; subfertility in the male
Interestingly, the first study on the importance of varicocelectomy to male infertility (Tulloch, 1952 ) reported spontaneous pregnancy after varicocele repair in an azoospermic man
Tulloch, W.S Edinb. Med. J , 59, 29–34.

19. Results of ligation of internal spermatic vein in the treatment of infertility in azoospermic patients.
10 azoospermic patients
2 pregnancies
Mehan DJ. Fertil Steril Jan;27(1):110-4.

20. Inguinal Varcocelectomy in Azoospermic patients
13 azo inguinal varicocelectomy
Induction of spermatogenesis was achieved in 3 (23%) patients
Two of them had hypospermatogenesis and one had maturation arrest at spermatid stage
No pregnancies by natural intercourse
Cakan M. Arch Androl May-Jun;50(3):145-50

21. Sclerotherapy for Varicocele in Azoospermic patients
14 Azo sclerotherapy
7/14 produced sperms
Sperm con 3.1 ± 1.2 × 106/mL
Mean sperm: 2.2 ± 1.9%
mean sperm normal morphology: 7.8 ± 2.2%
2 pregnancies
Poulakis V. Asian J Androl Sep;8(5):613-9.

22. Embolization of Varicocele
32 men with azoospermia
Improved in 18/32:
sperm concentration in the ejaculate 3.81±1.69 x 106/ml
mean sperm motility: 1.20±3.62%
mean sperm morphology: 8.30±2.64
Nine pregnancies (26%)
Four (12%) unassisted
Five (15%) by ICSI
Gat Y. Human Reproduction (4):

23. Is the Effect Durable? 27 azoospermia microsurgical varicocelectomy
Induction of spermatogenesis was achieved in nine men (33.3%)
Sperm conc 1.2 x 10(6)/mL to 8.9 x 10(6)/mL
Motility 24% to 75.7%,
One patient with maturation arrest established pregnancy
Five relapsed into azoospermia 6 months after the recovery of spermatogenesis
Pasqualotto FF, Fertil Steril Mar;85(3):635-9.

24. How long does it take for the sperms to appear?
17 azo microsur
Spermatozoa in the ejacultae 47% (8/17)
Only 35% (6/17) of them had motile sperm
Mean time for appearance of spermatozoa in the ejaculates was 5 months (3 to 9 months).
Esteves SC. Int Braz J Urol Nov-Dec;31(6):541-8.

26. Predictors of Success

27. Response to varicocelectomy in oligospermic men with and without defined genetic infertility.
33 men with infertility & varicocele
7 has coexisting genetic infertility:
Abnormal karyotype in 4
Y chromosome microdeletion in 3
26 No defect
Same semen parameters
All had varicocelectomy
54% VS 0% improvement
CONCLUSIONS: From this early experience, men with varicocele and genetic lesions appear to have a poorer response to varicocele repair than men without coexisting genetic lesions.

28. Donkol RH. J Ultrasound Med. 2007 May;26(5):593-9.
Paternity after varicocelectomy: preoperative sonographic parameters of success.
What are the sonographic findings that could predict the outcome of varicocele repair in the treatment of male infertility?
107 patients with varicocele.
CONCLUSIONS: The best preoperative sonographic parameters of success of varicocele repair are:
The presence of normal-sized testes
Clinically palpable veins
Bilateral varicocele
Donkol RH. J Ultrasound Med May;26(5):593-9.

29. Relationship between varicocele size and response to varicocelectomy.
grade 1--small (22 patients)
grade 2--medium (44)
grade 3--large (20)
Sperm count, per cent motility, per cent tapered forms were measured preoperatively and postoperatively.
Conclusion: infertile men with a large varicocele have poorer preoperative semen quality but repair of the large varicocele in those men results in greater improvement than repair of a small or medium sized varicocele.
Goldstein M.J Urol Apr;149(4):769-71

30. Azoospermia: Predictors of Success
FSH
Histology

31. FSH
Preoperative FSH levels between men who did (14.8 ± 3.1 IU/L) and did not (19.4 ± 3.8 IU/L) show improvement in semen parameters after sclerotherapy were not significantly different
Czplick M. Arch Androl. 1979;3(1):51-5

32. Histology Germinal Aplasia Maturation arrest at spermatocyte stage
Hypospermatogenisis
Maturation arrest at spermatid stage

33. ….continue: predectors of success
13 Azoospermic patients
Age
Preoperative sex hormones
Unilaterl VS Bilateral
Varicocele grade
Hypospermatogenesis and late maturation arrest
No association
Arch Androl May-Jun;50(3):145-50

34. TOTAL 275 108 (39.27%) Author Year No. of pts Tech.
% of pts with sperms
Pregnancy(%)
Czaplicki
1979 33
Micro
12(34%)
3 patients
Matthews
1998 22
12(55%)
3PTS
Kadioglu
2001 24
5(20.8%) ?
Kim
1999 28
12(43%) 2
Schlegel
2004 31
7(22%)
Nil
Cakan 13
Inguin
3(23%)
Pasqualotto
2006 27
9(33.3) 1
Lee
2007 19
7(36.4%)
Esteves
2005 17
8(47%)
1 Spontan
4 ICSI
Gat 32
Embo.
18(56.2%)
9(26%)
Poulakis 14
Sclero
7(50)
Osmonov 15
sclerot
8(53) all <0.1m/cc
TOTAL
275
108 (39.27%)

35. Subclinical Varicocele
subclinical in 73 patients
Clinical in 66 patients, based on palpation in addition to ultrasonography.
Conclusion: ligation of varicoceles detected using Doppler ultrasonography, whether palpable or not, results in an increase in sperm concentration and motility.
Pierik FH, Rotterdam, The Netherlands. Int J Androl Oct;21(5):

36. 76 underwent varicocele repair
Improvement: Clinical VS subclinical:67% VS 41%
But: Equal number were worse postoperatively and, thus, mean sperm count was unchanged for the group with subclinical varicocele
Conclusion: The results of our study suggest that subclinical varicocelectomy is of questionable benefit.
Jarow JP North Carolina, USA. J Urol Apr;155(4):

37. Aboulghar M. Fertil Steril. 1997 Jul;68(1):108-11
Fertilization and pregnancy rates after intracytoplasmic sperm injection using ejaculate semen and surgically retrieved sperm.
350 patients:
Ejaculated sperm
Epididymal
Testicular
CONCLUSION: The fertilizing ability of sperm in ICSI is highest with normal ejaculated semen and lowest with sperm extracted from a testicular biopsy in non-obstructive azoospermia.
Aboulghar M. Fertil Steril Jul;68(1):108-11

38. Conclusion
Varicocele may cause any variation of severity in spermogram including azoospermia.
The treatment of varicocele may significantly improve spermatogenesis and renew sperm production.
Adequate treatment may spare the need for TESE as preparation for ICSI in >30% of azoospermic patients.
Since achievement of pregnancy in IVF units is higher when spermatogenesis is better, the treatment of varicocele is an effective medical adjunct for IVF units prior to the treatment.
In men with spermatogenic failure, freshly ejaculated sperm are easier to use, and fertilization ability in ICSI is higher with normal semen than with sperm retrieved by TESE

40. Thank You