Male Factor Infertility

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Male Factor Infertility
Lewis E. Harpster, M.D.4/11/2002
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Definition

• Male factor infertility exists when there is
  failure to conceive, and, a persistently abnormal
  semen analysis and/or findings on exam associated
  with male factor infertility.

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Introduction

• Infertility affects 20 of couples in U.S.
• In 20 of couples, an isolated male factor is
  present.
• In 40 of couples, both male and female factors
  are present.
• Thus, in 60 of infertile couples, a male factor
  is at least partially responsible.

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Overview

• Normal male reproductive function requires
  adequate semen production and transport, delivery
  of sperm to the ovum, and, successful penetration
  of the ovum by the sperm.
• Abnormalities of any of these processes can lead
  to male factor infertility.

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Topics To Discuss

• Genitourinary Embryology
• Spermatogenesis
• Sperm Transport and Delivery
• Erectile Function
• Causes of Male Factor Infertility

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Genitourinary Embryology
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XX genotype (female) in absence of Y
chromosome, female gonads developMesonephric
duct regresses (lack of testosterone) Mullerian
duct persists (lack of MIF)
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XY genotype (male) in presence of Y chromosome,
male gonads developMesonephric duct persists
(presence of testosterone from Leydig
cells) Mullerian duct regresses (presence of MIF
from Sertoli cells)
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Spermatogenesis
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Leydig Cells Secrete testosterone in response to
LH from anterior pituitary Testosterone required
for spermatogenesis Testosterone feedback
inhibits LH secretion from anterior pituitary
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Sertoli Cells Provide support to developing
sperm in response to FSH from anterior
pituitary Secrete Inhibin, which feedback
inhibits FSH secretion from anterior
pituitary Secrete androgen binding
protein Tight junctions form blood testis
barrier
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Germ Cells Line basement membrane of
tubules Development proceeds intraluminally Sper
matids must undergo spermiogenesis to become
spermatozoa Spermatogenesis takes 74 days
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Sperm Transport and Delivery
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Semen Analysis
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Capacitation Freshly ejaculated sperm do not
possess the capacity to fertilize ovum. This
capacity to fertilize is acquired in the female
genital tract, and, appears to involve a reversal
of inhibitory factors secreted by the epididymis.
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Acrosome Reaction The acrosomal cap forms during
spermiogenesis. Upon contact with the ovum, the
acrosomal cap binds with the cell membrane of the
ovum. This allows release of digestive enzymes,
mainly acrosin, which digest the cell membrane of
the ovum allowing the sperm contents to enter.
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Erectile Dysfunction
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Erectile Function Corpora cavernosa of the penis
are innervated with both sympathetic and
parasympathetic fibers Sympathetic originates
from T-10 to L-2 Parasympathetic originates from
S-2,3,4 Cerebral input can modulate autonomic
impulses and thus facilitate / inhibit erectile
response
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Erectile Function At rest, sympathetic tone
predominates within the penile vasculature Thus,
a state of vasoconstriction exists, the vascular
lacunae are empty, and the penis is flaccid The
main sympathetic neurotransmitter in the penis is
norepinephrine
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Erectile Function At erection, parasympathetic
tone predominates within the penile
vasculature Thus, a state of vasodilatation
exists, the vascular lacunae are engorged, and
the penis is erect The main parasympathetic
neurotransmitter in the penis is Nitric Oxide
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Evaluating Male Factor Infertility
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Male Factor Infertility Abnormalities of any
of the previously described processes may lead
to male factor infertility.
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• Male Factor Infertility
• Evaluation of the infertile male includes
• History
• Physical Exam
• Semen Analysis
• Testosterone, FSH, LH

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History Cryptorchidism Teste cancer Cystic
fibrosis Torsion Postpubertal
mumps Trauma Gonadotoxins Hernia
Repair Radiation exposure Chemotherapy
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Physical Exam Secondary sex characteristics Gynec
omastia Teste size, consistency Presence /
absence of vas Varicocele Seminal Vesicles
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Semen Analysis Normal Single Abnormal
Parameter Multiple Abnormal Parameters Azospermi
c
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• Klinefelters Syndrome
• hypergonadotropic hypogonadism
• XXY Male
• testes small, firm
• global testicular dysfunction
• azospermia
• increased FSH, LH decreased T

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• Kallmanns Syndrome
• hypogonadotropic hypogonadism
• due to failure of pituitary to elaborate FSH,
  LH
• associated midline defects include cleft lip,
  anosmia
• Semen analysis variable
• Decreased FSH, LH, Testosterone

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• Spermatogenic Arrest
• idiopathic germ cell failure
• may occur at any age
• testes small, soft
• semen analysis oligospermic
• increased FSH normal LH, T

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• Cryptorchidism
• 10 of infertile males
• unilateral - 50 infertile
• bilateral - 70 infertile
• semen analysis oligoasthenospermia
• FSH normal or increased LH and T normal

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• Testicular Torsion
• ischemic damage leads to loss of germ cells
• in addition, blood-testes barrier is disrupted
• anti-sperm antibodies may develop
• SA reveals sperm agglutination
• normal FSH, LH, Testosterone

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• Varicocele
• most common treatable cause of male factor
  infertility
• 15 of fertile men
• 40 of infertile men
• semen quality improves in 60 following
  varicocele ligation
• pregnancy rates 40 after ligation

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• Idiopathic Infertility
• when specific cause of infertility can not be
  found, empiric therapy may be reasonable
• Clomiphene citrate (Clomid)
• Aromatase inhibitors
• Testosterone Rebound

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