Infertility
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Infertility. Infertility. The inability to conceive following unprotected sexual intercourse 1 year (age < 35) or 6 months (age >35) Normally a fertile couple has approximately a 20 % chance of conception in each ovulatory cycle. Infertility. Primary infertility

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Infertility

Infertility


Infertility1

Infertility

  • The inability to conceive following unprotected sexual intercourse

    • 1 year (age < 35) or 6 months (age >35)

      Normally a fertile couple has approximately a 20 % chance of conception in each ovulatory cycle


Infertility2

Infertility

  • Primary infertility

    • a couple that has never conceived

  • Secondary infertility

    • infertility that occurs after previous pregnancy regardless of outcome


Requirements for conception

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


Infertility statistic

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%


Causes for infertility

Causes for infertility


Cause of female infertility

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)


Cause of female infertility congenital or developmental factors

Cause of Female Infertility CONGENITAL OR DEVELOPMENTAL FACTORS


Cause of female infertility congenital or developmental factors1

Cause of Female Infertility CONGENITAL OR DEVELOPMENTAL FACTORS


Cause of female infertility congenital or developmental factors2

Cause of Female Infertility CONGENITAL OR DEVELOPMENTAL FACTORS


Cause of female infertility congenital or developmental factors3

Cause of Female Infertility CONGENITAL OR DEVELOPMENTAL FACTORS


Cause of female infertility tubal peritoneal factors

Cause of Female Infertility TUBAL/PERITONEAL FACTORS

  • Chlamidial infection

  • Pelvic infections (ruptures appendix, STIs)


Cause of female infertility uterine factors

Cause of Female Infertility UTERINE FACTORS

Uterine fibroids


Cause of female infertility uterine factors1

Cause of Female Infertility UTERINE FACTORS

Endometrial tumor


Cause of female infertility uterine factors2

Cause of Female Infertility UTERINE FACTORS

Asherman syndrome


Cause of female infertility vaginal cervical factors

Cause of Female Infertility VAGINAL-CERVICAL FACTORS

  • Vaginal-cervical infection

  • Sperm antibody


Cause of male infertility

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


Cause of male infertility structural or hormonal disorders

Cause of Male Infertility STRUCTURAL OR HORMONAL DISORDERS


Evaluation of the infertile couple

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


Assessment of woman

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 (chronic&hereditary disease), medication, family problem, sexual development, galactorrhea

  • 7. Surgical: abdominal or pelvic surgery


Infertility

  • 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:

  • a.No evidence of developmental anomalies of penis,testicular atrophy, or varicocele (varicose veins onthe spermatic vein in the groin)

  • b.No evidence of infection in prostate, seminal vesi­cles, and urethra

  • c.Testes are more than 4 cm in largest diameter

  • 6.Semen is supportive of pregnancy:

  • a.Sperm (number per milliliter) are adequate in ejacu­late

  • b.Most sperm show normal morphology

  • c.Most sperm are motile, forward moving

  • d.No autoimmunity exists

  • e.Seminal fluid is normal


Abnormalities of spermatogenesis

Abnormalities of Spermatogenesis


Normal

Normal

  • Sperm made in seminiferous

    tubules

  • Travel to

    epididymis to

    mature


Normal1

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


Semen analysis sa

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


Normal values for sa

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


Causes for abnormal sa

Causes for Abnormal SA

Abnormal Count

  • No sperm

    • Klinefelter’s syndrome

    • Sertoli only syndrome

    • Ductal obstruction

    • Hypogonadotropic-hypogonadism

  • Few sperm

    • Genetic disorder

    • Endocrinopathies

    • Varicocele

    • Exogenous (e.g., Heat)


Continues causes for abnormal sa

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

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

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 sa

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


Evaluation of ovulation

Evaluation of Ovulation


Female reproductive system

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

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


Ovulation

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


Diagnostic studies to confirm ovulation

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


Basal body temperature

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

Serum Progesterone

  • Progesterone starts rising with the LH surge

    • drawn between day 21-24

  • Mid-luteal phase

    • >10 ng/ml suggests ovulation


Salivary estrogen tci ovulation tester 92 accurate

Salivary Estrogen: TCI Ovulation Tester- 92% accurate


Add saliva sample

Add Saliva Sample


Non ovulatory saliva pattern

Non-Ovulatory Saliva Pattern


High estrogen ovulatory saliva pattern

High Estrogen/ Ovulatory Saliva Pattern


Anovulation

Anovulation


Anovulation symptoms evaluation

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


Anatomic disorders of the female genital tract

Anatomic Disorders of the Female Genital Tract


Sperm transport fertilization implantation

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


Fertilization

Fertilization


Implantation

Implantation


Acquired disorders

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


Hysterosalpingogram

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%


Hysterosalpingogram1

Hysterosalpingogram

  • The endometrial cavity

    • Smooth

    • Symmetrical

  • Fallopian tubes

    • Proximal 2/3 slender

    • Ampulla is dilated

  • Dye should spill promptly


Hsg tubal infertility

HSG: Tubal Infertility


Unexplained infertility

???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%

      ???


Treatment of the infertile couple

Treatment of the Infertile Couple


Inadequate spermatogenesis

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


Anovulation1

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

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


Superovulatory medications

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

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

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

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

Artificial Insemination

  • Sperm donation or sperm aspiration


In vitro fertilization

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 fertilization1

In Vitro Fertilization


Ivf protocol

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


Ivf protocol1

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

IVF Protocol, cont’d.

  • 3 to 5 embryos are injected to increase chances of pregnancy

  • woman given progestagen to prevent miscarriage


Ivf protocol cont d1

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/sampleivfcalendar.htm


Gift and zift

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 zift1

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

Surrogate mother

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


Emotional impact

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

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.


Infertility

Thank You

for attention!


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