Transcript Causes of Male infertility

Genetics and Infertility
By
Salwa Hassan Teama
M.D. N.C.I .Cairo University, Egypt
Contents
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Infertility
Causes of Male infertility
Male Partner Diagnostic Tests
Semen Analysis
Female Partner Diagnostic Tests
Normal karyotype
Genetic Tests of Infertility
IVF
Infertility
Definition; "failure to conceive following one year
of unprotected sexual intercourse." For young
and healthy heterosexual couples having
frequent intercourse, about 85% will be
pregnant after one year of trying and about 93%
will be pregnant after two years of trying to
conceive.
Infertility :Timely Evaluations
Initial infertility evaluations should be
individualized, taking into consideration the
medical history of the couple and the age of the
female partner.
Helping you build your family
Infertility
True infertility only occurs in a few specific situations:
 Women with blocked fallopian tubes.
 Women that has no uterus or no egg follicles
(menopause or premature ovarian failure).
 Men who have no sperm.
In these situations, successful conception will only occur with
the use of specific medical technology, sometimes the use
of a third party is necessary to provide eggs, sperm or a
uterus to carry the pregnancy.
Sub- Fertility
Any other diagnoses in couples, besides the
mentioned…, consider some degree of sub-fertility.
That is, there is some chance, even small of
conception without the assistance of fertility
treatments.
The role of the fertility specialist is to guide the patient
towards timely evaluations and treatment decisions
that will significantly improve their chances of
becoming parents.
Causes of Male infertility
The primary causes of male infertility are:
 Impaired sperm production,
 Impaired sperm delivery, and
 Testosterone deficiency (hypogonadism).
Infertility can result from a condition that is present at
birth (congenital) or that develops later (acquired).
Causes of male infertility
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Chemotherapy
Defect or obstruction in the reproductive system such
as failure of testes to descend into the scrotum
(cryptorchidism) or absence of one or both testicles
(anorchism).
Disease (e.g., cystic fibrosis, sickle cell anemia,
sexually transmitted diseases [STDs]).
Causes of male infertility
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Hormone dysfunction (testosterone deficiency; caused by a
disorder in the hypothalamic-pituitary-gonadal axis).
Infection (e.g., prostatitis, epididymitis, orchitis; can cause
irreversible infertility if occur before puberty).
Injury (e.g., testicular trauma).
Medications to treat high blood pressure (hypertension) and
digestive disease.
Metabolic disorders such as hemochromatosis (affects how the
body uses and stores iron).
Systemic disease (high fever, infection, kidney disease).
Testicular cancer.
Varicocele.
Causes of male infertility
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Retrograde ejaculation: Occurs when impairment of the
muscles or nerves in the bladder neck prohibit it from closing
during ejaculation, allowing semen to flow backward into the
bladder and causing infertility.
- It may result from bladder surgery,
- Congenital defect in the urethra or bladder, Or
- Disease that affects the nervous system. Diminished or
"dry" ejaculation and cloudy urine after ejaculation are signs
of this condition.
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Testicular trauma, resulting from injury, surgery, or infection
Male Partner Diagnostic Tests
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Semen Analysis
For sperm count and characteristics. It is obtained
after three days of sexual abstinence.
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Other Possible Tests:
Blood tests, such as FSH, LH, Prolactin and a
testosterone level may be drawn.
Male Partner Diagnostic Tests
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The sperm penetration assay (SPA), or sperm-oocyte
interaction test, examines the ability of sperm to
penetrate the egg by combining it with a hamster egg.
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The immunobead test looks at semen for the presence
of antibodies that damage sperm.
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Post-ejaculation urinanalysis may identify diseases
that affect fertility, such as kidney disease, diabetes,
and repeated urinary tract infection (UTI).
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Blood tests identify disorders that impair testosterone
and sperm production.
Six sperm factors are analyzed in semen analysis:
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Concentration (sperm/milliliter; cc)
Morphology (sperm shape; normal structure
associated with sperm health)
Motility (or mobility; % sperm movement)
Standard semen fluid test (thickness, color)
Total motile count (total number of moving
sperm)
Volume (total volume of ejaculate)
Semen Analysis
Parameter Results
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Colour
Coagulate?
Liquefy ?
If yes, time in minutes
Volume (ml)
pH
Sperm concentration
Grade of sperm motility
Motile sperm count
White blood cells
Agglutination
Morphology
Normal Values
Gray
Yes
Yes
< 30
2 to 6
7.5 to 8.0
20-200 ( million per ml)
(forward progressive)
motility > 50%
> 10 million per ml
< 1 million/ml
nil
> 30 % normal forms
Female Partner Diagnostic Tests
It include some or all of the following:
History
 Physical Exam
 Pelvic Exam with pap smear and cultures
 Uterine Measurement (by ultrasound)
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Female Partner Diagnostic Tests
Cycle Day 1,2, or 3 Blood Tests
Follicle stimulating hormones (FSH),
Luteinizing hormone (LH),
Prolactin, and Estradiol levels (E2) on either Day 1, 2, or 3 of your
cycle.
N.B. Generally, Cycle Day 1 is defined as the first day of flow (i.e.
not spotting). These are baseline hormones that give us an idea
of how sensitive the ovaries are to fertility drugs.
N.B. Hormonal level vary according to phase of the cycle or from
lab to lab.
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Thyroid panel is also done since an abnormal
thyroid level may interfere with normal ovulation.
Female Partner Diagnostic Tests
LH Surge/Ovulation:
Usually on Cycle Day 10 (10 days from the first day of your
menses). Positive result, means ovulation within 24-36 hours.
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Progesterone Level:
It is a blood test drawn seven (7) days after ovulation. A level of
above 10 ng/ml indicates a healthy ovulation.
Post Coital Test
This tests for the sperm’s ability to penetrate the cervical
mucus. It is performed like a pap test on the female partner the
day before ovulation.
Preparation:
Normal sexual relations (without the use of lubricants) the night
of your LH surge. Six to 12 hours after intercourse.
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Female Partner Diagnostic Tests
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Sonohysterogram (water ultrasound)
This is a test to examine the uterine cavity for abnormalities,
such as polyps or fibroids. It is performed between cycle day 612. It takes approximately 10 minutes and is associated with
minimal discomfort.
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Other Possible Tests
Androgens (DHEA-S, testosterone).
Normal Karyotype
Genetic Tests of Infertility
Men take tests that look for:
 Changes in chromosome structure or number
 Missing regions on the Y chromosome (also called
Y deletion)
 Changes in the cystic fibrosis gene
Women take tests that look for:
 Changes in chromosome structure or number.
 Changes in the Fragile X region of the X
chromosome.
Genetic & Infertility
Single-gene Defects and Infertility (mutation in the gene
that causes the disease Cystic Fibrosis):
Men who are unaffected with CF, but carry a single copy
of the gene (a "carrier" for CF), are at high risk of
"congenital absence of the vas deferens." Men with
this condition do not have sperm in the ejaculate, but
have abundant sperm in epididymus and testicle,
which is retrievable for IVF and ICSI.
All men with congenital absence of the vas deferens
should be tested for CF gene mutations. Their female
partners need to be tested in order to know whether or
not the couple will be at risk to have a child with the
disease.
Genetic & Infertility
Y-Chromosome Partial Deletions
However, research work have reported that about 10-15% of men
with severe male factor infertility (less than 2 million sperm per
cc), when specifically tested, will be found to have a small
portion of genetic material (DNA) missing from the Y
chromosome. This is a particular type of single-gene mutation
that is associated with low sperm counts or lack of any sperm in
the ejaculate. It does not appear that this deletion is associated
with any abnormality other than male infertility. Many men have
been able to conceive with this condition through IVF with ICSI.
Genetic &Infertility
Ovary gene may explain certain aspects of infertility
Ovary gene whose absence from mouse egg cells
produced severe pregnancy complications.
The gene, Fmn2, which produces the protein formin2, is similar in mice and humans and offers promise
for understanding embryo loss, birth defects, and
infertility in women.
The study appears in the December Nature Cell Biology.
Schematic Representation of the Hypothalamic-Pituitary-Gonadal Axis and
Anterior Pituitary Development
Mutations in genes reported to affect fertility or gonadal development in
humans white boxes.
http://mend.endojournals.org/content/vol13/issue6/images/large/mg0690301001.jpeg
Reported Mutations in the FSH and LH ßSubunits (top panel) and Inactivating Mutations
of the FSH/LH Receptor (composite diagram,
lower panel) For clarity, activating mutations of
the LH receptor and FSH receptor are not
depicted.
Genetic & Infertility
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Gene (GlcNAc-6-OST) gets transcribed and then
translated into a protein and this particular protein
functions as an enzyme," "It has been shown to be
expressed specifically during the window of
implantation, that this particular gene, for no reason, is
abnormally expressed in women with endometriosis
which results in the embryo not being able to find the
appropriate place to bind to the endometrium leading
to a failure or defect in the implantation process."
References: http://www.endometriosis.org/
The development of IVF has allowed many couples to
have the families they may otherwise have been
unable to have.
At the same time, this technology has also allowed
researchers to begin to study the genetic make-up of
the earliest stages of embryos.
These advances are providing some insights into how
genetics and infertility might be linked, just beginning
to understand how defects (mutations) in specific
genes may result in male and female infertility.
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References & Online Further Reading
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http://www.dnadirect.com/tests/infertility/karyotype.jsp
http://www.infertilitydoctor.com/welcome/welcome_intro.htm
http://www.eurekalert.org/pubnews.php
http://urologychannel.com/whfc/lab.shtml#analysis
http://www.ivf-infertility.com/infertility/index.php
http://www.drmalpani.com/index.html
http://www.ktvb.com/
http://www.bcm.edu/fromthelab/index.htm