Male Reproductive Problems

Male Reproductive Problems
By:Fertilization Specialists
Joshua Prince
Preston Moore
Candace Lindler

Infertility
* Infertility is the inability of a couple to become pregnant
* 6.1 million people in the United States are effected

Treatment
Normospermia with functional defects
Asthenospermia and teratozoospermia
Oligospermia
Untreatable subfertility
Reversible toxin effects
Disorders of sexual function
Gonadotropin deficiency
Obstructive azoospermia
Sperm autoimmunity
Treatable conditions
Primary seminiferous tubule failure
Untreatable sterility
FREQUENCY (%)

TYPE OF INFERTILITY
Table 1. Classification Of Male Infertility By Effectiveness Of Medical Intervention To Improve Natural Conception Rate

* Sperm count equals the number of sperm per cm3 or cc
* The average has dropped in the past 20 years
* 85-90% are treated with medication or surgery
* Lifestyle changes

Normal Reproduction
* Ovulation
* Spermatogenesis
* Sperm meets with egg in fallopian tube
* Fertilization
* Implantation

Male Reproductive System
Female Reproduction System
Normal Spermatogenesis
Testes

* Normal Testes
* 10-14 grams
* Body of the testis
o Epididymis
o Spermatic Cord
* Embryonal Carcinoma
o hemorrhage and necrosis
* Spermatogonium (2N)
Differentiation
* Primary Spermatocyte (2N)
Meiosis I
* Secondary Spermatocytes
Meiosis II
* Spermatids
Differentiation
* Spermatozoa

Spermatogenesis
* Seminferous Tubules
90% of the testis
* Thousands of sperm per second although spermatogenesis 8-10 weeks
* Stored for months
* Degraded and deposited into the circulatory system if not ejaculated

Klinefelter Syndrome
* XXY instead of XX or XY
* usually male
* lower levels of testosterone
* improper formation of semineferous tubules

Bilateral Anorchia
* vanishing testes syndrome
* testes originally present but reabsorbed before or after birth

Oligospermia
* having too few sperm
* due to:
fever
excessive alcohol
smoking
varicocele
orchitis

Azoospermia
* total lack of sperm in ejaculate
* due to:
fever
undescended testicle
obstructions of seminal vesicles
testicle infection

Cryptorchidism
* 30% of males born premature
* 3% of males carried to term
* Predisposes the person to risk of torsion
* Androgen receptor
* Bilateral has six times the impact on infertility
* Increase in Temperature
* Testicular atrophy
* Treated at Childhood

Abnormalities
* Testicular torsion
of the spermatic cord cuts off the venous drainage, leading to hemorrhagic infarction
It is the twisting of the spermatic cords
Immediate treatment
* Testicular cancer

Illnesses
* Acute
o Hypogonadism
+ Suppression of gonadotropin secretion
o Fever
+ The elevated temperature can induce declines in sperm production for months
* Chronic
o elevated gonadotropin secretion
+ leading to primary testicular disorder

Orchitis
* testicle inflammation
* due to:
mumps
infection
trauma
STD
STDs
* Fibropapilloma
o papilloma virus
o induces testicular warts
o inhibits spermatogenesis
* Chlamydia and gonorrhea
o cause scar tissue which results in duct blockage and
o inhibits spermatogenesis

Stimulants
* Heroin and other opiates
o suppression of LH secretion
* Cocaine and Marijuana
o temporarily can decrease 50% of sperm count
o compounds bind to sperm receptors affecting motility and entry to the secondary oocyte
* Smoking Tobacco
o lowers sperm motility
o reduces sperm life

Age

* Hypoplasia via testicular degeneration
* Nutritional factors, systemic infections, toxins, and other environmental factors
* Basement membrane becomes thickened
* Folds and wrinkles leading to tubular collapse
* Can lead to immune-mediated inflammatory response
* DNA Fragmentation

Gynecomastia
* Testicular Failure
* Androgen receptors
* Cirrhosis
* Tumors
* Illegal steroid
* Feminine characteristics

Examination
* Inflammation would cause pain
* Lack of hair
o Androgen deficiency
* Normal volume equals 15 to 35 ml
* Small is equal to 5 ml or less and would also signal androgen deficiency
* Hard lumps would signal tumors
* Softness would signal reduced spermatogenesis

Varicoceli
* Enlarged and twisted varicose veins
* 15-20% of men
* Elevates the temperature
* Obstructs passage of semen
* Obstructs oxygen supply

Environmental
* Polychlorinated biphenyls
o Teratogens
+ bind to the aryl hydrocarbon receptor
+ mimic estrogen, inhibiting the Leydig cells
* Testosterone
o activates mitogen-activated protein kinase
* Pesticides
o DDT
+ mimics estrogen
* Free Radicals
* Emotional stress
o inhibits secretion of GnRH

Physical Obstruction to Gamete Movement
* Blocked or absent seminal ducts
* Seminal fluid disorders
* Retrograde ejaculation
* Inability to ejaculate

Blocked or Absent Ducts
* Bilateral congenital absence of the vas deferens
* Obstruction of the epididymis or vas deferens
* Mechanical blockage during hernia repairs
* Blocked seminal vesicles

Seminal Fluid Disorders
* Absent antioxidant factors
* Abundant circulating free radicals

Retrograde Ejaculation
* Reverse ejaculation into the bladder
* Causes:
o Prostate surgery
o Certain medications
o Diabetes
o Spinal cord injuries

Inability to Ejaculate
* Erectile dysfunction
o Diabetes
o Prostate surgery
o Urethra surgery
o Blood pressure medications

Hormonal Obstruction to Gamete Movement
* Endocrine disorders
* Steroids
* Unexplained low levels of needed hormones

Endocrine Disorders
* Pituitary disorder
* Feminization
* Kallmann’s syndrome
* Hypothyroidism
* Other Causes
o Steroid Use
o Unexplained low levels of hormones

Improper Fusion of Sperm and Egg
* Antisperm Antibodies
o Immobilization
o Agglutinating
o Sperm-cervical mucus interaction
o Penetration of the egg
o Sperm fertilization
o Zygote development

Improper Fusion of Pronuclei
* CD9 and CD81 antibodies
Miscarriage
* 50% of pregnancies
* occur early in development
chemical miscarriage
molar pregnancy

Chemical Miscarriage
* before pregnancy is know
* dies almost immediately after conception
* causes:

chromosomal abnormalities
uterine abnormalities
hormonal deficiency

Molar Pregnancy
* Complete
egg contributes no DNA
two copies of paternal chromosomes
* Partial
egg does contribute DNA
two copies of paternal chromosomes

References
Male Reproductive Problems

Read more...

Male Obesity and Semen Analysis Parameters

Male Obesity and Semen Analysis Parameters
By:Joseph Petty, MD
Samuel Prien, PhD
Amantia Kennedy, MSIV
Sami Jabara, MD

Background: Obesity

* Obesity is a growing problem.
* The Behavioral Risk Factor Surveillance System, in conjunction with the CDC, conducted a national survey and found that in 2000, the prevalence of obesity (BMI >30 kg/m2) was 19.8%, a 61% increase since 1991.
* Obesity affects female and male fertility.
* In a study comparing IVF success rates and female obesity, it was shown that a 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle 2.
* In couples complaining of infertility, male factor plays a role in up to 40% of cases.

Background: Semen Parameters
* What parameters best predict fertility?
* National Cooperative Reproductive Medicine Network: 765 infertile couples (no conception after 12 months), and 696 fertile couples
* greatest discriminatory power was in the percentage of sperm with normal morphologic features.

Hypothesis
* Since there is an observed correlation between obesity and male factor infertility, our hypothesis is that an increased BMI is associated with higher rate of abnormal semen parameters, especially sperm morphology.

Recent Studies
* Danish study by Jensen et al. enrolled 1,558 young men (mean 19 years old) when they presented for their compulsory physical exam as part of their country’s military drafting system.
* The authors showed decreased sperm counts and concentration (39 million/mL vs. 46million/mL) in those with an elevated BMI (>25kg/m2). They did not, however, observe a difference in morphology.
* Hormonal differences
* Kort et al. looked at semen analysis results in 520 men
* grouped according to their BMI, and measured the average normal-motile-sperm count (NMS = volume x concentration x %motility x %morphology)
* Kort concluded that men with high BMI values (>25) present with few normal-motile sperm cells
* Hammoud et al., showed a increased incidence of oligospermia and increased BMI and also showed decreased levels of progressively motile sperm
* Considered each parameter separately.

Sexual function
* Agricultural study: The association between BMI and infertility was similar for older and younger men, disproving the theory that erectile dysfunction in older men is a significant factor.
* Hammoud et al., though primarily concerned with hormones, looked at erectile dysfunction directly and showed that there was no correlation with increases in BMI
* Nguyen et al., effect of BMI is essentially unchanged regardless of coital frequency, suggesting that decreased libido in overweight men is not a significant factor

Hormonal Profile
* Danish study, observed decreased FHS and inhibin B levels in the obese.
* Pauli et al., observed with increases in BMI a decreased total T, decreased SHBG, increased estrogen and decreased FSH and inhibin B.
* Inhibin B, cited for its usefulness as a novel marker for spermatogenesis and its role in pituitary gonadotropin regulation.
* Pauli: no correlation of BMI or skinfold thickness with semen analysis parameters, though it was observed that men with proven paternity versus those without had lower BMI.

Interventions: Gastric Bypass
* One case series of 6 male patients after bariatric surgery showed secondary azoospermia with complete spermatogenic arrest.
* none of the subjects had a semen analysis before the bariatric surgery, but all had fathered a pregnancy previously
* malabsorption of nutrients
* Hammoud et al., part of Utah Obesity Study
* effect of the gastric bypass surgery on sex steroids and sexual function
* Cohort of 64 severely obese men
* Along with a significant decrease in BMI, they found decreased levels of estradiol, and increases in total and free testosterone along with a reported improvement in quality of sexual function.
* Semen analysis parameters were not considered in this study

Study Design
* Retrospective chart review for all couples and individual patients presenting for an infertility consultation and evaluation at the Texas Tech Physicians Center for Fertility and Reproductive Surgery from September 2005 through January 2008.
* Intake questionnaire: demographic, medical, surgical and fertility history.

Questionnaire
* Previous pregnancies fathered: current or previous partner
* Psychiatric disorders included any degree of depression, bipolar disorder or any other psychiatric disorder requiring medical therapy.
* Tobacco and alcohol users: whether they admitted to light, moderate, or heavy use, patient underreporting.
* Chemical exposures: contact with pesticides, herbicides, and heavy metals.
* Sexual dysfunction: mainly erectile dysfunction and decreased libido.
* Genitourinary anomalies: hypospadias, varicocele, genitourinary surgery, testicular torsion or inguinal hernia or trauma
* Other medical problems included mainly diabetes, hypertension, thyroid disease, autoimmune disease, and cancer.
* Patients grouped according to their BMI as normal (20-24 kg/m2, N = 24), overweight (25-30 kg/m2, N = 43), or obese (>30 kg/m2, N = 45), as standardized by the World Health Organization
* Semen analysis parameters: morphology, volume, concentration, percent motility, and presence of absence of agglutination, in accordance with World Health Organization (WHO) guidelines
* SPSS statistical software was used to run analysis of variance (ANOVA) and post-hoc Tukey HSD tests between the groups. A p-value <0.05 was considered statistically significant.

Exclusion Criteria
* questionnaire was missing or if they had an otherwise incomplete chart.
* missing vital statistics (i.e. height and weight),
* 235 total charts reviewed,
o 60 no semen analysis or outside lab.
o 63 patients had either missing vital statistics or a missing questionnaire
o This left a total of 112 patients with valid data to be considered.


Results
* The BMI groups were statistically similar as far as demographic characteristics and confounding variables
* There was no statistically significant difference between the semen parameters of all three BMI groups.
* slight trend towards a decreasing sperm concentration with increases in BMI

Conclusion
* In this study, overweight and obese men did not have an increased rate of teratozoospermia, asthenospermia, or oligospermia.

Discussion
* Inconsistencies
* Small sample size
* Kort and data interpretation
* Change the normal hormonal milieu, addressed by Jensen study.
* Sertoli cell function, increased aromatase, role of leptin
* Aggerholm study: altered hormones not correlated with semen abnormalities in overweight men (25.1-30.0 kg/m2), slightly decreased sperm concentration in overweight but not in obese


Future Studies
* What affects morphology specifically?
o Hormones
o Result of secondary disease, i.e.. Diabetes
o Genetic mutations
o Weight loss surgery and other interventions
* Overall, there is no doubt that increases in BMI have a detrimental effect on male fertility, but a satisfactory explanation of the mechanism for this phenomenon has yet to be given.

References
Male Obesity and Semen Analysis Parameters

Read more...

Management of Radiation Accident victim

Physician and Hospital Responses to Radiological Incidents
By: Robert E Henkin, MD, FACNP, FACR
Professor of Radiology
Director, Nuclear Medicine

Robert H. Wagner, MD, MSMIS
Associate Professor of Radiology
Section on Nuclear Medicine/Department of Radiology
Loyola University
Maywood, IL

Experience of Authors

* Dr Wagner trained at Loyola and the DOE in Oak Ridge - Radiation Emergency Assistance Center/Training Site (REAC/TS)
* Drs Wagner and Henkin co-wrote the original manual for hospital management that was used by the State of Illinois
* Dr Wagner is has been consultant for Radiation Management Consultants since 1990 and trains and drills approximately 5 hospitals/year until 1998. Developed the plan for radiation accidents at Loyola

* Dr Henkin is a member of the Radiation Information Network of the American College of Nuclear Physicians
* Drs Wagner and Henkin are Board Certified by ABNM

Radiation and Terrorism
* Public perceptions of radiation
* The good news and the bad news
* Terrorism scenarios
* Types of radiation injuries
* Hospital response to radiation incidents

The Public Perceptions
The Bad News
* Almost nothing creates more terror than radiation
o It’s invisible to touch, taste, and smell
o Most people have unrealistic ideas about radiation
o Most physicians don’t even understand it
* The objective of the terrorist is as much or more panic than it is physical harm

The Good News

* Nuclear Medicine and Radiation Therapy professionals are well trained in the fundamentals of radiation
* Respect radiation, but do not fear it
* Understand what radiation can and cannot do
* There have been industrial radiation accidents that we have learned much from
* It is easily detected in contrast to biological and chemical agents

What Can We Expect?
* Radiological/Nuclear Terrorism
o A true nuclear detonation
o A failed nuclear detonation
o Radiation dispersal device
* Power Plant attacks

A Nuclear Detonation
* Least likely scenario (fortunately)
* Most likely from a stolen nuclear weapon
* Results would be devastating, both psychologically and in terms of damage

The Unthinkable
* Effects of a 1 megaton detonation in Chicago
o 30% of all hospitals destroyed in 50 mile radius
o Transportation and infrastructure compromised
o Emergency vehicles and professionals unable to respond
o Walking wounded with burns may have been fatally irradiated – unknown effects for days to weeks

Radiological Devices
* Not a “nuclear explosion”
* Consists of a bomb designed to disperse radioactive materials in air and water
o Designed to create panic
o Difficult to clean up, material spreads
o Biological effects may take years to appear
* “A Dirty War” HBO/BBC Films 2005

Failed Nuclear Detonation
* Most likely from an improvised nuclear device (IND)
* Beyond the scope of an individual terrorist – would need 10-15 people
* Greatest barrier is availability of weapons grade material
* Would create a critical mass or explosion, but not the same degree as a true nuclear detonation.
* Nuclear material needs to stay in contact for a longer period of time to allow flux to form

Radiological Dispersal Device
* The most likely scenario
* Simply a bomb loaded with radioactive materials
* Uses stolen hospital or industrial materials
* Acute effects are limited to psychological and traumatic injury
* Long term effects would be on contamination of large areas
* Huge expense for cleanup

Chernobyl Comparison
Co-60 food irradiation pencil in a RDD
Radiation Levels
* Inner ring – same as permanently closed around Chernobyl
* Middle ring – same as permanently controlled area around Chernobyl
* Outer ring – same as periodically controlled zone around Chernobyl

Cancer Deaths
Co-60 food irradiation pencil in a RDD

Increase risk of cancer
* Inner ring – 1 per 100 people
* Middle ring – 1 per 1,000 people
* Outer ring – 1 per 10,000 people

What do I Need to Know?
* Fundamental Radiobiology
o Radiation effects are delayed
o Burns if you see them are chemical or thermal in origin.
o Dose limits
* Key personnel
* Contamination control
* Focus on the medical problems

1. Radiation - Fundamentals
* Types of Radiation
* All radiation is part of the electromagnetic spectrum
* This spectrum ranges from infrared through radio/TV transmission and beyond
* Ranges of common exposures

Radiation - Definition
* Energy that is transferred through space
* Examples
o Microwaves
o Radio waves
o Visible Light
o Nuclear radiation (Alpha, Beta, Gamma)
o X-Radiation

Effectiveness of a Lead Apron
Isotope
Percent Stopped
Don’t wear one during an accident!
Measurement Units
* Roentgen – radiation dose measured in air
* Radiation Absorbed Dose (RAD) – a pseudo biologic unit
* Gray – 100 RADS
* Radiation Effective Dose Man (REM) – a biologically corrected dose
* Millrem - .001 REM

We Live in Radioactive World
* Naturally occurring radioactive elements abound
* Cosmic radiation
* Man-made radiation accounts for less than 1% of total radiation
* Average human dose 150 to 170 mR/year
* Dose varies by geographic location

Low Level Radiation 500 - 5,000 mR
High Level Radiation 5- 50 R
Decrease In Sperm Count (transient)
High Level Radiation 500- 5,000 R
LD 50/60 (Estimated With Intensive Support - Possible BMT)
Neurological syndromes
Typical Therapy for Cancer (Divided Doses)
Contamination In Perspective

Radiation Injuries
* Dependent on dose
o Non-Stochastic effects (Dose related)
+ Decrease in sperm count – 15 R
+ Hematological effects – 150 R
+ Gastrointestinal effects, epilation – 300 R
+ CNS effects – 1000 R
o Stochastic Effects (Non-dose related)
+ Increase in cancer risk
+ Genetic abnormalities
Burns From Radiation
* Generally do not appear immediately
* Healing is extremely poor
* Not likely to be seen in the acute setting

2. Introduction to Radiobiology
* Mechanism of Cellular Injury
* Comparison of Tissue Sensitivities
* Dose Effect Relationships
* Genetic Effects
* Carcinogenic Effects
* Embryonic and Fetal Effects
* How to Limit Exposure
Mechanism of Cellular Injury
DNA STRAND
Biological Effects of Radiation Depend on:
* Total Dose Received
* Rate of Exposure
* Total or Partial Body
Radiation In Perspective
Genetic Effects
Radiation In Perspective
Carcinogenic Effects
Embryonic and Fetal Effects
Methods of Decreasing Exposure to Staff

* Time – linear relationship
* Distance – geometric relationship
* Shielding – half value layers.....

What’s My Role?

* Learn the institutional protocols
* Do not wait for the disaster to train
* Know who and where your resources are
* Do not contribute to panic with uninformed statements
* Refer questions to the scene commanders

Management of Radiation Accident victim

Read more...