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Infertility
SOHAIL KHAN
08-185
BATCH J
FINAL YEAR MBBS
Requirements for
Conception
• Production of healthy egg and sperm
• Unblocked tubes that allow sperm to
reach the egg
• The sperms ability to penetrate and
fertilize the egg
• Implantation of the embryo into the uterus
• Finally a healthy pregnancy
Infertility
• The inability to conceive following
unprotected sexual intercourse
–Affects 15% of reproductive couples
–Men and women equally affected
Infertility - Statistics
• causes are identified in 90 % of patients
• 30 % of couples have male AND female
factors
• Of 100 sub fertile couples the break down is
as follows:
• 40 % male factor etiology
• 20 % female hormonal imbalance
• 30 % female peritoneal factor
• 5 % ‘hostile’ cervical environment
• 5 % unexplained
• psychological impact can be significant
Infertility
• Reproductive age for women
– Generally 15-44 years of age
– Fertility is approximately halved between 37th and
45th year due to alterations in ovulation
– 20% of women have their first child after age 30
– 1/3 of couples over 35 have fertility problems
• Ovulation decreases
• Health of the egg declines
• With the proper treatment 85% of infertile
couples can expect to have a child
Infertility
• Primary infertility
–a couple that has never conceived
• Secondary infertility
–infertility that occurs after previous
pregnancy regardless of outcome
Causes for infertility
• Male
– Drugs
– Tobacco
– Health problems
– Radiation/Chemotherapy
– Age
– Enviromental factors
• Pesticides
• Lead
• Female
– Age
– Stress
– Poor diet
– Athletic training
– Over/underweight
– Tobacco
– STD’s
– Health problems
Causes of Infertility
• Anovulation (10-20%),
• Anatomic defects of the female
genital tract (30%)
•
Abnormal spermatogenesis (40%)
• Unexplained (10%-20%)
Evaluation of the
Infertile couple
• History and Physical exam
• Semen analysis
• Thyroid and prolactin evaluation
• Determination of ovulation
– Basal body temperature record
– Serum progesterone
• Hysterosalpingogram
Abnormalities of
Spermatogenesis
Normal
• Sperm made in
seminiferous
tubules
• Travel to
epididymis to
mature
• Sperm exit through
vas deferens
• Semen produced
in prostate gland,
seminal glands,
cowpers glands
• Sperm can live 5-7
days
Normal
Male Factor
• 40% of the cause for infertility
• Sperm is constantly produced by the
germinal epithelium of the testicle
– Sperm generation time 73 days
– Sperm production is thermoregulated
• 1° F less than body temperature
• Both men and women can produce anti-
sperm antibodies which interfere with the
penetration of the cervical mucus
Normal Values for
SEMEN ANALYSIS.
Volume
Sperm Concentration
Viscosity
Morphology
pH
WBC
– 2.0 ml or more
– 20 million/ml or more
– Liquefication in 30-60
minutes.
– 30% or more normal
forms
– 7.2-7.8
– Fewer than 1 million/ml
Causes for Abnormal
SEMEN ANALYSIS.
• No sperm
– Klinefelter’s
syndrome
– Sertoli only
syndrome
– Ductal obstruction
– Hypogonadotropi
c-hypogonadism
• Few sperm
– Genetic disorder
– Endocrinopathies
– Varicocele
– Exogenous (e.g.,
Heat)
Abnormal Count
Continues: causes for
abnormal SA
• Abnormal Morphology
– Varicocele
– Stress
– Infection (mumps)
• Abnormal Motility
– Immunologic factors
– Infection
– Defect in sperm
structure
– Poor liquefaction
– Varicocele
• Abnormal Volume
– No ejaculate
• Ductal obstruction
• Retrograde ejaculation
• Ejaculatory failure
• Hypogonadism
– Low Volume
• Obstruction of ducts
• Absence of vas deferens
• Absence of seminal
vesicle
• Partial retrograde
ejaculation
• Infection
Causes for male
infertility
• 42% varicocele
– repair if there is a low count or decreased
motility
• 22% idiopathic
• 14% obstruction
• 20% other (genetic
abnormalities)
Abnormal Semen
Analysis
• Azoospermia
– Klinefelter’s (1 in
500)
– Hypogonadotropic-
hypogonadism
– Ductal obstruction
(absence of the Vas
deferens)
• Oligospermia
– Anatomic defects
– Endocrinopathies
– Genetic factors
– Exogenous (e.g.
heat)
• Abnormal volume
– Retrograde
ejaculation
– Infection
– Ejaculatory failure
Evaluation of Abnormal
SEMEN ANALYSIS.
• Repeat semen analysis in 30 days
• Physical examination
– Testicular size
– Varicocele
• Laboratory tests
– Testosterone level
– FSH (spermatogenesis- Sertoli cells)
– LH (testosterone- Leydig cells)
• Referral to urology
Evaluation of Ovulation
Female Reproductive System
• Ovaries
– Two organs that
produce eggs
– Size of almond
– 30,000-40,000 eggs
– Eggs can live for
12-24 hours
Menstruation
• Ovulation occurs 13-14 times per year
• Menstrual cycles on average are of 28 days
with ovulation around day 14
• Luteal phase
– dominated by the secretion of progesterone
– released by the corpus luteum
• Progesterone causes
– Thickening of the endocervical mucus
– Increases the basal body temperature (0.6° F)
• Involution of the corpus luteum causes a fall
in progesterone and the onset of menses
Ovulation
• A history of regular menstruation suggests
regular ovulation
• The majority of ovulatory women experience
– fullness of the breasts
– decreased vaginal secretions
– abdominal bloating
• Absence of these symptoms may suggest
anovulation
– mild peripheral edema
– slight weight gain
– depression
Diagnostic studies to
confirm Ovulation
• Basal body
temperature
– Inexpensive
– Accurate
• Endometrial biopsy
– Expensive
• Serum
progesterone
– After ovulation rises
– Can be measured
• Urinary ovulation-
detection kits
– Measures changes
in urinary LH
– Predicts ovulation
but does not
confirm it
Basal Body Temperature
• Excellent screening tool for ovulation
– Biphasic shift occurs in 90% of ovulating women
• Temperature
– drops at the time of menses
– rises two days after the lutenizing hormone (LH)
surge
• Ovum released one day prior to the first rise
• Temperature elevation of more than 16 days
suggests pregnancy
Serum Progesterone
• Progesterone starts rising with the LH
surge
– drawn between day 21-24
• Mid-luteal phase
– >10 ng/ml suggests ovulation
Anovulation
Anovulation Symptoms
Evaluation*
• Irregular menstrual
cycles
• Amenorrhea
• Hirsuitism
• Acne
• Galactorrhea
• Increased vaginal
secretions
• Follicle stimulating
hormone
• Lutenizing hormone
• Thyroid stimulating
hormone
• Prolactin
• Androstenedione
• Total testosterone
Sperm transport, Fertilization,
& Implantation
• The female genital tract ,,,
– facilitates sperm transport
– cervical mucus traps the coagulated ejaculate
– the fallopian tube picks up the egg
• Fertilization must occur in the proximal
portion of the tube
– the fertilized oocyte cleaves and forms a zygote
– enters the endometrial cavity at 3 to 5 days
• Implants into the secretory endometrium for
growth and development
Fertilization
Implantation
Acquired Disorders
• Acute salpingitis
– Alters the functional integrity of the fallopian tube
• N. gonorrhea and C. trachomatis
• Intrauterine scarring
– Can be caused by curettage
• Endometriosis, scarring from surgery, tumors
of the uterus and ovary
– Fibroids, endometriomas
• Trauma
Congenital Anatomic
Abnormalities
Hysterosalpingogram
• An X-ray that
evaluates the
internal female
genital tract
– architecture and
integrity of the
system
• Performed between
the 7th and 11th day
of the cycle
• Diagnostic accuracy
of 70%
Hysterosalpingogram
• The endometrial
cavity
– Smooth
– Symmetrical
• Fallopian tubes
– Proximal 2/3 slender
– Ampulla is dilated
• Dye should spill
promptly
HSG: Tubal Infertility
TREATEMENT OF
INFERTILE COUPLE
Inadequate
Spermatogenesis
• Clomiphene citrate is occasionally used for
induction of spermatogenesis
– 20% success
• Eliminate alterations of thermoregulation
• In vitro fertilization may facilitate fertilization
• Artificial insemination with donor sperm is
often successful
• Laparoscopy surgery
Anovulation
• Restore ovulation
– Administer ovulation inducing agents
• Clomiphene citrate
– Antiestrogen
– Combines and blocks estrogen receptors
at the hypothalamus and pituitary causing
a negative feedback
– Increases FSH production
• stimulates the ovary to make follicles
Clomid
• Given for 5 days in the early part of the
cycle
• Maximum dose is usually 150mg
• 50mg dose - 50% ovulate
• 100mg -25% more ovulate
• 150mg lower numbers of ovulation
Superovulatory
Medications
• If no response with clomid then
gonadotropins- FSH (e.g. pergonal) can be
administered intramuscularly
– This is usually given under the guidance of
someone who specializes in infertility
• This therapy is expensive and patients need
to be followed closely
• Adverse effects
– Hyperstimulation of the ovaries
– Multiple gestation
– Fetal wastage
Anatomic Abnormalities
• Surgical treatments
– Lysis of adhesions
– Septoplasty
– Tuboplasty
– Myomectomy
• Surgery may be performed
– laparoscopically
– hysteroscopically
• If the fallopian tubes are beyond repair one
must consider in vitro fertilization
Assisted Reproductive
Technologies (ART)
• Explosion of ART has occurred in the
last decade.
• Theses technologies help provide
infertile couples with tools to bypass the
normal mechanisms of gamete
transportation.
• Probability of pregnancy in healthy
couples is 30-40% per cycle, live birth
rate 25%.
– this varies depending on age
Intrauterine insemination
(artificial insemination)
• definition: sperm introduced into female
reproductive tract by means other than
coitus
• sperm can come from donor / sperm
bank or from husband
• usually, several ejaculations are pooled
• often used when male has low sperm
count or antibodies present in ejaculate
Artificial Insemination
• Sperm donation or
sperm aspiration
In Vitro Fertilization
• “test - tube babies”
• 1st performed in 1978 (Louise Joy Brown)
• often performed on infertile women with
tubal blockage
• Sperm and egg combined in the lab,
fertilization
• Zygote placed back into the uterus
• Very expensive and not always successful
• Oldest woman in the US to give birth
using in vitro was 62 years old and an
Romanian woman gave birth at 66
In Vitro Fertilization
IVF Protocol
• GnRH agonist (e.g. Lupron) for 7 days
• FSH agonist (follistim, Gonal-F,
Repronex) until follicles measure 17-20
mm in diameter
• hCG given to induce egg maturation.
IVF protocol
• sperm and ova added to dish;
fertilization occurs 12-14hrs.
• eggs transferred to new dish and cell
division occurs
• embryos squirted into uterus at 4- to 32-
cell stage (optimal: blastocyst stage)
IVF Protocol, cont’d.
• 3 to 5 embryos are injected to increase
chances of pregnancy
• woman given progestagen to prevent
miscarriage
IVF Protocol, cont’d.
• new variations / improvements:
– Intracytoplasmic sperm injection (ICSI)
– use of frozen embryos
• 27,000 attempts made per year; 18.6%
successful (success rates are increasing)
• http://www.advancedfertility.com/sampleivfcal
endar.htm
GIFT and ZIFT
• GIFT = gamete intrafallopian transfer
• useful for tubal blockage
• ova are collected and inserted into
oviducts below point of blockage
• husband’s sperm are placed in oviduct
GIFT and ZIFT
• woman is treated with hormones to prevent
miscarriage
• 4200 attempts made / year; 28% successful
• ZIFT = zygote intrafallopian transfer
• ZIFT is like IVF, only zygotes (1 cell stage)
are inserted below blockage in oviduct (24%
success rate)
Surrogate mother
–Woman unable to have children may
have IVF in another woman who has
the child
Emotional Impact
• Infertility places a great emotional burden on
the infertile couple.
• The quest for having a child becomes the
driving force of the couples relationship.
• The mental anguish that arises from infertility
is nearly as incapacitating as the pain of other
diseases.
• It is important to address the emotional needs
of these patients.
Conclusion
• Infertility should be evaluated after one
year of unprotected intercourse.
• History and Physical examination
usually will help to identify the etiology.
• If patients fail the initial therapies then
the proper referral should be made to a
reproductive specialist.
Thank 2
All Of U..

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Infertillity presentation

  • 2. Requirements for Conception • Production of healthy egg and sperm • Unblocked tubes that allow sperm to reach the egg • The sperms ability to penetrate and fertilize the egg • Implantation of the embryo into the uterus • Finally a healthy pregnancy
  • 3. Infertility • The inability to conceive following unprotected sexual intercourse –Affects 15% of reproductive couples –Men and women equally affected
  • 4. Infertility - Statistics • causes are identified in 90 % of patients • 30 % of couples have male AND female factors • Of 100 sub fertile couples the break down is as follows: • 40 % male factor etiology • 20 % female hormonal imbalance • 30 % female peritoneal factor • 5 % ‘hostile’ cervical environment • 5 % unexplained • psychological impact can be significant
  • 5. Infertility • Reproductive age for women – Generally 15-44 years of age – Fertility is approximately halved between 37th and 45th year due to alterations in ovulation – 20% of women have their first child after age 30 – 1/3 of couples over 35 have fertility problems • Ovulation decreases • Health of the egg declines • With the proper treatment 85% of infertile couples can expect to have a child
  • 6. Infertility • Primary infertility –a couple that has never conceived • Secondary infertility –infertility that occurs after previous pregnancy regardless of outcome
  • 7. Causes for infertility • Male – Drugs – Tobacco – Health problems – Radiation/Chemotherapy – Age – Enviromental factors • Pesticides • Lead • Female – Age – Stress – Poor diet – Athletic training – Over/underweight – Tobacco – STD’s – Health problems
  • 8. Causes of Infertility • Anovulation (10-20%), • Anatomic defects of the female genital tract (30%) • Abnormal spermatogenesis (40%) • Unexplained (10%-20%)
  • 9. Evaluation of the Infertile couple • History and Physical exam • Semen analysis • Thyroid and prolactin evaluation • Determination of ovulation – Basal body temperature record – Serum progesterone • Hysterosalpingogram
  • 11. Normal • Sperm made in seminiferous tubules • Travel to epididymis to mature
  • 12. • Sperm exit through vas deferens • Semen produced in prostate gland, seminal glands, cowpers glands • Sperm can live 5-7 days Normal
  • 13. Male Factor • 40% of the cause for infertility • Sperm is constantly produced by the germinal epithelium of the testicle – Sperm generation time 73 days – Sperm production is thermoregulated • 1° F less than body temperature • Both men and women can produce anti- sperm antibodies which interfere with the penetration of the cervical mucus
  • 14. Normal Values for SEMEN ANALYSIS. Volume Sperm Concentration Viscosity Morphology pH WBC – 2.0 ml or more – 20 million/ml or more – Liquefication in 30-60 minutes. – 30% or more normal forms – 7.2-7.8 – Fewer than 1 million/ml
  • 15. Causes for Abnormal SEMEN ANALYSIS. • No sperm – Klinefelter’s syndrome – Sertoli only syndrome – Ductal obstruction – Hypogonadotropi c-hypogonadism • Few sperm – Genetic disorder – Endocrinopathies – Varicocele – Exogenous (e.g., Heat) Abnormal Count
  • 16. Continues: causes for abnormal SA • Abnormal Morphology – Varicocele – Stress – Infection (mumps) • Abnormal Motility – Immunologic factors – Infection – Defect in sperm structure – Poor liquefaction – Varicocele • Abnormal Volume – No ejaculate • Ductal obstruction • Retrograde ejaculation • Ejaculatory failure • Hypogonadism – Low Volume • Obstruction of ducts • Absence of vas deferens • Absence of seminal vesicle • Partial retrograde ejaculation • Infection
  • 17. Causes for male infertility • 42% varicocele – repair if there is a low count or decreased motility • 22% idiopathic • 14% obstruction • 20% other (genetic abnormalities)
  • 18. Abnormal Semen Analysis • Azoospermia – Klinefelter’s (1 in 500) – Hypogonadotropic- hypogonadism – Ductal obstruction (absence of the Vas deferens) • Oligospermia – Anatomic defects – Endocrinopathies – Genetic factors – Exogenous (e.g. heat) • Abnormal volume – Retrograde ejaculation – Infection – Ejaculatory failure
  • 19. Evaluation of Abnormal SEMEN ANALYSIS. • Repeat semen analysis in 30 days • Physical examination – Testicular size – Varicocele • Laboratory tests – Testosterone level – FSH (spermatogenesis- Sertoli cells) – LH (testosterone- Leydig cells) • Referral to urology
  • 21. Female Reproductive System • Ovaries – Two organs that produce eggs – Size of almond – 30,000-40,000 eggs – Eggs can live for 12-24 hours
  • 22. Menstruation • Ovulation occurs 13-14 times per year • Menstrual cycles on average are of 28 days with ovulation around day 14 • Luteal phase – dominated by the secretion of progesterone – released by the corpus luteum • Progesterone causes – Thickening of the endocervical mucus – Increases the basal body temperature (0.6° F) • Involution of the corpus luteum causes a fall in progesterone and the onset of menses
  • 23. Ovulation • A history of regular menstruation suggests regular ovulation • The majority of ovulatory women experience – fullness of the breasts – decreased vaginal secretions – abdominal bloating • Absence of these symptoms may suggest anovulation – mild peripheral edema – slight weight gain – depression
  • 24.
  • 25. Diagnostic studies to confirm Ovulation • Basal body temperature – Inexpensive – Accurate • Endometrial biopsy – Expensive • Serum progesterone – After ovulation rises – Can be measured • Urinary ovulation- detection kits – Measures changes in urinary LH – Predicts ovulation but does not confirm it
  • 26. Basal Body Temperature • Excellent screening tool for ovulation – Biphasic shift occurs in 90% of ovulating women • Temperature – drops at the time of menses – rises two days after the lutenizing hormone (LH) surge • Ovum released one day prior to the first rise • Temperature elevation of more than 16 days suggests pregnancy
  • 27.
  • 28. Serum Progesterone • Progesterone starts rising with the LH surge – drawn between day 21-24 • Mid-luteal phase – >10 ng/ml suggests ovulation
  • 30. Anovulation Symptoms Evaluation* • Irregular menstrual cycles • Amenorrhea • Hirsuitism • Acne • Galactorrhea • Increased vaginal secretions • Follicle stimulating hormone • Lutenizing hormone • Thyroid stimulating hormone • Prolactin • Androstenedione • Total testosterone
  • 31. Sperm transport, Fertilization, & Implantation • The female genital tract ,,, – facilitates sperm transport – cervical mucus traps the coagulated ejaculate – the fallopian tube picks up the egg • Fertilization must occur in the proximal portion of the tube – the fertilized oocyte cleaves and forms a zygote – enters the endometrial cavity at 3 to 5 days • Implants into the secretory endometrium for growth and development
  • 34.
  • 35. Acquired Disorders • Acute salpingitis – Alters the functional integrity of the fallopian tube • N. gonorrhea and C. trachomatis • Intrauterine scarring – Can be caused by curettage • Endometriosis, scarring from surgery, tumors of the uterus and ovary – Fibroids, endometriomas • Trauma
  • 37. Hysterosalpingogram • An X-ray that evaluates the internal female genital tract – architecture and integrity of the system • Performed between the 7th and 11th day of the cycle • Diagnostic accuracy of 70%
  • 38. Hysterosalpingogram • The endometrial cavity – Smooth – Symmetrical • Fallopian tubes – Proximal 2/3 slender – Ampulla is dilated • Dye should spill promptly
  • 41. Inadequate Spermatogenesis • Clomiphene citrate is occasionally used for induction of spermatogenesis – 20% success • Eliminate alterations of thermoregulation • In vitro fertilization may facilitate fertilization • Artificial insemination with donor sperm is often successful • Laparoscopy surgery
  • 42. Anovulation • Restore ovulation – Administer ovulation inducing agents • Clomiphene citrate – Antiestrogen – Combines and blocks estrogen receptors at the hypothalamus and pituitary causing a negative feedback – Increases FSH production • stimulates the ovary to make follicles
  • 43. Clomid • Given for 5 days in the early part of the cycle • Maximum dose is usually 150mg • 50mg dose - 50% ovulate • 100mg -25% more ovulate • 150mg lower numbers of ovulation
  • 44. Superovulatory Medications • If no response with clomid then gonadotropins- FSH (e.g. pergonal) can be administered intramuscularly – This is usually given under the guidance of someone who specializes in infertility • This therapy is expensive and patients need to be followed closely • Adverse effects – Hyperstimulation of the ovaries – Multiple gestation – Fetal wastage
  • 45. Anatomic Abnormalities • Surgical treatments – Lysis of adhesions – Septoplasty – Tuboplasty – Myomectomy • Surgery may be performed – laparoscopically – hysteroscopically • If the fallopian tubes are beyond repair one must consider in vitro fertilization
  • 46. Assisted Reproductive Technologies (ART) • Explosion of ART has occurred in the last decade. • Theses technologies help provide infertile couples with tools to bypass the normal mechanisms of gamete transportation. • Probability of pregnancy in healthy couples is 30-40% per cycle, live birth rate 25%. – this varies depending on age
  • 47. Intrauterine insemination (artificial insemination) • definition: sperm introduced into female reproductive tract by means other than coitus • sperm can come from donor / sperm bank or from husband • usually, several ejaculations are pooled • often used when male has low sperm count or antibodies present in ejaculate
  • 48. Artificial Insemination • Sperm donation or sperm aspiration
  • 49. In Vitro Fertilization • “test - tube babies” • 1st performed in 1978 (Louise Joy Brown) • often performed on infertile women with tubal blockage • Sperm and egg combined in the lab, fertilization • Zygote placed back into the uterus • Very expensive and not always successful • Oldest woman in the US to give birth using in vitro was 62 years old and an Romanian woman gave birth at 66
  • 51. IVF Protocol • GnRH agonist (e.g. Lupron) for 7 days • FSH agonist (follistim, Gonal-F, Repronex) until follicles measure 17-20 mm in diameter • hCG given to induce egg maturation.
  • 52. IVF protocol • sperm and ova added to dish; fertilization occurs 12-14hrs. • eggs transferred to new dish and cell division occurs • embryos squirted into uterus at 4- to 32- cell stage (optimal: blastocyst stage)
  • 53. IVF Protocol, cont’d. • 3 to 5 embryos are injected to increase chances of pregnancy • woman given progestagen to prevent miscarriage
  • 54. IVF Protocol, cont’d. • new variations / improvements: – Intracytoplasmic sperm injection (ICSI) – use of frozen embryos • 27,000 attempts made per year; 18.6% successful (success rates are increasing) • http://www.advancedfertility.com/sampleivfcal endar.htm
  • 55. GIFT and ZIFT • GIFT = gamete intrafallopian transfer • useful for tubal blockage • ova are collected and inserted into oviducts below point of blockage • husband’s sperm are placed in oviduct
  • 56. GIFT and ZIFT • woman is treated with hormones to prevent miscarriage • 4200 attempts made / year; 28% successful • ZIFT = zygote intrafallopian transfer • ZIFT is like IVF, only zygotes (1 cell stage) are inserted below blockage in oviduct (24% success rate)
  • 57. Surrogate mother –Woman unable to have children may have IVF in another woman who has the child
  • 58. Emotional Impact • Infertility places a great emotional burden on the infertile couple. • The quest for having a child becomes the driving force of the couples relationship. • The mental anguish that arises from infertility is nearly as incapacitating as the pain of other diseases. • It is important to address the emotional needs of these patients.
  • 59. Conclusion • Infertility should be evaluated after one year of unprotected intercourse. • History and Physical examination usually will help to identify the etiology. • If patients fail the initial therapies then the proper referral should be made to a reproductive specialist.