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Male Factor InfertilitySimplified Evalua�on and Treatment*†^

* In 20 minutes or less † In 20 slides ^ 5 minute office visit

ALWAYS EVALUATE THE MALE &&&& THE FEMALE

Why1. To help the couple achieve 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

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History & Exam

History• Pregnancies

• Duration of infertility

• Intercourse

• Surgery/trauma/infections in the inguinal, pelvic or gonadal areas

• Gonadotoxins

• Other

ExamBest 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 2017 23(6):660

Zhu et al. Hum Reprod 2016 31:511

Blood• Prolactin

• Testosterone

• FSH (Follicle Stimulating Hormone)

• LH (Luteinizing Hormone)

• Estradiol

• TSH

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Flags Results Reference Range ­ Units

Semen Analysis

Semen Analysis

Place of collection Home Collection

Collection Date 2018­06­01

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 4 2­7 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.,

2010.

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

345:1388­93.

Please note that none of these measures are diagnostic of infertility

and that this is an analysis of the male factor for in­vivo conception

only.

Semen Analysis

• Volume

• Concentration

• Motility

• Morphology

Semen

Analysis is

Rarely

Diagnostic

‘The reference limits should not be over-interpreted 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 2011

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Semen Analysis Looses Diagnostic Specificity

in Real Life because of Disease PrevalencePublication

• 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

CITES: Fertility vs. Infertility vs. Sterility

Success Year 2

Success Year 3

Success Year 4

Success Year 5 and After

Never Successful

Semen Analysis

Azoospermia

Non-Azoospermia

CITES – Canadian Infertility Therapy Evaluation Study; Collins, Burrow, Willams.

Prognosis for live birth among untreated infertile couples. Fertil Steril 1995

WALCHEREN Primary Care Study Hum Reprod

1998 12(7):1582

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CONCENTRATION and Pregnancy with SEX

Slama et al. Time to pregnancy and semen parameters… Human Reproduction 2002 17(2):503-515

MORPHOLOGY and Pregnancy via SEX

Slama et al. Time to pregnancy and semen parameters… Human

Reproduction 2002 17(2):503-515

Lipshultz et al. Men with a complete absence of normal sperm morphology exhibit

high rates of success without assisted reproduction. Asian J of Andrology 2017

19:39-42

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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 2017 199:812-822

MORPHOLOGY and Pregnancy via IVF

Shabtaie et al. Role of Abnormal Sperm Morphology in Predicting Pregnancy Outcomes. Curr Urol Rep 2016 17:67

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Semen AnalysisCollection Date 2018­06­01

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

2010.

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 forComplete 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

CONCENTRATION

VOLUME

MOTILITY

MORPHOLOGY

Endocrine Evaluation

TESTS

• LH and FSH should be <6

• Testosterone

• Prolactin

DIAGNOSES

• Hypogonadism

• Testosterone use

• Pituitary tumors

Corradi et al. Urologic Clin North Amer 2016 43(2):151

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Assess

Predict/Improve

Select From Options

Intercourse

Insemination

IVF

Pregnancy rate

Risks

Costs

Family planning

Preferences/Beliefs

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 2017 23(6):660

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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

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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)

1

Refer if you’re unsure or for specialized care

2

Semen analysis is a crude test and is rarely diagnostic. Concentration can help predict success.

3

FSH, LH, prolactin, testosterone +/-estradiol, TSH

Don’t give testosterone

4

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