Female infertility,Prof.Salah Roshdy

Female Infertility
Prof.Salah Roshdy,MD
Prof. of Obstetrics & Gynecology
Sohag University
2018

Objectives
 know definitions of primary and secondary
infertility
 • understand the causes of infertility
 • know the initial investigations of the
infertile couple
 Investigate male factor
 • Test for ovulation
 • Test for tubal patency
 • Investigation role of laparoscopy and
hysteroscopy

INTRODUCTION
 Infertility is a common condition with important
psychologic, economic, demographic, and
medical implications.
 Infertility is a unique medical condition because
it involves a couple, rather than a single
individual
 Demand for infertility services has grown
substantially even though the prevalence of
infertility has been stable.

DEFINITIONS
 It is defined as inability of a couple to
conceive after 12 months of regular
intercourse without use of contraception in
women less than 35 years of age; and
 after six months of regular intercourse
without use of contraception in women 35
years and older.
 Some clinicians use the term subfertility to
describe this failure to conceive unless the
couple has been proven to be sterile.

Primary infertility
is the term used to describe
a couple that has never
been able to conceive ,after
at least 1 year of
unprotected intercourse.

Secondary infertility
Secondary infertility describes
couples who have previously
been pregnant at least once,
but have not been able to
achieve another pregnancy.

Fecundability
the probability of achieving a
pregnancy in one menstrual
cycle, is a more accurate
descriptor because it
recognizes varying degrees
of infertility.

NORMAL FERTILITY
 A study examined the number of months to
conception in 5574 normal women who had
unprotected intercourse and who became
pregnant . Eighty-five percent of the women
conceived within 12 months.
 Five to 15 percent of apparently normal couples
will conceive in the second 12 months of
attempted conception so that after 24 months ,
95 percent of couples will have conceived.

Natural Cumulative Pregnancy
Rate
1
2
3
4
5
6
7
8
9
10
11
12
24
0
10
20
30
40
50
60
70
80
90
1 2 3 4 5 6 7 8 9 10 11 12 24
% pregnant/month
Months of trying

PREVALENCE Of INFERTILITY
ranges from 12 to 18 %.
women 15 to 34 years (7.3 to
9.1 percent)
 35 to 39 years (25 percent)
40 to 44 years (30 percent).

 The World Health Organization (WHO) task
force on Diagnosis and Treatment of Infertility
performed a study of 8500 infertile couples and
utilized standard diagnostic criteria to determine
the medical conditions contributing to infertility.
 female factor : 38 %
 Male factor : 20%
 Both : 27%
 UI : 15%

Male factor
 1-Endocrine and systemic disorders
(hypogonadotropic hypogonadism)2-5%
 A-Congenital disorders
 Congenital GnRH deficiency (Kallmann
syndrome).
 Multiorgan genetic disorders (Prader-Willi
syndrome, Laurence-Moon-Beidl
syndrome, familial cerebellar ataxia).

 B- Acquired disorders
 A Pituitary and hypothalamic tumors (pituitary
macroadenoma, craniopharyngioma)
 Pituitary and hypothalamic infiltrative disorders
(sarcoidosis, histiocytosis, tuberculosis, fungal
infections)
 Pituitary and hypothalamic lymphocytic
infundibulitis or hypophysitis
 Head trauma, intracranial radiation, or surgery

 Vascular (pituitary infarction, aneurysm)
 Hormonal (hyperprolactinemia, androgen
excess, estrogen excess, cortisol excess)
 Drugs (exogenous androgens, opioids and
psychotropic drugs, GnRH agonists or
antagonists)
 C-Systemic disorders:
 Severe systemic illness,Nutritional
deficiencies,Morbid obesity

2-Primary testicular defects in
spermatogenesis(65 to 80 %)
 A-Congenital disorders;
 Klinefelter syndrome (XXY) and its variants
(XXY/XY; XXXY)
 Cryptorchidism
 Myotonic dystrophy-Functional prepubertal
castrate syndrome (congenital anorchia)
 Androgen insensitivity syndromes-5-alpha-
reductase deficiency-Estrogen receptor or
synthesis disorders

 B-Acquired disorders
 Varicocele
 Infections – Viral orchitis (mumps, echovirus,
arbovirus); granulomatous orchitis (leprosy,
tuberculosis); epididymo-orchitis (gonorrhea,
chlamydia)
 Drugs - Alkylating agents, alcohol,
antiandrogens, ketoconazole, spironolactone,
histamine 2 receptor antagonists, ionizing
radiation

 Environmental toxins - Dibromochloropropane,
carbon disulfide, cadmium, lead, mercury,
environmental estrogens and phytoestrogens;
smoking; hyperthermia
 Immunologic disorders, including polyglandular
autoimmune disease and antisperm antibodies
 Trauma
 Testicular torsion

 C-Systemic illness
 Idiopathic dysspermatogenesis
 Renal failure, hepatic cirrhosis, cancer, sickle
cell disease, amyloidosis, vasculitis, celiac
disease
 D-Genetic causes of dysspermatogenesis
Y chromosome microdeletions and related
disordersAutosomal and X chromosome
defectsMutations causing severe defects in
sperm morphology

 D-Sperm transport disorders(5%)
 Epididymal dysfunction (drugs,
infection)Abnormalities of the vas deferens
(congenital absence, Young syndrome,
infection, vasectomy)Seminal vesicles and
prostate-Ejaculatory ducts disorders
 E-Sexual dysfunction:
Infrequent vaginal intercourse, erectile
dysfunction, and premature ejaculation
 F-Idiopathic male infertility(10-20%)

 Male factor ----- 26 %
 ● Ovulatory dysfunction – 21 %
 ● Tubal damage – 14 %
 ● Endometriosis – 6 %
 ● Coital problems – 6 %
 ● Cervical factor – 3 %
 ● Unexplained – 28 %

 Ovulatory disorders ● (25 percent)
 ● Endometriosis (15 percent)
 ● Pelvic adhesions (12 percent)
 ● Tubal blockage (11 percent)
 ● Other tubal abnormalities (11 percent)
 ● Hyperprolactinemia (7 percent)

1-OVARY
 Ovulatory disorders:
Infrequent ovulation (oligoovulation)
or
absent ovulation (anovulation).
Oocyte aging:
 Ovarian cysts:

An
Anovulation
Hypothalamic
Pituitary
Ovarian
Physiologic
• Adolescence
• Perimenopause
• Lactation
• Pregnancy
Hyperandrogenic
• PCOS
• CAH
• Androgen tumors
Hypothalamic Dysfunction
• Primary hypothalamic
• Anorexia Nervosa
• Extreme exercise
• Hyperprolactinemia
• Thyroid disease
• Primary pituitary disease
• Medications
• Premature ovarian failure
• Iatrogenic (chemo/rad)
Hyperinsulinemic
• PCOS
• DM/Pre-diabetes
• Metabolic syndrome
• Obesity
Endometrial

Causes of ovulatory dysfunction
 1-Primary hypothalamic-pituitary dysfunction:
 Intense exercise -Eating disorders –Stress
 Idiopathic hypogonadotropic hypogonadism
 Hyperprolactinemia -Lactational amenorrhea
 Pituitary adenoma or other pituitary tumors
 Kallman's syndromeTumors,
 Trauma, or radiation of the hypothalamic or pituitary area
 Sheehan's syndrome -Empty sella syndrome
 Lymphocytic hypophysitis (autoimmune diseases)

 2-Other disorders:
 Polycystic ovary syndrome
 Hyperthyroidism or hypothyroidism
 Hormone producing tumors (adrenal, ovarian)
 Chronic liver or renal disease
 Cushing's disease-Congenital adrenal
hyperplasia
 Premature ovarian failure, which may be
autoimmune, genetic, surgical ,idiopathic, or
related to drugs or radiation
 Turner syndrome-Androgen insensitivity S.

 3-Medications:
 Estrogen-progestin contraceptives
 Progestins
 Antidepressant and antipsychotic
drugs
 Corticosteroids
 Chemotherapeutic agents

World Health Organization
classification of anovulation
 WHO class 1: Hypogonadotropic
hypogonadal anovulation
(hypothalamic amenorrhea):
 low or low-normal serum (FSH) and
 low serum estradiol concentrations due to
decreased hypothalamic secretion of
(GnRH) or pituitary unresponsiveness to
GnRH.

WHO class 2: Normogonadotropic
normoestrogenic anovulation
 These women may secrete normal
amounts of gonadotropins and estrogens.
However, FSH secretion during the
follicular phase of the cycle is subnormal.
 This group includes women with polycystic
ovary syndrome (PCOS). Some ovulate
occasionally, especially those with
oligomenorrhea.

 WHO class 3: Hypergonadotropic
hypoestrogenic anovulation:
The primary causes are premature ovarian
failure (absence of ovarian follicles due to
early menopause) and ovarian resistance
(follicular form).
 Hyperprolactinemic anovulation

Anovulation
LHRH
FSHLH
Hypothalamo-
pituitary
WHO Type 1:
Hypogonadotrophic
Nearly everyone conceives
Anovulation WHO Type 2:
Normogonadotrophic
Most women conceive
Ovarian failure WHO Type 3:
Hypergonadotrophic
Conception remote chance
without donated oocytes

The Clues
Hot flushes
Irregular/absent periods
Short cycle
Amenorrhoea
Weight loss/Exercise/Stress
Drug-induced
Other disease
LHRH
FSHLH
Irregular menses
Weight gain
PCOS signs/symptoms

 NIH Criteria 1990:
 Menstrual irregularity due to
anovulation or oligo-ovulation
 Evidence of clinical or biochemical
hyperandrogenism
 Hirsutism, acne, male pattern baldness
 High serum androgen levels
 Exclusion of other causes (CAH,
tumors, hyperprolactinemia)

 Rotterdam Criteria (2 out of 3)2003:
 Menstrual irregularity due to
anovulation oligo-ovulation
 Evidence of clinical or biochemical
hyperandrogenism
 Polycystic ovaries by US
 presence of 12 or more follicles in each ovary
measuring 2 to 9 mm in diameter and/or increased
ovarian volume.
* In addition, other etiologies (congenital adrenal
hyperplasias, androgen-secreting tumors, Cushing's
syndrome) must be excluded.

 AES criteria 2006:
Presence of three features
 Androgen excess (clinical and/or
biochemical hyperandrogenism)
 Ovarian dysfunction (oligo-anovulation
and/or polycystic ovarian morphology)
 Exclusion of other androgen excess or
ovulatory disorders

Polycystic Ovaries Cystic Follicles
Uterus
Tube
Anatomic Features of
the Polycystic Ovary

Oocyte aging
 Age is an important factor affecting a woman's
fertility . The decrease in fecundability with aging
is likely due to a decline in both the quantity and
quality of the oocytes.
 The germ cell complement of the ovary reaches
its apex of 6 to 7 million follicles in the
midgestation female fetus, followed by a steady
attrition from 1 to 2 million follicles at birth to
300,000 follicles at the onset of puberty . The
rate of follicle loss accelerates after the woman
reaches her midthirties.

Oocyte aging
 Other insults to the ovary such as cigarette
smoking, radiation,chemotherapy, and
autoimmune disease also accelerate
follicular loss.
 Women with a depleted ovarian follicle
pool may continue to ovulate regularly, but
have infertility due to the poor quality of
oocytes remaining in the terminal follicular
pool.

Oocyte aging
 The loss of oocyte quality as a woman ages is
thought to be due to an increase in meiotic
nondisjunction.
 Hypothesized mechanisms involve differences
between germ cells when formed during fetal
life, damage in germ cells that accumulates over
the course of a woman’s life, or age related
changes in the quality of the granulosa cells
surrounding the oocyte.

Ovarian cysts
 A review of epidemiologic data, drawn
mainly from comparative studies and
cohorts,concluded that it is unclear
whether small (<3 to 6 cm) ovarian cysts
have a role in infertility and that the effects
of surgical treatment are often more
harmful than the cyst itself to the ovarian
reserve.

2-FALLOPIAN TUBE
ABNORMALITIES/PELVIC ADHESIONS
 Tubal disease and pelvic adhesions
prevent normal transport of the oocyte and
sperm through the fallopian tube.
 PID
 Severe endometriosis
 Previous surgery or nontubal infection (eg,
appendicitis, inflammatory bowel disease),
 Pelvic TB, and salpingitis isthmica nodosa
(ie, diverticulosis of the fallopian tube)

 Women with distal tubal obstruction may
develop hydrosalpinges, which decrease the
success rate of (IVF). In addition to obstruction
to sperm migration, hydrosalpinges appear to
reduce fertility by
 retrograde flow of tubal contents into the
endometrial cavity, which creates a hostile
environment to implantation of an embryo.
 Removal of the hydrosalpinges increases the
success of IVF

Hydrosalpinx:
 There is good evidence for recommending
 laparoscopic salpingectomyor
 proximal tubal occlusion
 to improve IVF pregnancy rates.

 Treatment of hydrosalpinx before IVF
Negative effect on PR, IR, early pregnancy loss
& LBR. LBR are reduced by 50%
 WHY?
 The fluid of hydrosalpinx:
 1.Mechanical barrier to implantation: embryo to float
 2.Deficient to support the developing embryo
 3.Toxic to the developing embryo

Classification of Tubal disease
 British Fertility Society
 Minor
 Proximal occlusion without tubal fibrosis
 Distal occlusion without tubal distension
 Healthy mucosal appearance at HSG,
salpingoscopy
 Flimsy peritubal/ovarian adhesions.

 Intermediate
 Unilateral severe tubal damage
 Limited dense adhesions of tubes & ovaries
 Severe
 Bilateral severe tubal damage
 Extensive tubal fibrosis
 Tubal distension >1.5 cm
 Abnormal mucosal appearance
 Bipolar occlusion
 Extensive dense adhesion

3-UTERUS
 Impaired implantation, either mechanical or due
to reduced endometrial receptivity, are the basis
of uterine causes of infertility
 Uterine leiomyomata:A meta-analysis showed
 that only leiomyomata with a submucosal or
intracavitary component were associated with
lower pregnancy and implantation rates.
 The likely mechanism is inhibition to normal
implantation.

 Uterine anomalies; Uterine abnormalities are
thought to cause infertility by interfering with
normal implantation. Müllerian anomalies are a
significant cause of (RPL), with the septate
uterus associated with the poorest reproductive
outcome .
 Other structural abnormalities associated with
infertility include endometrial polyps, and
synechiae from prior pregnancyrelated
curettage.

 ENDOMETRIOSIS —
Mechanisms which decrease fertility in women
with endometriosis include
 Anatomic distortion from pelvic adhesions,
damage to ovarian tissue by endometrioma
formation and surgical resection,
 and the production of substances such as
cytokines and growth factors which impair the
normal processes of ovulation, fertilization, and
implantation.

4-CERVICAL FACTORS
 Normal midcycle cervical mucus
facilitates the transport of sperm.
 Congenital malformations and trauma
to the cervix (including surgery) may
result in stenosis and inability of the
cervix to produce normal mucus,
thereby impairing fertility.

5-IMMUNE FACTORS
 Antiphospholipid syndrome :
 It may lead to immunological rejection of
the early pregnancy or placental damage.
 Evaluation for this disorder depends upon
the patient's medical and family history and
whether infertility is related to recurrent
early pregnancy failure (workup indicated)
or failure to conceive (workup not
indicated).

6-GENETIC CAUSES
 Infertile couples have been shown to have a
higher prevalence of karyotype abnormalities
(trisomies, mosaics, translocations, etc) than the
general population .
 The frequency varies according to the cause of
infertility and clinical history.
 The most common aneuploidies associated with
infertility are 45, X (Turner syndrome) in women
and 47, XXY (Klinefelter syndrome) in men.

7-UNEXPLAINED
 Unexplained infertility is the
diagnosis given to couples after a
thorough evaluation has not revealed
a cause. Many cases of unexplained
infertility may be due to small
contributions from multiple factors.

When To start Workup
( investigations)?
 An infertility evaluation is usually initiated after
one year of regular unprotected intercourse in
women under age 35 years and after six months
of unprotected intercourse in women age 35
years and older.
 However, the evaluation may be initiated sooner
in women with irregular menstrual cycles or
known risk factors for infertility, such as
endometriosis, a history of PID, or reproductive
tract malformations.

The Most Important
Factor in the
Evaluation of the
Infertile Couple Is:
History

From: The diagnosis of male infertility: an analysis of the evidence to support the development of global WHO guidance—
challenges and future research opportunities
Hum Reprod Update. 2017;23(6):660-680. doi:10.1093/humupd/dmx021
Hum Reprod Update | © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction
and Embryology.This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the

History-General
 Both couples should be present
 Age
 Previous pregnancies by each partner
 Duration of infertility
 Sexual history
 Frequency and timing of intercourse
 Use of lubricants
 Impotence, dyspareunia
 Contraceptive history

History-Female
 Previous female pelvic surgery
 PID
 Appendicitis
 IUD use
 Ectopic pregnancy history
 Endometriosis
 Leiomyoma

History-Female
 Irregular menses, amenorrhea, detailed
menstrual history
 Molimina
 Vasomotor symptoms
 Changes of hair growth.breast discharge
 Stress
 Weight changes
 Exercise-drug –radiation -chemotherapy
 Cervical and uterine surgery

Physical Exam-Female
 Thyroid exam
 BMI
 Hair distribution
 Galactorrhea
 Scar in the abdomen
 Pelvic masses
 Uterosacral nodularity
 Abdominopelvic tenderness
 Uterine enlargement
 Uterine mobility
 Cervical abnormalities
 Abnormal vaginal discharge

 Very long list of tests, have been
advocated to assist in
determining the cause of the
infertility in the diagnostic
evaluation of infertile couple.
 The necessity and cost effectiveness
of performing many of these tests and
correcting the abnormalities found by
them have not been demonstrated.

1-Investigations of Male Factor
 Conventional semen analysis
 Computer- assisted sperm analysis (CASA)
 Strict sperm morphology "Tygerberg strict criteria“
 A variety of sperm function tests
- The acrosome reaction test
- Hypo-osmotic swelling test
- Measurement of generation of Reactive oxygen species
- Sperm capacitation assays
- Hemizona-binding assay
- Hamster penetration test
- Human sperm-zona penetration assay
 A variety of imaging techniques for detection of varicocele

Semen Analysis
 Semen analysis is the key laboratory
assessment of the male partner of an infertile
couple. The standard semen analysis
consists of the following:
 Semen volume and pH
 ● Microscopy for
• Sperm concentration, count, motility, and
morphology • Debris and agglutination
• Leukocyte count• Immature germ cells

Semen Analysis
 The semen sample should be collected
after two to seven days ejaculatory
abstinence.
 If possible, the patient should collect the
sample by masturbation at the doctor's
office. If not possible, then the sample may
be
 collected at home and delivered to the
laboratory within an hour of collection.

Semen Analysis
 Volume – 1.5 ● mL (95% CI 1.41.7)
 ● Sperm concentration – 15 million
spermatozoa/mL (95% CI 1216)
 ● Total sperm number – 39 million
spermatozoa per ejaculate (95% CI 33-
46)
 ● Morphology – 4 percent normal forms
(95% CI 34),

Semen Analysis
 using "strict" Tygerberg method :
 ● Vitality – 58 percent live (95% CI 5563)
 ● Progressive motility – 32 percent (95%
CI 3134)
 ● Total (progressive + nonprogressive)
motility – 40 percent (95% CI 3842)

2-Assessment of ovulation
 Basal body temperature
 Urine LH kits
 Mid luteal serum progesterone
 Routine hormonal profile: FSH, LH, Prolactin,TSH
 Endometrial biopsy
 Serial pelvic Ultrasonography.
 A variety of tests for assessment of ovarian reserve such as D3
FSH & E2, Inhibin B, Clomid challenge test, Gondotropin
agonist stimulation test, TVS for ovarian volume, antral follicle
count and Stromal blood flow.

Evidence of ovulation:
 1. Menstrual history of regular cycles.
 2. Serum progesterone in the mid-luteal
phase of their cycle (day 21 of a 28-day
cycle) even if they have regular menstrual
cycles.
 3. Serum gonadotrophins ( FSH & LH) on
Day2-3 especially in irregular periods.
 (N.B.: No role for basal body temperature
charts)

Further investigations
 Ovarian reserve
 -More important in >35 years old, suspected
ovarian failure and to detect response to
ovulation induction.
 1. Total antral follicle count.
 2. AMH of less than or equal to 5.4 pmol/l for a
low response and greater than or equal to 25.0
pmol/l for a high response
 3. FSH greater than 8.9 IU/l for a low response
and less than 4 IU/l for a high response.

D 3 FSH
 Both the day 3 FSH level (where day 1 is the
first day of full menstrual flow)and the CCCT,
which is a provocative test for measurement of
FSH, are widely used for screening ovarian
reserve.
 The CCCT involves oral administration of 100
mg clomiphene citrate on cycle days 5 through 9
with measurement of day 3 and day 10 FSH
levels and day 3 estradiol level.
 A value less than 10 mIU/mL suggestive of
adequate ovarian reserve.

Antral follicle count (AFC)
 Ultrasound examination can be used to
determine the number of antral follicles (defined
as follicles measuring 2 to 10 mm in diameter).
On transvaginal ultrasound,
 The ovaries are visualized in their transverse
and longitudinal planes and the antral follicles
are counted and measured; the size of the
follicle is the mean of two perpendicular
diameters, one of which should be the largest
dimension of each follicle

AFC
 A low AFC ranging from <4 to 10 antral
follicles between days two and four of a
regular menstrual cycle suggests poor
ovarian reserve.
 Although AFC is a good predictor of
ovarian reserve and response,
 it is less predictive of oocyte quality,the
ability to conceive with IVF, and pregnancy
outcome.

Antimüllerian hormone (AMH)
 is expressed by the small (<8 mm) preantral and
early antral follicles. The AMH level reflects the size
of the primordial follicle pool, and may be the best
biochemical marker of ovarian function across an
array of clinical situations.
 The AMH level appears to be an early, reliable, direct
indicator of declining ovarian function.
 AMH level correlates with the number of oocytes
retrieved after stimulation, and is the best biomarker
for predicting poor and excessive ovarian response.

AMH
 Unlike the day 3 FSH, AMH can be
measured anytime during the menstrual
cycle.
 AMH <0.5 ng/mL predicts reduced ovarian
reserve with less than three follicles in an
IVF cycle
 ● AMH <1.0 ng/mL predicts baseline
ovarian reserve with a likelihood of limited
eggs at retrieval.

AMH
 ● AMH >1.0 ng/mL but <3.5 ng/mL
suggests a good response to stimulation
 AMH >3.5 ng/mL predicts a vigorous
response to ovarian stimulation and
caution should be exercised in order to
avoid ovarian hyperstimulation syndrome.

No evidence for:
 - ovarian volume
 - ovarian blood flow
 - inhibin B
 -estradiol (E2)

3-Investigations of tubal factor
 Hysterosalpingography (HSG)
 Hysterosalpingo-contrast sonography
(HyCoSy)
 Laparoscopy with chromotubation
 Hydrolaparoscopy.
 Fluoroscopic/hysteroscopic-
selective tubal cannulation.
 Falloscopy

Assessment of the uterine cavity
 Modalities to assess the uterine cavity
include :
 Saline Infusion Sono-
hysterography (SIS)
 Three dimensional sonography
 Hysterosalpingography (HSG)
 Hysteroscopy

ROLE OF LAPAROSCOPY
 Laparoscopy is indicated in women in
whom endometriosis or pelvic
adhesions/tubal disease is suspected
based on physical examination, HSG, or
history (e.g.,, pelvic infection, pelvic
surgery, or ectopic pregnancy).

Laparoscopy as a diagnostic tool in
infertility has diminished markedly
 Today, we rarely perform diagnostic laparoscopy
in infertile women. (Tulandi, 2017)
 1.The benefit of diagnostic laparoscopy with no
risk factors for intra-abdominal adhesions: small.
 2.Treatment of stage I or II endometriosis: small
increase in PR.
 3.Alternative treatments of infertility are available
 Superovulationwith IUI
 IVF.

Indications
 1.Abnormal HSG or US
 2.Young women with history or symptoms
suggestive of pelvic disease. Even if HSG indicates
patency in one or both tubes
 1.A history of PID,
 2.Ectopic pregnancy.
 3.Pelvic surgery.
 4.Chronic pelvic pain
 .5 current dysmenorrhea, pelvic pain, or deep
dyspareunia; previous complicated appendicitis

 3. Three cycles of super ovulation with IUI are
unsuccessful.
 diagnostic laparoscopy or
 IVF treatment (ASRM, 2012; TulandiT 2017)
 4. After failed IVF
 -Laparoscopy after failed IVF:(Littman et al., 2005).
 Pathology in 50%
 endometriosis or adhesions
 No RCTs have confirmed this rate.

HSG Vs Laparoscopy:
 false-negatives are more
 tubal blockages are often false-positives
 obstructions diagnosed by laparoscopy are
most likely true positives.
 Prognosis of a tubal obstruction (unilateral
and/or bilateral) is poorer when diagnosed with
laparoscopy than with HSG (Speroffand Fritz
2011).

TESTS OF LIMITED CLINICAL
UTILITY
 PCT for assessment of the cervical factor.
 Chlamydia trachomatis antibodies .
 Endometrial biopsy
 Basal body temperature records
 Zonafree hamster oocyte penetration test
 Mycoplasma cultures
 Testing for antibodies; antiphospholipid, antisperm,
antinuclear, and antithyroid antibodies.
 Karyotype

The basic infertility evaluation of
all couples consists of:
 Semen analysis
 Assessment of ovulatory function
 Determination of tubal patency and presence or absence
of abnormalities of the uterine cavity,usually by HSG.
 Diagnostic laparoscopy is indicated for women with
suspected endometriosis or pelvic adhesions.
 Ovarian reserve is assessed with day 3 (FSH) and
estradiol levels in women over 35 years of age and in
younger women with risk factors for premature ovarian
failure.

Controversies
 Lack of agreement exists among
trained infertility specialists with regard
to prognostic utility as well as criteria of
normality of many of these tests?
 There is no consensus on which tests
are essential before reaching the exact
diagnosis ?

Investigations of infertile couple
Evidence Medicine Based Era
National Evidence-Based Clinical Guidelines
“Assessment and treatment for people with fertility problems
developed by the National Collaborating Centre for
Women and Children's Health on behalf of
the National Institutefor Clinical Excellence (NICE)”
February 2004

Grading – Evidence Based Recommendations
A
recommendation
I evidence
B
recommendation
II evidence
C
recommendation
III evidence
D
recommendation
IV evidence
I a- meta-analysis
of RCTs trials,
I b- at least one
RCT.
II a - at least one
controlled study
without
randomization
II b - at least one
other type of
quasi-
experimental
study
non-experimental
descriptive
studies, such as
comparative
studies,
correlation
studies and case
control studies
from expert
committee reports
or opinions and/or
clinical experience
of respected
authorities
• GPP Good practice point : The view of the Guideline Development Group
•The design of a quasi-experiment relates to a particular type of experiment or other study in which one has little or no control over the
allocation of the treatments or other factors being studied.

1-Semen analysis
• CASA is not superior to conventional
semen analysis (Grade A)
• Screening for antisperm antibodies
should not be offered because there is
no evidence of effective treatment to
improve fertility. (GPP)

What To Do if Semen analysis Is
Abnormal?
 Repeat confirmatory test ( 3 months after
the initial analysis & ttt). (Grade B).
 If azoospermia or severe oligozoospermia ,
repeat test as soon as possible. (GPP)

Where & When Testicular Biopsy
(TB) be done In Azoospermia?
TB should be performed only in a
tertiary service where there are
facilities for
 Sperm recovery ,
 Cryopreservation and
 ART( C )

2-Assessment of Ovulation
Women with fertility problems should
be asked about the frequency and regularity
of menstrual cycles.
 Women with regular monthly menstrual
cycles are likely to be ovulating. (Grade B)
 The use of basal body temperature charts to
confirm ovulation does not reliably predict
ovulation and is not recommended. (Grade B)

Assessment of Ovulation
 Women with regular menstrual cycles and
more than 1 year’s infertility are offered a
blood test to measure serum progesterone
in the mid-luteal phase of their cycle (day
21 of a 28-day cycle) to confirm ovulation.
(Grade B)

 Ovulation is most easily documented by a
midluteal phase serum progesterone level,
which should be obtained approximately one
week before the expected menses.
 For a typical 28day cycle, the test would be
obtained on day 21. A progesterone level >3
ng/mL is evidence of recent ovulation.

 Women with prolonged irregular menstrual
cycles should be offered a blood test to
measure serum progesterone. Depending on the
timing of menstrual periods, this test may need
to be conducted later in the cycle (for example
day 28 of a 35-day cycle) . (GPP)
 For such women direct or indirect
measurement of progesterone is unnecessary
until after therapy is initiated.

 Women with irregular menstrual cycles
should be offered a blood test to measure
serum FSH & LH (GPP).
 Blood test for prolactin should only be
offered to women who have an ovulatory
disorder, galactorrhoea or a pituitary
tumor. (Grade C)

 Tests of ovarian reserve currently have limited
sensitivity and specificity in predicting fertility.
However, women who have high levels of
gonadotrophins should be informed that they
are likely to have reduced fertility. (Grade C)
 The value of assessing ovarian reserve using
Inhibin B is uncertain and is therefore not
recommended. (Grade C)

 Women with possible fertility problems are no
more likely than the general population to have
thyroid disease and the routine measurement of
thyroid function should not be offered.
Estimation of thyroid function should be
confined to women with symptoms of thyroid
disease. (Grade C).

 Women should not be offered an
endometrial biopsy to evaluate the luteal
phase as part of the investigation of
fertility problems because there is no
evidence that medical treatment of luteal
phase defect improves pregnancy rates
(Grade B).

3-Assessment of tubal factor
The results of semen analysis and assessment of
ovulation should be known before a test for tubal
patency is performed.
 Women who are not known to have co-morbidities
(such as pelvic inflammatory disease, previous
ectopic pregnancy or endometriosis) should be
offered HSG to screen for tubal occlusion because
this is a reliable test for ruling out tubal occlusion,
and it is less invasive and makes more efficient use
of resources than laparoscopy. (Grade B)

Assessment of tubal factor
 Where appropriate expertise is available,
screening for tubal occlusion using
hysterosalpingo-contrast-ultrasonography
should be considered because it is an
effective alternative to HSG for women
who are not known to have co-morbidities
(Grade A)

Assessment of tubal factor
Women who are thought to
have co-morbidities should be
offered laparoscopy and dye so
that tubal and other pelvic
pathology can be assessed at
the same time. (Grade B)

4-Assessing uterine abnormalities
 Women should not be offered hysteroscopy on
its own as part of the initial investigation unless
clinically indicated, because the effectiveness of
surgical treatment of uterine abnormalities on
improving pregnancy rates has not been
established. (Grade B)
women with infertility and a normal HSG had no abnormalities of the
uterine cavity when subsequently examined by hysteroscopy.

HSG should
be
performed
Under
Fluoroscopy
( Grade :D)

Removal of the
speculum
before
scanning
Application of
traction by the
tenaculum during
filling of the uterus
often results in
improved uterine
visualization.
. A complete view
of the
endometrial
cavity and
cervical canal
should be the
aim.
Grade D

Flushing of the tubes with oil-soluble
media increases subsequent
pregnancy rates (It may flush tubal
"plugs" ).
The Cochrane Library, Issue 2 2004.
Oil-soluble # Water Soluble Media for HSG

Sonohysterography # HSG?
The use of sonohysterography
should be considered as an
effective alternative to HSG
(Grade A).
 TVS can add evaluation of pelvis.

Unnecessary laparoscopy!!!
 It is not cost effective to do
diagnostic laparoscopy as part of
the initial infertility evaluation
when:
History, and physical examination,
TVS, HSG, and Midluteal progesterone
are all normal (Grade B)

When To Do Laparoscopy For tubal
evaluation?
 When associated pelvic co
morbidities (PID, previous Ectopic,
endometriosis ..etc) :evaluation of the
pelvis is required.
(Grade B)

Hysteroscopy has NO
role in routine
evaluation
of infertility

Indications of Hysteroscopy as workup of
infertility?
 Abnormal HSG
 When Laparoscopy is indicated as in
Unexplained infertility ?
 Before IVF in cases of
unexplained infertility ?!!!!
 After Failed IVF ?

No Role for...
1. Postcoital test.
2. Endometrial biopsy
3. Antisperm antibodies
4. Routine cervical cultures
5. Thyroid function ( in absence of symptoms
suggestive of of thyroid disease)
6.Prolactin (in absence of galactorrhoea and
…)

Optimum Time For Referral To ART Centers
1. Age > 35 Y.
2. Failed 3 IUI.
3. Severe male subfertility.
4. Number of mature follicles >4 (do not give HCG).
5. Number of follicles (>12 mm) >8 (do not give
HCG).
6. Extensive endometriosis.
7. Need for cryopreservation of semen.
8. Non optimized office.

Female infertility,Prof.Salah Roshdy

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