Infertility

• Infertility is defined as the inability to conceive

after 1 year of unprotected intercourse.

• It has been estimated that 93% of healthy

couples practicing unprotected intercourse
should expect to conceive within 1 year, and
100% will be successful within 2 years.
• Primary infertility
refers to couples or patients
who have had no previous successful
pregnancies.
• Secondary infertility
encompasses patients who have
previously conceived, but are currently
unable to conceive.
 Male Infertility

• Evaluation of Semen
Semen analysis measures (1) ejaculate
volume, (2) pH, (3) sperm
count, (4) motility, (5) forward progression,
and (6) morphology. Semen should be
analyzed within 1 hour after collection.
Male Infertility Factors
Male Infertility Factors
 Evaluation of Obstruction

• Obstruction of the male reproductive tract

results in male infertility.
• Testosterone produced after administration of
hCG causes the (1) seminal vesicles, (2)
epididymis, and (3) prostate to increase the
volume of ejaculate.
• An appropriate increase in serum testosterone
without change in the ejaculate volume may
indicate mechanical blockage
 Evaluation of Endocrine Parameters

• If severe oligospermia (low sperm count) or

azoospermia (no measurable sperm in semen)
is found, then measure
(1) serum testosterone, (2) LH, and (3) FSH
concentrations (4) prolactin
and (5) TSH concentrations.
Hyperprolactinemia is a cause of secondary
testicular dysfunction.
• If hyperprolactinemia is found then
check for hypothyroidism, because
elevated TRH concentrations result in
hyperprolactinemia.
• Pituitary adenomas and drugs, such as
(1) anxiolytics, (2) antihypertensives, (3)
serotonergics, and (4) histamine H2
receptor antagonists also increase
serum prolactin.
• Hyperthyroidism and hypothyroidism will
alter spermatogenesis.
• Hyperthyroidism affects both pituitary and
testicular function with alterations in the
secretion of releasing hormones
and increased conversion of androgens to
estrogens
 Hypergonadotropic Hypogonadism

• Measurement of the concentration of FSH is

indicated in men with sperm count lower than 5
to 10 million/mL.
• Elevated concentrations of FSH indicate (1)
Sertoli cell dysfunction and, in azoospermic men,
(2) primary germinal cell failure, (3) Sertoli cell–
only syndrome (a condition resulting in sterility
due to the absence of living sperm cells in the
semen).
• 4) genetic conditions, such as Klinefelter
syndrome (47,XXY karyotype).

• Elevated FSH (>120 mIU/mL) in the setting of

decreased testosterone (<200 ng/dL) and
oligospermia indicate primary testicular ailure
 Hypogonadotropic Hypogonadism

• Decreased concentrations of testosterone

(<200 ng/dL) and decreased concentrations o
FSH (<10 mIU/mL) are suggestive o
hypogonadotropic hypogonadism.
• Administering GnRH may help to distinguish
between gonadal insufficiencies caused by
pituitary versus hypothalamic dysfunction.
• One approach to this test involves the intravenous
injection of 100 µg of GnRH with measurement of FSH
and LH concentrations at 0, 30, 60, 120, and 180
minutes after injection.
• An increase in serum gonadotropins of 10 mIU/mL or
more over baseline is normal.
• If little to no increase in gonadotropins is seen,
pituitary disease is likely.
• Patients with hypothalamic disease demonstrate a
delayed but significant increase of 7 mIU/mL or more
within 180 minutes
Female Infertility Factors
Female Infertility Factors
 Evaluation of Female Infertility

• The initial evaluation

1 Physical Examination.
• (1) the external genitalia and hair pattern ( or
signs of androgen excess including cliteromegaly,
hirsutism, and virilization),
• (2) the pelvis ( for masses,nodularity or
tenderness
• (3) breasts ( for signs of galactorrhea),
2 A thorough medical and surgical history
(1) the patient’s gravidity and parity,
(2) coital frequency,
(3) duration of infertility
(4) prior work up and treatment for infertility.
(5 ) history of sexually transmitted infections
(6) assessment of previous cervical cytologic
and HPV testing and treatment
(7) menstrual history should be obtained
• menstrual cycles are absent or irregular or if
there are signs of galactorrhoea or thyroid
abnormalities
(1)TSH,
(2) Testosterone,
(3) Prolactin
 Evaluation of Ovulation

• No confirmatory lab tests. HOWEVER

• Mid-luteal Plasma Progesterone does
indicate that a corpus luteum was formed.

LH surge (to predict ovulation) and basal body

temperature (to detect a rise in progesterone)
have been used to assess ovulation.
 Clinical Utility of Progesterone
Measurements.
• Beginning immediately after ovulation,
serum progesterone concentrations
rise and peak within 5 to 9 days during the
mid-luteal phase (days 21 to 23).
• If ovulation does not occur, the corpus
luteum fails to form, and the expected cyclic
rise in progesterone concentration is
subnormal.
• If pregnancy occurs, hCG maintains the corpus
luteum, and progesterone production
continues to rise.
• Mid-luteal progesterone concentrations
greater than 3 ng/mL indicate that ovulation
has taken place, although concentrations of 10
ng/mL or more are more common in
conception cycles.
 Clinical Utility of Measurement of
Basal Body Temperature
• cost-effective indicators of ovulation……
a rapid rise in body temperature (by 0.5 °F),
which persists through the luteal phase due
to increased quantities of progesterone.
• Progesterone and rise in body temperature
does not predict imminent ovulation in a way
helpful for timing intercourse
Clinical Utility of the Measurement of
the Luteinizing Hormone Surge.
• LH appears in the urine just after the serum
LH surge and 24 to 36 hours before ovulation
• indicates when ovulation should occur and
provides a guide with which to time intercourse.

• Home LH kits provide information as to the

timing of ovulation
 Evaluation of Endocrine Parameters

• Disorders of the (1) hypothalamus, (2)

pituitary, and (3) ovary are endocrine causes
of infertility in women
 Hypergonadotropic Hypogonadism

• In women younger than 40 years,

hypergonadotropic hypogonadism is indicated by
repeatedly elevated basal FSH concentrations
(>30 IU/L) or a single elevation of greater than
40 IU/L.
• These patients are hypoestrogenic
• endometrium is atrophic.
• Basal serum FSH has been used as an indicator of
relative ovarian reserve
 Assessing Ovarian Reserve.

• Women in their mid to late 30s and early 40s

with infertility constitute the largest portion
of the total infertility population and are at
increased risk for pregnancy loss.
• This reflects a diminished ovarian reserve as a
result of follicular depletion and a decline in
oocyte quality.
• As women age, serum FSH concentrations in the
early follicular phase begin to increase
• In general, day 3 FSH concentrations greater
than 20 to 25 IU/L are considered to be elevated
and associated with poor reproductive outcome.
• Basal Estrogen concentrations greater than 75 to
80 pg/mL are associated with poor response to
ovarian stimulation and pregnancy outcome.
• Inhibin is produced by gonadal tissue and thus is
thought to be a more direct marker of gonadal
activity and ovarian reserve than pituitary
hormones alone.
 Hypogonadotropic Hypogonadism

• In hypogonadotropic hypogonadism, serum

Estrogen concentrations are less than 40
pg/mL (110 pmol/L)
• Quantities of LH (<10 IU/L) and FSH (<10 IU/L)
are decreased.
• Hyperprolactinemia causes
hypergonadotropic hypogonadic infertility.
• The upper limit of normal plasma prolactin in
an amenorrheic, hypoestrogenic, nonpregnant
woman is 400 to 500 mIU/mL .
• If estrogen status is normal, maximum
prolactin concentrations vary from 600 to
800 mIU/mL
• TSH should be measured to exclude
hypothyroidism
• Prolactin concentrations are elevated in
patients with PCOS and those taking
medications, such as (1) antidepressants, (2)
cimetidine, and (3) methyldopa, and (4) in
stressful conditions.
• Radiographic imaging of the pituitary is
indicated to rule out pituitary adenoma or
empty sella syndrome.