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Al-YaqdhanAl-Atbi
81559
InfertIlIty
InfertIlIty
Case:
Case:
 A 33 years old Omani lady k/o primary infertility was present to the A&E with referral
from private clinic .
 She presented with sever lower abdominal pain from 3 days which get worse
with time. It was colicky in nature, not radiating, and she can’t tolerated
with it. There was history of abdominal distention, SOB, vomiting and
diarrhea.
 4 days before pt. underwent Intra cytoplasmic sperm injection (ICSI)
 12-19/1/2013 : fertility medication used for inducing final oocyte maturation
 Married for 6 years
 2 years back, Intrauterine insemination (IUI) had been done in Muscat
private hospital but failed.
 She doesn’t have any thyroid problems, no abnormal weight gain or weight
loss, no excessive hair growth.
Menstrual History:
Menstrual History:
 Her menarche age is 15 years. Menstrual periods were
irregular. The character of the flow is normal without
clots. No inter menstrual bleeding .Her LMP was on
10/1/2013.
Contraceptive History:
She didn’t use any kind of contraception methods.
Past obstetric history
primary infertility
Marital history
Marital history
 She is the first wife of her husband. She is married once. They sleep
together normally with adequate frequency. She does not have any
bleeding or dysuria with sexual intercourse.
 Her husband is a 34 years old Omani man works as a office worker
in the educational ministry. His health condition is good. He has no
problems during intercourse and his work does not affect his
relationships with his wife.
 Previous medical & surgical History
 Systemic review:(unremarkable)
 Family history:
 Related to her husband
 Her father and mother are consanguinity.
 Her father has DM & HTN.
 Her sisters and brother had thyroid problems & under medication.
Social history:
 She is a teacher, living with her husband . She is not
smoking or alcohol consumer.
Unexplained primary infertility presenting with
ovarian hyperstimulation syndrom
INFERTILITY
Requirements for Conception
Requirements for Conception
Production of healthy egg and sperm
egg and sperm
Unblocked tubes
Unblocked tubes that allow sperm to reach the egg
The sperms ability to penetrate
ability to penetrate and fertilize the egg
Implantation
Implantation of the embryo into the uterus
Finally a healthy pregnancy
Infertility
Infertility
The inability to conceive following unprotected sexual
intercourse
1 year (age < 35) or 6 months (age >35)
Affects 15% of reproductive couples
Men and women equally affected
Infertility
Infertility
Reproductive age for women:
Reproductive age for women:
 Generally 15-44 years
15-44 years of age
 20% of women have their first child after age 30
1/3 of couples
1/3 of couples over 35 years have fertility problems:
 Ovulation decreases
 Health of the egg declines
 Health problems develop
With the proper treatment 85% of infertile couples can
85% of infertile couples can
expect to have a child
expect to have a child
Infertility
Infertility
Primary infertility
Primary infertility
a couple that has never conceived
Secondary infertility
Secondary infertility
infertility that occurs after previous pregnancy regardless of outcome
Causes of Infertility
Causes of Infertility
Anovulation (10-20%)
(10-20%)
Anatomic defects of the female genital tract (30%)
(30%)
Abnormal spermatogenesis (40%)
(40%)
Unexplained (10%-20%)
(10%-20%)
Causes:
Causes:
Male causes
Female causes
Combined causes
Male Factor
Male Factor
40% of the cause for infertility
Sperm is constantly produced by the germinal epithelium of
Sperm is constantly produced by the germinal epithelium of
the testicle
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
anti-sperm antibodies
which interfere with the penetration of the cervical mucus
MALE FACTORS
MALE FACTORS
infertility-140601034142-phpapp02 2.pdf
A. Gonadotropin Deficiency (Kallmann Syndrome)
failure of GnRH neurons to migrate
GnRH neurons to migrate to the proper
location in the hypothalamus.
Kallmann syndrome
Kallmann syndrome is associated with midline defects
such as anosmia, cleft lip and cleft palate, deafness,
cryptorchidism, and color blindness.
Men can be fertile when given FSH and LH to stimulate
given FSH and LH to stimulate
sperm production
sperm production. Virilization can be obtained with
testosterone or human chorionic gonadotropin (hCG)
–C. Isolated FSH Deficiency
there is insufficient FSH production by the pituitary. Patients are
normally virilized, as LH is present. FSH levels are low. Sperm
counts range from azoospermia to severely low numbers
(oligospermia).
–D. Congenital Hypogonadotropic Syndromes
Prader-Willi syndrome Bardet-Biedi syndrome.
–A. Pituitary Insufficiency
Pituitary insufficiency may result from tumors, infarcts, surgery,
from tumors, infarcts, surgery,
radiation, sickle cell
radiation, sickle cell anemia.
–B. Hyperprolactinemia
–most common cause is prolactin-secreting pituitary adenoma.
–Elevated prolactin results in decreased FSH, LH levels and
Elevated prolactin results in decreased FSH, LH levels and
causes infertility
causes infertility.
–Associated symptoms include loss of libido, impotence,
include loss of libido, impotence,
galactorrhea, and gynecomastia.
galactorrhea, and gynecomastia.
–C. Exogenous or Endogenous Hormones
1. Estrogens, GH, androgens, glucocorticoids, Hyper- and
Estrogens, GH, androgens, glucocorticoids, Hyper- and
hypothyroidism
hypothyroidism
infertility-140601034142-phpapp02 2.pdf
Chromosomal Causes
• Klinefelter syndrome (47,XXY)
Klinefelter syndrome (47,XXY)
– most common genetic reason for azoospermia. classic triad:
small firm testes; gynecomastia; and azoospermia
small firm testes; gynecomastia; and azoospermia.
– XX Male Syndrome
XX Male Syndrome
– presents as gynecomastia at puberty or as azoospermia in
gynecomastia at puberty or as azoospermia in
adults
adults. Average height is below normal, and hypospadias
hypospadias is
common. Male external and internal genitalia are otherwise normal.
– XYY Syndrome
XYY Syndrome
– Typically, men with 47,XYY are tall. Semen analyses show either
oligospermia or azoospermia.
–Causes of Male infertility - Gonadotoxins
Radiation
Radiation :
– Sertoli and germ cells are extremely radiosensitive.
Drugs:
Drugs:
–Use of alcohol, cigarettes, caffeine, and marijuana may lead to
testicular failure.
–Chemotherapy: toxic to actively dividing cells The most toxic
drugs are the alkylating agents such as cyclophosphamide.
– Systemic Disease - Causes of Male infertility
A.Renal Failure
B. Liver Cirrhosis
C. Sickle Cell Disease
– Causes of Male infertility - Testis Injury
Orchitis
Orchitis
– Inflammation of testis tissue is most commonly due to bacterial
infection, termed epididymo-orchitis.
Testicular Torsion
Testicular Torsion :
Ischemic injury to the testis secondary to twisting of the testis on the
spermatic cord. Torsion may result in inoculation of the immune
system with testis antigens that may predispose to later
immunological infertility.
Trauma
Trauma
Can invoke an abnormal immune response in addition to atrophy
resulting from injury. Both may contribute to infertility.
–Causes of Male infertility - Cryptorchidism
–Males with either unilaterally or bilaterally undescended testes are at
risk for infertility later in life. Prophylactic orchidopexy is generally
performed by 2 years of age
–Varicocele
–A varicocele is defined as dilated and tortuous veins within the
pampiniform plexus of scrotal veins.
–Increased intratesticular temperature, reflux of toxic metabolites
–
–Idiopathic
–at least 25%-50% of male infertility has no identifiable cause
infertility-140601034142-phpapp02 2.pdf
–Posttesticular Causes of Male infertility
–The posttesticular portion of the reproductive tract includes the
epididymis, vas deferens, seminal vesicles, and associated
epididymis, vas deferens, seminal vesicles, and associated
ejaculatory apparatus
ejaculatory apparatus
–1. Cystic fibrosis -
–98% of men with CF having missing
parts of the epididymis. In addition, the
vas deferens, seminal vesicles, and
ejaculatory ducts are usually atrophic, or
completely absent
–2.Bacterial infections - Bacterial infections (E coli in men age
> 35) or Chlamydia trachomatis in young men) may involve the
epididymis, with scarring and obstruction.
–Retrograde ejaculation:
–This is caused by an open bladder neck during
ejaculation.
–Retrograde ejaculation may be due to causes such as
diabetes, bladder neck surgery, TURP, colon or rectal surgery,
diabetes, bladder neck surgery, TURP, colon or rectal surgery,
multiple sclerosis, or spinal cord injury.
multiple sclerosis, or spinal cord injury.
–Diagnosis is made by observing 10-15 sperm per high-
power field (HPF) in the postejaculatory urine.
–Disorders of Sperm Function or Motility
A. Immotile Cilia Syndromes
–B. Immunologic Infertility
Autoimmune infertility has been implicated as a cause of infertility in 10% of
10% of
infertile couples..
infertile couples..
– Autoimmune infertility may result from an abnormal exposure to sperm antigens
after, for example, Vasectomy, testis torsion, or biopsy, which then a pathologic
Vasectomy, testis torsion, or biopsy, which then a pathologic
immune response.
immune response.
–Antibodies disturb sperm transport or normal sperm-egg interaction.
–Antibodies may cause agglutination of sperm, which inhibits passage,
– or may block normal sperm binding to the oocyte
–C. Infection
–Disorders of Coitus - Causes of Male infertility
A. Impotence
B. Sexual issues.
– Often treatable, problems with sexual intercourse Difficulties with
erection of the penis (erectile dysfunction), premature ejaculation,
painful intercourse (dyspareunia), or psychological or relationship
problems can contribute to infertility. Use of lubricants such as oils or
petroleum jelly can be toxic to sperm and impair fertility.
–C. Hypospadias
May not place the semen at the cervical os.
–D. Timing and Frequency
Simple problems of coital timing and frequency can be corrected by a review of
the couple’s sexual habits. An appropriate frequency of intercourse is every 2
days, performed within the periovulatory period.
Components
Components of
of the
the infertility
infertility history
history.
Fertility history
Fertility history
 Previous pregnancies (present and with other partners)
 Duration of infertility
 Previous infertility treatments
 Female evaluation
Sexual history
Sexual history
 Erections
 Timing and frequency
 Lubricants
Medical history
Medical history
 Fevers
 Systemic illness—diabetes, cancer, infection
 Genetic diseases—cystic fibrosis, Klinefelter syndrome
Surgical history
Surgical history
Orchidopexy, cryptorchidism
Herniorraphy
Trauma, torsion
Pelvic, bladder, or retroperitoneal surgery
Transurethral resection for prostatism
Pubertal onset
Medication history
Medication history
Nitrofurantoin
Cimetidine
Sulfasalazine
Spironolactone
Alpha blockers
Family history
Family history
Cryptorchidism
Midline defects
(Kartagener syndrome)
Hypospadias
Social history
Social history
Ethanol
Smoking/tobacco
Cocaine
Anabolic steroids
Occupational history
Occupational history
Exposure to ionizing radiation
Chronic heat exposure
Pesticides
Heavy metals (lead)
Laboratory Diagnosis of Male Infertility
Laboratory Diagnosis of Male Infertility
Urinalysis
Urinalysis
It may indicate the presence of infection, hematuria, glucosuria, or renal
disease, and suggest anatomic or medical problems within the urinary tract
Semen Analysis
Semen Analysis
•A normal semen analysis excludes male factor 90% of the time
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
Abnormal Semen Analysis
Abnormal Semen Analysis
Azospermia
Azospermia
Klinefelter’s (1 in 500)
Hypogonadotropic-
hypogonadism
Ductal obstruction
(absence of the Vas
deferens)
Oligospermia
Oligospermia
Anatomic defects
Endocrinopathies
Genetic factors
Exogenous (e.g. heat)
Cont. causes for abnormal SA
Cont. causes for abnormal SA
Abnormal Morphology
Abnormal Morphology
Varicocele
Stress
Infection (mumps)
Abnormal Motility
Abnormal Motility
Immunologic factors
Infection
Defect in sperm structure
Poor liquefaction
Varicocele
Abnormal Volume
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
Hormone Assessment :
Hormone Assessment :
A routine part of the initial evaluation is testing of specific serum hormone
levels, which usually includes FSH, LH, testosterone, and prolactin.
Adjunctive Tests
Adjunctive Tests:
:
 Semen Leukocyte Analysis
 Antisperm Antibody Test
 Hypoosmotic Swelling Test
 Sperm Penetration Assay
 Sperm-Cervical Mucus Interaction
 Chromosomal Studies
 Cystic Fibrosis Mutation Testing
 Y Chromosome Microdeletion Analysis
 Radiologic Testing
 Testis Biopsy & Vasography
 Fine-Needle Aspiration "Mapping" of Testes
 Semen Culture
FEMALE FACTORS
FEMALE FACTORS
Menstruation
Menstruation
Ovulation occurs 13-14 times per year
13-14 times per year
Menstrual cycles on average are 28 days
are 28 days with ovulation around day 14
Luteal phase
 dominated by the secretion of progesterone
dominated by the secretion of progesterone
 released by the corpus luteum
released by the corpus luteum
Progesterone causes
 Thickening of the endocervical mucus
Thickening of the endocervical mucus
 Increases the basal body temperature (0.6° F)
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
mild peripheral edema
 slight weight gain
 depression
Diagnostic studies to confirm Ovulation
Diagnostic studies to confirm Ovulation
Basal body temperature
Basal body temperature
Inexpensive
Accurate
Endometrial biopsy
Endometrial biopsy
Expensive
Static information
Serum progesterone
Serum progesterone
After ovulation rises
Can be measured
Urinary ovulation-
Urinary ovulation-
detection kits
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
Excellent screening tool for ovulation
Biphasic shift occurs in 90% of ovulating women
Temperature
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
infertility-140601034142-phpapp02 2.pdf
Serum Progesterone
Serum Progesterone
Progesterone starts rising with the LH surge
drawn between day 21-24
Mid-luteal phase
>10 ng/ml suggests ovulation
FEMALE FACTORS
FEMALE FACTORS
–endometriosis (15-30%)
–multiple factors (30%)
Ovulatory Dysfunction (15-20%):
Ovulatory Dysfunction (15-20%):
hypothalamic
hypothalamic (hypothalamic amenorrhea)
ƒpituitary
pituitary (prolactinoma, hypopituitarism)
ƒovarian:
ƒovarian:
PCOS
ƒpremature ovarian failure
ƒsystemic diseases:
ƒsystemic diseases:
thyroid, Cushing’s syndrome, renal/hepatic failure
ƒcongenital:
congenital:
Turner’s syndrome, gonadal dysgenesis or gonadotropin
deficiency
ƒstress, poor nutrition, excessive exercise
stress, poor nutrition, excessive exercise
outflow tract abnormality
outflow tract abnormality
 ƒTubal factors (20-30%):
Tubal factors (20-30%):
PID
adhesions (previous surgery, peritonitis, endometriosis)
ligation/occlusion (e.g. previous ectopic pregnancy)
 ƒ
ƒCervical factors (5%):
Cervical factors (5%):
hostile or acidic cervical mucus
anti-sperm antibodies
structural defects
ƒUterine factors (<5%):
ƒUterine factors (<5%):
congenital anomalies (e.g. prenatal DES exposure), bicornuate uterus, uterine
septum
intrauterine adhesions (e.g. Asherman’s syndrome)
infection (endometritis, pelvic TB)
fibroids/polyps (particularly intrauterine)
endometrial ablation
Sperm transport, Fertilization, &
Sperm transport, Fertilization, &
Implantation
Implantation
The female genital tract is not just a passage:
The female genital tract is not just a passage:
facilitates sperm transport
cervical mucus traps the coagulated ejaculate
the fallopian tube picks up the egg
Fertilization must occur in the proximal portion of
Fertilization must occur in the proximal portion of
the tube
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
Implants into the secretory endometrium for growth
and development
and development
Congenital Anatomic Abnormalities
Congenital Anatomic Abnormalities
Anovulation
Anovulation
Symptoms Evaluation
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
Investigations:
Investigations:
ovulatory
ovulatory
 day 3: FSH, LH, TSH, PRL ± DHEA, free testosterone (if hirsute)
 day 21-23: serum progesterone to confirm ovulation
 initiate basal body temperature monitoring (biphasic pattern)
 post-coital test (Sims-Huhner's Test) cervical mucus after 2-6hrs of intercourse to look
for present motile sperm
 • tubal factors
tubal factors
 HSG (can be therapeutic – opens fallopian tube)
 laparoscopy with dye insufflation
 • peritoneal/uterine factors
peritoneal/uterine factors
 HSG, hysteroscopy
 • other
other
karyotype
–Ultrasound scans  can detect the development
of the follicle and its collapse after ovulation. Vaginal
ultrasound scan gives a much clearer picture than the
abdominal scan. The follicle is usually ready for
ovulation when it measures 1.8 - 2.5 cm in diameter.
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%
Hysterosalpingogram
Hysterosalpingogram
The endometrial cavity
Smooth
Symmetrical
Fallopian tubes
Proximal 2/3 slender
Ampulla is dilated
Dye should spill promptly
–laparoscopy and dye test  is the golden standard method to check the Fallopian tubes.
– Most infertile couples require a diagnostic laparoscopy for complete evaluation of their
infertility.
Treatment of the Infertile Couple
Inadequate Spermatogenesis
Inadequate Spermatogenesis
Conservative management:
Conservative management:
Intercourse every 1-2 days during periovulatory period
(12-16)
Women advice to lie on her bake at least 15 min after
coitus prevent rapid loss of semen from vagina
Use non-toxic lubricant
Smoking should be reduced or stopped.
Eliminate alterations of thermoregulation
MALE INFERTILITY
MALE INFERTILITY
Clomiphene citrate is occasionally used for induction of
spermatogenesis (20% success)
Administration of bromocriptine for hyperprolactinemic
patient.
Injection of human menaposa gonadotropins (hMG) for
oligospermia and low motility of sperm.
In vitro fertilization may facilitate fertilization
Artificial insemination with donor sperm is often successful
Intracytoplasmic sperm injection
Anovulation
Anovulation
Restore ovulation
Administer ovulation inducing agents
Weight modulation — Ovulation dysfunction and subfertility may
occur in women who are far above or below ideal body weight
Clomiphene citrate
Anti-estrogen
Combines and blocks estrogen receptors at the
hypothalamus and pituitary causing a negative feedback
Used in the treatment of polycystic ovarian syndrome.
Contraindication hepatic disease, ovarian cysts, hormone
dependent tumours, abnormal uterine bleeding of
undetermined cause
Increases FSH production
stimulates the ovary to make follicles
Human menopause gonadotropin (hMG) (FSH &LH)
used for whom don't ovulate due to problems with the pituitary
gland, acts directly on the ovaries to stimulate ovulation.
Follicle-stimulating hormone (FSH) causes the ovaries to
begin the process of ovulation.
Gonadotropin-releasing hormone (Gn-RH) analog used
for whom don't ovulate regularly or ovulate before the egg is ready
Metformin use for PCOS, lower the levels of testosterone.
Bromocriptine for ovulation problems due to high levels of
prolactin.
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
Management of unexplained infertility
Management of unexplained infertility
The most efficient management is clomiphene citrate and
performance of intrauterine insemination (IUI).
 If this has not resulted in pregnancy, it appears most useful to
subsequently perform in vitro fertilization (IVF).
The administration of clomiphene citrate is intended to achieve
ovulation induction or ovarian hyperstimulation.
Human chorionic gonadotropin (hCG) is given to trigger
ovulation, and the intrauterine insemination is performed within 2
days of hCG administration.
Ovarian hyper stimulation syndrome
(OHSS):
Is a complication from some form of fertility medication
Causative medication: HCG used for inducing final oocyte
maturation
Clinical features of OHSS:
Prevention of OHSS:
Prevention of OHSS:
monitoring of FSH therapy to use this medication judiciously, and by
withholding hCG medication.
Regarding dopamine agonists as prophylaxis.
TREATMENT:
Mild:
Mild: conservative management with monitoring of abdominal girth,
weight, and discomfort on an outpatient basis until either conception or
menstruation occurs
Moderate
Moderate: bed rest, fluids, and close monitoring of labs such as
electrolytes and blood counts. Ultrasound may be used to monitor the size
of ovarian follicles
Aspiration of accumulated fluid
Aspiration of accumulated fluid
opioids for the pain
opioids for the pain
Assisted Reproductive Technologies
Assisted Reproductive Technologies
(ART)
(ART)
Theses technologies help provide infertile couples with tools to
bypass the normal mechanisms of gamete transportation.
ART  is a term that describes several different methods used
to help infertile couples. It involves removing eggs, mixing them
with sperm in the laboratory and putting the embryos back into a
woman's body.
Types of ART
Types of ART
 In vitro fertilization (IVF)  often used when a woman's fallopian tubes are
blocked or when a man produces too few sperm.
 Gamete intrafallopian transfer (GIFT) involves transferring eggs and sperm
into the woman's fallopian tube.
 Intracytoplasmic sperm injection (ICSI) is often used for couples in which
there are serious problems with the sperm, older couples, or for those with failed IVF
attempts. In ICSI, a single sperm is injected into a mature egg. Then the embryo is
transferred to the uterus or fallopian tube.
 Artificial insemination:
 is the deliberate introduction of semen into a female's vagina
It is the medical alternative to sexual intercourse, or natural insemination.
Techniques:
 Intracervical insemination
 Intrauterine insemination
 Intrauterine tuboperitoneal insemination
 Intratubal insemination
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.
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.
THANK YOU

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infertility-140601034142-phpapp02 2.pdf

  • 2. Case: Case:  A 33 years old Omani lady k/o primary infertility was present to the A&E with referral from private clinic .  She presented with sever lower abdominal pain from 3 days which get worse with time. It was colicky in nature, not radiating, and she can’t tolerated with it. There was history of abdominal distention, SOB, vomiting and diarrhea.  4 days before pt. underwent Intra cytoplasmic sperm injection (ICSI)  12-19/1/2013 : fertility medication used for inducing final oocyte maturation  Married for 6 years  2 years back, Intrauterine insemination (IUI) had been done in Muscat private hospital but failed.  She doesn’t have any thyroid problems, no abnormal weight gain or weight loss, no excessive hair growth.
  • 3. Menstrual History: Menstrual History:  Her menarche age is 15 years. Menstrual periods were irregular. The character of the flow is normal without clots. No inter menstrual bleeding .Her LMP was on 10/1/2013. Contraceptive History: She didn’t use any kind of contraception methods. Past obstetric history primary infertility
  • 4. Marital history Marital history  She is the first wife of her husband. She is married once. They sleep together normally with adequate frequency. She does not have any bleeding or dysuria with sexual intercourse.  Her husband is a 34 years old Omani man works as a office worker in the educational ministry. His health condition is good. He has no problems during intercourse and his work does not affect his relationships with his wife.  Previous medical & surgical History  Systemic review:(unremarkable)
  • 5.  Family history:  Related to her husband  Her father and mother are consanguinity.  Her father has DM & HTN.  Her sisters and brother had thyroid problems & under medication. Social history:  She is a teacher, living with her husband . She is not smoking or alcohol consumer. Unexplained primary infertility presenting with ovarian hyperstimulation syndrom
  • 7. Requirements for Conception Requirements for Conception Production of healthy egg and sperm egg and sperm Unblocked tubes Unblocked tubes that allow sperm to reach the egg The sperms ability to penetrate ability to penetrate and fertilize the egg Implantation Implantation of the embryo into the uterus Finally a healthy pregnancy
  • 8. Infertility Infertility The inability to conceive following unprotected sexual intercourse 1 year (age < 35) or 6 months (age >35) Affects 15% of reproductive couples Men and women equally affected
  • 9. Infertility Infertility Reproductive age for women: Reproductive age for women:  Generally 15-44 years 15-44 years of age  20% of women have their first child after age 30 1/3 of couples 1/3 of couples over 35 years have fertility problems:  Ovulation decreases  Health of the egg declines  Health problems develop With the proper treatment 85% of infertile couples can 85% of infertile couples can expect to have a child expect to have a child
  • 10. Infertility Infertility Primary infertility Primary infertility a couple that has never conceived Secondary infertility Secondary infertility infertility that occurs after previous pregnancy regardless of outcome
  • 11. Causes of Infertility Causes of Infertility Anovulation (10-20%) (10-20%) Anatomic defects of the female genital tract (30%) (30%) Abnormal spermatogenesis (40%) (40%) Unexplained (10%-20%) (10%-20%) Causes: Causes: Male causes Female causes Combined causes
  • 12. Male Factor Male Factor 40% of the cause for infertility Sperm is constantly produced by the germinal epithelium of Sperm is constantly produced by the germinal epithelium of the testicle 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 anti-sperm antibodies which interfere with the penetration of the cervical mucus
  • 15. A. Gonadotropin Deficiency (Kallmann Syndrome) failure of GnRH neurons to migrate GnRH neurons to migrate to the proper location in the hypothalamus. Kallmann syndrome Kallmann syndrome is associated with midline defects such as anosmia, cleft lip and cleft palate, deafness, cryptorchidism, and color blindness. Men can be fertile when given FSH and LH to stimulate given FSH and LH to stimulate sperm production sperm production. Virilization can be obtained with testosterone or human chorionic gonadotropin (hCG)
  • 16. –C. Isolated FSH Deficiency there is insufficient FSH production by the pituitary. Patients are normally virilized, as LH is present. FSH levels are low. Sperm counts range from azoospermia to severely low numbers (oligospermia). –D. Congenital Hypogonadotropic Syndromes Prader-Willi syndrome Bardet-Biedi syndrome.
  • 17. –A. Pituitary Insufficiency Pituitary insufficiency may result from tumors, infarcts, surgery, from tumors, infarcts, surgery, radiation, sickle cell radiation, sickle cell anemia. –B. Hyperprolactinemia –most common cause is prolactin-secreting pituitary adenoma. –Elevated prolactin results in decreased FSH, LH levels and Elevated prolactin results in decreased FSH, LH levels and causes infertility causes infertility. –Associated symptoms include loss of libido, impotence, include loss of libido, impotence, galactorrhea, and gynecomastia. galactorrhea, and gynecomastia. –C. Exogenous or Endogenous Hormones 1. Estrogens, GH, androgens, glucocorticoids, Hyper- and Estrogens, GH, androgens, glucocorticoids, Hyper- and hypothyroidism hypothyroidism
  • 19. Chromosomal Causes • Klinefelter syndrome (47,XXY) Klinefelter syndrome (47,XXY) – most common genetic reason for azoospermia. classic triad: small firm testes; gynecomastia; and azoospermia small firm testes; gynecomastia; and azoospermia. – XX Male Syndrome XX Male Syndrome – presents as gynecomastia at puberty or as azoospermia in gynecomastia at puberty or as azoospermia in adults adults. Average height is below normal, and hypospadias hypospadias is common. Male external and internal genitalia are otherwise normal. – XYY Syndrome XYY Syndrome – Typically, men with 47,XYY are tall. Semen analyses show either oligospermia or azoospermia.
  • 20. –Causes of Male infertility - Gonadotoxins Radiation Radiation : – Sertoli and germ cells are extremely radiosensitive. Drugs: Drugs:
  • 21. –Use of alcohol, cigarettes, caffeine, and marijuana may lead to testicular failure. –Chemotherapy: toxic to actively dividing cells The most toxic drugs are the alkylating agents such as cyclophosphamide. – Systemic Disease - Causes of Male infertility A.Renal Failure B. Liver Cirrhosis C. Sickle Cell Disease
  • 22. – Causes of Male infertility - Testis Injury Orchitis Orchitis – Inflammation of testis tissue is most commonly due to bacterial infection, termed epididymo-orchitis. Testicular Torsion Testicular Torsion : Ischemic injury to the testis secondary to twisting of the testis on the spermatic cord. Torsion may result in inoculation of the immune system with testis antigens that may predispose to later immunological infertility. Trauma Trauma Can invoke an abnormal immune response in addition to atrophy resulting from injury. Both may contribute to infertility.
  • 23. –Causes of Male infertility - Cryptorchidism –Males with either unilaterally or bilaterally undescended testes are at risk for infertility later in life. Prophylactic orchidopexy is generally performed by 2 years of age –Varicocele –A varicocele is defined as dilated and tortuous veins within the pampiniform plexus of scrotal veins. –Increased intratesticular temperature, reflux of toxic metabolites – –Idiopathic –at least 25%-50% of male infertility has no identifiable cause
  • 25. –Posttesticular Causes of Male infertility –The posttesticular portion of the reproductive tract includes the epididymis, vas deferens, seminal vesicles, and associated epididymis, vas deferens, seminal vesicles, and associated ejaculatory apparatus ejaculatory apparatus –1. Cystic fibrosis - –98% of men with CF having missing parts of the epididymis. In addition, the vas deferens, seminal vesicles, and ejaculatory ducts are usually atrophic, or completely absent –2.Bacterial infections - Bacterial infections (E coli in men age > 35) or Chlamydia trachomatis in young men) may involve the epididymis, with scarring and obstruction.
  • 26. –Retrograde ejaculation: –This is caused by an open bladder neck during ejaculation. –Retrograde ejaculation may be due to causes such as diabetes, bladder neck surgery, TURP, colon or rectal surgery, diabetes, bladder neck surgery, TURP, colon or rectal surgery, multiple sclerosis, or spinal cord injury. multiple sclerosis, or spinal cord injury. –Diagnosis is made by observing 10-15 sperm per high- power field (HPF) in the postejaculatory urine.
  • 27. –Disorders of Sperm Function or Motility A. Immotile Cilia Syndromes –B. Immunologic Infertility Autoimmune infertility has been implicated as a cause of infertility in 10% of 10% of infertile couples.. infertile couples.. – Autoimmune infertility may result from an abnormal exposure to sperm antigens after, for example, Vasectomy, testis torsion, or biopsy, which then a pathologic Vasectomy, testis torsion, or biopsy, which then a pathologic immune response. immune response. –Antibodies disturb sperm transport or normal sperm-egg interaction. –Antibodies may cause agglutination of sperm, which inhibits passage, – or may block normal sperm binding to the oocyte
  • 29. –Disorders of Coitus - Causes of Male infertility A. Impotence B. Sexual issues. – Often treatable, problems with sexual intercourse Difficulties with erection of the penis (erectile dysfunction), premature ejaculation, painful intercourse (dyspareunia), or psychological or relationship problems can contribute to infertility. Use of lubricants such as oils or petroleum jelly can be toxic to sperm and impair fertility. –C. Hypospadias May not place the semen at the cervical os. –D. Timing and Frequency Simple problems of coital timing and frequency can be corrected by a review of the couple’s sexual habits. An appropriate frequency of intercourse is every 2 days, performed within the periovulatory period.
  • 30. Components Components of of the the infertility infertility history history. Fertility history Fertility history  Previous pregnancies (present and with other partners)  Duration of infertility  Previous infertility treatments  Female evaluation Sexual history Sexual history  Erections  Timing and frequency  Lubricants Medical history Medical history  Fevers  Systemic illness—diabetes, cancer, infection  Genetic diseases—cystic fibrosis, Klinefelter syndrome
  • 31. Surgical history Surgical history Orchidopexy, cryptorchidism Herniorraphy Trauma, torsion Pelvic, bladder, or retroperitoneal surgery Transurethral resection for prostatism Pubertal onset Medication history Medication history Nitrofurantoin Cimetidine Sulfasalazine Spironolactone Alpha blockers
  • 32. Family history Family history Cryptorchidism Midline defects (Kartagener syndrome) Hypospadias Social history Social history Ethanol Smoking/tobacco Cocaine Anabolic steroids Occupational history Occupational history Exposure to ionizing radiation Chronic heat exposure Pesticides Heavy metals (lead)
  • 33. Laboratory Diagnosis of Male Infertility Laboratory Diagnosis of Male Infertility Urinalysis Urinalysis It may indicate the presence of infection, hematuria, glucosuria, or renal disease, and suggest anatomic or medical problems within the urinary tract Semen Analysis Semen Analysis •A normal semen analysis excludes male factor 90% of the time
  • 34. 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
  • 35. Abnormal Semen Analysis Abnormal Semen Analysis Azospermia Azospermia Klinefelter’s (1 in 500) Hypogonadotropic- hypogonadism Ductal obstruction (absence of the Vas deferens) Oligospermia Oligospermia Anatomic defects Endocrinopathies Genetic factors Exogenous (e.g. heat)
  • 36. Cont. causes for abnormal SA Cont. causes for abnormal SA Abnormal Morphology Abnormal Morphology Varicocele Stress Infection (mumps) Abnormal Motility Abnormal Motility Immunologic factors Infection Defect in sperm structure Poor liquefaction Varicocele Abnormal Volume 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
  • 37. Hormone Assessment : Hormone Assessment : A routine part of the initial evaluation is testing of specific serum hormone levels, which usually includes FSH, LH, testosterone, and prolactin.
  • 38. Adjunctive Tests Adjunctive Tests: :  Semen Leukocyte Analysis  Antisperm Antibody Test  Hypoosmotic Swelling Test  Sperm Penetration Assay  Sperm-Cervical Mucus Interaction  Chromosomal Studies  Cystic Fibrosis Mutation Testing  Y Chromosome Microdeletion Analysis  Radiologic Testing  Testis Biopsy & Vasography  Fine-Needle Aspiration "Mapping" of Testes  Semen Culture
  • 40. Menstruation Menstruation Ovulation occurs 13-14 times per year 13-14 times per year Menstrual cycles on average are 28 days are 28 days with ovulation around day 14 Luteal phase  dominated by the secretion of progesterone dominated by the secretion of progesterone  released by the corpus luteum released by the corpus luteum Progesterone causes  Thickening of the endocervical mucus Thickening of the endocervical mucus  Increases the basal body temperature (0.6° F) Increases the basal body temperature (0.6° F) Involution of the corpus luteum causes a fall in progesterone and the onset of menses
  • 41. 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 mild peripheral edema  slight weight gain  depression
  • 42. Diagnostic studies to confirm Ovulation Diagnostic studies to confirm Ovulation Basal body temperature Basal body temperature Inexpensive Accurate Endometrial biopsy Endometrial biopsy Expensive Static information Serum progesterone Serum progesterone After ovulation rises Can be measured Urinary ovulation- Urinary ovulation- detection kits detection kits Measures changes in urinary LH Predicts ovulation but does not confirm it
  • 43. Basal Body Temperature Basal Body Temperature Excellent screening tool for ovulation Excellent screening tool for ovulation Biphasic shift occurs in 90% of ovulating women Temperature 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
  • 45. Serum Progesterone Serum Progesterone Progesterone starts rising with the LH surge drawn between day 21-24 Mid-luteal phase >10 ng/ml suggests ovulation
  • 48. Ovulatory Dysfunction (15-20%): Ovulatory Dysfunction (15-20%): hypothalamic hypothalamic (hypothalamic amenorrhea) ƒpituitary pituitary (prolactinoma, hypopituitarism) ƒovarian: ƒovarian: PCOS ƒpremature ovarian failure ƒsystemic diseases: ƒsystemic diseases: thyroid, Cushing’s syndrome, renal/hepatic failure ƒcongenital: congenital: Turner’s syndrome, gonadal dysgenesis or gonadotropin deficiency ƒstress, poor nutrition, excessive exercise stress, poor nutrition, excessive exercise
  • 49. outflow tract abnormality outflow tract abnormality  ƒTubal factors (20-30%): Tubal factors (20-30%): PID adhesions (previous surgery, peritonitis, endometriosis) ligation/occlusion (e.g. previous ectopic pregnancy)  ƒ ƒCervical factors (5%): Cervical factors (5%): hostile or acidic cervical mucus anti-sperm antibodies structural defects ƒUterine factors (<5%): ƒUterine factors (<5%): congenital anomalies (e.g. prenatal DES exposure), bicornuate uterus, uterine septum intrauterine adhesions (e.g. Asherman’s syndrome) infection (endometritis, pelvic TB) fibroids/polyps (particularly intrauterine) endometrial ablation
  • 50. Sperm transport, Fertilization, & Sperm transport, Fertilization, & Implantation Implantation The female genital tract is not just a passage: The female genital tract is not just a passage: facilitates sperm transport cervical mucus traps the coagulated ejaculate the fallopian tube picks up the egg Fertilization must occur in the proximal portion of Fertilization must occur in the proximal portion of the tube 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 Implants into the secretory endometrium for growth and development and development
  • 52. Anovulation Anovulation Symptoms Evaluation 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
  • 53. Investigations: Investigations: ovulatory ovulatory  day 3: FSH, LH, TSH, PRL ± DHEA, free testosterone (if hirsute)  day 21-23: serum progesterone to confirm ovulation  initiate basal body temperature monitoring (biphasic pattern)  post-coital test (Sims-Huhner's Test) cervical mucus after 2-6hrs of intercourse to look for present motile sperm  • tubal factors tubal factors  HSG (can be therapeutic – opens fallopian tube)  laparoscopy with dye insufflation  • peritoneal/uterine factors peritoneal/uterine factors  HSG, hysteroscopy  • other other karyotype –Ultrasound scans  can detect the development of the follicle and its collapse after ovulation. Vaginal ultrasound scan gives a much clearer picture than the abdominal scan. The follicle is usually ready for ovulation when it measures 1.8 - 2.5 cm in diameter.
  • 54. 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%
  • 55. Hysterosalpingogram Hysterosalpingogram The endometrial cavity Smooth Symmetrical Fallopian tubes Proximal 2/3 slender Ampulla is dilated Dye should spill promptly –laparoscopy and dye test  is the golden standard method to check the Fallopian tubes. – Most infertile couples require a diagnostic laparoscopy for complete evaluation of their infertility.
  • 56. Treatment of the Infertile Couple
  • 57. Inadequate Spermatogenesis Inadequate Spermatogenesis Conservative management: Conservative management: Intercourse every 1-2 days during periovulatory period (12-16) Women advice to lie on her bake at least 15 min after coitus prevent rapid loss of semen from vagina Use non-toxic lubricant Smoking should be reduced or stopped. Eliminate alterations of thermoregulation
  • 58. MALE INFERTILITY MALE INFERTILITY Clomiphene citrate is occasionally used for induction of spermatogenesis (20% success) Administration of bromocriptine for hyperprolactinemic patient. Injection of human menaposa gonadotropins (hMG) for oligospermia and low motility of sperm. In vitro fertilization may facilitate fertilization Artificial insemination with donor sperm is often successful Intracytoplasmic sperm injection
  • 59. Anovulation Anovulation Restore ovulation Administer ovulation inducing agents Weight modulation — Ovulation dysfunction and subfertility may occur in women who are far above or below ideal body weight Clomiphene citrate Anti-estrogen Combines and blocks estrogen receptors at the hypothalamus and pituitary causing a negative feedback Used in the treatment of polycystic ovarian syndrome. Contraindication hepatic disease, ovarian cysts, hormone dependent tumours, abnormal uterine bleeding of undetermined cause Increases FSH production stimulates the ovary to make follicles
  • 60. Human menopause gonadotropin (hMG) (FSH &LH) used for whom don't ovulate due to problems with the pituitary gland, acts directly on the ovaries to stimulate ovulation. Follicle-stimulating hormone (FSH) causes the ovaries to begin the process of ovulation. Gonadotropin-releasing hormone (Gn-RH) analog used for whom don't ovulate regularly or ovulate before the egg is ready Metformin use for PCOS, lower the levels of testosterone. Bromocriptine for ovulation problems due to high levels of prolactin.
  • 61. 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
  • 62. Management of unexplained infertility Management of unexplained infertility The most efficient management is clomiphene citrate and performance of intrauterine insemination (IUI).  If this has not resulted in pregnancy, it appears most useful to subsequently perform in vitro fertilization (IVF). The administration of clomiphene citrate is intended to achieve ovulation induction or ovarian hyperstimulation. Human chorionic gonadotropin (hCG) is given to trigger ovulation, and the intrauterine insemination is performed within 2 days of hCG administration.
  • 63. Ovarian hyper stimulation syndrome (OHSS): Is a complication from some form of fertility medication Causative medication: HCG used for inducing final oocyte maturation
  • 65. Prevention of OHSS: Prevention of OHSS: monitoring of FSH therapy to use this medication judiciously, and by withholding hCG medication. Regarding dopamine agonists as prophylaxis. TREATMENT: Mild: Mild: conservative management with monitoring of abdominal girth, weight, and discomfort on an outpatient basis until either conception or menstruation occurs Moderate Moderate: bed rest, fluids, and close monitoring of labs such as electrolytes and blood counts. Ultrasound may be used to monitor the size of ovarian follicles Aspiration of accumulated fluid Aspiration of accumulated fluid opioids for the pain opioids for the pain
  • 66. Assisted Reproductive Technologies Assisted Reproductive Technologies (ART) (ART) Theses technologies help provide infertile couples with tools to bypass the normal mechanisms of gamete transportation. ART  is a term that describes several different methods used to help infertile couples. It involves removing eggs, mixing them with sperm in the laboratory and putting the embryos back into a woman's body.
  • 67. Types of ART Types of ART  In vitro fertilization (IVF)  often used when a woman's fallopian tubes are blocked or when a man produces too few sperm.  Gamete intrafallopian transfer (GIFT) involves transferring eggs and sperm into the woman's fallopian tube.  Intracytoplasmic sperm injection (ICSI) is often used for couples in which there are serious problems with the sperm, older couples, or for those with failed IVF attempts. In ICSI, a single sperm is injected into a mature egg. Then the embryo is transferred to the uterus or fallopian tube.  Artificial insemination:  is the deliberate introduction of semen into a female's vagina It is the medical alternative to sexual intercourse, or natural insemination. Techniques:  Intracervical insemination  Intrauterine insemination  Intrauterine tuboperitoneal insemination  Intratubal insemination
  • 68. 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. It is important to address the emotional needs of these patients.
  • 69. 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.