Reproduction-Related Disorders - PowerPoint Presentation

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Reproduction-Related Disorders

Part

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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 successfulwithin 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.

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Infertility

Infertility problems often arise as a result of hormonal dysfunction of the hypothalamic-pituitary-gonadal axis. Measurements of peptide and steroid hormones in the serum are therefore essential aspects of the evaluation of infertility, and are the focus of this section.

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Male Infertility

A list of the most common male infertility factors is given in the table.Laboratory evaluation of male infertility should begin with evaluation of semen, which should be followed by evaluation of endocrine parameters.

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Male Infertility Factors

Abnormal SpermatogenesisUnexplained azoospermiaChromosomal abnormalitiesMumps orchitisCryptorchidismChemical or radiation exposure Abnormal MotilityAbsent cilia (Kartagener syndrome)Antibody formation PsychosocialUnexplained impotenceDecreased libido

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Endocrine Disorders

Hypothalamic dysfunction (

Kallmann

syndrome)

Pituitary failure (tumor, radiation,…)

Hyperprolactinemia (drug, tumor)

Exogenous androgens

Thyroid disorders

Adrenal hyperplasia

Testicular failure

Anatomic

Congenital absence of vas deferens

Obstructed vas deferens

Congenital abnormalities of ejaculatory system

Varicocele

Retrograde ejaculation

Male InfertilityEvaluation of Semen

Semen analysis measures: Semen should be analyzed within 1 hour after collection.Although this assay reveals useful information for the initial evaluation of the infertile male, it is not a test of fertility.It provides no insights into the functional potential of the spermatozoon to fertilize an ovum or to undergo the subsequent maturation processes required to achieve fertilization. It is important to understand that while the results may correlate with “fertility,” the assay is not a direct measure of fertility

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Ejaculate volume

pH

Forward progression

Sperm count

Motility

Morphology

Male InfertilityEvaluation of Semen

If semen analysis is abnormal, it should be repeated in ≈6 weeks. Additional investigations may include measurement of sperm protein SP-10 via immunoassay. SP-10 is testis-specific, arises within the acrosomal vesicle during spermatogenesis, and is associated with the acrosomal membranes and matrix of mature sperm. A version of the test is available to check the success of vasectomy.

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Male InfertilityEvaluation of Obstruction

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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.

Obstruction

of

the male reproductive tract results in

male infertility

, and analysis

of specific

semen parameters has proved a

useful

adjunct to physical examination in the evaluation

of

male reproductive tract obstruction.

Male InfertilityEvaluation of Endocrine Parameters

If severe oligospermia (low sperm count) or azoospermia (no measurable sperm in semen) is found, then measurement of (1) serum testosterone, (2) LH, & (3) FSH concentrations is necessary, with or without measurement of (4) prolactin and (5) TSH concentrations. Hyperprolactinemia is a cause of secondary testicular dysfunction. If hyperprolactinemia is found, it is vital to check for hypothyroidism, because elevated TRH concentrations result in hyperprolactinemia.

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Male InfertilityEvaluation of Endocrine Parameters

Pituitary adenomas and drugs, such as antihypertensives, 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.

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Male InfertilityEvaluation of Endocrine Parameters

Patients with borderline or suppressed testosterone conc. are evaluated with an hCG stimulation test.With this test, an injection of 5000 IU hCG is administeredintramuscularly following collection of a basal, early morning testosterone sample. Serum testosterone is measured 72 hours later. Hypogonadal men show a depressed rise in testosterone concentration in response to this challenge. Doubling of testosterone concentration over baseline is consistent with normal Leydig cell function. Failure to increase testosterone concentrations to greater than 150 ng/dL indicates primary hypogonadism.

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Male InfertilityEvaluation of Endocrine Parameters

Hypergonadotropic HypogonadismMeasurement of the concentration of FSH is indicated in menwith sperm count lower than 5 to 10 million/mL. Elevated concentrations of FSH indicate: 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), or (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 failure.

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FSH Adult male:

1.5 to 12.4

mIU

/ml; Test. Avg

. Adult

Male: 270 – 1070

ng/

dL

Male InfertilityEvaluation of Endocrine Parameters

Hypogonadotropic HypogonadismDecreased concentrations of testosterone (<200 ng/dL) anddecreased concentrations of FSH (<10 mIU/mL) are suggestive of 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.

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Male InfertilityEvaluation of Endocrine Parameters

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.

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Female Infertility

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Female InfertilityEvaluation of Female Infertility

The initial evaluation of female infertility includes a detailed history and physical examination. The physical examination should include evaluation of: The external genitalia and hair pattern (for signs of androgen excess including cliteromegaly, hirsutism, and virilization), The pelvis (for masses, nodularity or tenderness), The breasts (for signs of galactorrhea), Neurological findings (sense of smell and visual impairments), The thyroid (for enlargement or nodules), and Body mass index.

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Female InfertilityEvaluation of Female Infertility

All abnormalities in the history and physical examination should be tracked. A thorough medical and surgical history is also necessary including an assessment of: The patient’s gravidity and parity, Coital frequency,Duration of infertility, and Prior work up and treatment for infertility. Also, History of sexually transmitted infections, Assessment of previous cervical cytologic and HPV testing and treatment, and A menstrual history should be obtained.

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Female InfertilityEvaluation of Female Infertility

Concentrations of (1) TSH, (2) testosterone, and (3) prolactin should be measured if menstrual cycles are absent or irregular or if there are signs of galactorrhoea or thyroid abnormalities. Ovulation reserve testing as discussed belowshould be considered in cases where diminished ovarian reserve is suspected.

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