approach to infertility

1. Al-YaqdhanAl-Atbi
81559
InfertIlItyInfertIlIty

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 historyMarital 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

6. INFERTILITY

7. Requirements for ConceptionRequirements for Conception
Production of healthy egg and spermegg and sperm
Unblocked tubesUnblocked tubes that allow sperm to reach the egg
The sperms ability to penetrateability to penetrate and fertilize the egg
ImplantationImplantation of the embryo into the uterus
Finally a healthy pregnancy

8. InfertilityInfertility
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. InfertilityInfertility
Reproductive age for women:Reproductive age for women:
 Generally 15-44 years15-44 years of age
 20% of women have their first child after age 30
1/3 of couples1/3 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 can85% of infertile couples can
expect to have a childexpect to have a child

10. InfertilityInfertility
Primary infertilityPrimary infertility
a couple that has never conceived
Secondary infertilitySecondary infertility
infertility that occurs after previous pregnancy regardless of outcome

11. Causes of InfertilityCauses 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 FactorMale Factor
40% of the cause for infertility
Sperm is constantly produced by the germinal epithelium ofSperm is constantly produced by the germinal epithelium of
the testiclethe testicle
Sperm generation time 73 days
Sperm production is thermoregulated
1° F less than body temperature
Both men and women can produce anti-sperm antibodiesanti-sperm antibodies
which interfere with the penetration of the cervical mucus

13. MALE FACTORSMALE FACTORS

15. A. Gonadotropin Deficiency (Kallmann Syndrome)
failure of GnRH neurons to migrateGnRH neurons to migrate to the proper
location in the hypothalamus.
Kallmann syndromeKallmann 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 stimulategiven FSH and LH to stimulate
sperm productionsperm 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 cellradiation, sickle cell anemia.
–B. Hyperprolactinemia
–most common cause is prolactin-secreting pituitary adenoma.
–Elevated prolactin results in decreased FSH, LH levels andElevated prolactin results in decreased FSH, LH levels and
causes infertilitycauses 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- andEstrogens, GH, androgens, glucocorticoids, Hyper- and
hypothyroidismhypothyroidism

19. Chromosomal Causes
• Klinefelter syndrome (47,XXY)Klinefelter syndrome (47,XXY)
– most common genetic reason for azoospermia. classic triad:
small firm testes; gynecomastia; and azoospermiasmall firm testes; gynecomastia; and azoospermia.
– XX Male SyndromeXX Male Syndrome
– presents as gynecomastia at puberty or as azoospermia ingynecomastia at puberty or as azoospermia in
adultsadults. Average height is below normal, and hypospadiashypospadias is
common. Male external and internal genitalia are otherwise normal.
– XYY SyndromeXYY Syndrome
– Typically, men with 47,XYY are tall. Semen analyses show either
oligospermia or azoospermia.

20. –Causes of Male infertility - Gonadotoxins
RadiationRadiation :
– 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
OrchitisOrchitis
– Inflammation of testis tissue is most commonly due to bacterial
infection, termed epididymo-orchitis.
Testicular TorsionTesticular 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.
TraumaTrauma
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 associatedepididymis, vas deferens, seminal vesicles, and associated
ejaculatory apparatusejaculatory 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% of10% 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 pathologicVasectomy, 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

28. –C. Infection

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. ComponentsComponents ofof thethe infertilityinfertility historyhistory.
Fertility historyFertility history
 Previous pregnancies (present and with other partners)
 Duration of infertility
 Previous infertility treatments
 Female evaluation
Sexual historySexual history
 Erections
 Timing and frequency
 Lubricants
Medical historyMedical history
 Fevers
 Systemic illness—diabetes, cancer, infection
 Genetic diseases—cystic fibrosis, Klinefelter syndrome

31. Surgical historySurgical history
Orchidopexy, cryptorchidism
Herniorraphy
Trauma, torsion
Pelvic, bladder, or retroperitoneal surgery
Transurethral resection for prostatism
Pubertal onset
Medication historyMedication history
Nitrofurantoin
Cimetidine
Sulfasalazine
Spironolactone
Alpha blockers

32. Family historyFamily history
Cryptorchidism
Midline defects
(Kartagener syndrome)
Hypospadias
Social historySocial history
Ethanol
Smoking/tobacco
Cocaine
Anabolic steroids
Occupational historyOccupational history
Exposure to ionizing radiation
Chronic heat exposure
Pesticides
Heavy metals (lead)

33. Laboratory Diagnosis of Male InfertilityLaboratory Diagnosis of Male Infertility
UrinalysisUrinalysis
It may indicate the presence of infection, hematuria, glucosuria, or renal
disease, and suggest anatomic or medical problems within the urinary tract
Semen AnalysisSemen 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 AnalysisAbnormal Semen Analysis
AzospermiaAzospermia
Klinefelter’s (1 in 500)
Hypogonadotropic-
hypogonadism
Ductal obstruction
(absence of the Vas
deferens)
OligospermiaOligospermia
Anatomic defects
Endocrinopathies
Genetic factors
Exogenous (e.g. heat)

36. Cont. causes for abnormal SACont. causes for abnormal SA
Abnormal MorphologyAbnormal Morphology
Varicocele
Stress
Infection (mumps)
Abnormal MotilityAbnormal Motility
Immunologic factors
Infection
Defect in sperm structure
Poor liquefaction
Varicocele
Abnormal VolumeAbnormal 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 TestsAdjunctive 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

39. FEMALE FACTORSFEMALE FACTORS

40. MenstruationMenstruation
Ovulation occurs 13-14 times per year13-14 times per year
Menstrual cycles on average are 28 daysare 28 days with ovulation around day 14
Luteal phase
 dominated by the secretion of progesteronedominated by the secretion of progesterone
 released by the corpus luteumreleased by the corpus luteum
Progesterone causes
 Thickening of the endocervical mucusThickening 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. OvulationOvulation
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 OvulationDiagnostic studies to confirm Ovulation
Basal body temperatureBasal body temperature
Inexpensive
Accurate
Endometrial biopsyEndometrial biopsy
Expensive
Static information
Serum progesteroneSerum progesterone
After ovulation rises
Can be measured
Urinary ovulation-Urinary ovulation-
detection kitsdetection kits
Measures changes in urinary
LH
Predicts ovulation but does
not confirm it

43. Basal Body TemperatureBasal Body Temperature
Excellent screening tool for ovulationExcellent screening tool for ovulation
Biphasic shift occurs in 90% of ovulating women
TemperatureTemperature
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 ProgesteroneSerum Progesterone
Progesterone starts rising with the LH surge
drawn between day 21-24
Mid-luteal phase
>10 ng/ml suggests ovulation

46. FEMALE FACTORSFEMALE FACTORS

47. –endometriosis (15-30%)
–multiple factors (30%)

48. Ovulatory Dysfunction (15-20%):Ovulatory Dysfunction (15-20%):
hypothalamichypothalamic (hypothalamic amenorrhea)
ƒpituitarypituitary (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 exercisestress, poor nutrition, excessive exercise

49. outflow tract abnormalityoutflow tract abnormality
 ƒTubal factors (20-30%):Tubal factors (20-30%):
PID
adhesions (previous surgery, peritonitis, endometriosis)
ligation/occlusion (e.g. previous ectopic pregnancy)
 ƒƒCervical 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, &
ImplantationImplantation
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 ofFertilization must occur in the proximal portion of
the tubethe tube
the fertilized oocyte cleaves and forms a zygote
enters the endometrial cavity at 3 to 5 days
Implants into the secretory endometrium for growthImplants into the secretory endometrium for growth
and developmentand development

51. Congenital Anatomic AbnormalitiesCongenital Anatomic Abnormalities

52. AnovulationAnovulation
Symptoms EvaluationSymptoms 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:
ovulatoryovulatory
 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 factorstubal factors
 HSG (can be therapeutic – opens fallopian tube)
 laparoscopy with dye insufflation
 • peritoneal/uterine factorsperitoneal/uterine factors
 HSG, hysteroscopy
 • otherother
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. HysterosalpingogramHysterosalpingogram
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. HysterosalpingogramHysterosalpingogram
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 SpermatogenesisInadequate 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 INFERTILITYMALE 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. AnovulationAnovulation
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 AbnormalitiesAnatomic 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 infertilityManagement 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

64. Clinical features of OHSS:

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
ModerateModerate: 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 fluidAspiration of accumulated fluid
opioids for the painopioids for the pain

66. Assisted Reproductive TechnologiesAssisted 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 ARTTypes 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 ImpactEmotional 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. ConclusionConclusion
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.

70. THANK YOU