Infertility

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Infertility
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Infertility

• The inability to conceive following unprotected
  sexual intercourse
• 1 year (age lt 35) or 6 months (age gt35)
• Normally a fertile couple has approximately a 20
  chance of conception in each ovulatory cycle

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Infertility

• Primary infertility
• a couple that has never conceived
• Secondary infertility
• infertility that occurs after previous pregnancy
  regardless of outcome

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Requirements for Conception

• normally developed reproductive tract in both the
  male and female partner
• normal functioning of an intact
  hypothalamic-pituitary-gonadal axis supports
  gametogenesis (the formation of sperm and ova).
• timing of intercourse
• Unblocked tubes that allow sperm to reach the egg
• The sperms ability to penetrate and fertilize the
  egg
• Implantation of the embryo into the
  hormone-prepared endometrium
• Finally a healthy pregnancy

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Infertility. Statistic

• A female factor (ovulatory dysfunction, pelvic
  factor) is in approximately 50
• A male factor (sperm and semen abnormalities) is
  in approximately 35
• Unexplained factors and causes (e.g., coital
  techniques) related to both partners are in
  approximately 15

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Causes for infertility
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Cause of Female Infertility

• CONGENITAL OR DEVELOPMENTAL FACTORS
• Abnormal external genitals
• Absence of internal reproductive structures
• HORMONAL FACTORS
• Anovulation-primary
• Pituitary or hypothalamic hormone disorder
  Adrenal gland disorder
• Congenital adrenal hyperplasia
• Anovulation-secondary
• Disruption of hypothalamic-pituitary-ovarian axis
  Early menopause
• Amenorrhea after discontinuing OCP
  Increased prolactin levels
• TUBAL/PERITONEAL FACTORS
• Absence of fimbriated end of tube
  Tubal motility reduced
• Absence of a tube Inflammation within the tube
  Tubal adhesions
• UTERINE FACTORS
• Developmental anomalies
• Endometrial and myometrial tumors
• Asherman syndrome (uterine adhesions or scar
  tissue)

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Cause of Female Infertility CONGENITAL OR
DEVELOPMENTAL FACTORS
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Cause of Female Infertility CONGENITAL OR
DEVELOPMENTAL FACTORS
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Cause of Female Infertility CONGENITAL OR
DEVELOPMENTAL FACTORS
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Cause of Female Infertility CONGENITAL OR
DEVELOPMENTAL FACTORS
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Cause of Female Infertility TUBAL/PERITONEAL
FACTORS

• Chlamidial infection
• Pelvic infections (ruptures appendix, STIs)

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Cause of Female Infertility UTERINE FACTORS
Uterine fibroids
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Cause of Female Infertility UTERINE FACTORS
Endometrial tumor
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Cause of Female Infertility UTERINE FACTORS
Asherman syndrome
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Cause of Female Infertility VAGINAL-CERVICAL
FACTORS

• Vaginal-cervical infection
• Sperm antibody

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Cause of Male Infertility

• STRUCTURAL OR HORMONAL DISORDERS
• Undescended testes
  Hypospadias
  Testicular damage
• Varicocele
  Low testosterone
  levels caused by
  mumps
• OTHER FACTORS
• Endocrine disorders
  Genetic disorders
  Psychologic disorders
• Sexually transmitted infections
  Exposure of scrotum to high
  temperatures
• Exposure to workplace hazards such as radiation
  or toxic substances
• SUBSTANCE ABUSE
• Changes in sperm (Smoking, heroin, marijuana,
  amyl nitrate, butyl nitrate, ethyl chloride,
  methaqualone, Monoamine oxidase)
• Decrease in sperm (Hypopituitarism, Debilitating
  or chronic disease, Trauma, Gonadotropic
  inadequacy, Decrease in libido
• Heroin, methadone, selective serotonin reuptake
  inhibitors, and barbiturates)
• Impotence (Alcohol, Antihypertensive medications)
• OBSTRUCTIVE LESIONS OF THE EPIDIDYMIS AND VAS
  DEFERENS
• NUTRITIONAL DEFICIENCIES

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Cause of Male Infertility STRUCTURAL OR HORMONAL
DISORDERS
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Evaluation of the Infertile couple

• History and Physical exam
• Semen analysis
• Thyroid and prolactin evaluation
• Determination of ovulation
• Basal body temperature record
• Serum progesterone
• Ovarian reserve testing
• Hysterosalpingogram

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Assessment of woman

• 1.Age
• 2. Duration of infertility (length of
  contraceptive and noncontraceptive exposure)
• 3. Obstetric
• A. number of pregnancies, miscaridges and
  abortion
• B. Length of time required to initiate each
  pregnancy
• C. Complication of pregnancy
• D. Duration of lactation
• 4. Gynecologic detailed menstrual history
• 5. Previous tests and therapy of infertility
• 6. Medical general (chronichereditary disease),
  medication, family problem, sexual development,
  galactorrhea
• 7. Surgical abdominal or pelvic surgery

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• 1. Follicular development, ovulation, and luteal
  development are supportive of pregnancy
• a. Basal body temperature (presumptive
  evidence ofovulatory cycles) is biphasic, with
  temperature elevation that persists for 12 to
  14 days before menstruation
• b. Cervical mucus characteristics change
  appropriatelyduring phases of menstrual cycle
• c. Laparoscopic visualization of pelvic organs
  verifiesfollicular and luteal development
• 2. The luteal phase is supportive of pregnancy
• a. Levels of plasma progesterone are adequate
• b. Findings from endometrial biopsy samples are
  consistent with day of cycle
• 3. Cervical factors are receptive to sperm during
  expectedtime of ovulation
• a. Cervical os is open
• b. Cervical mucus is clear, watery, abundant, and
  slippery and demonstrates good spinnbarkeit and
  arborization (fern pattern)
• c. Cervical examination does not reveal lesions
  or infections
• d. Postcoital test findings are satisfactory
  (adequatenumber of live, motile, normal sperm
  present in cervical mucus)
• e. No immunity to sperm demonstrated
• 4. The uterus and uterine tubes are supportive
  of pregnancy
• a. Uterine and tubal patency are documented by
• Spillage of dye into peritoneal cavity
• Outlines of uterine and tubal cavities of
  adequatesize and shape, with no abnormalities
• b. Laparoscopic examination verifies normal
  development of internal genitals and absence
  of adhesions, infections, endometriosis, and
  other lesions
• 5. The male partner's reproductive structures are
  normal

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Abnormalities of Spermatogenesis
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Normal

• Sperm made in seminiferous
• tubules
• Travel to
• epididymis to
• mature

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Normal

• Sperm exit through vas deferens
• Semen produced in prostate gland, seminal glands,
  cowpers glands
• Sperm only 5 of ejaculation
• Sperm can live 5-7 days

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Semen Analysis (SA)

• Obtained by masturbation
• Provides immediate information
• Quantity
• Quality
• Density of the sperm
• Morphology
• Motility
• Abstain from coitus 2 to 3 days
• Collect all the ejaculate
• Analyze within 1 hour
• A normal semen analysis excludes
• male factor 90 of the time

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Normal Values for SA

• Volume
• Sperm Concentration
• Motility
• Viscosity
• Morphology
• pH
• WBC

• 2.0 ml or more
• 20 million/ml or more
• 50 forward progression
• 25 rapid progression
• Liquification in 30-60 min
• 30 or more normal forms
• 7.2-7.8
• Fewer than 1 million/ml

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Causes for Abnormal SA
Abnormal Count

• No sperm
• Klinefelters syndrome
• Sertoli only syndrome
• Ductal obstruction
• Hypogonadotropic-hypogonadism

• Few sperm
• Genetic disorder
• Endocrinopathies
• Varicocele
• Exogenous (e.g., Heat)

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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

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Causes for male infertility

• 42 varicocele
• repair if there is a low count or decreased
  motility
• 22 idiopathic
• 14 obstruction
• 20 other (genetic
• abnormalities)

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Abnormal Semen Analysis

• Azoospermia
• Klinefelters (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

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Evaluation of Abnormal SA

• 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

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Evaluation of Ovulation
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Female Reproductive System

• Ovaries
• Two organs that produce eggs
• Size of almond
• 30,000-40,000 eggs
• Eggs can live for 12-24 hours

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Menstruation

• Ovulation occurs 13-14 times per year
• Menstrual cycles on average are Q 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

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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 PMS symptoms may suggest anovulation

• mild peripheral edema
• slight weight gain
• depression

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Diagnostic studies to confirm Ovulation

• Basal body temperature
• Inexpensive
• Accurate
• Endometrial biopsy
• Expensive
• Static information

• Serum progesterone
• After ovulation rises
• Can be measured
• Urinary ovulation-detection kits
• Measures changes in urinary LH
• Predicts ovulation but does not confirm it

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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

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Serum Progesterone

• Progesterone starts rising with the LH surge
• drawn between day 21-24
• Mid-luteal phase
• gt10 ng/ml suggests ovulation

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Salivary Estrogen TCI Ovulation Tester- 92
accurate
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Add Saliva Sample
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Non-Ovulatory Saliva Pattern
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High Estrogen/ Ovulatory Saliva Pattern
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Anovulation
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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

• Order the appropriate tests based on the clinical
  indications

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Anatomic Disorders of the Female Genital Tract
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Sperm transport, Fertilization, Implantation

• The female genital tract is not just a conduit
• 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

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Fertilization
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Implantation
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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

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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

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Hysterosalpingogram

• The endometrial cavity
• Smooth
• Symmetrical
• Fallopian tubes
• Proximal 2/3 slender
• Ampulla is dilated
• Dye should spill promptly

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HSG Tubal Infertility
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??? Unexplained infertility ???

• 10 of infertile couples will have a completely
  normal workup
• Pregnancy rates in unexplained infertility
• no treatment 1.3-4.1
• clomid and intrauterine insemination 8.3
• gonadotropins and intrauterine insemination 17.1
• ???

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Treatment of the Infertile Couple
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Inadequate Spermatogenesis

• Eliminate alterations of thermoregulation
• Clomiphene citrate is occasionally used for
  induction of spermatogenesis
• 20 success
• In vitro fertilization may facilitate
  fertilization
• Artificial insemination with donor sperm is often
  successful

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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

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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
• No changes in birth defects If no pregnancy in 6
  months refer for advanced therapies
• 7 risk of twins 0.3 triplets

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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

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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

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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

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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

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Artificial Insemination

• Sperm donation or sperm aspiration

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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

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In Vitro Fertilization
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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
• Egg retrieval (transvaginally) 34-35 h later

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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)

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IVF Protocol, contd.

• 3 to 5 embryos are injected to increase chances
  of pregnancy
• woman given progestagen to prevent miscarriage

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IVF Protocol, contd.

• 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/sampleivfcalendar
  .htm

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GIFT and ZIFT

• GIFT gamete intrafallopian transfer
• useful for tubal blockage
• ova are collected and inserted into oviducts
  below point of blockage
• husbands sperm are placed in oviduct

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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)

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Surrogate mother

• Woman unable to have children may have IVF in
  another woman who has the child

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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.

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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.

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Thank You
for attention!
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