Infertility is defined as the inability to conceive after one year of unprotected intercourse if the woman is under 35 years old, or after 6 months if the woman is over 35. Approximately 15% of reproductive couples struggle with infertility. Both male and female factors can contribute to infertility, with common causes including problems with ovulation, fallopian tubes, uterine or cervical factors, as well as hormonal imbalances, autoimmune disorders, and genetic conditions. A full medical workup evaluates both partners and may include tests to assess hormone levels, egg reserve, sperm count, thyroid function, and more. While the causes of infertility can be complex, many cases can be treated successfully with lifestyle changes, medication, surgery, or assisted

2. Infertility
• The inability to conceive following unprotected sexual
intercourse
• 1 year (age < 35) or 6 months (age >35)
• Affects 15% of reproductive couples
• 6.1 million couples
• Men and women equally affected

3. WHO Data
• 1.9% of child-seeking women aged 20–44 y were unable
to have a first live birth - primary infertility and
• 10.5% of child-seeking women with a prior live birth were
unable to have an additional live birth - secondary
infertility

4. Infertility Causes

5. Etiology of Infertility
• Reproductive age for women
• Generally 15-44 years of age
• Fertility is approximately halved between 37th
and 45th
year due to
alterations in ovulation
• 20% of women have their first child after age 30
• 1/3 of couples over 35 have fertility problems
• Ovulation decreases
• Health of the egg declines
• With the proper treatment 85% of infertile couples can
expect to have a child

6. Infertility
• Primary infertility
• a couple that has never conceived
• Secondary infertility
• infertility that occurs after previous pregnancy regardless of
outcome

7. Causes of Infertility - Male
• Testicular injury
• Exposure to chemicals or toxins
• Use of anabolic steroids
• Hormonal imbalances
• Klinefelter syndrome

8. Causes of Infertility - Female
Causes of Infertility in the Female partner include
• disorders of ovulation,
• tubal disease, and uterine or cervical factors.
• Uterine fibroids
• Endometriosis
• Autoimmune disorders, which produce antibodies against fetal tissue
• Diabetes
• Hypothyroidism
• Eating disorders

9. • Endocrinological abnormalities are frequently
encountered and most effectivly treated causes of
infertility.

10. Evaluation of Infertility
• Infertility is a problem that involves both partners

11. Cut-offValues* for the Most
Commonly Used Ovarian Reserve
Tests

12. LaboratoryWorkup of Male
Infertility

13. Laboratory Workup of Female
Infertility

14. Ovarian Function
• Number of follicles in the ovaries decreases from birth
• from the age of 30 onward a slow decline in fertility
occurs
• first sign of reduced ovarian activity is the shortening of
the follicular phase

15. Complete Hormonal Evaluation
• dehydroepiandrosterone sulfate (DHEAS),
• cortisol,
• Thyroid function tests
• Luteinizing Hormone
• Follicle Stimulating Hormone
• Estradiol
• Progesterone
• Prolactin
• Androstenedione
• HCG
• AMH

16. FSH
• Follicle-stimulating hormone (FSH) stimulates the
development of the egg
• For women, a FSH test - third day of the menstrual
cycle
• is used to evaluate egg supply.
• too high or too low, it can signal fertility issues
preventing conception from occurring
• For men, to determine sperm count;
• it regulates the production and transportation of
sperm.

17. Interferences
FSH results can be increased with use of certain drugs, including
• cimetidine,
• clomiphene,
• digitalis, and
• levodopa.
FSH results can be decreased with oral contraceptives, phenothiazines,
and hormone treatments.
A recent nuclear medicine scan may interfere with results of the FSH
test if it is measured by a radioimmunoassay

18. Estradiol
• stimulates the growth of the follicles and the production of cervical
mucus from the cervix, and prepares the uterine lining for
implantation of a fertilized egg
• As they develop, the level continues to rise.This rise can further
indicate that the oocyte within the follicles is reaching its maturity.
• Estradiol is an important form of estrogen. An estradiol test is used
to measure a woman’s ovarian function and to evaluate the quality of
the eggs.

19. Estradiol - Interpretation
• estradiol vary from person to person.
• blood levels can’t always be interpreted with complete certainty in the first cycles.Without prior
cycles to ’calibrate’ the levels,
• level usually means-- what it ’probably’
• a level in the range of 150 to 500 pg/ml is reasonable for the eighth day of a stimulated cycle.
• doubling of this level every 48 hours - sign of continued good follicle development.
• stimulation response depends upon physical height, weight, lean mass
• failure to rise estradiol follicles are not responding appropriately, and that the oocytes within will
not be of good quality.

20. Estradiol - Interpretation
• daily and cyclic variations,
• illnesses - high blood pressure (hypertension), anemia,
and impaired liver and kidney function can affect
estradiol levels.
• drugs, such as glucocorticosteroids, ampicillin, estrogen-
containing drugs, phenothiazines, and tetracyclines,
increase estradiol.

21. Prolactin
• Prolactin is a hormone that plays an active role in stimulating milk production
after the delivery of a child.
• increases during pregnancy, and work to inhibit ovulation
• High levels stop ovulation and cause menstrual cycles to cease.
• Causes intermittent ovulation or take a long time for ovulation to occur.
• Cause inadequate production of the hormone progesterone after ovulation,
commonly known as the luteal phase defect.

22. Interpretation
• diurnal variations
• Prolactin levels peak during REM sleep, and in the early morning.
• Levels can rise after exercise,
• high-protein meals,
• sexual intercourse,
• breast examination,
• minor surgical procedures,
• following epileptic seizures
• due to physical or emotional stress

23. Luteinizing Hormone Level
• stimulates the release of the egg from the follicles
• In men, it stimulates the hormone testosterone which affects sperm
production.
• LH surge may cause undesirable changes in egg quality, or cause
early egg release decreasing the chance of pregnancy.
• testing blood or urine every three to four hours for egg retrieval.
• This timing is necessary to be certain that the oocytes are mature.

24. Interpretations
LH
increases,
• anticonvulsants,
• clomiphene, and
• naloxone,
while others cause LH to decrease,
• digoxin,
• oral contraceptives, and
• hormone treatments

25. Serum Progesterone
• Stabilizes the uterine lining for implantation of a fertilized
egg and supports early pregnancy.
• Progesterone levels increase towards the end of a cycle -
the testing is advised in luteal phase
• progesterone suppositories advised if levels inadeqaute

26. Interpretations
• luteal ovarian cysts,
• molar pregnancies, and
• with a rare form of ovarian cancer.

27. Androgen
• Testosterone is probably the most well-known androgen
and it affects the sexual functioning of both men and
women.
• Androgens - small amounts women;
• Excess interferes with development of the follicles,
ovulation and cervical mucus production
• Low or deficiency of testosterone may indicate low sperm
count leading to infertility
• To find the cause of a low sex drive, the inability to get an
erection

28. Interpreatations
• Alcoholism and liver disease in males can decrease
testosterone levels.
• Drugs, including androgens and steroids, can also
decrease testosterone levels.
• Prostate cancer responds to androgens, so many
men with advanced prostate cancer receive drugs
that lower testosterone levels.
• Drugs such as anticonvulsants, barbiturates, and
clomiphene can cause testosterone levels to rise.
• Women taking estrogen therapy may have increased
testosterone levels.

29. Thyroid
• hypothyroid women due to associated ovarian
dysfunction.
• Both hypo- and hyperthyroidism disrupt reproductive
hormone balance.
• hypothyroidism has been associated with reduced FSH
and LH levels
• hypothyroidism may impact on fertility is by altering the
peripheral metabolism of oestrogen and by decreasing
SHBG production
• hyperprolactinaemia, due to increasedTRH production,
and altered GnRH pulsatile secretion, leading to a delay in
LH response and inadequate corpus luteum, have been
reported

30. Interpreatations
Increases, decreases, and changes (inherited or
acquired) in the proteins that bind T4 and T3
Pregnancy
Estrogen and other drugs
Liver disease
Systemic illness
Resistance to thyroid hormones
Nonthyroidal illnesses
Extreme stress and acute illness

31. Polycystic Ovarian Syndrome
• Polycystic ovarian syndrome (PCOS), for example, is an
endocrine disorder that affects as many as 10 percent of
women
• PCOS is also one of the most common causes of infertility
among women of reproductive age
• PCOS is characterized by irregular or lack of ovulation,
irregular or lack of menstrual periods, elevated levels of
androgens (hyperandrogensim) including testosterone,
androstenedione and dehydroepiandrosterone sulfate (DHEA-
S), abnormal levels of LH, FSH and estrogen and small cysts
covering enlarged ovaries (polycystic ovaries

32. DHEA –The Mother of All Hormones
• Building block of all hormones - testosterone estrone, estradial, and estriol.
• Key roles in the reproduction cycle
• increased quality in their egg production and the number of eggs that drop
into the fallopian tubes.This allows for an increased chance of conception.
• base point of a normal person at the age of 20 - only 5% remains at the age
of 80.
• DHEA supplements for older women - increase the chances of conception.
• increased quality of egg production and number of eggs that drop into the
fallopian tubes.
• increased chance of conception.

33. DHEA-SO4
• Sulphate form of DHEA
• DHEAS may be elevated with polycystic ovarian
syndrome (PCOS).

34. Interpreatations
• People taking DHEA supplements will have elevated
blood levels of DHEAS.
• Certain antidiabetic drugs (such as metformin and
troglitazone), prolactin, danazol, calcium channel
blockers, and nicotine may also increase DHEAS
levels.
• Decreased levels include insulin, OC, corticosteroids,
dopamine, hepatic enzyme inducers
(carbamazepine, imipramine, phenytoin), fish oil,
and vitamin E.

35. SHBG
• SHBG is a protein that binds tightly to the hormones
testosterone, dihydrotestosterone (DHT), and estradiol
(an estrogen).
• In this bound state, SHBG transports these hormones in
the blood as biologically inactive forms.
• affect the amount of hormone that is available to be used
by the body's tissues.
• Measurement of SHBG in addition to testosterone is
especially helpful when total testosterone results are
inconsistent with clinical signs

36. Interpreatations
• SHBG concentrations are normally high in children of
both sexes.
• Levels are normally stable in adults and then begin to
increase in the elderly male.
• In postmenopausal women, SHBG concentrations
decrease as hormone production by the ovaries tapers off

37. Interpretations
Increased SHBG
• Liver disease
• Hyperthyroidism
• Eating disorders (anorexia nervosa)
• Corticosteroids or estrogen use (hormone replacement therapy and oral contraceptives)
• Decreased sex hormone production (hypogonadism)
• Pregnancy
• Decreases in SHBG are seen with:
Decreased
• Obesity
• Polycystic ovary syndrome
• Hypothyroidism
• Androgen (steroid) use
• Cushing disease

38. • Even slight increases in testosterone production can disrupt
the balance of hormones and cause symptoms such as
irregular or missed menstrual periods, infertility, acne, and
excess facial and body hair (hirsutism).These signs and
symptoms and others are often seen with polycystic ovary
syndrome (PCOS), a condition characterized by an excess
production of male sex hormones (androgens). SHBG and
testosterone testing may be useful in helping to detect and
evaluate excess testosterone production and/or decreased
SHBG concentrations and in evaluating women suspected of
having PCOS.

39. Anti-Müllerian hormone (AMH)
• AMH plasma levels reflect the continuous non-cyclic growth of small
follicles,
• suggestive of the size of the resting primordial follicle pool
• marker of ovarian reserve.
• predictive of the ovarian response to stimulation
• use of AMH in a variety of ovarian pathological conditions, including
polycystic ovary syndrome, granulosa cell tumors and premature
ovarian failure

40. Interpretations
• not affected by oral contraceptives or pregnancy
• AMH is increased in ovarian granulosa cell tumors

42. Few things in life are perfect, and unfortunately this also applies to
medical diagnostic procedures such as clinical laboratory testing

43. A patient with an Escherichia coli septicemia was found to have increased immunoassay results
for cardiac troponin I, thyroid stimulating hormone, hCG, a-fetoprotein, and CA-125, but none
of these results was consistent with the clinical findings. Serum protein electrophoresis
revealed that the patient also had a restricted IgM l peak. This was identified as the cause of
the falsely increased values in the immunometric assays.

44. Immunoassays Commonly
Affected

45. Interference in Immunoassays
Cross
reactivity
Hook
Effec
t
Antibody
Interfere
nce
Signal
Interferen
ce
Matrix
Effect

46. Cross Reactivity

47. High Dose Hook Effect

49. False Negative From
Heterophilic Antibody