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Infertility and Genetics
Lecture 13
I.
The Couple Experiencing Infertility
A.
Incidence
1.
Definition: Inability to conceive and carry a pregnancy
to viability after at least one year of regular
sexual intercourse without contraceptive use
a.
Primary-never pregnant
b.
Secondary-had been pregnant in the past
B.
2.
Problem for 10-15% of reproductive-aged couples
3.
Women over age 35-21% chance of infertility
Risk Factors
1.
Females
a.
abnormal external genitals
b.
abnormal internal reproductive structures
c.
anovulation
-pituitary/hypothalamus hormone disorders
-adrenal gland disorders
d.
amenorrhea after stopping OCP
e.
early menopause
f.
increased prolactin levels
g.
tubal motility reduced
h.
inflammation within the tube
i.
tubal adhesions
j.
endometrial/myometrial tumors
k.
Asherman’s syndrome-uterine adhesions/scars
2.
Males
a.
undescended testes
b.
hypospadias
c.
varicocele
d.
low testosterone levels
e.
testicular damage-trauma, mumps
f.
endocrine disorders
g.
genetic disorders
h.
STI’s
i.
exposure to hazardous substances
j.
change in sperm
-smoking, heroin, marijuana, amyl nitrate, butyl
nitrate, methaqualone
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2
k.
l.
m.
n.
C.
decrease in sperm
-hypopituitarism
-chronic disease
-gonadotropic inadequacy
obstruction of the vas deferens or epididymis
decreased libido
impotency
Components of Fertility
1.
Sperm viable in female reproductive tract for up to
48+ hours
-fertility potential-24 hrs
2.
Ova viable for about 24 hours
-optimum time for fertilization may be only 1-2 hours
3.
Blastocyst must implant within 7-10 days into the
hormonally prepared endometrium
4.
Women account for 50% of infertility cases
a.
male problems-35%
b.
unexplained factors-15%
5.
Assessment of female infertility
a.
complete history
-duration of infertility
-past obstetrical events
-sexual history
-review medical/surgical history
-assess exposure to hazardous substances
b.
physical exam
-assess endocrine systems for abnormalities
-visualize secondary sex characteristics
-tests to evaluate uterus and fallopian tubes
-bimanual exam of organ mobility
-lab tests
c.
testing
-HSG-hysterosalpingogram
-postcoital test
Sims-Huhner test-ck cervical mucus
abstain from intercourse for2-3 days
performed several hours after ejaculation
examine cervical mucus/sperm under
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microscope
-sperm immobilization antigen-antibody reaction
-assessment of cervical mucus
spinnbarkeit-the formation of thread by
mucus from the cervix when spread on
a glass slide and drawn out by a cover
glass
-U/S dx of follicular collapse
-serum assay of plasma progesterone
-hormone analysis
estrogen, progesterone
FSH, LH
thyroid
-basal body temperature (BBT)
biphasic-↑ temp 12-14 days before menses
ck temp before rising
0.5-1.00 rise=surge of LH, progesterone
ova released 24-36 hrs before ↑ temp
intercourse-3-4 days prior to 2-3 after
-endometrial biopsy
-laparoscopy
-U/S
6.
D.
Assessment of male infertility
a.
H&P
b.
semen analysis
-sperm density-20-200 million cells/ml
-may vary day to day-collect over a month
-effects of cervical mucus on sperm’s motility and
survival
-ck sperm’s ability to penetrate an ova
Infertility management
1.
Psychosocial
a.
may need counseling to deal with issues of loss
or inadequacy
b.
dx of infertility may lead to problems with
couple’s personal relationship
c.
discuss alternatives, i.e. adoption
2.
Nonmedical therapies
a.
water soluble lubricants
b.
change to boxer shorts
c.
use of condoms if woman has immunologic
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reaction to sperm-will reduce antisperm
antibody production
3.
Medical therapies
a.
ovulatory stimulants
-Clomid (clomiphene) stimulates the ovarian
follicle
-multifetal rates-less than 10%
-Parlodel (bromocriptine) inhibits release of
prolactin (elevated levels of prolactin have
an amenorrhea effect on the body)
-Bravelle, Menopur (human menopausal
gonadotropin)
extremely potent
requires daily monitoring
daily IM for 7-14 days-first half of
cycle
incidence of multifetal > 25%
-HCG-may be given to induce ovulations
after ovaries stimulated with HMG
-GnRH (gonadotropin-releasing hormone)
used with hypothalamic-pituitary
dysfunction or failure to respond
to clomiphene
b.
hormone replacement therapy
-use conj. estrogen and medroxyprogesterone
c.
male tx
-thyroid/adrenal gland correction
-abx for STI
-clomiphene-unsure effectiveness
-HCG-stimulates androgens-↑ spermatogenesis
4.
Surgical treatments
a.
excise ovarian tumors
b.
removal of adhesions
c.
hysterosalpingography-may unblock tubes
d.
if uterine cavity too small to carry pregnancy,
no medical tx available-each successive
pregnancy enlarges uterus
e.
may be able to reconstruct uterus R/T bicornuate
f.
myomectomy
g.
chemo/thermocautery to eliminate chronic
inflammation and infection
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5.
E.
II.
Reproductive alternatives
a.
assisted reproductive alternative
(higher risk for ectopic)
-IVF-ET-in vitro fertilization-embryo transfer
-GIFT-gamete intrafallopian transfer
*after ovulation, ova and sperm moved into tube
-ZIFT-zygote intrafallopian transfer
-ovum transfer (oocyte donation)
-embryo adoption
-intracytoplasmic sperm injection
-assisted hatching
-TDI-therapeutic donor insemination
b.
preimplantation genetic diagnosis
-eliminate defect embryos before implantation
c.
surrogate mothers
-use surrogate’s ova and husband’s sperm
-use mother’s ova and husband’s sperm
d.
adoption
Nursing diagnoses
1.
Body image disturbance
2.
Decisional conflict
3.
Altered patterns of sexuality
4.
Risk for social isolation
The Family Experiencing a Genetic Disorder
A.
Chromosomal abnormalities
1.
Human Genome Project-1990-international effort to
map and sequence the genetic makeup of
humans-Completed 2003
a.
ELSI-Ethical, Legal, and Social Implications
Program-sentinel to prevent discrimination
or use of material for eugenic purposes
(selective breeding)
b.
initial sequencing complete 06/00
c.
goal-to facilitate study of hereditary diseases
and provide potential for altering genes
to treat and/or prevent occurrence
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2.
Chromosomes
a.
karyotype-pictorial analysis of chromosomesusually from peripheral blood but may
come from any body tissue
b.
autosomal chromosomes-22 pairs
control traits of the body
c.
allosomal (sex) chromosomes-pair 23
determines sex
controls some other traits
XX-female
XY-male
d.
dominant gene-their trait is expressed over
another (AA or Aa)
e.
recessive gene-only expressed when another
another recessive is present (aa)
f.
terms-allele-gene that determines a specific trait
each trait has a pair of alleles
genotype-genetic makeup of an individual
genetics-study of a particular gene
genome-entire set of genetic instructions
found in a cell (23 pairs of
chromosomes)
genomics-study of an organism’s entire
genome
phenotype-expression of gene’s function
either measurable or observed
homozygous-has identical alleles on
each chromosome in the same locus
hetrozygous-2 different alleles at a given
locus
→http://www.genome.gov/glossary/
3.
Abnormalities in chromosomal numbers (aneuploidy)
a.
usually caused by nondisjunction
b.
occurs during meiosis when pair fails to separate
c.
trisomy-additional autosomal chromosome
-21-Down Syndrome
-18-Edwards Syndrome
-13-Patau Syndrome
(18 & 13-poor prognosis: cardiac &
respiratory problems)
d.
lack of an autosomal chromosome (45)=death of
embryo
e.
mosaicism-some cells have normal #, others
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f.
4.
B.
missing/having an additional chromosome
sex chromosome abnormalities
-45X-Turner’s
juvenile external genitalia
undeveloped ovaries
short in stature
webbing of the neck
impaired intelligence
most affected embryos SAB
-47XXY-Klinefelter’s
poorly developed secondary sexual
characteristics
small testes-infertile
tall, effeminate
subnormal intelligence usually present
Abnormality of chromosome structure
a.
translocation-genetic material moved from
one chromosome to another-may
create an imbalance of materials
no problem if all information present
b.
additions/deletions
gamete produced has too many/too few
gene-effect may be mild→severe
Patterns of Inheritance
1.
Multifactorial
a.
combination of genetic and other factors such
as environment
i.e.: cleft lip/palate, neural tube defects
b.
malformation may be mild to severe depending
on # of genes affected
c.
tend to occur in families
d.
some malformations more common in one sex
e.
polygenic, multifactorial diseases: coronary
artery disease, obesity, HTN, psychiatric disorders
2.
Unifactorial-Single-gene disorders
a.
one gene controls a particular trait, disorder, or
defect
b.
# of unifactorial abnormalities exceed the # of
chromosomal abnormalities
-50-100,000 genes in 23 chromosomes
c.
autosomal dominant inheritance
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d.
e.
f.
C.
-abnormal gene with trait is expressed even with
a normal member of the pair-no carriers
-mutation of the gene-spontaneous, permanent
change
-affected individual comes from a family with
generations of the disorder-50% chance of
have mutant allele if parent was affected
-ex: Marfan’s-disorder of connective tissue
achondroplasia-dwarfism
polydactyly-extra digits
Huntington disease
autosomal recessive inheritance
-both genes in the pair carry the abnormality
-heterozygous-carriers of the recessive trait
-ex: Tay-Sachs
sickle cell anemia
cystic fibrosis
-phenylketonuria
X-linked dominant inheritance
-occur in males and heterozygous females
-ex: Fragile X syndrome-mental retardation
X-linked recessive inheritance
-no male to male transmission
-50% chance that carrier mother will pass
abnormal gene to each son who
will be affected (therefore, 50% of
males will be unaffected)
-50% chance that carrier mother will pass
abnormal gene to each daughter
who will become carriers
-for daughters to be affected, father must
be affected and mother be a carrier
or affected as well
-ex: hemophilia-defect in clotting factor VIIIc
Duchenne muscular dystrophy
Testing
1.
Prenatal testing-see booklet
a.
MSAFP
b.
CVS/amniocentesis
c.
blood tests for:
-Tay-Sachs
-Sickle Cell Anemia
-Thalassemia
-Cystic Fibrosis
d.
U/S-fetoscopy
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2.
D.
Newborn testing-see booklet
a.
PKU-mental retardation
b.
congenital hypothyroidism-retardation
c.
galactosemia-dehydration/sepsis
d.
maple syrup urine disease-neurologic
e.
homocystinuria-neurologic
f.
congenital adrenal hyperplasia-electrolytes
g.
biotinidase deficiency-neurologic
Clinical management
1.
Genetic counseling
a.
understand facts about the disease-cause
and treatment
b.
understand how heredity contributes
c.
understand rate of recurrence
d.
aware of options
e.
course of action
f.
use of coping mechanisms/support systems
2.
Nursing roles
a.
identify risk factors
b.
identify physical/developmental abnormalities
c.
assess need for referral
d.
prepare for genetic counseling
e.
correct misconceptions
f.
demonstrate support and sensitivity
g.
explain typical outcomes
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