evaluation and management of nonobstructive azoospermia sang kon lee, m.d. college of medicine,...
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Evaluation and Management of NEvaluation and Management of Nonobstructive Azoospermiaonobstructive Azoospermia
Sang Kon Lee, M.D.
College of Medicine, Hallym University
Causes of AzoospermiaCauses of Azoospermia
Pretesticular failure
Testicualr failure
Post-testicular failure
Pretesticular failurePretesticular failure
– Genetic abnormality Kallmann’s syndrome Prader-Willi syndrome Cerebral ataxia with HH
– Idiopathic HH– Isolated LH deficeincy – Isolated FSH deficiency– Prolactin excess
Testicular failureTesticular failure Genetic abnormality
– Klinfelter’s syndrome: nonmosaic, mosaic– XYY syndrome– 46 XX male syndrome– Yq AZF gene deletion
Varicocele Bilateral anorchism, cryptorchidism Sertoli cell only syndrome Gonadotoxin : drug, radiation, chemical Orchitis
EvaluationEvaluation
History– Infertility : duration, pregnancy– Developmental– Medical, surgical– Sexual– Family
Physical exam. Semen analysis Endocrine test
Childhood and Developemental Childhood and Developemental
Crytorchidism, testicualr torsion, Mumps orchitis Herniorrhaphy Onset of puberty Secondary sexual development
– Onset axillary, pubic hair, start of shaving Onset of masturbation
Medical historyMedical historyMedical history
– Systemic illness: hepatic, renal failure– Gonadotoxins
sulfasalazine, cimetidine, nitrofuratoin, chemotherapeutic, anabolic androgen
Thermal injury Smoking, alcohol,marijuana
Surgical history– Herniorrhaphy, badder neck, orchiectomy, r
etroperitoneal surgery
Physical examinationPhysical examination
General appearanceGynecomastiaAxillary, pubic hairTestis volume, consistency Epididymis indurationVaricoceleDigital rectal examination
Semen analysisSemen analysis
At least 2 times analysisSecretory azoospermia
– Pellet inspected after centrifugation at 1,500-2,000 rpm for 10min
If ejaculatory vol < 1ml– Postejaculatory urine should be examined
Ultrasound examinationUltrasound examination
Scrotal US– Testis volume– Varicocele– Testis tumor
Transrectal US– Low volume azoospermia without absence
of testicular atrophy– Palpable abnormality on DRE
Volume(cc) = length x width x AP depth x 0.52
Hormonal status in clinical DxHormonal status in clinical Dx
Clinical status
FSH LH T
Germ cell aplagia
↑ Normal Normal
Testicualr failure
↑ Normal or ↓
HH ↓ ↓ ↓
↑
Indication of testicular biopsyIndication of testicular biopsy
Dignostic – DDX of ductal obstruction and testicular failure– Identification of mature sperm for ICSI– Identification of malignancy
Therapeutic– Harvesting of sperm for ICSI
Interpretation of testis biopsyInterpretation of testis biopsy
Severe hypospermatogenesisSetoli cell only syndromeMaturation arrest
– Spermatocyte stage– Spermatid stage
Tubular and peritubular sclerosis
DNA flowcytometryDNA flowcytometry
Advantage– Rapid, objective, quantitative– reproducible
Disadvantage– Inability of distinguishment between specifi
c type of 1N cells (spermatozoa and spermatid)
Normal spermatogenesis Hypospermatogenesis
Maturation arrest Sertoli cell only syndrome
Genetic evaluation of NOAGenetic evaluation of NOA
Sex chromosomal disorder– Klinfelter’s syndrome(1/500) :15% of NOA– XYY male(1/1,000), XX male(1/20,000)
Yq deletion : 10-20% of NOA X-linked :
– Kallamann’s syndrome– Androgen receptor deficiency– Kennedy syndrome (spinal-bulabar muscular atrophy)
Autosomal defect– Prader-Willi syndrome– Androgen synthesis deficiency
Genetic evaluation of NOAGenetic evaluation of NOA
Indication – NOA with clinical abnormality
Hypogonadism, anosmia, mental retardation – For genetic counselling
All couples with male infertility prior to ICSI Chromosomal abnormalities in 12% of men and 6%
of women in 150 couples prior to ICSI (Mau, 1997 , Hum Reprod)
– Research purpose Normal phynotype except infertility
Management of NOA (I)Management of NOA (I)
Hypogonadotropic hypogonadism– Treatment
Initial 1,000-2,500 IU HCG (x2/wk) followed by 75-150 IU HMG (x3/wk) (Finkel,1987)
Combination of HCG and HMG (Yong ,1997) GnRH sc or pulsatile infusion (Kliesch,1994) LHRH pulsatile treatment (Shargil,1987)
– Outcome IHH after puberty showed better results. Sperm count increase in 3-6mos.
Management of NOA (II)Management of NOA (II)
Varicocelectomy– Mehan DJ (1976, Fertil Steril)
Of 10 azoo men, 2 with varicocele results in pregnency– Matthews G, et al (1998, Fertil Steril)
Of 22 with azoo, sperm recovery rate is 55%– Kim ED, et al (1999, J Urol)
Of 28 men, 12(43%): mean post-op sperm count 1.2x106 /ml
Indication: severe hypospermatogenesis, MA spermatid stage
Management of NOA(III)Management of NOA(III)
ICSI– Ejaculatoy sperm:
less invasive,cost effective HH, varicocele, mosaic Klinfelter’s synd.
– TESE Presence of spermatozoa in SCO, MA Nonmosaic Klinfelter’s syndrome (Bourne,1997 , Hum R
eprod)
– ROSI MA spermatid stage
Genetic risk of ICSIGenetic risk of ICSI
Congenital anomaly : Autosomal abberation: <2% Y chromosomal abberation: 13%
– not results in major anomaly other than infertility Sex chromosomal abnormality
– Higher in ICSI than natural pregnancy 1%: 47XXY, XXX, 45X, etc (Liebaers,1995)
– Major malformation in Turner Infertility obligate in Klinfelter’s synd
– No major congenital handicaps No increased rate of mental retardation
Secondary NOA Secondary NOA Case 1.Case 1.
M/31: infertility for 18 mos History
– 4 yrs PTV impregnated hx– Allergic rhinitis for 12 yrs
Antiallergic administered for 3-4 mos. every year During medication, anorexia, 5-6 kg wt loss
– Noticed testis atrophy 3 yrs PTV Study
– Both testis 8cc– S/A: azoospermia– FSH 18.5 IU/ml T 2.5 ng/ml, 46,XY– Testis biopsy : MA spermatocytic stage
Secondary NOA Secondary NOA Case 2.Case 2.
M/30: infertility for 6 yrs History
– 2yrs PTV necrospermia– 10 mos PTV spontaneous abortion– Worked in Rayon manufacture industry for 11 yrs
Study– Both testis 12 cc– S/A: azoospermia, – FSH 13.0 mIU/ml, T 9.4 ng/ml– Testis bopsy: Spermatocytic MA
ConclusionConclusion
NOA may be a local presentation of systemic illnesses.
A complete careful evaluation is important for identification of etiology of male infertility which may open new approaches regarding prevention and treatment.