Infertility.pptx

Outline
• Definition
• Causes
• Evaluation
– Hx
– PE
– Workup
• Treatment
2
ሳሙኤል በዛብህ ህዳር 2006 ጎንደር

Definitions
• Infertility
• Subfertility
• Fecundity
• Fecundablity
• Sterility
ሳሙኤል በዛብህ ህዳር 2006 ጎንደር 3

DEFINITIONS
INFERTILITY- the inability to conceive after 1 year of
unprotected intercourse of reasonable frequency .
• affects 10 to 15% of reproductive-aged couples.
– primary infertility-no prior pregnancies, and
– secondary infertility-infertility following at least one prior
conception.
– 1/3rd of time attributed to the male , another 1/3rd to the
Female, 1/3rd to both
• Most couples will ultimately conceive if given enough
time.  SUBFERTILE, rather than infertile
– This concept of subfertility can be reassuring to couples
• In those attempting conception, approximately
– 50 % of women will be pregnant at 3 months,
– 75% will be pregnant at 6 months, and
– > 85% will be pregnant by 1 year (Guttmacher, 1956; Mosher, 1991).
4

DEFINITIONS
FECUNDABILITY is the ability to conceive,
– data from large population studies have shown a
monthly probability of conceiving of 20 to 25 %.
Fecundity - the probability that a single
menstural cycle will result in a live birth
STERILITY: incapablity to become / be
induced to become pregnant or to induce
pregnancy
5

Etiology
Female infertility
Ovulatory Dysfunction
Tubal /Peritoneal Factor
Uterine Factor
Cervical Factors
Vaginal Factors
Chronic systemic
diseases
Social personal
habit(illicit drugs)
Unexplained
Male factors
Pre-testicular
Testicular
Post-testicular
Idiopathic
6

Etiology of Infertility
• Male factor-------25%
• Ovulatory----------27%
• Tubal/ uterine----22%
• Other---------------9%
• Unexplained------17%
7

• Hypothalamic Disorders
• Anterior pitutary disorders
• Ovarian Abnormalities
– Premature Ovarian Failure (POF)
– Androgen excess
• Polycystic ovarian syndrome
• Nonclassic congenital adrenal hyperplasia
• Androgen-secreting tumors NMS
– Decreased ovarian reserve ( often age related)
8

WHO clasification of anovulatory disorders
Group I-
• Hypogonadotropic Hypogonadism
/ Hypoth. amenorrhea/ H-P failure
• Low GnRH/ Unresponsive Pitutary
Low FSH & E level, normal
prolactin level
• Stress, eating disorders, kallman S.
• Excludes women with P, H masses
GROUP II- PCOS
Normogtrotpic Normoestrogenic
anovulation/ H-P Dysfunction
Normal gonadotropin ( ~low follicular
Phase FSH), E, Prolactin level
Oligo/amenorrhoea, some may
occasionally ovulate
GROUP III Hypergonadotropic-
Hypoestrogenic anovulation
• Premature OF absence of follicles
b/se of early menopause
• Ovarian Resistance ( follicular form)
• Amenorrhoea + elevated FSH level
Hyperprolactinemic Anovulation
(Distinct entity)
• Elevated PRL inhibition of G and E
secretion
• Amenorrhoeic/
Oligomenorrhoeic/regular
anovulatory cycles
• Usually normal seum Gtropin level
9

ሀ፡Hypothalamic Disorders
result in Hypogonadotropic Hypogonadism
– Acquired-
• eating disorders,
• stress or
• extreme exercise
– Inherited-
• Kallmans Syndrome/ idiopathic hypothalamic
hypogonadism
10

OVULATORY DYSFUNCTION
ለ: Anterior Pitutary Disorders
Result in Hypogonadotropic hypogonadism
– Adenomas –
• most commonly prolactinomas
• Others that may compress gonadotropes or anterior P stalk
– Destruction by infiltrating tumors, sarcoidosis, TB,
inflammation
• Hyperprolactinemia
– Medications (many medication classes, including
antipsychotics that are dopamine receptor antagonists; a
typical example is haloperidol)
– Pituitary tumors
– Hypothyroidism (Increased thyrotropin-releasing hormone
[TRH] secretion stimulates prolactin secretion.) NMS
11

ሐ: Ovarian abnormalities-
Premature Ovarian Failure (POF)- loss of ovarian
function before 40
• At 35 1/ 250 at 40 1/ 100 woman
POF results in Hypergonadotropic
Hypogonadism
– ↑ LH, FSH, ↓ E, P
– menst irregularity,amenorrhoea,
– Symptoms of Hypoestroginism-hot flashes,
genital atrophy
– Family history of POF, up to 10% of cases of POF
may be familial.
12

POF causes
• Chromosomal
– 45X0 (Turner’s Syndrome)
– Mosaicism ( 45X/46XX, 45X/ 46XY)
– 46XX with defective X chromosome
 long arm deletion, Partial X chr Deletion, Fragile X chromosome
syndrome, ---
– Gondal agenesis 46XX
– Gonadal dysgenesis 46XY
• Other POF causes
– Autoimmunity, Infection,
– Iatrogenic chemo/radiotherapy, surgical removal of ovaries
– Resistant ovary syndrome
– Enzyme deficiencies ( 17 alpha OH, aromatase)
– Galactosemia ( toxic to oogonia)
– Idiopathic 13

Habits
– Smoking
• accelerated follicle depletion + mutation in gametes (and early
embryos)
– Alcohol
• heavy alcohol intake decreases fertility in women
• Based on a number of studies, 5 to 8 drinks per week negatively
impacts female fertility
– MALE-heavy alcohol intake has been associated with a
decrease in sperm counts and increase in sexual
dysfunction in men
– Caffein- increased dose response r/nship b/n Caffein and
infertility and miscarriage
– illicit drugs
14

Age related Infertility (Depletion of O reserve)
• Advancing age loss of viable oocytes ( depletion of
ovarian reserve + genetic abnormality in the remaining
like mitochondrial deletions ) decreased fertility/
increased misscarriage/Infertility
– Miscarriage risk at> 40yrs ~ 50-75%
• No of follicles
– 7million at mid gestation
– 3m at birth
– 300,000at puberty
– < 1000 at onset of menopause

Female Aging and Infertility
Female Age (years) Infertility
• 20–29 8.0%
• 30–34 14.6%
• 35–39 21.9%
• 40–44 28.7%

TUBAL + PERITONEAL FACTORS
• Pelvic adhesion and/ tubal obstruction
• Manifest with chronic pelvic pain and
dysmenorrhoea
• Interfer with tubal motility, ovum pick up and
transport of fertilized ovum
• RFs
– Hx of Pelvic infections/PID
– Hx of ectopic pregnancy- tubal damage even with
medical treatment
– Hx pelvic surgery- residual adhesions are inevitable
– Emdometriosis -chronic bleeding and inflammation
tubal obstruction or pelvic adhesion
17

UTERINE FACTORS
Congenital Anomalies
• In general, developmental uterine anomalies are
not causative for infertility, but may be associated
with miscarriage or later fetal loss, creating a
management dilemma
Acquired Abnormalities
– Endometrial Polyps-3-5% of women
• Intermenstrual and postcoital bleeding
– Leiomyomas- implantation
– Ashermans Syndrome/ synechae
18

CERVICAL FACTORS
• The cervical glands secrete mucus that is normally
thick and impervious to sperm and ascending
infections.
• High estrogen levels at midcycle change the
characteristics of this mucus, and it becomes thin,
copious, clear and stretchy (5cm)  SPINNBARKEIT.
Estrogen-primed cervical mucus:
– filters out non sperm components of semen and
– forms channels that help direct sperm into the uterus
– also creates a reservoir for sperm, allowing ongoing
release during the next 24 to 72 hours and extending the
potential time for fertilization . 19

Cervical Factor
• Mucus inadequacy/ hostile mucus
– Chronic infection,
– cervical surgery Eg Chryotherapy, LEEP, Conization
– anti E rx ( Chlomiphe Citrate for OI),
– Sperm antibodies
– Unexplained ( most)

EVALUATION OF PATIENT

Evaluation
• The infertility evaluation can be conceptually
simplified into confirmation of:
1. ovulation,
2. normal female reproductive tract anatomy, and
3. normal semen characteristics.
23

Evaluation
• Timing
– After an attempt to conceive for one year
– Earlier initiation ( as soon as possible) of evaluation is
recommended for
• those with Hx PID or pelvic surgery
• anovulatory woman (with irregular or absent menses)
• old age (>35-40),
• heavy smokers or in women with a history of ovarian
surgery, chemotherapy, or pelvic irradiation
• stigmata of chromosomal abnormalities(eg turners
syndrome) or
• a significant history in the male partner
24

Female History
GYNECOLOGIC
• Duration of infertility, 10 Vs 20 infertility
• Menstrual history-
– Frequency, duration, recent changes in pattern, dysmenorrhoea, hot
flashes
• Coital HX
– Frequency , dyspareunea (? Endometriosis)
• Prior use of contraceptives
• Hx of recurrent ovarian cysts, endometriosis, leiomyoma, STI/ PID
• Prior conception ( tubal patency and ovulation HX)
• Pregnancy complications
– eg. miscarriage, EP, preterm delivery, retained placenta, postpartD & C,
chorioamnionitis or fetal anomalies should be noted
• Abnormal pap smears + cervical conization abnormal cervical
mucus + cervical incompetence
25

Female History
Gynecologic Hx.
Menstrual Pattern- ovulation is likely with
– cyclic menses Q 25-35 days, 3-7 days duration
– MITTELSCHMERZ,
• midcycle pelvic pain associated with ovulation
– MOLIMINAL SYMPTOMS
• breast tenderness, acne, food cravings, and mood changes
– DYSMENORRHEA,
• Ovulatory cycles are more likely to be associated with
dysmenorrhea, although severe dysmenorrhea may suggest
the presence of endometriosis
26

Female History
Medical
– Symptoms of hyperprolactinemia, hypothyroidism,
Kallmans s
– Symptoms of androgen excess
• Eg hirsuitism, acne PCO, CAH
– Prior chemo / and radiotherapy  ovarian failure
– Medications Eg.
• NSAIDS ( ovulation inhibition  luteinized unruptured follicle
syndrome
• antipsychotics ( phenothyazines??block dopamine Rs
↑PRL
• MAOs ↓catecholamines↑PRLannovulation +
amenorrhoea
SURGICAL
– History of pelvic and abdominal surgery pelvic
adhesion, tubal blockage, Intraux adhesion 27

Female History
SOCIAL
• Eating habits ( AN , BN) ,exercise and stress
–  hypothalamic functional amrnorrhoea + anovulation
– BMI <17 & >25 associated with GnRH and gonadotropin
secretion Abnormalities
• Smoking
– accelerated follicle depletion + mutation in gametes (and
early embryos)
– High failure rate of ART
– Increased miscarriage + trisomy 21
• Alcohol
– heavy alcohol intake decreases fertility in women
• Based on a number of studies, 5 to 8 drinks per week negatively
impacts female fertility
– heavy alcohol intake has been associated with a decrease
in sperm counts and increase in sexual dysfunction in men
28

Female History-SOCIAL CONTD
• CAFFEIN
– 1cup of coffee ~ 115 mg caffein
– Caffeine consumption has also been linked to
decreased fecundability.
– Most studies suggest that consumption of > 250 mg
caffein per day by the female partner is associated
with a modest, but statistically significant, decrease
in fertility and increase in time to conception.
– Caffeine intake greater than 500 mg per day has also
been demonstrated to increase recurrent miscarriage
rates
29

Female History-SOCIAL CONTD
Illicit drugs may also impact fecundability.
– Marijuana suppresses the H-P- gonadal axis in both men
and women, and
– cocaine can impair spermatogenesis
Env’tal Exposures
• Heavy metals and Pesticides should also be avoided,
may decrease fertility rates as well as increase the risk
of recurrent miscarriage (Orejuela, 1998).
• Although uncommon, fecundability is reduced with
occupational exposure to the dry cleaning fluid
Perchloroethylene, and to Toluene used in the printing
business.
30

Female History
FAMILY HISTORY
• of infertility, POF, recurrent miscarriage, or
fetal anomalies may point to a genetic
etiology.
• Although the inheritance pattern is complex,
data suggest that both PCOS and
endometriosis occur in familial clusters
– For example, it has been estimated that a woman
carries a sevenfold increased risk of endometriosis
over the general population if a single first-degree
family member has the disease
31

Obesity and Environmental Factors Vs Fertility

Female PE
• Vital signs, height, and weight
– BMI <17 & >25 associated with GnRH and gonadotropin
secretion Abnormalities
• Hirsutism, alopecia, or acne indicates the need to
measure androgen levels.
• Acanthosis nigricans is consistent with insulin
resistance associated PCOS or much less commonly,
Cushing syndrome.
• Galactorrhea- Hyperprolactinemia
• Skin Hyperpgmentation~~ adrenal insufficiency
• Stigmata of Turners syndrome- short sture, schield
chest
• thyroid abnormalities- Goitre~~Aimmune
Thyroiditis
33

Female PE
A PELVIC EXAM
• Inability to place a speculum through the
introitus may raise doubts about coital frequency.
• Estrogen Adequacy- moist and rugated vagina,
and a reasonable amount of cervical mucus ,
– Hypoestrogenism-atrophic vaginitis
• uterus-
– enlarged or irregularly shaped uterus ~ leiomyomas,
– fixed uterus ~ presence of pelvic scarring due to
endometriosis or prior pelvic infection.
– Uterosacral nodularity or ovarian masses may
additionally implicate endometriosis.
34

Female PE
NB
– All women should have a normal Pap smear result
within the year preceding treatment.
– cultures for Neisseria gonorrhoeae and Chlamydia
trachomatis should be Negative --> to avoid
ascending infection on cervical manipulation .
• Breast- bilateral discharge galactorrhoea
due to hyperprolactinemia
35

Laboratory
• The initial laboratory tests to consider for the
female partner include
– CBC, blood type and antibody screen,
– cervical cytology,
– TSH , serum prolactin
– routine prenatal labs including rubella
antibodies,HBSAG , HIV and rapid plasma
reagent (RPR).
36

Summary of Workup
• Ovulatory dysfunction
– Serum midluteal progesterone
– Ovulation predictor kit
– Early follicular FSH ± estradiol level (ovarian reserve)
– + Serum AMH level
– ± Serum measurements (TSH, prolactin, androgens)
– ± Ovarian sonography
• Follicle Dvt & collapseovulation
• Early F antral follicle count- < 10 ↓ ovarian
reserve↓response for gonadotropin stimulation
• PCOS
– ± Basal body temperature chart
– ± Endometrial biopsy (luteal phase defect)???
37

contd.
Additional workups for ovulation
POF-
– ↑ serum FSH level (~>40)
• RO Polyglandular autoimmune failure look
for Endocrinopathies
– Thyroid(TSH) Parathyroid (serum Ca,
Phosphorus) FBS, Adrenal autoandibodies
• R/O other causes of
anovulation/oligo/amenorrhea
– PRL, TSH, hCG, Androgen
• Serum Testesterone PCOS , Ovarian
Tumos
• DHEAS adrenal Tumors
• 17-hydroxyprogesterone (to rule out 38

Summary of Workups
• Tubal/pelvic disease
– HSG
– Laparoscopy with
chromotubation
• Uterine factors
– HSG
– Transvaginal sonography
– Saline-infusion
sonography
– MRI
– Hysteroscopy
– Laparoscopy
• Cervical factor
– ± Postcoital test
• Male factor
– Semen analysis
39

Determination of Ovulation
Clinical features suggestive of ovulation
Eg Menstrual Pattern,MITTELSCHMERZ, MOLIMINAL
SYMPTOMS , Basal body temprature
40

BASAL BODY TEMPRATURE
• BIPHASIC TEMPERATURE pattern on graphically
charted morning oral tempratures
• Oral temp. 97.0- 98.0°F during the follicular
phase.
• Postovulation –BBT increases by ~ 0.4-0.8° F 
due to rise in progesterone levels
NB
– BBT method is insensitive in many women.
– Increase in BBT follows ovulation the window of
maximal fertility* is missed for couple wishing to
concieve
* 05 days preceding the presumed day of ovulation through the ovulation
day 41

OVULATION PREDICTOR KITS -LH surge determination
• Measure urinary LH conc by colorimetric assay
• Testing should begin 2 - 3 days prior to the
predicted LH surge, and testing should be
continued daily.
• There is no clear consensus regarding the
optimal time of day to test.
• LH surge spans only 48 to 50 hours.
• In most instances, ovulation will occur the day
following the urinary LH peak
42

MID LUTEAL SERUM PROGESTRONE (MLP)
• At day 21 ( 7days after ovulation)
• Levels > 4-6ng/ ml high correlation with
ovulation
– Hull and colleagues (1982) have reported that a MLP > 9.4
ng/mL is predictive of higher pregnancy rates than
those observed in patients with < 10 ng/mL.
• Follicular phase level < 2ng/ml
– NB. the midluteal progesterone level is best regarded
as an excellent measure for the occurrence of
ovulation, but not an absolute indicator of adequate
luteal function.
43

SONOGRAPHY
• Serial ovarian sonography
– demonstrate the development of a mature antral
follicle and its subsequent collapse during ovulation.
– time consuming and ovulation can be missed.
• Secretory endometrium  ovulation
– May be confounded with Prior hormonal rx
• Excellent approach for supporting the diagnosis
of PCOS with its associated oligo-anovulation -
44

ENDOMETRIAL BIOPSY
Biopsy taken late in the luteal phase
Luteal Phase Defect/ Out of Phase Biopsy histologic
appearance lagging >2 days relative to the actual day of
the cycle determined retrospectively (eg Day 22 histology
on Day 26)
Inadequate progesterone from the CL/ endometrial
response
Frequency in infertile women is agreed to be between 5
and 10 percent
NB
– High intra-observer and inter-observer variability
– Nearly comparable incidence of LPD among infertile and fertile
groups little predictive value
NO longer considered a routine part of the infertility evaluation.
45

Ovarian Reserve Assessment
• ↑ Age depletion of follicles + mutation↓
ovarian reserve ↓ fertility

Early Follicular phase FSH level (days1-3)
• Classically “Cycle Day 3” FSH level is measured,
but tests b/n days 2 to 4 are reasonable
– Declining Ovarian function↓ inhibin secretion (from
Gcells and Luteal cells)↓ luteal Inhibin↑ FSH level
– FSH >10miu/ml  significant loss of OR a need for
more rapid evaluation and more intensive treatment.
• In a large study evaluating IVF cycles, a day-3 FSH
level exceeding 15 mIU/mL was predictive of
significantly lower pregnancy rates (Muasher, 1988;
Scott, 1995; Toner, 1991).
47

Early Follicular Phase Estradiol level
• Along with FSH level measurement
• Decreases false positive results in FSH alone
• Elevated estradiol (>80pg/ml)  abnormal
Despite an overall follicular depletion, E level rises
early in the cycle of old women due to the
elevated FSH level which stimulates
steroidogenesis
48

Anti Mullerian Hormone level measurement
• AMH is expressed by Gcells of preantral follicles ,
but very limited expression from Gcells of larger
follicles
may have a role in recruitment of the dominant
follicle
• AMH Level corresponds to the number of
primordial follicle and not cycle stage dependent
• Advantageous over FSH and E , Inhibin B tests
– Drop before changes in FSH and E level are evident
– Expression of AMH is independent of cycle stage
can be tested at any stage of Menst cycle
• Elevated AMH in PCOS consistent with the
multiple early follicles seen in PCOS

Sonography
• TVUS to measure ovarian volume and obtain
an early follicular phase antral follicle count
• The number of small antral follicles reflects
the size of the resting follicular pool.
• Less than 10 antral follicles predicts poor
response to gonadotropin stimulation
50

Radiologic Evaluation
HSG
– Tubal patency
– Contour of the intrauterine cavity + shape and size
– Polyp, leiomyoma, intrauterine adhesion-
intrauterine filling defect
– Developmental uterine abnormalities
51

HSG-
• on days 5-10 b/se of less likelihood of
– clots that block tubal outflow or falsely appear pathologic
– pregnancy
• excellent predictor of tubal patency
• 65% sensitivity, 83% specificity for tubal obstruction
• less effective at identifying normal tubal function &
peritubal/pelvic adhesion
• False positive commonly due to proximal
tubal/cornual spasm
• Unilaterally patent tube is rare as tubal diseases affect
both tubes=>unilateral obstruction with Normal
contralateral tube ~ascent of dye along the low
resistance path
• pregnancy may be facilitated by the flushing of
intratubal debris with oil based dyes during HSG
52

HSG
• Powerful Ux cavity evaluating tool
• intrauterine “defect” in dye opacity –
– A polyp, leiomyoma, or adhesion within the cavity
• false positives may be obtained due to
– blood clots, mucus plugs, or shearing of the
endometrium during placement of the intrauterine
catheter
• One study- 98% sensitivity, 35%specificity,
70%PPV, 8% NPV
• Most misdiagnoses were due to an inability to
distinguish polyps from submucous leiomyomas.

Sonography
• TVUS may also be helpful in determining
uterine anatomy, particularly during the
luteal phase, when the thickened
endometrium acts as contrast to the
myometrium.
• Although not yet widely available, the
development of three-dimensional ultrasound
machines is advancing the discriminatory
abilities of sonography.
54

SIS
• SALINE ULTRASOUND, HYSTEROSONOGRAPHY,
SONOHYSTEROGRAPHY, OR SALINE-INFUSION
SONOGRAPHY (SIS) -the infusion of saline into
the endometrial cavity during follicular phase
provides another approach for achieving
contrast between the cavity and uterine walls
55

SIS
• SIS has been reported to have a sensitivity of 75%
and specificity of over 90%.
• It has an acceptable PPV of 50% and an excellent
NPV of 95%, which greatly exceeds the negative
predictive value of HSG (Soares, 2000).
• Moreover, SIS may be more sensitive than HSG in
determining whether a cavitary defect is a
pedunculated leiomyoma or a polyp .
• Perhaps more importantly, SIS can help determine
what portion of a submucous leiomyoma is within
the cavity, as only those with less than a 50%
intramural component should be approached by
hysteroscopy
56

SIS
• SIS is generally less painful than HSG and does
not require radiation exposure.
• Therefore, it is the preferred method if
information about tubal patency is not required,
such as in patients who are known to require IVF.
• The primary limitation of SIS is that it does not
provide information about the fallopian tubes,
although rapid loss of saline into the pelvis is
certainly consistent with at least unilateral
patency.
57

Laparoscopy
• The gold standard approachDirect inspection provides
the most accurate assessment of pelvic pathology . .
• Allows both diagnosis and immediate surgical treatment
Eg .Laparoscopic ablation of endometriotic lesions or
adhesions may increase subsequent pregnancy rates.
• Chromotubation may be performed for tubal patency,
a dilute dye is injected through an acorn cannula placed
against the cervix or a balloon catheter positioned within
the uterus . Tubal spill is evaluated through the
laparoscope Indigo carmine dye is preferable to methylene
blue, as the latter rarely may induce acute
methemoglobinemia, particularly in patients with G-6-PD
deficiency
• As laparoscopy is an invasive procedure, it is not advocated
in place of HSG as part of the initial infertility evaluation.
58

Hysteroscopy
• Endoscopic evaluation of the intrauterine cavity is
the primary method for defining intrauterine
abnormalities.
• Hysteroscopy can be performed in an office or
operating room.
• With improved instrumentation, the ability to
concurrently treat abnormalities in the office is
increasing,
• However, substantially more extensive
hysteroscopic surgery is possible in an operating
room setting
59

Post Coital test-PCT/Sims-Huhner test
• PCT provides basic information regarding Cervical mucus
production, appropriate intercourse practices, and
presence of motile sperm
• A couple will have intercourse on the day of ovulation.
• within a few hours, a sample of the cervical mucus is
obtained from the cervical os with forceps or by
aspiration and examined
• Normal findings
– Spinnbarkeit- clear, copious, stretchable to 5cm 9 b/n slides)
– At least five motile sperm /HPF some authorities feel that a
single, forward-moving sperm is adequate.
– a minimal number of other cell types, such as inflammatory
cells.
– ferning pattern When dried, due to an increased salt conc.
in the mucus prompted by ↑ preovulatory E levels
60

2 and 3
Decreased sperm motility
in Thick Hostile Mucus
1-Columns within
adequate cervical
mucus help direct
sperm into the
uterine cavity

Evaluation of the male Partner
History
• Pubertal development
• Sexual dysfunction
– Erectile D + decreased beard low testosterone level
• Ejacualtory dysfunction , dev’tal anomalies
– Eg Hypospadia sboptimal semen diposition
• STI, GU infections ( Epidimytis,Prostatitis) VD obstruction
• Mumps abnormal sperm stem cells 20 to testicular
inflammation
• Cryptorchidism, testicular torsion . Trauma abnormal
spermatogenesis
• Varicocele  increased scrotal temprature
– Effect of V on fertility- controversial
62

Evaluation of the male Partner
• Illicit drugs,
– alcohol, environmental toxins
– Anabolic steroids supress intratesticular
Testosterone productiondecreased sperm
production ( may have irreversible effect)
Medical Hx
– DM, HTN, Neurologic disorders Erectile dysfunction,
Retrograde ejaculation
– Chemo or localized radiotherapy
– Medications that worsen semen parameters
• Eg cimetidine, erythromycin, TTc, Gentamycin, spironlactone

Evaluation of the male Partner - PE
• As signs of testosterone production, normal SSCs Eg beard growth,
axillary and pubic hair, and perhaps male pattern balding should be
present.
• Gynecomastia or eunuchoid habitus may suggest Klinefelter
syndrome (47,XXY karyotype) (De Braekeleer, 1991).
• The penile urethra should be at the tip of the glans for proper
semen deposition in the vagina.
• Testicular length should be at least 4 cm with a minimal testicular
volume of 20 mL (Charny, 1960;Hadziselimovic, 2006). Small testes are unlikely to
be producing normal sperm numbers.
• A testicular mass may indicate testicular cancer, which can present
as infertility.
• The epididymis should be soft and nontender to exclude chronic
infection. Epididymal fullness may suggest vas deferens obstruction.
• pampiniform plexus of veins should be palpated for varicocele
(Jarow, 2001).
• Importantly, both vas deferens should be palpable. Congenital
bilateral absence of the VD is associated with mutation in the gene
responsible for cystic fibrosis (Anguiano, 1992).
• The prostate should be smooth, nontender, and normal size.

Male Workups
• Causes of male infertility can roughly be
categorized as
1. abnormalities of sperm production,
2. abnormalities of sperm function, and
3. obstruction of the ductal outflow tract.

Male Workup- Semen analysis
• Reflects events of the past 3months
– spermatogenesis requires an overall 90days
• Refrain from coitus for 2-3 days- masterbate/
sciilastic non lubricated condom--Sample to lab
within one hr
• Ideally the test is done 2x- at least a month apart
(once if N result)
• Doesnot provide information about sperm
function ultimate abilty to fertilize lack
absolute predictive value

Male Workup-Abnormalities In semen A
Low volume
• causes
– Short absteinence
– VD obstruction (partial/complete)- infection, tumor,
Test or inguinal surgery, trauma
– Retrograde Ejaculation- backward flow of semen into
bladder bse of failure of closure of bladder neck
during ejaculation
• RE causes- neuropathy in DM,SC injury, Prostate/ Retrop
surgery. Beta blockers contribute
• DX- Post ejaculatory UA ( Viable sperms can be retrieved frpm a
well alkalinized urine for CSI)

Male Workup-Abnormalities In semen A
• Oligospermia (low count)-concentration of fewer than 20 million sperm
/ml,(counts less than 5 m/ml are considered severe)
• Azoospermia (No sperm)
– Prevalence ~1% of all men
– Obstructive- outflow obstruction- infection, vasectomy, Congenital absence of
VD
– Non-Obst- Testicular Failure)-careful centrifugation and analysis may identify a
small number of motile sperm adequate for IVF use. Alternatively, viable sperm
may be obtained through either epididymal aspiration or testicular biopsy
• Asthenospermia- decreased total progressive movement
Progressive Movement graded in some labs
G 3 and 4- rapid, G 2- slow G 0-1- no progressive movement
Total progressive motility- %ge of sperms exhibiting forward movement ( G2-4)
• cause- prolonged absteinence , antisperm Abs , GT infections and vaicocele
• Hypo Osmotic swelling test differentiate b/n dead and alive non motile
sperms- alive sperms swell (functional membrane) and coil their tail – can
be used for ICSI
• Teratospermia- abnormal morphology

Male workup-Abnormalities In semen A
• Round cells in a sperm sample may represent either
leukocytes or immature sperm.
Lukocytospermia
• WBCs can be distinguished from immature sperm using
a variety of techniques, including a myeloperoxidase
stain for WBCs (Wolff, 1995).
• True leukocytospermia is defined as greater than 1
million WBCs per milliliter and may indicate chronic
epididymitis or prostatitis. In this scenario, many
andrologists consider empiric antibiotic treatment
prior to obtaining a repeat semen analysis.
• A common protocol would include doxycycline at a
dosage of 100 mg orally twice daily for 2 weeks.
• Alternative approaches include culture of any
expressible discharge or of the semen sample.

Male Infertility Workup
Other workups for male infertility include
• Antisperm antibodies assay
• DNA Fragmentation test
• Sperm Function assays
– Mannose fluoresence assay
– Hemizonal assay
– Sperm penetration assay
– Acrosomal reaction
• Hormonal Tests
– FSH
– Testosterone
– Prolactin
– Tyroid Function Tests
• Testicular Biopsy

Male Genetic Testing
• Genetic abnormalities- incorrectable but need
identification bse of their implication on the
health of the pt and offsprings
• Kleinfelters S (47XXY)
• Y chr microdeletion
• Cystic Fibrosis (Congenital Bilateral Absence of
Vas Deferens)

TREATMENT
74

Infertility Rx
• Treatment of infertility depends on
– cause
– Duration of problem
– Age (esp. of females)
75

Infertility Rx
Life style Therapy
– Environmental toxins
– Smoking
– Alcohol
– Caffeine
– Weight optimization
– Nutrition
– Exercise
– Stress management
Correction of identified causes
– Correction of ovarian dysfunction
76

Hyperprolactinomeia rx
• Treat/ correct underlying causes
– Treat hypothyroidism
– Avoid triggering drugs-----
• Treatment of PRL secreting Pitutary adenomas
– Medical mg’t -Dopamine agonists (bromocriptine,
cabergoline)
– Surgical mg’t – for medical rx resistant adenomas
77

Ovulation Induction
• Stimulation of ovulation for
– Ovarian dysfunction or
– Normally ovulating woman ( super ovulation, ---
• Frequent causes of OD are
– PCOS
– Diminished ovarian reserve
• Less commonly-Central ( H, P) disorders, Thyroid D,
• Rarely Ovarian tumors and adrenal abnormalities
Common ovulation inductions agents
– Clomiphene citrate
– CC + glucocorticoids
– Insulin sensitizers--Biguanides and Thiazolidinediones
– Gonadotropins
– Aromatase inhibitors
78

Correction of Anatomic Abnormalities
• Impair ova , sperm , embryo transport,
implantation of fertilized ovum
• Three primary types
– Tubal
– Peritoneal
– uterine
79

Tubal Factors
• Tubal occlusion Congenital, Infection,
Iatrogenic, idiopathic (rare)
– Proximal- ostium, isthmus ampulla
• Resection,obliteration,mucus/debris plugging
– Distal- on fimbrae-
• typically 20 to prior pelvic infection and adnexal
adhesion
Rx- IVF, Surgical
80

Tubal Factors-Treatment
• Proximal Occlusion
– Tubal Cannulation
• Selective salpingography for proximal occlusions
• Hysteroscopic cannulation
– Resection and anastomosis
• Distal occlusion
– Neosalpingostomy- new opening
• ( high risk of EP, low~50% pregnancy, reocclusion)
– Fimbrioplasty- adhesion release,
81

Treatment of Uterine Factors
• Leiomyomas
– Myomectomy appears to improve fertility
ie Both spontaneous and assisted conception
• Endometrial polyps- surgical removal
Studies show
– increased pregnancy rate and few early losses after
polypectomy
– Pregnancy rate doubled in intraux insemination( IUI )
after polypectomy than in those without
polypectomy
• IU adhesions- surgical release, Estrogen
82

Cervical abnormalities- Treatment
• Rx of infection if Mucus exam reveals cervicitis
• E estradiol supplementation, Guaifenesin rx (
mucolytic expectorant)
– Unconfirmed benefit+ EE may affect follicular dv’t
• Intra Uterine Insemination- for non infectious
cervical mucus abnormalities(preferd by most
clinicians)
83

ART
• ASRM Def of ART: procedures and treatments
that involve handling of human oocytes and
sperm or embryo with the intent of establishing
pregnancy
– Includes IVF +- ICSI but not artificial insemination and
superovulation drug therapy (ACOG, AAP Perinatal care guideline)
• ART, conventionally, involves egg retrival at one
point
• employed when direct correction of 10 cause is
not feasible
85

ART- perinatal Risks
• Perinatal risks associated with ART include
– High order MG
– Prematurity
– LBW,
– SGA
– C Delivery
– Pprevia
– Abruptio placentae
– PE
– Birth Defects
• The extent of relation, of these adverse outcomes
specifically to ART procedures Vs underlying factors in
the couple, is unclear,
(ACOG,AAP- Guidelines for perinatal care 7th Ed , 2012)

ART
Invitro Fetilization( IVF )
• Controlled Ovarian Hyperstimulation (COH)
egg retrival ( US guided vaginally) mixing with
sperm insertion of embryos/ zygote
transcervically ( US guided)
• COH with Gonadotropin ( FSH/ hMG) + ovulation
supression with GnRH analog
• Removal of hydrosalpinx/ salpinges and tubal
interruption facilitates implantation and
decreases miscarriage risk
87

ART
Intracytoplasmic Sperm Injection (ICSI)
• A variant of IVF
• Single sperm injected into ovum through ZP
and Cell memebrane after enzymatic digestion
of cumulus
• Applicable for male factor infertility ( eg by
sperm extraction from testes / epidydimis in
azospermia)
88

ART
Gestational Carrier Surrogacy
• Variant of IVF- fertilized ovum is placed in the
uterus of a surrogate mother for Women
– with incorrectable Ux factor
– Pregnancy poses life threatening hazards
– With repeatitive unexplained miscarriages
89

ART
Egg donation
– In ovarian failure/ diminished OR
– To protect the offspring from maternal genetically inheritable
diseases
• Fresh egg is preferable to croypreserved one
 need to synchronize cycle of the donor(D) with endometrial
preparation of recipient (R)
• For premenopausal R- GnRH is adminstred followed by
Estrogen to create artificial cycle
• D recieves GT and finally hCG and eggs are retrived after 36
hrs
• When D gets hCG, R starts to get progestrone
• E and P adminstration continues through 1st trimester
90

ART
Gamete Intrafallopian Transfer (GIFT)
For unexplained infertility
Largely replaced by IVF
• Egg retrival after COH
• Deposition of sperm and egg in FTs through
the fimbrae laparoscopically
91

Downregulation GnRH agonist protocol.
/long protocol. COCpill pretreatment- to
avoid cyst formation by initial GT flare
effect of GnRH rx .
GnRH agonist supress endogenous GT
secretion and premature LH surge
hCG- LH surge surrogate

GnRH agonist flare cycle protocol/ Short protocol–GnRH agonists initially bind
gonadotropes and stimulate FSH and LH release. This initial
flare of gonadotropes stimulates follicular development. Following this initial surge of
gonadotropins, the GnRH agonist causes receptor downregulation and an ultimately
hypogonadotropic state. Gonadotropin injections begin 2 days later to continue follicular
growth. As with the long protocol, continued GnRH agonist therapy prevents premature
ovulation.

GnRH antagonist protocol. As with GnRH agonists, these agents are combined with
gonadotropins to prevent premature LH surge and ovulation. This protocol attempts
tominimize risk of ovarian hyperstimulation syndrome (OHSS) and GnRH side effects,
such ashot flashes, headaches, bleeding, and mood changes.

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