Investigation of Infertility

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Investigation of Infertility
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OBJECTIVES

• Definition of infertility
• The laboratory approach to infertility in the
  women
• Interpretation of results of investigation of
  infertility in female and male
• Understand the diagnostic approach to infertility
  in male
• Hyperprolactinaemia
• Polycystic Ovary Syndrome

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Requirements for Conception

• Production of healthy egg and sperm
• Unblocked tubes that allow sperm to reach the egg
• The sperms ability to penetrate and fertilize the
  egg
• Implantation of the embryo into the uterus
• Finally a healthy pregnancy

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Infertility/ Subfertility

• The inability to conceive following unprotected
  sexual intercourse
• 1 year (age lt 35) or 6 months (age gt35)

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Infertility Etiology
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Female Factors
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Female Infertility

• Ovulation Disorders
• Aging
• Diminished ovarian reserve
• Endocrine Disorder
• Polycystic Ovary Syndrome (PCOS)
• Premature Ovarian Failure
• Tubal Factors
• Obstruction
• History of Pelvic Inflammatory Disease (PID)
• Tubal Surgery
• Previous ectopic and salpingectomy
• Uterine/Cervical Factors
• Congenital uterine anomaly
• Fibroids
• Poor cervical mucus quantity/quality
• Smoking
• Infection

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Male Infertility

• Primary Hypogonadism
• Radiation
• Testicular Trauma
• Varicocele
• Orchitis
• Systemic disorder
• Altered Sperm Transport
• Absent vas deferens or obstruction
• Epididymal absence or obstruction
• Erectile dysfunction (ED)
• Retrograde ejaculation
• Secondary Hypogonadism
• Androgen/Estrogen excess
• Infiltrative disorder (Sarcoid, TB)
• Pituitary adenoma
• Trauma

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Diagnostic approach to infertility in the woman
History Examination
Amenorrhoea, Oligomenorrhoea
Normal menses
No further tests required
ve
?Ovulating Measure Progesterone in day 21 (mid
luteal)
Perform pregnancy test
-ve
gt30nmol/L
lt10nmol/L
Measure LH, FSH, Prolactin
Ovulating
Not ovulating
High Prolactin
High FSH. ( LH)
High LH Low FSH
All Normal
Further tests indicated
Further investigate hyperprolactinaemia
Ovarian failure
PCOS
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Diagnostic approach to subfertility in the man
History examination
Abnormal sperm count
Normal sperm analysis, eugonadal
No endocrine tests are required
Measure testosterone, gonadotrophins, and
Prolactin
?Testosterone ?Gonadotrophins
?Testosterone ? Gonadotrophins

• Testosterone
• ? Prolactin

Hypogonadotrophic hypogonadism due to
hypothalamic-pituitary disease
Hyperprolactinaemia rare
Primary testicular failure
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Primary Testicular Failure

• Damage to both the interstitial cells and tubules
  ? ?Testosterone ?Gonadotrophins (LH FSH)
• Only tubular impairment ? selective ?in FSH,
  while androgen may be normal (azoospermia)
• Azoospermia with normal FSH and normal
  testicular volume indicates bilateral genital
  tract obstruction

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Evaluation of the Infertile couple

• History and Physical exam
• Semen analysis
• Thyroid and prolactin evaluation
• Determination of ovulation
• Basal body temperature record
• Serum progesterone
• Ovarian reserve testing
• Hysterosalpingogram

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• Infertility may be caused by endocrine problems
• This is common in the female
• But rare in the male
• Endocrine investigation is of diagnostic value
  for women who have
• Irregular or no menstruation
• No ovulation

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Endocrine causes of infertility in women

• Primary ovarian failure
• postmenopausal hormonal pattern (?
  gonadotrophins ? oestradiol)
• Hormone replacement therapy can be given (this
  will not treat the infertility)

• Hyperprolactinaemia
• PCOS
• Cushings syndrome
• Hypogonadotrophic hypogonadism
• Rare
• due to hypothalamic-pituitary lesion

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Cushing Syndrome

• Overproduction of cortisol by the adrenal cortex
• Prolonged exposure of body tissues to cortisol or
  other glucocorticoids
• Causes infertility in women due to
• Increased production of androgens and hirsutism

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Prolactin and Hyperprolactinaemia

• Prolactin is an anterior pituitary hormone
• Its secretion is tightly regulated
• stimulated by TRH from the hypothalamus
• inhibited by dopamine from hypothalamus
• It acts directly on the mammary glands to
  control lactation
• Hyperprolactinaemia
• It is elevated circulating Prolactin
• It is a common condition
• It causes infertility in both sexes due to
  gonadal fucntion impairement.
• Early indication of hyperprolactinaemia
• In women amenorrhoea galctorrhoea
• In men none

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Causes of hyperprolactinaemia

• Stress
• Drugs
• e.g. oestrogens, phenothiazines, metoclopramide,
  a-methyl dopa
• Seizures
• 1ary hypothyroidism (prolactin is stimulated by
  the raised TRH)
• Other pituitary disease
• Prolactinoma (commonly microadenoma)
• Idiopathic hypersecretion (e.g. due to imparied
  secretion of dopamine that usually inhibits
  prolactin release.

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Diagnosis of the cause of Hyperprolactinaemia

• Exclude
• Stress
• Drugs
• Other disease
• Differential diagnosis
• prolactinoma or
• idiopathic hypersecretion
• Detailed pituitary imaging
• Dynamic tests of Prolactin secretion
• administration of TRH, then measure serum
  prolactin
• if ? idiopathic hyperprolactinaemia,
• If no rise pituitary tumor

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Polycystic Ovarian Syndrome

• The common features of PCOS are menstrual
  irregularities, signs of androgen excess, and
  obesity
• The classical profile of PCOS is that of
  hypersecretion of LH(60), androgen excess and
  normal concentration of FSH
• It is imp. To exclude disorders with similar
  presenting features as androgen, secreting tumors
  and CAH

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Polycystic ovarian syndrome, continued

• Associated with
• Insulin resistance (in 50 of patients) and
  excessive androgen production (very common)
• Obesity (40 of cases)
• Hirsutism
• Chronic anovulation
• Glucose intolerance
• Hyperlipidemia

• Hypertension
• Menstrual disorders
• Hypersecretion of leutinizing hormone (LH) and
  androgens

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Polycystic ovarian syndrome, continued

• Diagnosis done by measuring
• Free testosterone (total testosterone is less
  sensitive than free testosterone, androgens often
  increase in PCOS)
• Sex hormone-binding globulin (SHBG often
  decreases in PCOS ? tends to? total
  testosterone ? free testosterone)
• Leutinizing hormone (LH ? in 60 of cases)
• Follicle stimulating hormone (FSH often normal
  in PCOS)
• LH/FSH Ratio (? in gt 90 of patients)

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Biochemical, metabolic endocrine changes in PCOS
LH ? FSH ?
Stimulation of ovarian stroma theca by LH
? plasma oestrone
Anovulation
Hirsutism
Aromatisation in adipose tissue
? Androgens free androgens
?SHBG
Insulin resistance
Obesity
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• Treatment is directed towards interrupting the
  cycle by
• lowering LH levels with oral contraceptive pills,
  
• weight reduction in obese patients
• enhancement of FSH production by clomiphen