MALE INFERTILITY & SEMEN ANALYSIS
DISCLOSURE Relevant relationships with commercial entities none Potential for conflicts of interest within this presentation none Steps taken to review and mitigate potential bias N/A
LEARNING OBJECTIVES This lecture is designed to meet the following end-of-week learning objectives: 1. List the common causes of infertility in the male 2. Interpret LH, FSH and testosterone levels in relation to primary and secondary male hypogonadism
MODULE OBJECTIVES By the end of this module, you should be able to: 1. List the common causes of infertility in the male 2. Interpret LH, FSH and testosterone levels in relation to primary and secondary male hypogonadism 3. Understand the steps in spermatogenesis 4. Outline steps in collection of semen sample 5. Outline an approach to interpretation of semen analysis
SPERMATOZOA https://upload.wikimedia.org/wikipedia/commons/3/39/human_spermatozoa.png
SPERMATOGENESIS Lumen Sperm cells progress from spermatogonia spermatozoa 72d duration Immature cells start at basement membrane lumen of seminiferous tubules Basement membrane Http://scientopia.Org/blogs/scicurious/2010/03/10/basics-guest-post-2-spermatogenesis/ 6
INFERTILITY Affects 15% of couples 1 Investigate after 1y unprotected intercourse 1 50% of cases due to male factor (either alone or in combo with female factor) 2 Overall, affects 7% of men Medical pathology found in only 6% of infertile men 3 1) Thonneau, P. et al. Hum. Reprod. 6, 811 816 (1991). 2) http://www.cdc.gov/nchs/data/series/sr_23/sr23_026.pdf (2010). 3) Kolettis, P. N. & Sabanegh, e. S. Significant medical pathology discovered during a male infertility evaluation. J. Urol. 166, 178 180 (2001).
SEMEN ANALYSIS Most important test in evaluation of male factor infertility Need at least 2 samples over a period of a few months Preceded by 2-7d of abstinence from ejaculation Sperm density can increase by 25% per day of abstinence up to 4 days! 1 1) Carlsen, e., Petersen, J. H., Andersson, A. M. & Skakkebaek, N. Fertil. Steril. 82, 358 366 (2004).
STEPS IN SEMEN ANALYSIS
WHY NEED 2 OR MORE SEMEN ANALYSES? Sperm count / concentration are highly variable day-to-day Image courtesy of Dr. J. Bain
SEMEN ANALYSIS IN DETAIL Many parameters reported in semen analysis Which are most important to know? 1. Semen volume 2. Sperm count and concentration 3. Sperm motility 4. Sperm morphology
WHAT ARE NORMAL SEMEN PARAMETERS Parameter Normal Value Semen volume 1.5mL Sperm concentration 15 million/ml Sperm count 39 million per ejaculate Sperm motility 40% Sperm morphology 4% normal forms (by strict criteria) Motility most closely correlated with pregnancy outcome! Adapted from: Hwang, K. et al. Nat. Rev. Urol. 8, 86 94
SEMEN ANALYSIS EXAMPLE
IN DETAIL: CONCENTRATION Normal: 15 million/ml Oligospermia: < 15 million/ml Severe oligospermia: < 5 million/ml Azoospermia: 0 Consider genetic contributor!
KLINEFELTER S SYNDROME: AZOOSPERMIA
IN DETAIL: MORPHOLOGY Recall: normal morphology is >4% normal forms by strict criteria https://upload.wikimedia.org/wikipedia/commons/thumb/5/5e/abnormalsperm.svg/1000px-abnormalsperm.svg.png
IN DETAIL: MOTILITY Motility: amount of sperm that are swimming, or moving normal >40% Progressive motility: amount of sperm that are moving forward Twitching, or moving in circles doesn t count normal >32% https://upload.wikimedia.org/wikipedia/commons/thumb/5/5e/abnormalsperm.svg/1000px-abnormalsperm.svg.png
DIFFERENTIAL DIAGNOSIS: ABNORMAL SEMEN ANALYSIS Abnormal Semen Analysis Impaired Production Idiopathic 40-50% Obstruction 10-20% Primary Hypogonadism 30-40% Secondary Hypogonadism 1-2% 18
CAUSES OF MALE HYPOGONADISM 1. Primary (Hypergonadotropic hypogonadism) Testicular insult High LH, FSH Low T 2. Secondary (Hypogonadotropic hypogonadism) Hypothalamic or pituitary insult Low LH, FSH Low T 19
PRIMARY HYPOGONADISM (TESTICULAR INSULT) Congenital Klinefelter s Syndrome*, undescended testes Infectious Trauma Drugs mumps orchitis physical, radiation chemotherapy Infiltration hemochromatosis (Iron deposition disorder) Idiopathic 20
SECONDARY/TERTIARY HYPOGONADISM Neoplasia Pituitary/hypothalamic lesion Congenital Kallman s Syndrome Trauma TBI, radiation Drugs Opiates Infiltration hemochromatosis Anorexia Idiopathic Hyperprolactinemia 21
QUESTION 1 Spermatogenesis is characterized by a sequential series of steps. Which one of the following is correct? A. The process takes one month B. Spermatozoa arise from Sertoli cells C. As spermatozoa develop, they migrate from basement membrane to lumen D. Flagellated sperm cells are termed spermatocytes
QUESTION 2 Hypogonadism can be primary or secondary. Which of the following is always a secondary cause of hypogonadism? A. Prolactin excess B. Mumps C. Chemotherapy D. Trauma