Male Factor Infertility

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1 Male Factor Infertility Simplified Evaluaon and Treatment* ^ * In 20 minutes or less In 20 slides ^ 5 minute office visit ALWAYS EVALUATE THE MALE & THE FEMALE Why 1. To help the coupleachieve a pregnancy 2. Infertility may be the presenting symptom of serious disease: Tumors (testis, pituitary) Hypogonadism Genetic abnormalities e.g. Klinefelter s syndrome and cystic fibrosis When Always No pregnancy within 1 year Earlier if at increased risk for infertility Do NOT: Delay until after the partner has been evaluated Delay/stop if there is a partner issue 1

2 History & Exam History Pregnancies Duration of infertility Intercourse Surgery/trauma/infections in the inguinal, pelvic or gonadal areas Gonadotoxins Other Exam Best done with patient standing* Virilization Penis Testicular volume/consistency Vas deferens Varicocele * Vasovagal reactions Lab Testing Semen Single semen analysis 4 days of abstinence Repeat semen analysis if abnormal value Barratt et al. Hum Rep Update (6):660 Zhu et al. Hum Reprod :511 Blood Prolactin Testosterone FSH (Follicle Stimulating Hormone) LH (Luteinizing Hormone) Estradiol TSH 2

3 Semen Analysis Volume Concentration Motility Morphology Flags Results Reference Range Units Semen Analysis Semen Analysis Place of collection Home Collection Collection Date Collection Time 06:57 Received Time 07:30 Analysis Time 08:17 Time Since Collection A 80 <=60 MINUTES Complete Sample? YES YES Sexual Abstinence Duration DAYS Semen Appearance OPAQUE OPAQUE Semen Viscosity A MODERATE NORMAL Semen Liquefaction A >60 <=60 MINUTES Semen ph 8.1 >=7.2 Semen Volume 3.3 >=1.5 ml Sperm Concentration 102 >=15 Mil/ml Total Motility/Ejaculate A 36.8 >=40 % Motility Progressive 32.4 >=32 % Normal Forms 4 >=4 % Viscosity treatment used. High round cell count at 2.2 Mil/mL. Sample was received 73 minutes after collection. Reference Ranges as per World Health Organization Laboratory Manual for the Examination and Processing of Human Serum, 5th ed., SubFertility Index SFI Concentration 1 SFI Total Motility 1 SFI Morphology 2.88 SFI Total Composite A 2.9 (1.0 = Most Fertile, 15.8 = Least Fertile) SubFertility Index is an Odds Ratio of probability of belonging to the subfertile male group vs that of the fertile male group. As per publication by David Guzick et al, on New Engl J Med Vol 345: Please note that none of these measures are diagnostic of infertility and that this is an analysis of the male factor for in vivo conception only. Semen Analysis is Rarely Diagnostic The reference limits should not be overinterpreted to distinguish fertile from infertile men accurately, but they do represent semen characteristics associated with a couple s [chances of] achieving pregnancy within 12 months of unprotected sexual intercourse Cooper et al WHO reference values for human semen characteristics Hum Rep Update 2009 comparing a patient s semen parameters to the distribution of results for fertile men is not in itself sufficient to determine whether or not the patient is fertile or infertile Bjorndahl What is normal semen quality? Hum Fertil

4 Semen Analysis Looses Diagnostic Specificity in Real Life because of Disease Prevalence Publication Fertile : Infertile 1 : 1 True +ve: False +ve 6 : 2 Real Life Fertile : Infertile 6 : 1 True +ve: False +ve 6 : 12 Semen Analysis is Predictive WALCHEREN Primary Care Study Hum Reprod (7):1582 CITES: Fertility vs. Infertility vs. Sterility Semen Analysis Azoospermia Non-Azoospermia Success Year 2 Success Year 3 Success Year 4 Success Year 5 and After Never Successful CITES Canadian Infertility Therapy Evaluation Study; Collins, Burrow,Willams. Prognosis for live birth among untreated infertile couples. Fertil Steril

5 CONCENTRATION and Pregnancy with SEX Slama et al. Time to pregnancy and semen parameters Human Reproduction (2): MORPHOLOGY and Pregnancy via SEX Slamaet al. Time to pregnancy and semen parameters Human Reproduction (2): Lipshultz et al. Men with a complete absence of normal sperm morphology exhibit high rates of success without assisted reproduction. Asian J of Andrology :

6 MORPHOLOGY and Pregnancy via IUI Kohn et al. Effect of Sperm Morphology on Pregnancy Success via Intrauterine Insemination: A Systematic Review and Meta-Analysis. J Urology : MORPHOLOGY and Pregnancy via IVF Shabtaie et al. Role of Abnormal Sperm Morphology in Predicting Pregnancy Outcomes. Curr Urol Rep :67 6

7 Semen Analysis CONCENTRATION VOLUME MOTILITY MORPHOLOGY Collection Date Collection Time 06:57 Received Time 07:30 Analysis Time 08:17 Time Since Collection A 80 Complete Sample? YES Sexual Abstinence Duration 4 Semen Appearance OPAQUE Semen Viscosity A MODERATE Semen Liquefaction A >60 Semen ph 8.1 Semen Volume 3.3 Sperm Concentration 102 Total Motility/Ejaculate A 36.8 Motility Progressive 32.4 Normal Forms 4 Viscosity treatm was received 73 Reference Range Manual for the E SubFertility Index SFI Concentration 1 SFI Total Motility 1 SFI Morphology 2.88 SFI Total Composite A 2.9 SubFertility Inde Collection Date 16/04/06 Complete Sample? Yes Time Since Collection 175 Semen Liquefaction Complete Semen Viscosity Normal Semen Colour Normal Semen Volume 2.7 Sperm Concentration L 0.0 Total Sperm Count/Ejaculate L 0.0 Pathologist Comments Azoospermia. Reference ran Manual for Complete Sample? YES Sexual Abstinence Duration 3.5 Semen Appearance OPAQUE Semen Viscosity NORMAL Semen Liquefaction <30 Semen ph 8.1 Semen Volume 1.9 Sperm Concentration 210 Total Motility/Ejaculate 75.0 Motility Progressive 72.6 Normal Forms A 1 High round ce Reference Ran Manual for the Endocrine Evaluation TESTS LH and FSH should be <6 Testosterone Prolactin DIAGNOSES Hypogonadism Testosterone use Pituitary tumors Corradi et al. Urologic Clin North Amer (2):151 7

8 Assess Pregnancy rate Intercourse Predict/Improve Risks Costs Insemination Select From Options Family planning Preferences/Beliefs IVF General Advice Antioxidants Folic acid (folate) L-carnitine Zinc Vitamin E/C Coenzyme Q10 Weight loss Smoking cessation Avoid excessive wet heat Showell et al. Cochrane Systematic Review 2014 Issue 12, Barrat et al. Global WHO Guidance Male Infertility Human Reprod Update (6):660 8

9 Medications SOMETIMES (Off Label) SERMs: Clomiphene, Tamoxifen Aromatase Inhibitors: Anastrazole, Letrozole GNRH agonists Gonadotropins: FSH, LH NEVER Exogenous Testosterone is CONTRACEPTIVE in males Subspecialty Infertility SUBSPECIALTY ASSESSMENT Very low/no sperm Endocrine abnormalities Prolonged duration of infertility Genetic testing TREATMENT Varicocelectomy Surgical reconstruction Surgical sperm retrieval Comprehensive and Integrated Care with the Reproductive Endocrinologist 9

10 Azospermia Absence of Spermatogenesis Microdissection Testicular Sperm Extraction MicroTeSE: 30-50% of men who have no sperm in the ejaculate Concurrent IVF with fresh sperm generally recommended Schlagel Hum Reprod 1999 Jan;14(1):131-5 SUMMARY Always evaluate the male (and the female) Refer if you re unsure or for specialized care Semen analysis is a crude test and is rarely diagnostic. Concentration can help predict success. FSH, LH, prolactin, testosterone +/- estradiol, TSH Don t give testosterone metrovanurology.com 10

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