Reproductive Tract Cancers: Prevention, Early

Diagnosis & Treatment Modalities for Knowledge &

Awareness

Prof. N. K. Lohiya, FNASc, FAMS, FIAES, FEMSI

Emeritus Medical Scientist & President - ISSRF
Centre for Advanced Studies
Department of Zoology
University of Rajasthan
Jaipur-302 004

DST-INSPIRE Internship Camp for X pass school students to be organized at

Sir Padampat Singhania University, Udaipur, December 19-23, 2015
 REPRODUCTIVE HEALTH

Health as a state of complete physical,

mental and social well-being, and not
merely the absence of disease or infirmity,
reproductive health, or sexual health /
hygiene, addresses the reproductive
processes, functions and system at all
stages of life.
 Male
Reproductive System
Male Reproductive System
Testes
Testes are the male gonads.
• seminiferous tubules- form sperm
• Leydig cells (interstitial cells)- produce
androgens (ex. Testosterone, ABP).
 Seminiferous Tubules
Spermatozoa Spermatids

Sertoli/
sustenacular cell
2º
spermatocyte
1º
spermatocyte

spermatogonium
Interstitial
cells
Testes are located in the scrotum, outside
the body cavity.
• This keeps testicular temperature cooler than
the body cavity.
• The testes develop in the body cavity and
descend into the scrotum just before birth.
 Sperm Pathway

Membranous
urethra

Prostatic urethra
 Physiology of Male System
• Sperm Analysis
– One of the first tests done to determine male infertility
– Sterile if less than 20 million sperm per ml
• Erection
– Controlled by the parasympathetic nervous system
– Nitric oxide causes the smooth muscles to relax and the
blood vessels to dilate
• Ejaculation
– Controlled by the sympathetic nervous system
– Also called climax or orgasm
Semen
• Seminal fluid is thick, cream whitewish,
and alkaline.
• It contains mucus, fructose, a coagulating
enzyme, ascorbic acid, and prostaglandins.
• Accessory glands:
1. seminal vesicle
2. prostate gland
3. bulbourethral gland
Seminal vesicle:
• A pair of glands that secrete a liquid
component of semen into the vas deferens.
• Secretion is alkaline
• Contains fructose, asorbic acid, coagulating
enzyme, prostaglandin

Seminal Vesicle
Prostate gland:
• Location- surrounds and opens into the urethra where it
leaves the bladder.
• Secretion- slightly alkaline fluid that activates the sperm
and prevents them from sticking together
• Prostate problems are common in males over 40.
• Prostate cancer is one of the most common cancers
in men.

Prostate
Bulbourethral gland (Cowper’s gland):
• Location- paired glands that lie beneath the prostate
• Secretion- a thick, clear alkaline mucous that drains into
the membranous urethra.
• Function- It acts to wash residual urine out of the urethra
when ejaculating semen-- raises pH; neutralizes acidity of
urine.

Bulbourethral
gland
Spermatogenesis
 Mature Spermatozoa

acrosome
head
nucleus
tail

mitochondria
Sperm
Maturation &
Development
 Female
Reproductive System
 Female Reproductive System

uterine tube
Ovary

uterus

cervix Bladder
vagina

clitoris
urethra
l. majora
l. minora
• Vagina uterus
• Cervix uterine tube
• Fallopian tube
(uterian
tube/oviducts)
• Fimbrae
• Ovary
• Uterus fimbriae
ovary endometrium
- Endometrium myometrium
- Myometrium perimetrium
- Perimetrium
cervix
vagina
Oogenesis in the Ovary
Oogenesis
Ovary- contains 400,000 oocytes; release about
500 in a lifetime
• Ovary- under influence of FSH. The follicles
mature every 28 days
• Primary follicle produces estrogens
• And primary oocyte completes its 1st division
produces 2ndary oocyte and polar body
Oogenesis
• Aprox 1/2 way through the 28 day cycle the
follicle reaches the mature Vesticular or Graffian
follicle stage.
Oogenesis

• Estrogen levels rise and release LH and FSH

and triggers ovulation.
Oogenesis
• The 2ndary oocyte travels down the uterine tube
to the uterus.
• If fertilized by sperm, it will produce a zygote

Ovum in uterine tube

Ectopic Pregnancy
Ovarian Cyst
Endometriosis
Oogenesis
Hormones Involved in the Female
Reproductive Cycle

• Gonadotropin Releasing Hormone (GnRH

(GnRH))
• Follicle Stimulating Hormone (FSH)
• Luteinizing Hormone (LH)
• Estrogen
• Progesterone
• Inhibin
• Relaxin
The Uterine Cycle
Hormone
Fluctuation
Contraception
Evaluation of Contraceptive Methods

Do they work?
Are they safe?
Are they available?
Are they affordable?
Do they protect against sexually
transmitted diseases (STDs)
 Abstinence
Surgical sterilization
essentially permanent
Vasectomy
Progesterone-only contraceptives may be
a little safer but not quite as effective

• Minipill (every day)

• Depo-Provera (3 months)
• Norplant (5 years)
 Is there a male pill?
Strategies:
• shut off testosterone
• lowers sperm count, but linked with reduced sex drive and
erectile dysfunction
• supplemental dose of testosterone

Inhibit FSH?
high rate of permanent sterility
Inhibit GnRH?
does not completely inhibit sperm production in everyone, but is
reversible

Answer: not yet

 Intra-Uterine Device

Safe and effective

Risk of inflammatory disease, and

subsequent sterility

Recommended for women who don’t want

future pregnancy or are not at risk for STD
Barrier methods

• Diaphragms
• Cervical caps
• Condoms (male and female)

Spermicides

Not as effective in pregnancy prevention

Do provide protection against STDs

Availability
Fertility awareness (“natural family
planning”)

Minute knowledge of woman’s cycle

Indicators of ovulation
• body temperature
• cervical mucus
Infertility
 Infertility
• Clinically defined as inability to conceive
after more than one year of intercourse
without contraception
• World Health Organization
– Defines sub-fertility as diminished ability to
conceive
– Infertility as complete inability to ever
conceive
• Personally
– Means changing your entire life plan
 Infertility Statistics
• Affects about 1 in 6 couples in USA
• Cause can be identified in about 85% of
cases
• Can be treated successfully in about 85
– 90 % of couples
• Problem in female – 50%
• Problem in male – 30%
• Problem in both partners – 20%
 Lifestyle and Infertility

Sex, Weight, Smoking, Drug, Alcohol, Caffeine, Exercise,

Environmental Factors will affect your Fertility

Body Mass Index (BMI) 20-25, Alcohol 4 or fewer drinks

per week, Caffeine intake less than 250 mg/day, Smoking
cessation
 Main Causes of Infertility

Cervical Uterine
3% 11%
Male
34%

Tubal
23%

Hormonal
29%

Multiple relatively minor abnormalities, either with 1 partner or both,

account for 30% of all causes
 Male Infertility
Problems:
• Oligospermia – low sperm count
– Caused by: hormones, environment, physical
• Poor sperm quality
– Motility – sperm can’t swim
– Abnormality – sperm are abnormally shaped
• Antibodies against own sperm
– Autoimmune disorder
Genetics of Male Infertility
• Oligospermia – low sperm count
– Genes: hormones, Y chromosome
abnormalities, testicular/prostrate development
– Environment: drugs, toxins, heat (kills)
• Poor sperm quality
– Genes: hormones, enzymes to harness energy
– Environment: drugs, toxins, heat (mutates)
• Antibodies against own sperm
– Genes: Immune system malfunctioning
Treatment of Male Infertility
• Primary – change environment
– Avoid heat, drugs, toxins
– Timing intercourse
• Secondary – correct hormone levels,
surgery corrects physical problems,
immune suppressants
• Final – Assisted Reproduction
Technologies
 Female Infertility
Problems:
• Irregular/malfunctioning ovulation
– Hormone imbalance, malfunctioning or absent
ovaries or tubes
• Physical blockage
– Fibroids or Endometriosis
– Blocked/abnormal Fallopian tubes
• Vaginal secretions
– Hormones or certain diseases
Genetics of Female Infertility
• Irregular/malfunctioning ovulation
– Genes: Hormones, thyroid, pituitary problems
– Environment: Birth control, stress
• Physical blockage
– Genes: Cancer, developmental defect
– Environment: Cancer or infections
• Vaginal secretions
– Genes: Hormones, mucus disorders, immune
 Treatment of Female Infertility

• Primary – change environment

– Timing intercourse - checking for ovulation
– Decrease stress, diet, exercise, etc
• Secondary – correct hormone levels,
surgery to correct physical problems
• Final – Assisted Reproduction Technologies
– More often necessary for female infertility
 Infertility Testing
• Couple seek testing after trying for more
than one year
• Tests:
– Semen Analysis (male)
– Hormone levels checked (female)
– Physical exams (both)
– Hysterosalpingogram (HSG; female)
– Endometrial Biopsy (female)
– Post coital exam (done on female)
 What is IVF?

• IVF or In Vitro Fertilization is a method of assisted

reproduction to increase the possibility of pregnancy.

• As the term ‘in vitro fertilization’ or ‘test tube baby’ explains

itself, it is the procedure to fertilize eggs with sperm outside
the human body.
 Who needs IVF?

There are different reasons why IVF is recommended which

include: blocked or damaged fallopian tubes, abnormal sperm,
endometriosis or immunologic problems, failed attempts of
artificial insemination or other
infertility treatment, advanced maternal age.
 Indication for IVF
• Tubal factor infertility

• Male factor infertility

• Pelvic factor infertility

• Unexplained infertility

• Failed conservative management

 Procedures of IVF & ET
1. Controlled Superovulation (COH) (Clomiphene, hMG,
uFSH, rFSH )

2. Monitoring (Ultrasound, E2)

3. Egg retrieval & IVF (or ICSI)

4. Embryo culture

5. Embryo Transfer (ET)

6. Luteal phase support (progesterone)

7. Pregnancy test
 1. Controlled Ovarian Hyperstimulation
with Exogenous Gonadotropins

2. Monitoring: E2, Ultrasound

2. Ultrasound monitoring of follicles
3. Ultrasound Guided Oocyte Retrieval
 4. Embryo Culture

Pronucleus

8-cell embryo

blastocyst
5. Embryo Transfer Retrieval
Assisted Reproductive Technologies

• IVF & ET
• Embryo Freezing and Storage
• ICSI (intracytoplasmic sperm injection)
• AH (assisted hatching)
• Blastocyst culture
• PGD (preimplantation genetic diagnosis)
• Donor egg IVF
• TESE (testicular sperm extraction)
• MESA (microsurgical epididymal sperm aspiration)
Freezing and Storage of superflous
embryos

Cryopreservation
1. Sperm
2. Embryos
3. Oocytes
4. Ovarian Tissue
Intracytoplasmic sperm injection (ICSI)
ICSI is a highly technical procedure designed to insert a sperm into the
cytoplasm of egg using a thin glass tube under the special microscope
with a manipulator.

Indications:
• Severe male factor infertility
• Poor quality eggs with thickened shell (zona)
• Prior or repeated fertilization failure with standard IVF
• Anti-sperm antibodies
• Use of surgically retrieved sperm directly from the epididymis or testis
Intracytoplasmic sperm
injection (ICSI)
71
 Factors affecting IVF results

• Age !!!!!!!!!!!!
• Sperm quality
• Causes of infertility
• Responsiveness to ovulation induction
• IVF lab quality
• Embryo transfer technique
 THE BIOLOGY OF CANCER
A group of diseases identified by uncontrolled cell growth
and proliferation

Normal Abnormal
cell cell
growth growth

Viruses Genetic make-up Immune status Radiation Carcinogens

 DEVELOPMENT OF CANCER
First Mutation Second Mutation

Fourth Mutation Third Mutation

Tumor formation Angiogenesis Invasion Metastasis

 CANCER WORLDWIDE

More than 1300 Indians die every day due to cancer

Between 2012 and 2014, the mortality rate due to cancer increased
by approximately 6%
In 2012, there are 4,78,180 deaths out of 29,34,314 cases reported
In 2013 there are 4,65,169 death out of 30,16,628 cases
In 2014, 4,91,598 people died in 2014 out of 28,20,179 cases
 Prostate Cancer
• The most common type of cancer in
men and second most frequent cause
of cancer-related death in men

• A malignant (cancerous) tumor that

begins in the prostate gland

• Some prostate cancers grow very

slowly and may not cause problems for
years

• Prostate cancer is somewhat unusual

in that many men with advanced cancer
respond to treatment
Symptoms of Prostate Cancer
Staging of Prostate Cancer
Staging of Ovarian Cancer
Cervical Cancer

A very serious
cancer of the
women’s
reproductive
system
Cervical Cancer
87
88
Staging of Endometrial Cancer

89
FOCUS
 Reduce Your Risk
1. Don’t use tobacco

2. Maintain a healthy weight and adopt a physically

active lifestyle

3. Consume a healthy diet with an emphasis on

fruits and vegetables

4. Protect yourself from the sun

5. Get recommended screening tests

 Maintain a Healthy Weight

Balance caloric intake with physical

activity
Avoid excessive weight gain throughout
life
Achieve and maintain a healthy weight
if currently overweight or obese
Consume a Healthy Diet
 Treatment
• Prevention
• Early diagnosis
• Surgery Percent Surviving
• Radiation 5 Years

• Bone Marrow and Stem Cell transplants

• Chemotherapy/Biotherapy
• Targeted Therapies
 New Hope In Cancer Treatments

Remove less surrounding tissue during surgery

Combine surgery with radiation or chemotherapy

Immunotherapy

Cancer-fighting vaccines

Gene therapy

Neoadjuvant chemotherapy

Stem cell research