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Presented by Dr.

Surya
Moderator: Dr Shailaja

Definition
Epidemiology
Risks
Ovarian Reserve Tests
Etiology
Investigations

Female Infertility

Definition

Infertility
1 year of unprotected intercourse without conception.

Subfertility
not sterile but exhibit decreased reproductive efficiency

Female Infertility

Primary infertility- no previous pregnancies

Secondary infertility-a prior pregnancy,


although not necessarily a live birth

Female Infertility

Fecundability __probability that a cycle will


result in pregnancy (estimated at 20% to 25%)

Fecundity is the probability that a cycle will


result in a live birth.

On the basis of this estimate, about 90% of


couples should conceive after 12 months of
unprotected intercourse
5

Female Infertility

Epidemiology

Affects 10-15% of reproductive age couple

Reproductive efficiency averages 20%

Female Infertility

Time required for conception Among


couples who will attain pregnancy
Month of exposure

% pregnant

3 months

57%

6 months

72%

1 year

85%

2 years

93%

Female Infertility

The human reproductive process is complex, but


for purposes of evaluation, it can be dissected
into its most important and basic components.

Sperm must be deposited at or near the cervix at or near


the time of ovulation, ascend into the fallopian tubes, and
have the capacity to fertilize the oocyte (male factor).

Ovulation of a mature oocyte must occur, ideally on a


regular and predictable basis (ovarian factor).

Female Infertility

The cervix must capture, filter, nurture, and release


sperm into the uterus and fallopian tubes (cervical factor).

The uterus must be receptive to embryo implantation and


capable of supporting subsequent normal growth and
development (uterine factor).

The fallopian tubes must capture ovulated ova and


effectively transport sperm and embryos (tubal factor).

Female Infertility

Causes of infertility %

Male factor

25-40%
Unusual problems; 5%

Female factor Unexplained; 10%


40-55%

Male problems; 35%

Ovulatory disfunction; 15%

Both male & female

10%

Unexplained infertility

10%

Tubal and pelvic pathology; 35%

10

Female Infertility

Prevalence of causes of infertility


in female %
Ovulatory dysfunction

30-40%

Unexplained infertility

10-15%

Miscellaneous causes

10-15%

Unusual problems; 10
Unexplained; 10
Tubal and Pelvic Pathology; 40
Tubal & peritoneal factor
30-40%

Ovulatory dysfunction; 40

11

Female Infertility

What Increases the Risks?

Age
Stress
Poor diet
Smoking
Alcohol
STDs
Overweight
Underweight
Caffeine intake
Too much exercise

12

Female Infertility

Majority of spontaneous conception ____ within 6


months
Conception rate depends upon the age

Age

Conception rate

26 to 30
25 years

73%
Conception rate
74%
73%

26-30years
31 to 35
31-35years
>35
> 35years

74%
62%
62%
27%
27%
& lower

Age

<25 yrs

13

Female Infertility

Likelihood

of success declines by
5% for each additional year of the female
15-25% for each added year of infertility

Fertility rate % Age


20-24
Fertility rate
Age
4-8
25-29
Peaks
20-24yrs
15-19
30-34
4-8%
25-29yrs
26-46
35-39
15-19%
30-34yrs
95
40-45
26-46%
35-39yrs
95%

40-45yrs
Female Infertility

14

Physiology of reproductive aging,


1,2,3,4,5,6,7
During fetal life, germ cell proliferation
mitosis

6-7 million oogonia by 16-20wks


enters 1st meiotic division

Oocyte

1-2 million at birth

about 3,00,000 by onset of puberty


400-500 oocytes ovulate(35-40 yrs)
Female Infertility

15

At the time of menopause, 1000 follicles remains

Rate of follicular depletion relatively constant,


during reproductive years

Accelerates over 10-15 years

16

Female Infertility

Fertility with aging

Progressive follicular depletion

High abnormalities in aging oocyte

High prevalence of spontaneous miscarriage

High prevalence of benign uterine pathology

17

Female Infertility

naturally

starts to
decline after late
20's.
After 35 decreases
rapidly.
with time, the supply
diminishes, the EGG.
The remaining eggs
also age along with
the rest of the body.
18

Female Infertility

Ovarian reserve tests


Aimed

at identifying individuals at risk for a


disease, (DOR).
Should have high specificity,
Aim to decrease false-positive results,
Avoiding aggressive treatment or
inappropriate recommendations in women
with a normal ovarian reserve.

19

Female Infertility

Treating

women with unrecognized DOR is


undesirable
To minimize the risk for a falsepositive result.
Justified in,
1.
2.
3.
4.

Age over 35.


Unexplained infertility.
Family history of early menopause.
Previous ovarian surgery (ovarian cystectomy or
drilling, unilateral oophorectomy), chemotherapy,
or radiation.
5. Smoking.
6. Demonstrated poor response to exogenous
gonadotropin stimulation.
20

Female Infertility

Ovarian reserve tests..

Basal FSH and Estradiol concentrations


Clomiphene Citrate Challenge Test(CCCT)
Inhibin B
Antimullerian Hormone
Antral Follicular Count
Ovarian Volume

21

Female Infertility

Basal FSH and Estradiol


Rising

FSH levels are one of the


earliest signs of reproductive aging
The basal FSH concentration :
Simplest and still most widely applied
measure
Vary significantly across the cycle,
Best obtained during the early
follicular phase (cycle day 2-4).
22

Female Infertility

Assays

(using IRP 78/549), FSH levels


greater than 10 IU/L (10-20 IU/L) have
high specificity (80-100%;)

Predicts

poor response to stimulation

Sensitivity

generally low (10-30 %;) and


decreases with the threshold value
Although most women who are tested (including those
with DOR) will have a normal result, the test is still useful
because those with abnormal results are very likely to
have DOR.
23
Female Infertility

Serum estradiol
By

itself has little value as an


ovarian reserve test,
Provide additional information for
interpretation of the basal FSH level
Basal FSH is normal

24

Female Infertility

Normal Basal FSH

Elevated

Clomiphene Citrate Challenge Test(CCCT)

Provocative and more sensitive test


Probes the endocrine dynamics of the cycle under both
basal and stimulated conditions,
Before (cycle day 3 FSH and estradiol) and after
(cycle day 10 FSH) treatment with clomiphene citrate
(100 mg/d, cycle days 5-9)
A frankly elevated cycle day 10 FSH concentration can
identify women with DOR who might otherwise go
unrecognized if evaluated with basal cycle day 3
FSH and estradiol levels alone.

27

Female Infertility

Overall, stimulated FSH levels have higher


sensitivity but lower specificity than the
basal FSH
Day 3 FSH and estradiol

CCCT

In

studies evaluating CCCT results,


stimulated concentrations of FSH,
estradiol, and inhibin B have varied
widely, limiting the value of the test.

2006

systematic review of the predictive


value of the CCCT over a range of day 10
FSH concentrations (10-22 IU/L) test had

47-98%; specificity and 35-93%; sensitivity for


predicting poor response to stimulation, and
67-100%; specificity and 13-66%; sensitivity for
predicting treatment failure.
29

Female Infertility

Inhibin B
Secreted

primarily during the follicular phase


by the granulosa cells of smaller antral follicles, and
might therefore be expected to have some value as an
ovarian reserve test.
However,

serum inhibin B concentrations


increase in response to exogenous GnRH
or FSH stimulation and vary widely across
and between menstrual cycles.
Inhibin B is generally not regarded as a
reliable measure of ovarian reserve.
30

Female Infertility

low

threshold values (40-45


pg/mL) have only
64-90%; specificity and
40-80%; sensitivity for predicting poor
response

31

Female Infertility

Antimullerian Hormone
Produced

by

granulosa cells of preantal and small antral follicles,


beginning when primordial follicles start development and
ending when they reach a diameter of 2-6 mm.
Small

antral follicles: larger numbers of


granulosa cells and a more developed
microvasculature: likely source
Levels are gonadotropin-independent
and exhibit little variation within and
between cycles
32

Female Infertility

In

the general IVF population, low AMH


threshold values (0.2-0.7 ng/mL)

40-97%; sensitivity,
78-92%; specificity,
22-88%; PPV and
97-100%; NPV for predicting poor response to stimulation
(<3 follicles, or <2-4 oocytes),
but have proven neither sensitive nor specific for
predicting pregnancy
Very

promising screening test for DOR,


More useful in a general IVF population or
in women at high risk for DOR than in
women at low risk for DOR
33

Female Infertility

Antral Follicle Count


20-150

growing follicles in the ovaries


at any time, although only a few are
large enough to be imaged (2
mm) by TVS
Follicles of that size have reached a
stage of development where they are
responsive to FSH, which stimulates
and supports more advanced stages of
development.
34

Female Infertility

Histology- proportional

The antral follicle count (AFC; total number of antral follicles


measuring 2-10 mm in both ovaries) thus provides an
indirect but useful measure of ovarian reserve
35

Female Infertility

In

the general IVF population, including


women at low and high risk for DOR, an AFC
threshold value of three to four follicles
has
High specificity (73-100%;)
For predicting poor response to ovarian stimulation and
failure to conceive (64-100%;)

low AFC has high specificity for


predicting poor response to ovarian
stimulation and treatment failure,
making it a useful test, but low sensitivity
limits its overall clinical utility.
36

Female Infertility

Ovarian Volume
Decreases with follicular depletion.
High inter-cycle and inter-observer
variability,
ovarian pathology such as endometriomas
and polycystic ovary syndrome, results
have limited generalizability.
Ovarian volume (length width depth
0.52) generally correlates with the number
of oocytes retrieved, but poorly with
pregnancy.

37

Female Infertility

A low ovarian volume (< 3mL)


High specificity (80-90%;) and
Widely ranging sensitivity (11-80%;)
For predicting poor response to ovarian stimulation.

The PPV for poor response can be as low as


17%; among women at low risk for DOR, and
as high as 53%; in women at high risk.
Overall, ovarian volume has very limited clinical
utility as an ovarian reserve test.
38

Female Infertility

Ovarian factors
ANOVULATION AND OLIGOOVULATION

Hypothalamic

anovulation
Psychological factors
Low BMI and obesity
-disrupts hypothalamic pituitary ovarian axis

- Anorexia nervosa, vigorous athletic training and


malnutrition
- Female athlete triad: Secondary amenorrhea
eating disorder,
osteopenia/osteoporosis
Female
Infertility

39

weight gain ideal treatment


- caloric intake and weight gain
resumption of
menses in 90%, sponaneous conception in 73%
- mean weight gain by 3.6kg sufficient for
resumption of ovulation

Congenital hypothalamic
failure( Kallmann syndrome)
Psychotropic drugs
Tranquilizers

40

Female Infertility

Pituitary

Sheehans syndrome

- Postpartum pituitary necrosis due


to postpartum haemorrhage f/b
panhypopituitarisim FSH/LH

41

Female Infertility

Tumor: Prolactinomas
- Prolactin level inhibitory effect on
pulsatile GnRH release hypogonadotropic
effect
-granulosa cell number and FSH binding
-granulosa cell estradiol production
-causes inadequate
luteinization and
Female Infertility

42

Hypothalamic-pituitary axis
dysfunction
Anovulation due to hypogonadotropic-hypogonadism
- Presence of serum LH, FSH and estradiol
- Causes :

Craniopharyngioma
Pituitary adenomas
Arteriovenous malformation
Central space occupying lesion

- Systemic diseases: chronic liver disease,


renal failure

chronic
43

Female Infertility

Thyroid

Prevalence of abnormal TSH in infertility


population
6.3%
4.8%
2.6%
1.55%

Anovulatory infertility
Unexplained infertility
Tubal infertility
Male infertility

In one study 23% women with hypothyroidism


had irregular menses, likely anovulation
Both hypothyroidism and hyperthyroidism
44

Female Infertility

Adrenal: Congenital adrenal hyperplasia


Ovarian causes

Polycystic ovarian syndrome


- Most common cause of anovulation and
oligovulation in infertility
- LH pulse frequency, FSH
- No folliculogenesis

Formation of atretic follicles

- No ovulation

cyst formation
45

Female Infertility

Premature ovarian failure


- Presence of persistently elevated gonadotropins
- Associated with estrogen therapy
formation on the follicles
- gonadotropins
development

Activate receptor

stimulates follicular growth and

- Reported with autoimmune disorder


- Demonstration of ovarian autoantibodies
46

Female Infertility

Luteinized unruptured follicle


syndrome
- Ovum trapped inside the follicle gets luteinized
- No ovulation beyond 36hours of LH surge
- Pelvic endometriosis, hyperprolactinomas

47

Female Infertility

LUTEAL PHASE DEFECT


-

During follicular
endometrium exhibit proliferative
During luteal
secretory transformation
Inadequate corpus luteum progesterone regarded as cause
of infertility and early pregnancy loss

progesterone level with luteal phase deficiency


Delayed endometrial maturation

48

Female Infertility

Shift in the implantation window


Long delays may threaten embryo viability
Prevent implantation

Causes
Disturbances in pituitary gonadotropin secretion pattern
- GnRH pulse
FSH level
Ass. With poor luteal function
- Rapid GnRH pulse frequency and LH frequency during mid
cycle surge and reduced LH bioactivity

49

Female Infertility

Endocrinopathies:
affect hypothalamo-pituitary-ovarian axis
Hyperthyroidism and hypothyroidism
Changes SHBG level Feedback inhibition in
gonadotropin secretion
- Primary hypothyroidism
TRH
Stimulates lactotrophs directly
prolactin gene transcription

activates

Hyperprolactinemia
Inhibit GnRH secretion
No luteal function
Progesterone level

50

Female Infertility

Other causes
- Endometriosis
- Dysfunctional uterine bleeding

51

Female Infertility

Tubal factors

30-40% of cases of infertility


Tubal blockage, peritubal adhesion, fimbrial end blockage
Causes :
Infection - Post abortal, puerperal nfection
- STI ( gonococcal , clamydial)
- PID
- Tubercular salphingitis
Endometriosis
Peritubal adhesions : Previous surgeries

52

Female Infertility

INFECTION
-

Polymicrobial in nature, involving both the tubes

Organisms:
STI: Gonococcus, Chlamydia, Mycoplasma
Pyogenic: Streptococcus, E.coli,Staphylococcus, Gp
B streptococcus, Bacteroide fragilis, actinomycoses
Tubercular: M. tuberculosis

53

Female Infertility

Mode of spread:
Ascending infection
- Gonococcal infection may affect the tubes during initial
exposure or from Bartholins gland and cervix
- Pyogenic infection follow: Delivery, induced abortion,
minor procedure like D & C, hysterosalphingography,
IUCD, infected polyp
- Recently, chlamydia is regarded as common cause,
ascends up from the cervix

Direct spread : appendicitis, diverticulitis, pelvic


peritonitis
54

Female Infertility

Pathogenesis
Pyogenic: Infection from uterine cavity & cervix
Pelvic cellulitis Perisalphingitis

Lumen directly infected

Endosalphingitis

Produces cornual blockage


Gonococcal: directly ascends to tube through
continuity and contiguity
Endosalphingitis
Female Infertility

55

Pathology
Pyogenic: Outer coat is involved, adhesion are
more and dense
Gonococcal : - Mainly endosalphingitis, adhesions
are less and filmsy
- Fimbriae gets phymotic, edematous and
indrawn by cicatricle contraction closure of
abdominal ostium
defective ovum pick up
- Loss of cilia
infertility

56

Female Infertility

Site of obstruction
Proximal :
- Prevents sperm to reach distal portion ..hinders
fertilization
- Causes: tubal spasm, temporary mucous
plugging,salpingitis isthmica nodosa(23-60%)
- Risk of perforation with cannulation ranges from 3%11%
Distal:
- Prevents ovum capture
- Exhibits a spectrum: mild( tubal obstruction),
moderate( fimbrial phimosis) to severe
( complete obstruction)
- Causes: Pelvic infection, Endometriosis, prior
abdominal and pelvic surgery
57

Female Infertility

Genital tuberculosis ( Tubercular salphingitis)


- Accounts for 5-10% cases of infertility
- Infertility , the most common symptom(70-80%)
- Secondary to primary infection elsewhere : Lungs (50%),
lymph nodes, urinary tract, bones and joints
- Fallopian tubes : Invariably the primary site
Mode of spread:
- Hematogenous (90%)
- Lymphatic - Peritoneum, bowel, mesenteric
- Ascending Contact with males with
urogenital TB

nodes

58

Female Infertility

Pathology

- Commonest site:Fallopian tube, endometrium


- Both tubes involve simultaneously
- Initially involve submucosal layer
- Spread medially to muscles: Fibrosis
- Spread inward to mucosa
-

Fimbriae everted ostium is patent


Tubercle burst into lumen
pyosalphinx
Spread outside
perisalphingitis
Formation of diverticula
Salphingitis isthmica
nodosa
59

Female Infertility

ENDOMETRIOSIS
-

20-40% of infertile women

Mechanism of infertility:
Distorted adenexal anatomy
Blockage of tubo-ovarian motility due to adhesion
Interference with oocyte development or early
embryogenesis
Reduced endometrial receptibility

60

Female Infertility

PELVIC SURGERY

Appendicectomy

Divurticulectomy

Surgeries for ectopic pregnancy

61

Female Infertility

Peritoneal factors

Causes:
Pelvic inflammatory disease
Endometriosis
Previous surgeries

Distorted anatomy and pelvic adhesion : main


mechanism of infertility

62

Female Infertility

PELVIC INFLAMMATORY DISEASE

Ascending infection and inflammation of the upper


genital tract

Polymicrobial:
STI: N. Gonorrhea 30%
Chlamydia trachomatis 30%
Mycoplasma 10%

Aerobic: E. coli, group B streptococcus,


staphylococcus

Anaerobic: Bacteroids, Peptococcus,


peptostreptococcus
63

Female Infertility

Pathology
Initiated in endosalphinx
Destruction of
epithelial cells, cilia and microvilli
All three layers gets involved
hyperemic

Edematous and

Exfoliated cells and exudates pour into lumen and


agglutinate
mucosal fold & plugs
Abdominal ostium closed by indrawing of fimbriae
Uterine end closed by congestion

64

Female Infertility

Closure of both ostia


Formation of pyosalphix, hydrosalphix
Filmsy adhesions of tube and surrounding
structures
Pouring of exudates though the abdominal ostia
Pelvis peritonitis, pelvic abscess, tubo-ovarian
abscess
65

Female Infertility

Risk

of infertility

Single episode of PID is significant and


increases rapidly with subsequent
episodes

Episodes of
Episode of PID
PID
1
1st 2
2nd3
3rd
st

nd

rd

Female Infertility

% of
% of infertility
infertility
10-12%
10

12
23-35%
23- 35
54-75%
54- 75

66

Uterine Factors

Mechanism: Defective nidation and implantation

Causes:
CONGENITAL : - Absence of uterus
Uterine hypoplasia
CONGENITAL MALFORMATION:- Uterine
didelphus(25%), Unicornuate(38%), Septate(25-47%)
- Pregnancy outcome depends upon site of blastocyst
implantation
67

Female Infertility

In utero EXPOSURE TO DIETHYLSTIBESTEROL


-

risk for congenital malformation and obstetric


complication

70% exposed had uterine malformation

Most common malformation: T shaped uterus

Infertility associated with constriction of upper segment


of reproductive tract

68

Female Infertility

UTERINE LEIOMYOMA
-

Various factors affect pregnancy: size, location, number


and presence of associated symptoms
Possible mechanism:

Altered uterine contractility: Disrupt normal sperm


migration, embryo transport
Cornual occlusion by myoma, compression of interstitial
segment of the tube
69

Female Infertility

Adversely affect vascular and molecular profiles of


implantation
Poor regional blood flow
focal endometrial attenuation or ulceration
-

A meta-analysis showed:
Pregnancy rate increased to 57-67% after
abdominal myomectomy for infertiltiy

70

Female Infertility

ENDOMETRIAL POLYP
-

Incidence of asymptomatic endometrial polyp in


infertility ranges: 10-32%

Overall prevalence after hysteroscopy : 3-5%

Higher in patients with other symptoms and with


endometriosis
Rare in young women

71

Female Infertility

INTRAUTERINE SYNECHIAE( ASHERMANS


SYMDROME)
-

Menstrual symptoms( hypomenorrhoea, amenorrhoea,


dysmenorrhoea) and infertility
Pathophysiology:Scant or poorly vascularised and dysfuncitonal
endometrium resulting from
- Intraop or postoperative complication
- Intrauterine infection

72

Female Infertility

Intraop and postop complication

90% in curattage of pregnancy termination


22% in postpartum curettage.. risk of endometritis
Evacuation of missed abortion, H. mole or after
cesarean section
Abdominal or hysteroscopic myomectomy,
septoplasty, uterine surgery

Intrauterine infection
Genital tuberculosis( tubercular endometritis)
Schistosomiasis
73

Female Infertility

CHRONIC ENDOMETRITIS
-

Uncommon cause, true prevalence not known


Mucopurulent cervicitis associated with
Chlamydia trachomatis, Mycoplasma genitalis
Significant cause of chronic endometritis with tubal
factor infertility
Chlamydia produces silent tubal infection
Mycoplasma & Ureaplasma recovered from cervix
mucous of infertile couple
47% of couple who conceived
53% of couple who remained infertile

74

Female Infertility

Cervical factors
ANATOMIC
- Congenital elongation of cervix
- Cervical stenosis( pinhole Cx os)
PHYSIOLOGICAL
- Fault in compositon of cervical mucous
- Antisperm antibodies

75

Female Infertility

Fault in cervical mucous

Becomes abundant, clear, watery and easily


penetrable by the sperm
Scant and poorly estrogenised cervical mucous
- Cervicitis
- Previous injury to cervical glands
- Treatment with antiestrogen( Clomiphene
citrate)

76

Female Infertility

Anti

sperm antibodies

Either autoimmune or allogenic response


Mostly immunoglobulins, Can be free/ agglutinating
- IgA: Cervical mucous, seminal plasma
- IgG: Cervical mucous, semen
- IgM: serum( larger difficult traversing the genital tract)
Causes:
- Coital trauma, genital tract infection
- Testicular trauma: Torsion
- Occlusion of vas deference : Inguinal herniorrhaphy, cystic
fibrosis, Vasectomy reversal

77

Female Infertility

Effect
- Interference with
- Capacitaton
- Acrosomal reaction
- Sperm egg recognition & fusion
- Cleavage of early embryo

78

Female Infertility

Vaginal factors

Vaginal atresia( partial / complete)

Transverse vaginal septum

Septate vagina
Narrow introitus
Vaginitis
Vaginismus
Vulvodynia

79

Female Infertility

Unexplained infertility
-

Is the diagnosis of exclusion, after systematic evaluation


fails to identify the cause
All standard elements of the infertility evaluation yield
normal results

Incidence 10%, as high as 30%

Avg. fecundity rate in untreated women 2-4%

Role of diagnostic laparoscopy


29% of women conceived after 36 weeks of t/t laparoscopy
compared to 17%

80

Female Infertility

Life style & Environmental factors


BODY WEIGHT
-

Overweight BMI >27, Obese BMI >30

Underweight BMI < 17

Disorders of hypothalamic GnRH, Pituitary


gonadotroin release
Mean wt loss of 10.2kg/m2,spontaneous ovulation
and pregnancy occurred in 90% and 30% resp

81

Female Infertility

Im healthy
strong
person I
would not
have any
problem
producing
a baby

OBESITY
AN EMERGING MENACE

1. > 1 Billion overweight

2. > 300 Million Obese

3. 26% of non pregnant


women ages 20 39
are overweight / obese

Are obese women at


risk of infertility ?

An Obese Woman is
about Thrice as likely
to be Infertile as a
normal woman

Yes

Obesity and Infertility


Chances of
pregnancy is
reduced by
5% for every
BMI unit
that exceeds
29 kg/m2

MOST COMMONLY USED INDEX TO


QUANTIFY OBESITY IS BMI

High prevalence of Infertility in


Obese women

Obesity can be
Main
Secondary or
Accompanying
infertility factor

The impact of obesity on A.R.T.


outcomes is debatable

Obesity is strongly
associated with

PCOS

CENTRAL PLAYER
Insulin
resistance
Hyperandroge
nism
Elevated leptin
Leptin
resistance

both
regular or irregular cycle

UNDERLYING MECHANISM

anovulation
release of oocytes with
reduced fertilization potential
endometrial abnormalities
Both seed and soil defective

British Fertility Society guidelines

Infertility
treatment should
be deferred until
BMI<35 kg/m2
preferably
BMI<30 kg/m2 in
young women
with good
ovarian reserve

Treatment Modalities
For Infertility in Obesity

Life Style &


Nutrition
Changes

Diet
Exercise
Psychologic
al
Counseling

ART

IUI
IVF
ICSI

Surgical
Intervention
Bariatric
surgery

Pharmacological intervention

Appetite suppressant, Weight Loss Drugs


(Orlistat)

Even 5% Weight loss


improves fertility outcome

OBESITY & ASSISTED


REPRODUCTION
Obese women : not only have a
lower chance of pregnancy
following In Vitro Fertilization
They require higher doses of
gonadotropins and
Have an increased miscarriage
rate

obesity and endometrium


Bellver et al, 2007

2656 first oocyte donation cycles

Lower implantation and pregnancy rates


as BMI increases
Higher miscarriage rate as BMI increases
Lower ongoing pregnancy rate in OW
and OB
ongoing
PR
in
BMI<25:
45.5%
in
BMI>25:
38.3%

Pregnancy after
Bariatric Surgery

Pre-Pregnancy
Counselling

When ever possible,


pregnancy should be
delayed till weight
loss stabilizes for 1224 months.

Weight loss is one of the corner


stone to achieve a healthy

Smoking
-13% of female infertility relate to smoking
-

Higher prevalence of infertility, lower fecundability,


longer time of conception

Mechanism:
- Accelerated follicular depletion
- Loss of ciliary function
- Menstrual cycle abnormalities
- Gamete or embryo mutagenesis
100

Female Infertility

Substance abuse
-

Marijuana inhibits secretion GnRH


Interferes with ovulatory function
Cocaine impairs spermatogenesis, risk of tubal
disease

ALCOHOL
- Heavy alcohol consumption: fertility
- Moderate alcohol consumption: fecundability
- Associated with lower pregnancy rate achieved with
ART
101

Female Infertility

CAFFINE
-

Ingestion of >250mg/day : adverse effect


Higher level consumption: Delay conception,
pregnancy loss

ENVIRONMENTAL & INSECTICIDS EXPOSURE


- Perchloethylene( dry cleaning), toluene ( printing)
- Ethylene oxide
- Mixed solvents
- Herbicides/ fungicides
- Pesticides, chlorinated hydrocarbons
102

Female Infertility

General factors

Coital errors
Dyspareunia
Frequency and timing coitus
Use of spermicide
Anxiety / apprehension
Family disposition, genetic and constitutional
factors

103

Female Infertility

Evaluation

Evaluation of infertility focuses on the couple


regardless of past reproductive performances

Objective:
To identify and correct specific causes of infertility
To provide accurate information
To provide emotional support
To guide for alternatives ART, use of donar gamete
and adoption
Counseling must be the ongoing process

104

Female Infertility

Principle

Couple-centered management
Access to evidence-based information
(verbal and written)
Counseling from someone not directly involved in
management of the couples fertility problems
Contact with fertility support groups
Specialist teams

105

Female Infertility

Indication

All couples who failed to conceive after a year or


more of unprotected coitus

106

Female Infertility

Female infertility evaluation


-

Starts with a careful history and physical


examination as ususal

HISTORY
- Age , duration of marriage, previous marriage
- Occupation
- Duration of infertility/ previous evaluation and
treatment
- Coital frequency/time of cycle/ sexual dysfunction
- Vaginal discharge/ chronic pelvic pain
107

Female Infertility

MENSTRUAL HISTORY
-

Menarche, regularity, characteristics


Mittelschmerz, midcycle spotting, permenstrual
mastalgia
Dysmenorrhoea( onset), dyspareunia
Intermenstrual, post coital bleeding

OBSTETRIC HISTORY
- Parity, pregnancy outcomes/losses & complications
- Pregnancy termination, septic abortion, ectopic
pregnancy
108

Female Infertility

PAST HISTORY
-

Medical illness, previous surgeries, wound infection


H/o thyroid disease, galactorrhoea, headache, visual
field defect, hirsutism
H/o PID , STD
Previous abnormal pap smear, D&C, Cx biopsy, DC
cautery, HSG
H/o tuberculosis, contact history
Drug history, h/o contraception
109

Female Infertility

FAMILY HISTORY
- Early menopause, reproductive failure
PERSONAL HISTORY
- Use of tobacco, alcohol, smoking, drug abuse
- Eating habit, exercise
PHYSICAL EXAMINATION
- Weight/ BMI/ Secondary sexual characteristic
- Signs of androgen excess
- Thyroid enlagement, nodules, tenderness
- Breast secretion, character

110

Female Infertility

SYSTEMIC EXAMINATION
-

Renal disease, hepatic disease


Abdominal masses, pelvic masses
Vaginal abnormality, cervical abnormality
Abnormal secretions and discharge
Size of the uterus, adenexal masses, tenderness
on cx motion, nodularity in adenexae or cul-de-sac

111

Female Infertility

Initial advice for people concerned about delays in


conception:

Cumulative probability of pregnancy in general


population:
84% in 1st year
92% in 2nd year
Fertility declines with a womans age

112

Female Infertility

Lifestyle advice:
Sexual intercourse every 23 days
12 units alcohol/week for women; 34
units/week for men
Smoking cessation programme for smokers
Body mass index of 1929
Information about prescribed, over-the-counter
and recreational drugs
Information about occupational hazards

113

Female Infertility

Offer preconceptional advice:


Folic acid
Rubella susceptibility and cervical screening

114

Female Infertility

Investigation
Any investigation for infertility couple should begin
with:
- Semen analysis
- Confirmation of ovulation
- Documentation of tubal pathology

115

Female Infertility

Initial assesment
TLC/ DC/ Bl group/ RBS/ Hb/ ESR
Chest x ray/sputum AFB/ RFT/ LFT/HVS c/s

Assessment of ovulation
Frequency and regularity of menses
Endometrial biopsy (+ AFB culture)
Follicular study
Progesterone level/ FSH,LH level
Urinary LH excretion
BBT, Cx mucous study

116

Female Infertility

Test for tubal patency

HSG/ Laparoscopy chromotubation


TVS & Saline hysterosalphingography
(Transvaginal hydrolaparoscopy & fertiloscopy)
(Falloposcopy)

Test for uterine abnormality


Hysteroscopy
TVS & Saline hysterosalphingography

Laparoscopy
117

Female Infertility

Test for ovulatory factors

MENSTUAL HISTORY

BASAL BODY TEMPERATURE

Body temperature under basal condition


Procedure
Smoking forbidden
Principle: Thermogenic property of progesterone
Rise in 0.4to 0.8 f over the base line

119

Female Infertility

Recording is biphasic in nature


Falls to lowest before ovulation &
before menses
Objective evidence of ovulation and its
approx time
BBT is still useful and may be the best
method for couple who are reluctant or
unable to persue more formal and costly
evaluation

120

Female Infertility

PROGESTERONE CONCENTRATION

Level remains below 1ng/ml,


rise 1-2ng/ml on the day of LH surge,
peaks 7-8 days after ovulation

Mid luteal peak i.e day 21-23 of 28 days cycle

Level of 3ng/ml documents ovulation

Day of measurement: Day 21 of day 28, where ovulation


occur on day 14

122

Female Infertility

Normal cycle 21-35 days,


ideal 1 week before the expected date of menses
& morning hour is the best time to test
Has been used for quality of luteal function

There is no consensus minimum serum


progesterone concentration that defines normal
luteal function.

A midluteal serum progesterone level


greater than 10 ng/mL is a popular standard

A midluteal serum progesterone


concentration cannot define the quality of
luteal function and has little value beyond
documenting ovulation
123

Female Infertility

URINARY LH EXCRETION

Ovulation prediction kits/ LH kits , detects mid cycle LH


surge
LH surge is a brief event lasting 48-50hours
Ovulation occurs 12-26 hours after onset of LH surge
and almost always within 48 hrs
Consequently,the interval of greatest fertility includes the
day the surge is detected and the following 2 days
Using ELISA 40mIU/ml taken as threshold

124

Female Infertility

Short half life, rapidly cleared via urine, exceed threshold


level during LH surge

Done on daily basis, beginning 2-3 days before surge is


expected

Results sensitive to volume of urine and time of day

125

Female Infertility

ENDOMETRIAL BIOPSY
-

Based on the characteristic histological change


brought about by progesterone
Secretory endometrium implies recent ovulation
Simple office procedure
Performed on day 21-24
Pretreatment with NSAID, sedation, paracervical block
Until recently, EB to exclude luteal phase deficiency is no
longer practiced

126

Female Infertility

FOLLICULAR STUDY

TVS monitoring of the developing dominant follicle prior to and


immediately after ovum release

Gives detailed information of size and number of pre-ovulatory


follicle

Time of test: day 12 of menses till ovulation

Follicle reaches size upto 21-23mm


( 17mm 29mm)

127

Female Infertility

Ovulation documented: abrupt decrease in the


size of follicle & fluid in the posterior culde-sac

Abnormal pattern of follicular development


- at abnormal pace, collapse when follicle is still
small
- Continue to grow but fail to rupture & persists as
a cyst
- T/T with NSAID can disrupt ovulatory
process
128

Female Infertility

Test for tubal factors


HSG

Out patient procedure,


less costly, therapeutic
values
Uncomfortable and
painful
Risk of infectious
complication & radiation
exposure
Images uterine cavity and
reveals internal
architecture of tubal
lumen

Laparoscopy

- More invasive, requires GA


- Anaesthesia complication
- Accidental injuries to bowel

and blood vessels

- Detailed information of

pelvic anatomy including


adhesion, endometriosis &
ovarian pathology and
their treatment
129

Female Infertility

HYSTEROSALPHINGOGRAPHY (HSG)

Sensitivity of 85-100% in detecting tubal diseases


Specificity of 90% in detecting PID related disease
Indication
To establish tubal patency
To diagnose developmental anomalies of uterus
Can identify submucous myoma, endometrial polyp,
intrauterine adhesion
Time
Between cycle days 6and 11
Pretreatment: Antibiotic, NSAID

130

Female Infertility

Procedure
-

Vaginal cleansing
An acorn (Jascho) cannula or via ballon catheter
introduced
Contrast material is then injected
- Water soluble contrast media ( Meglumine
diatrizoate, Renografin 60)
- Oil-based (Ethiodol)
Volume of contrast
- Initial 3-4ml: outline of uterine cavity
- Further 5-10ml: demonstrate B/L tubal patency
131

Female Infertility

Water soluble contrast


-

Rapid absorption
Less risk

Better resolution tubal


architecture
No such action

Low

Pregnancy rate 17%

Oil based contrast


- Less rapid
- More risk of lipid embolism,

lipid granuloma formation


- Less
- Flushes out inspissated

mucus & debris


- High post procedure
pregnancy rate
- Pregnancy rate 33%

132

Female Infertility

Image intensification fluoroscopy should be used


with minimal radiation exposure
3 basic films are required
- A scout
- One to detect uterine countour & tubal patency
- Post evaluation to detect area of contrast
loculation
- Additional when uterus obscure tubes & uterine
cavity is abnormal
133

Female Infertility

Contraindication
-

Hydrosalphinx
Current PID
Cervicitis
Palpable adenexal mass
Tenderness on bimanual examination

134

Female Infertility

Complication
-

Infection(0.3%-1.3%)
Cx laceration
Uterine perforation
Haemorhage
Vasovagal reaction
Allergic response to dye
Radiation exposure

135

Female Infertility

Instruments of Hysterosalpingography:

Volsellum

Speculum

Higar dilator

Screw cannula

Contrast media

Timing : should be performed within 6and 11 day of


cycle .

1-Long thin tubal outline.


2-ill defined peritoneal spillage.
3-Anteverted triangular uterus,
Normal size : 2.5 5 cm.
1
3
2

Diagnosis: normal film.


Description: small uterus (nulliparous)

1-Long thin tubal outline.


2-ill defined peritoneal spillage.
3-Anteverted triangular uterus.
1
3
2

Diagnosis: normal film.


Description: large uterus (multiparous)

Diagnosis: normal film.


Description: very large uterus.

Diagnosis: retroverted uterus.


Description: deviation from medline.

Diagnosis: arcuate uterus.


Description: partial separation (forming right angle).

Diagnosis: unicornuate uterus.


Description: one cornua , one tube , one spillage.

Uterus Unicornis
1 tube
1 uterus

Diagnosis: unicornuate uterus.


Description: one cornua , one tube , one spillage.

Diagnosis: bicornuate uterus with filling defects.


Description: differential diagnosis: fibroids , air bubbles ,
bowel gas.

Diagnosis: bilateral hydrosalpinges with patent fallopian


tube.

Description: dilatation of tubes.

Diagnosis: bilateral hydrosalpinges with patent fallopian


tube.

Description: saccular dilatation of tubes.

Diagnosis: uterine fibroid.


Description: large, Irregular outline uterus with
multiple filling defects.

Diagnosis: Hydrosalpinx.
Description: take different size and shape of dilatation
(sacculation).

Diagnosis: uterine fibroids.


Description: constant filling defect (immobile).

Diagnosis: uterine fibroids.


Description: constant filling defect (immobile).

Diagnosis: adenomyosis.
Description: irregular outline, multiple diverticulum..

Diagnosis: small narrow uterus.


Description: differential diagnosis : Asherman , DC,TB
uterus.

Case 34

Diagnosis: fallopian tube ligation.


Description: absent uterine tube at both sides.

LAPAROSCOPY

Gold standard

Indication
- Abnormal HSG
- Failure to conceive of normal HSG
- Unexplained infertility
- Age > 35years

154

Female Infertility

Procedure
-

Scheduling, antibiotics and risk of infection


Performed under GA, deep anesthesia or local anesthesia
Systematic and thorough inspection of pelvis
Include uterus, anterior and posterior cul-de-sac, ovarian
surfaces and fossa and fallopian tubes
Chromotubation: Injection of dilute dye through the cervix
( Indigo carmine dye/ methylene blue)

155

Female Infertility

Operative finding : Photographed


Can identify
- Distal tubal occlusion( fimbrial agglutination)
- Pelvic or adenexal adhesion
- Endometriosis
Therapeutic
- Lysis of filmsy adhesion or focal lesion
- Ablation or excision of superficial
endometriosis
156

Female Infertility

SALINE
HYSTEROSALPHINGOGRAPHY
-

Sono hysterography has better sensitivity than HSG in


intrauterine lesion
Saline sono hysterosalphingography extension of the
procedure to asses tubal patency

Timing
- Proliferative phase : Endometrial polyp
- Secretory phase: Submucous fibroid
- Pregnancy to be ruled out

157

Female Infertility

Preparation
-

Pelvic infection ruled out, Prophylactic antibiotic,


NSAID
Standard Transvaginal USG carried out
Fibroid, adenexal masses, thickened endometrium
Introduction of saline through a catheter

Interpretation
- Detection of saline in POD indicated tubal patency
- Hysterosalphingo contrast sonography( HyCoSy)
Contrast media consisting of surfactan

158

Female Infertility

TRANSVAGINAL HYDOLAPAROSCOPY AND FRETILOSCOPY

Based on the technique COLDOSCOPY


Procedure
- Veres needle inserted through post. fornix LA
- 200ml saline introduced, endoscope introduced
- Pelvic pathology visualized
-

Fertiloscopy extension of hydrolaparoscoy, endoscope is


introduced through fimbrial end
- Allows visualization of tubal ostial spasm, Abn tubal mucosal
pattern, intraluminal debris

159

Female Infertility

Test for uterine factors

3 basic methods: HSG, TVS, Saline/ contrast


sonohysterography

TRANSVAGINAL USG
Modern transducers produce high resolution images
Endovaginal probes yield details of
- Uterus, ovaries or adenexal pathology
- Fallopian tubes cannot be visualised
Saline sonohysterosalphingography performed

160

Female Infertility

Indication
-

Identification of congenital malformation


Septate, bicornuate, unicornuate, didelphus
Adenexal mass
Endometrial polyp, submucous fibroid
Intrauterine adhesion

Timing
- In all phases of the cycle
Diagnostic accuracy can be compared with
hysteroscopy

161

Female Infertility

HYSTEROSCOPY
-

Gold standard for diagnosis & treatment

Indication
-

Abnormal HSG/ TVS: Endometrial polyp, myoma, uterine septum


or intrauterine adhesions
Unexplained infertility
Recurrent spontaneous abortion

162

Female Infertility

Procedure
-

Performed as office procedure

Prior administration of intravaginal Misoprostol


200g

In infertility, best initial choice for diagnosis and


treatment of suspicious intrauterine lesion

163

Female Infertility

Therapeutic
-

Endometrial polyp: Polypectomy


Submucous fibroid: Hysteroscopic myomectomy
Uterine septum: Division
Intrauterine adhesion: Adhesiolysis
Unmedicated IUD / ballon
catheter
Estrogen therapy 2 months

164

Female Infertility

Test for cervical factor


POST COITAL TEST

( SIMS HUNNER TEST)

Objective
- To assess quality of cervical mucous
- To assess presence of number or motile sperm
- To see interaction between Cx mucous and sperm
Prerequisite
- Absteinence for 48hrs, no lubricants, douching, medications
- Performed shortly before ovulation, examined within 212hours of coitus
- The post coital test for diagnosis of cervical factor is no longer
recommended
165

Female Infertility

Cervical mucous study

Volume : copius and thin


Clearity : watery and clear
PH: 6.8 - 7.4 at the time of ovulation
Cellularity:
Viscosity: Spinnbarkeit , length that can be stretched
10cm
Salinity: Fern pattern, complexity of network of crystal
Poor quality: Improper timing, cervicitis, CIN, anti
estrogens like chlomiphene citrate

166

Female Infertility

Presence of no. of motile sperm

Presence one motile sperm/hpf in most fields normal


Confirms effective coital technique and survival
Motile sperm predicts normal semen quality
Negative results
- Ineffective coital technique
- Failed ejaculation
- Poor semen quality
- Use of lubricants/spermicide

167

Female Infertility

Interaction between cervical mucous and sperm

Presence of >25% sperm exhibiting shaking and jerky


movement / immotile sperm Anti sperm antibodies

Test for antisperm antibodies


Sperm agglutination test
Sperm compliment dependant immobilization
Immunobead test
Mixed agglutination test

168

Female Infertility

Thank you