Reproduction-Related Disorders Part 3

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.

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.

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.

Male Infertility Factors 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 Abnormal Spermatogenesis Unexplained azoospermia Chromosomal abnormalities Mumps orchitis Cryptorchidism Chemical or radiation exposure Abnormal Motility Absent cilia (Kartagener syndrome) Antibody formation Psychosocial Unexplained impotence Decreased libido

Male Infertility Evaluation 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 Ejaculate volume pH Forward progression Sperm count Motility Morphology

Male Infertility Evaluation 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.

Male Infertility Evaluation of Obstruction 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. 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. Epididymis is a tube that connects a testicle to a vas deferens 

Male Infertility Evaluation 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. Thyrotropin-releasing hormone (TRH) Prolactin production can be stimulated by the hypothalamic peptides, thyrotropin-releasing hormone

Male Infertility Evaluation 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.

Male Infertility Evaluation 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 administered intramuscularly 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.

Male Infertility Evaluation of Endocrine Parameters 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: 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. Because its main function is to nourish the developing sperm cells through the stages of spermatogenesis, the Sertoli cell has also been called the "mother" or "nurse" cell. Sertoli cells secrete inhibin and activins  — secreted after puberty, and work together to regulate FSH secretion FSH Adult male: 1.5 to 12.4 mIU/ml; Test. Avg. Adult Male: 270 – 1070 ng/dL

Male Infertility Evaluation of Endocrine Parameters Hypogonadotropic Hypogonadism Decreased concentrations of testosterone (<200 ng/dL) and decreased 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.

Male Infertility Evaluation 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.

Female Infertility luteal phase defect, that lining doesn't grow properly each month. This can make it difficult to become or remain pregnant.

Female Infertility Evaluation 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. the development of male physical characteristics (such as muscle bulk, body hair, and deep voice) in a female

Female Infertility Evaluation 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.

Female Infertility Evaluation 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 below should be considered in cases where diminished ovarian reserve is suspected.