Female infertility

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FEMALE INFERTILITY
Prof. Aboubakr Elnashar
Benha university Hospital, Egypt
ABOUBAKR ELNASHAR
ABOUBAKR MOHAMED ELNASHAR
CONTENTS
 INTRODUCTION
1. ENDOMETRIOSIS ASSOCIATED INFERTILITY
2. OVARIAN FACTOR
3. TUBAL FACTOR
4. UTERINE FACTOR
5. UNEXPLAINED INFERTILITY
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INTRODUCTION
When to refer a couple for investigations?
After 40 y
Immediate evaluation in women.
35-40 Y
After 6 months of unprotected intercourse without
conception
<35 y
After one year
ABOUBAKR ELNASHAR
Indication for Immediate evaluation: (ACOG&ASRM, 2019)
1. Infertility at age > 40 years
2. Oligomenorrhea or amenorrhea
3. Known or suspected uterine, tubal, or peritoneal disease
4. Stage III or stage IV endometriosis
5. Known or suspected male infertility

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Infertility Evaluation (ACOG, ASRM, 2019)
I. History
II. Physical examination
III. Prepregnancy counselling & evaluation
IV. Evaluation for etiology of infertility
1. Male factor
2. Endometriosis
3. Ovulatory dysfunction
4. Tubal factor .
5. Uterine factor
I. HISTORY
 Personal
 Age.
 Duration of subfertility.
 Special habits: Smoking, number of units alcohol/w.
 Menstrual
 Cycle regularity & LMP (pregnancy test?).
 Pelvic pain (dysmenorrhoea; dyspareunia).
 Contraceptive history
 Sexual
 Frequency, timing
 FSD ABOUBAKR MOHAMED ELNASHAR
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 Obs
 Previous pregnancies.
 History of ectopic pregnancy.
 Past
 Surgical: Previous tubal or pelvic surgery.
 Medical:
 Previous or current STIs.
 Previous PID.
 Thyroid disease
 Drug history: drugs contraindicated in pregnancy
 Family
 birth defects, developmental delay
 early menopause, or reproductive problems
II. EXAMINATION
 General examination
 BMI
 Signs of endocrine disorder:
 Hyperandrogenism
 acne, hair growth, alopecia
 acanthosis nigricans: PCOS
 Thyroid disease: hypo- and hyperthyroidism
 Visual field defects: ? Prolactinoma
 Breast: secretions, tanner staging

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 Pelvic examination
• Exclude obvious pelvic pathology
• Adnexal masses
• Uterine fibroids
• Endometriosis
• painful, fixed uterus,
• Vaginismus.
• Cervical smear.
• Chlamydia screening.
III. PREPREGNANCY COUNSELLING & EVALUATION
1. To reduce the risk of adverse effects for the woman,
fetus, & neonate by:
 Optimize health, correct modifiable risk factors:
diabetes, hypertension, psychiatric, thyroid disease
 Education about healthy pregnancy
2. To maximize fertility
including timing & frequency of intercourse.
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European Society of Human Reproduction &
Embryology (ESHRE) (2000)
Infertility testing should be classified into 3 groups
depending on correlation with pregnancy rates
I. Tests that have an established association with
pregnancy:
1. Conventional semen analysis
2. Tubal patency tests
3. Tests of ovulation
ABOUBAKR ELNASHAR
II. Tests that are not consistently associated with
pregnancy:
 Post-coital test
 Antisperm antibody tests
 Zona-free hamster egg penetration test
III. Tests that have no association with pregnancy:
Endometrial biopsy
 Premenstrual endometrial biopsy
 Varicocele assessment
 Chlamydia testing
ABOUBAKR ELNASHAR

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Not indicated (ACOG, ASRM, 2019)
1. Post coital testing
2. Thrombophilia testing
No benefit if no history or family history of clotting
3. Immunologic testing
It is expensive & does not predict pregnancy
outcome.
Not routinely indicated
1. Endometrial biopsy: Except in
 suspected T.B. or
 endometrial hyperplasia
2. Laparoscopy for unexplained infertility: Unless suspicion of pelvic
pathology
3. Prolactin: Except in
 abnormal menstrual cycles or
 galactorrhea
4. DNA fragmentation testing: Indicated in clinical varicocele + borderline
/normal semen
5. Karyotype: Indicated in
 ↑FSH at <40 Y or
 abnormal sexual development
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1. ENDOMETRIOSIS ASSOCIATED
INFERTILITY
MECHANISM OF INFERTILITY
(Prentice, 2001)
 Infertility affects 30% to 50% of women with
endometriosis.
I- Advanced disease:
Mechanical interference with
Ovulation
Ovum pick up
Tubo-ovarian adhesion
Distorted tubal anatomy.

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II- Minimal & mild disease:
1. Coital problems: dysparunia.
2. Altered peritoneal environment: increase
volume of peritoneal fluid
activated macrophages:
phagocytosis of sperms
decreased sperm motility
Embyotoxicty
3. Altered foliccular maturation:
lutenized unruptured follicle
anovulation
luteolysis caused by prostaglandin F2
 No evidence that they are more common in E.
 On fertility has a detrimental effect. Due to
 Anatomical distortion & tubal damage or
occlusion secondary to pelvic adhesions
1. Poor ovarian reserve with a significant reduction
in the primordial follicle cohort secondary to fibrosis
from increased tissue oxidative stress
2. Poor quality of oocytes & embryo: inconclusive
3. Altered endometrial receptivity
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ENDOMETRIOSIS FERTILITY INDEX
 Clinical tool to predict PR
 Following surgical staging of endometriosis (Johnson et
al, 2017)
 For non IVF conception
 Natural
 OS
 IUI
 Considerable utility in developing treatment plans

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 The sliding sign (Arion et al, 2018)
 Positive
 when anterior rectum& rectosigmoid colon
glided freely across the posterior cervix& upper
posterior uterus, respectively.
 was associated EFI (6-9)
 Negative
 when there was attachment at least one site
between the colon& uterus-cervix.
 Patients tend to be older have a longer duration
of infertility& severe(stage III-IV) endometriosis
 was associated with lower EFI (2-6)
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1. EXPECTANT MANAGEMENT
 In women with infertility
 without notable pelvic pain
 Normal baseline parameters (ORT, ovulation,
fallopian tubal patency & semen)
 Young patients
 Short period of infertility.
 Conservative management of endometrioma (Somigliana,
2014)
 No evidence for
 Significant decrease in ovarian response to
COS or PR
 Progression of endometriosis
 Technical impairment to oocyte retrival or
rupture cyst
 Small increased risk of infected endometrioma (0-1.9%)
 Risk of pregnancy complications, abscess

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2. IUI WITH COS
Instead of expectant management
In Stage I/II
{increases LBR} (Tummon et al., 1997).{C}
within 6 months after surgical TT:
{PR are similar to those achieved in unexplained
infertility } (Werbrouck et al., 2006). {C}
 HORMONAL THERAPIES
Hormonal contraceptives, Progestagens, GnRH analogues
or Danazol
No need
For suppression of ovarian function to improve
fertility (Hughes et al., 2007).{A}
 Consequently in women desirous of pregnancy
who have pain caused by endometriosis, NSAID
appear to be the only medical option
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 NUTRITIONAL SUPPLEMENTS,
COMPLEMENTARY AND ALTERNATIVE
TREATMENTS
No evidence for a beneficial effect (GPP)
3. SURGERY
Stage I/II:
•Operative laparoscopy:
excision or
ablation of the endometriosis lesions
adhesiolysis
rather than
•Diagnostic laparoscopy only, to increase PR
(Nowroozi et al., 1987; Jacobson et al., 2010).{A}

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CO2 laser vaporization of endometriosis, instead of
monopolar electrocoagulation
{higher cumulative spontaneous PR } (Chang et al.,
1997).{C}
 Offer excision or ablation of endometriosis plus
adhesiolysis for endometriosis not involving the
bowel, bladder or ureter, because this improves the
chance of spontaneous pregnancy.
Endometrioma
Excision of the capsule
instead of drainage& electrocoagulation of the
endometrioma wall
{increase spontaneous PR}(Hart et al., 2008).{A}
ORT
If compromised: surgery is not recommended
Counseling:
Risks of reduced ovarian function after surgery
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Hormonal treatment
Before surgery to improve spontaneous PR:
No {evidence is lacking} (GPP)
For pain
Yes (GPP)
After surgery to improve spontaneous PR
No (Furness et al., 2004).{A}
Deep endometriosis
The effectiveness of surgical excision is
not well established with regard to reproductive
outcome (Bianchi et al.,2009; Papaleo et al., 2011).{C}

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Endometrioma
ORT
Counsel women:
risks of reduced ovarian function after surgery {A}
Cystectomy to improve
Endometriosis-associated pain or
Accessibility of follicles {GPP}
De Zigler et al, 2010
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2. OVARIAN FACTOR INFERTILITY
Prof. aboubakr elnashar
1. CAUSES OF ANOVULATION
WHO

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2. ASSESSMENT OF OVULATION
I. Symptoms:
1. Mid cycle pain: Mittelschmerz
2. Mid-cycle bleeding
3. Thinning of cervical mucus
4. Regular cycle
=variation no more than ±2 days
5%: anovulatory
5% to 18.5%: anovulatory using urinary LH alone
(Lynch et al, 2014)
A history of regular periods usually indicates ovulation.
II. Tests
 Routine
1. Ultrasound folliculometry
Costly
Time consuming
To be reserved for induction ovulation or COS
(NICE, 2013; Practice Committee of the ASRM, 2015;
UpToDat,2016)
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 Diagnosis of Spontaneous Ovulation
1. Mature F. (17 – 25 mm (Inner dimensions)
2. Reduction in size (40%) Or Disappearance (60%)
3. Intra peritoneal fluid
-Normal: 1-3 ml
-With ovulation: 4- 5 ml
4. CL: 4-8 days after ovulation
• Irregular thick wall .
• Hypoechoic
• May contain internal echos (hge.)
• 15 mm
2. Mid luteal serum progesterone
in regular and irregular cycles
Mid-luteal
 7 days before the next expected period
day 21 and day 28 in 28-day and 35-day cycles
In irregular prolonged cycles
depending upon the timing of menstrual periods, conducted later
in the cycle (for example day 28 of a 35-day cycle) and repeated
weekly thereafter until the next menstrual cycle starts
Advantages:
Reliable
Safe
Inexpensive ABOUBAKR MOHAMED ELNASHAR

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3. LH surge in urine
 Commercially available urinary LH detection kits
can detect the LH surge and can be used to time
intercourse with ovulation induction
 Inexpensive,
 Pinpoint the day of ovulation
 Reduced the uncertainty in interpretation of
progesterone levels by better-identifying the time of
peak progestrone secretion at which to obtain serum
May be done
1. Basal FSH and LH: Only in irregular prolonged cycles
2. Prolactin: Only in
 ovulatory disorder
 galactorrhoea or
 pituitary tumour
3. TSH
 Women with ovulatory dysfunction
 Infertile women
 Those with signs of thyroid disease.
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4. Ovarian reserve testing
 Woman’s age:
An initial predictor of overall chance of success
through natural conception or with IVF
 Predictors of ovarian response to Gnt stimulation
High response
Low response
16 or more
4 or less
Total AFC
3.5 or more
25
0.8 or less
5.5
AMH
ng/ml
pmol/l
Conversion ratio:7
4 or less
8.9 or more
FSH IU/L
 NICE, 2013: Do not use
 ovarian volume
 ovarian blood flow
 inhibin B
 E2

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Not recommended
Historically, the effects of progesterone on basal body
temperature, endometrial histology or cervical mucus
were commonly used.
1. PMEB:
histologic dating is not a valid diagnostic method
lacks both accuracy and precision
To evaluate the luteal phase: No
{no evidence that medical tt of luteal phase defect
improves pregnancy rates]
2. BBT
 Stressful
 Predicted the day of ovulation in10% of cycles
 Less accurate for confirming ovulation (Guermandi et
al, 2001)
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 If the patient has anovulation, what is the cause?
1. PCO on ultrasound
 ESHRE2013: with a 5–7 MHz transducer
 12 or more follicles, 2 - 9 mm in diameter and/or
 Ovarian volume >10 ml.
 in at least one ovary
 no corpora lutea, cysts or dominant follicles
visualizing an ovary in two dimensions, establishing its size
first
The preferred parameter is FNPO, not AFC(all follicle
count – sum of FNPO from both ovaries).
 TAS: ovarian volume is recommended.
 ESHRE2018 : with a frequency 8MHz
 follicle number per ovary of > 20 and/or
 ovarian volume ≥ 10ml,
 If 8 y since menarche, US should not used
 In patients with irregular menstrual cycles and
hyperandrogenism, an ovarian U/S sound is not
necessary for PCOS

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2. Clinical Hyperandrogenism
 Adult:
 Hirsutism: 60% of PCOS.
 Acne: 30% of PCOS
 Alopecia.
 Adolescent:
 Severe acne or hursutism
 Hirsutism: Modified Ferriman & Gallwey
 Ethnic/racial differences
 9 sites assessed (mFG)
Perception is more important than severity
Country Hirsutism
USA, UK 8
Mediterranean, Hispanic,
Middle Eastern
9-10
South American 6
Southern Chinese 7
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 Alopecia: Ludwig score
3. Biochemical hyperandrogenism (ESHRE, 2018)
 Assessment most useful when clinical hyperandrogenism is
unclear
 High quality assays such as liquid chromatography–mass
spectrometry(LCMS)/mass spectrometry&
extraction/chromatography immunoassays, should be used.
 Direct FT assays, such as radiometric or enzyme-linked
assays should not be used, as they demonstrate poor
sensitivity, accuracy and precision.
 DHEAS & androstenedione have limited role

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 Calculated FT, FAI or bioavilable T is recommended
 Use upper limits of reference ranges
 Hormonal contraception must be off for 3 months
 Normal range: 7-10
TREATMENT OF ANOVULATION
Types of ovarian stimulation
Controlled ovarian
stimulation
Super
ovulation
Induction of
ovulation
Anovulatory or ovulatory
Anovulatory
Patient
Multiple
> one
One mature
follicle
Objective
IVF
IUI
Unexp infert
Anovulatory
Example
Down regulation
Stimulation
Prevent premature
LH surge
Stimulation
Stimulation
Method
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Amenorrhea or severe oligomenorrhea
FSH & LH: low
Prolactin: normal
I. Hypogonadotrophic hypoestrogenic
Type I
1. Reverse the life style factors:
if BMI <19: increase wt
Normal BMI (>20 kg/m2): regular menstrual cycle in the
majority of patients (Stafford, 2005)
if high levels of exercise: Moderating exercise
 If stress: Treat stress
CC:
not effective

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2. Gonadotrphins with LH activity or
Pulsatile GnRH (pump)
3. luteal support
hCG or progesterone from time of ovulation induction
until sufficient hCG production by trophoblast
cells is necessary (Beckers et al., 2006)
II. Normogonadotrophic Normoestrogenic
Type II
PCOS
2 of 3 (Noterdam definition,2003):
•U/S PCO
•Hyperandrogenism (Clinical or Laboratory)
•Irregular or absent ovulation
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Weight reduction
letrozole
Obese &overweight
Normal weight &No weight loss & No ovulation
LOD
GnT
No ovulation after 3 cycles.
No pregnancy after 6 cycles.
No pregnancy
after 6 cycles.
No pregnancy after spontaneous,
CC, FSH ovulation
IVF
Other surgical indication
Difficult follow up
Less aggressive
No desire for
surgery
Add metformin
IGT &IR
III. Hypergonadotrophic hypoestrogenic
< 40 yr, 2ndry amenorrhea
Repeated FSH > 20 IU/L
Causes
1. Idiopathic.
2. Genetic.
3. Autoimmune
3. Viral/bacterial infection
4. Pelvic surgery, chemotherapy
5. Galactosemia

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1. Oral contraceptive suppression of gonadotrpins
followed by discontinuation
to allow a rebound in gonadotropins & ovarian
function.
2. GnRHa suppression of gonadotropins secretion
followed by high dose gonadotropin injection
3. Glucocorticoids suppression of immune system.
 Non of these tts has demonstrated efficacy in RCT
IV. Hyperprolactinaemia
I. Idiopathic
Dopamine agonist (anxiety, pregnancy).
Stop during pregnancy
II. Microadenoma
Dopamine agonist (anxiety, pregnancy).
Stop after 2-3 yr.
Surgery (rapid growth).
III. Macroadenoma
Dopamine agonist: long term
Surgery
(No response, suprasellar extension, pregnancy).
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3. Tubal factor infertility
Prof Aboubakr Elnashar
Benha University Hospital, Egypt
INCIDENCE
30% of infertile couples.
CAUSES
1. Infection
PID
Appendicitis
2. Endometriosis
3. Previous tubal surgery
4. Pelvic adhesions
5. Congenital anomalies of the tubes

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 PID
 one, two, or three episodes:
 12%, 23%, and 54%, respectively tubal disease
 Chlamydial infections: major cause of tubal factor
infertility
 Ruptured appendix: 5X tubal disease
 No identifiable risk factors: 50% of patients with
documented tubal factor infertility
1. Hysterosalpingography
The most commonly performed screening test for tubal
patency.
Advantages:
1.Position of tubal occlusion
2. Unilateral patency can be dd from bilateral patency.
3. Degree of damage to tubal endothelium
4. Peritubal adhesion.
5. Uterine cavity
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6. Relatively cheap & simple.
7. HSG
 in agreement with the laparoscopic findings: 2/3
 Sensitivity: 73
 Specificity: 83%
High specificity makes it useful in ruling in tubal
obstruction
8. Tubal flushing using oil based contrast medium
increases CPR within 6 months after randomization&
may increase LBR (Wang et al, 2SR, 2019)
 HSG (ACOG, 2019)
 Document distal tubal occlusion
 Demonstrate: salpingitis isthmica nodosa
 Suggest:
 Proximal tubal occlusion
 Fimbrial phimosis
 Peritubal adhesions
 Reveal tubal architectural detail of potential
prognostic value

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 Salpingitis Isthmica Nodosa
 It is a nodular thickening of the narrow part of the a
of the fallopian tube
 (diverticulosis) due to inflammation
Salpingitis Isthmica Nodosa
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Small Hydrosalpinex
 Distal tubal anatomy:
 rugal folds
 tubal diameter
 evidence of spillage.

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Raised R. Tube
 HSG findings:
1. Mucosal rugae
 Present:
 favorable prognostic factor for subsequent
pregnancy: 60% PR
 Absence:
 severely damaged tubal epithelium: 7.3%
PR
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Fimbrial rugae outline with Iodamide (a) and Iopramide (b).
Note the sharper outline of the fimbrial rugaes seen in the Iopramide group in
comparison with Iodamide group.
2. Periadnexal adhesions
 An irregular distribution of loculated contrast
medium around the fimbriated end of the tube
Not reliable in evaluation of peritubal adhesions

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 Disadvantages
1. The pelvis including the ovaries is exposed to
radiation:
significant problem if the patient had an early
pregnancy.
2. Abdominal pain
 which peaks 5 min after starting
 usually settles within 30 min.
3. Intravasation
Network of streaklike opacities adjacent to the
uterine cavity
extend toward the pelvic side walls and
subsequently migrate in a cephalad direction.
Early detection:
minimizes complications
injection should be discontinued immediately,
regardless of the contrast medium used.
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Proximal Tubal Obstruction
Fibrosis obliteration & SIN 40%
Endometriosis & Cornual polyp 10%
Cornual spasm 20%
Amorphous material 50%
Viscous secretions 30%
 Mucosal agglutination
 Stromal edema
Tubal catheterization can be used both as
diagnostic & therapeutic method
Valle 1996

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 Contraindications
 Absolute
 Possible pregnancy
 History of acute PID.
 Relative
 History suggestive of PID
 Recent uterine instrumentation,
 Iodine allergy.
 The risk for PID after HSG
1% to 3%
 Prophylactic antibiotics
before uterine instrumentation if screening for CT
has not been carried out (NICE, 2013)
 Doxycycline: 100 mg twice a day for 3 days for all
patients.
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2. Sono hystero salpingography
 An US contrast dye or saline (10-40 ml) is injected into the
uterus through the cervix by a Foley catheter
 Passage of the dye is followed by TVS.
 75% concordance rate with laparoscopy dye
 The addition of pulsed wave or color Doppler imaging
±improve the predictive value
 Experience
 effective alternative to HSG (NICE, 2013)
 The ideal test:
 HyCoSy which combines cavity check with tubal
assessment.
3. Laparoscopy
Indication
1. Abnormal HSG or US
2.History or symptoms suggestive of pelvic disease.
 PID
 Ectopic
 Pelvic surgery.
 Chronic pelvic pain
Why?: Normal HSG or no history suggestive of tubal disease:
probability of clinically relevant tubal disease or endometriosis is
very low: laparoscopy is not justified or cost effective (Fatum et al,
2002).

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Laparoscopy may reveal
 minimal or mild endometriosis or
 peritubal adhesions.
Surgery or medical treatment has not been proven to
improve fecunditity.
Normal HSG:
laparoscopy should be omitted in couples with
unexplained infertility (UI)
These patients should be treated as UI
3 cycles of combined gonadotropins & IUI
 if unsuccessful ART
Advantage
1. Direct visualization of the pelvic anatomy.
2. Determine:
 appearance of the fimbria
 presence of periadnexal adhesions
3. Correct timing will enable evidence of ovulation to be
obtained.
4. No exposure to radiation
5. Can be combined with salpingoscopy &/or hysteroscopy.
6. Adhesiolysis or tubal constructive surgery can be
performed.
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Hysteroscopy
Not an initial investigation unless clinically indicated
{effectiveness of surgical treatment of uterine
abnormalities on improving pregnancy rates has not
been established} (NICE, 2013)
4. Transvaginal hydrolaparoscopy (THL)
±Method of choice in
 symptom free patients with
 no suspicion of pelvic pathologies (Nawroth et al,2001).
THL in association with minihysteroscopy:
 more information
 better tolerated than HSG in outpatient infertility
investigation

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5. Chlamydia antibody testing (CAT)
HSG is more accurate than CAT in predicting tubal
disease (Elnashar et al,2000).
If both tests were negative
the tubal disease was identified on laparoscopy in
only 4 % of case.
TREATMENT
IVF
Main player for tt of tubal factor.
Indication
1. Moderate to severe tubal disease
 Distal tubal occlusion with hydrosalpiges >1.5 cm in
diameter
 Distortion of the intraluminal architecture or
endotubal adhesions detected by HSG,
salpingoscopy or falloscopy
2. Other factors
A. Sperm dysfunction
B. Age >36 yr ABOUBAKR MOHAMED ELNASHAR
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1. Laparoscopic Surgery:
Fimbrioplasty
 Lysis of fimbrial adhesions or
 dilation of fimbrial strictures.
Neosalpingostomy: Creation of a new opening in a
fallopian tube with a distal occlusion.
Adhesiolysis: more likely to work in the presence of
patent tubes & filmy adhesions

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2. Transcervical cannulation of proximal fallopian tube
 Methods
 hysteroscopy
 fluoroscopy, or
 sonography
 Results
 Successful catheterization
 80% to 90%
 Cumulative pregnancy
 23% and 39% within the first 6 to 12 months.
 Ectopic pregnancy
 5% to 13% ABOUBAKR MOHAMED ELNASHAR
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 Selective salpingography plus tubal catheterisation,
or hysteroscopic tubal cannulation
Proximal tubal disease
If no pregnancy within 12 mo of surgery: IVF

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3. Microsurgical reanastomosis of the fallopian
tubes:
 for tubal ligation reversal.
 performed by
 Laparotomy
 Laparoscopy
comparable rates of success
 IVF or ICSI:
IVF should be the initial treatment of choice (Bukulmez et
al,2000).
{No significant difference in PR. or take-home baby}.
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50
Bilateral salpingectomy or tubal disconection
for women undergoing IVF who have
1. Hydrosalpinges
adversely affect implantation rates during IVF,
because of antegrade flow of noxious fluid.
2. Tubal damage and history of ectopic pregnancy
{increased risk of a further ectopic pregnancy}.
4. UTERINE FACTOR INFERTILITY
Prof. Aboubakr Elnashar

11/2/2021
51
CAUSES
I. Size and shape
1. Agenesis
2. Congenital abnormalities
II. Myometrium:
1. Leiomyomas
2. Adenomyosis.
III. Endometrium:
1. Endometrial Polyps
2. Intrauterine adhesions
3. Thin endometrium
EVALUATION OF UTERINE FACTOR
1. HSG
2. TVS
3. SIS
1. 3DUS
2. MRI
3. Hysteroscopy.
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1. HSG
Assess
 patency of the fallopian tubes
 contour of the endometrial cavity
 complex communications of a müllerian anomaly.
Disadvantages:
1. Sensitivity to detect IU abnormalities: low (50%)
2. lack of information about the external uterine contour:
limited utility for evaluating ut. anomaly
use of TVS or HSG to evaluate the uterine cavity
: suboptimal assessment of the uterus.
2. TVS
Routine diagnostic tool for assessment of the pelvis,
including the uterus and adnexa.
Timing:
Secretory phase of the menstrual cycle:
better visualization of
Endometrium
Contour of the uterine cavity.

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 Advantages:
Specificity and sensitivity for detecting uterine
abnormalities: high
Accuracy:
excluding endometrial hyperplasia: high
Disadvantages:
dd SM fibroids & polyps: low (A).
Information
Uterus Assessment: Dimension, Endometrial: thickness, appearance
Abnormalities: Anomalies, Tumors
Ovaries Assessment: Position, Mobility, Volume, AFC
Abnormalities: PCOS, Cysts, Tumors
Tube Hydrosalpinx, Patency
Pelvis Free fluid, Mass
Basal Vaginal U/S
The Pivotal US (performed D8-12)
± Saline infusion sonography (SIS)
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54
3. SIS:
experience
effective alternative to HSG (NICE, 2013)
Effectively delineate
intracavitary space
internal and external uterine contours.
Most accurate for evaluating
Size
Location
intracavitary component of the myoma
SIS Vs office hysteroscopy:
•Comparable
•easier
•less uncomfortable
•less expensive

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55
4. 3 DUS
highly accurate imaging of pelvic anatomy including
detailed assessment of the uterus.
5. MRI
Excellent delineation of internal and external
uterine contours
Gold standard ” for the diagnosis of
müllerian anomalies
Can differentiate
 leiomyomas,
adenomyosis and adenomyomas.
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56
 Hysteroscopy
As a routine procedure in the infertility work-up:
still under debate
no consensus on its efficacy and effectiveness in improving
the prognosis of infertile couples (Sardo et al., 2016).
Not an initial investigation unless clinically indicated
(NICE, 2013)
{its effectiveness on improving reproductive outcome
has not been established}
 Diagnostic accuracy of hysteroscopy
Accurate in the diagnosis of IU abnormalities(van
Dongen et al, 2007)
High for:
Polyps
Submucous myomas
Moderate for:
Endometrial hyperplasia (Gkrozou et al, 2015)

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57
Endometrial biopsy:
1. Irregular or intermenstrual bleeding.
2. Abnormal endometrial thickening on TVS
1. CONGENITAL (MULLERIAN) ANOMALIES
Prevalence
Fertile and infertile women: 3 – 4%
Normal reproductive outcomes: 3.2%
1st T RM: 5%-10%
2nd T RM: 25% (Khati, et al., 2012; Grimbizis et al., 2016).
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58
Treatment:
I- Uterine septum for primary infertility:
Hysteroscopic metroplasty: (NICE 2015)
 Evidence on efficacy is inadequate: should only be done:
 Multidisciplinary team
 specialists in reproductive medicine
 uterine imaging
 hysteroscopic surgery.
 Clear written consent:
 uncertain efficacy
 risks
 audit or research
 special arrangements for clinical governance
II. Unicornuate uterus with obstructed uterine horn
{at higher risk for infertility, endometriosis, premature labor,
and breech presentations}.
Excision of the obstructed rudimentary blind horn
prevent
 endometriosis by eliminating reflux
 development of a pregnancy (and pregnancy
complications) in the obstructed uterine horn
(Khati, et al., 2012) .

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59
III. The Mayer-Rokitansky-Küster-Hauser syndrome
=congenital absence of the vagina with variable uterine
development
{müllerian agenesis} (Iverson et al ., 2016)
2014:
First live birth following uterus transplantation
uterine factor infertility, even when considered absolute, is
now treatable (Brannstrom et al. 2015).
3 more births proving the outcome of uterus transplantation in
this early stage of clinical implementation to be astonishing
(Brannstrom 2015)
2. FIBROID
Prevalence
Women of reproductive age: 20- 40%
Associated with infertility: 5- 10%.
Only cause of infertility: 2- 3%
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60
Indications of Myomectomy:
1. Distorting the cavity
Submucous: (Gambadauro,2012).
Intramural:
2. Not distorting
1. >5 cm
2. Multiple >3 (3 cm) (Bajekal & Li, 2000)
3. only cause of infertility
3. ADENOMYOSIS
Prevalence:
Hysterectomy specimens: 20-30% (Vercillini et al, 2006)
Healthy women: 12% (Hauth et al, 2007)
Following term delivery: 9% (Juang et al, 2007)
 Infertile women less than 40 years old
undergoing ART: 22% (Puente, 2016)

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 Diagnosis:
1. TVS: 3 or more of the followings:
1. Globular uterus: 95% of cases.
2. Asymmetrical thickening: Anterior or posterior myometrial
wall appearing thicker than its counterpart
3. Mottled heterogeneous myometrial texture: All cases.
4. Small myometrial hypoechoic cysts, which are cystic
glands within ectopic endometrial foci: 82%.
5. “Shaggy” indistinct endometrial strips: 82%.
6. Striated projections extending from the endometrium into
the myometrium
Adenomyosis. Sagittal TVS
Globular uterine enlargement
Asymmetric thickening
Heterogeneity of the myometrium (arrows)
Poor definition of the endomyometrial junction
(arrowheads). E = endometrium.
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2. Color or power Doppler
Adenomyosis: diffuse vascularity
Fibroid: peripheral vascularity
3. MRI
Indication:
diagnosis is inconclusive
 when further delineation would affect patient
management
when coexisting uterine myomas distort anatomy
(ACOG, 2014).

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63
Treatment: (Tsui et al, 2015).
1. Routine infertility investigation plus ORT
Normal: long agonist protocol and natural
conception
Abnormal: IVF
2. Failed natural conception or IVF:
repeat IVF
3. Failed IVF:
conservative surgery
IVF after 3 m
(Horng et al, 2014)
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64
4. ENDOMETRIAL POLYPS
Define:
hyperplastic overgrowths of endometrial glands and
stroma that forms a projection from the surface of the
endometrium (Stewart 2016).
Treatment

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65
5. INTRAUTERINE ADHESIONS
Prevalence
HSG: 1.5 %
History of postpartum uterine curettage: 21.5 %
(hysteroscopy) (Deans, 2010).
Treatment: Hysteroscopic adhesolysis.
6. REFRACTORY ENDOMETRIUM
Prevalence
Low: 2.4% (Kasius et al., 2014),
Causes
I. Surgical:
dilation and curettage
partial ablation
aggressive myomectomy
II. Radiotherapy
III. Infections
IV. Congenital Müllerian anomalies
V. Idiopathic
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 Treatment
I. Hysteroscopic adhesiolysis
II. Hormonal manipulation
Estrogen:High dose 6−8 mg from cycle day 1
High doses for long periods, up to 9 ws
vaginal
HCG injection in the proliferative phase:1500 iu SC, daily starting
from day 8 of the cycle For 7 days or until EnT 7mm
Midluteal GnRHa:
Single dose: Triptorelin: 0.1 SC 6 days after ICSI.
Multiple doses: Triptorelin: daily 0.1 mg SC until day of beta-HCG or 14 days
after OR
III. Improving endometrial perfusion
LDA
Pentoxifylline and vitamin E. Pentoxifylline: 800 mg vit E:
1000 IU daily for 6-9 months
Sildenafil: 25 mg/6 h in vaginal supp in the proliferative phase,
stopped prior to HCG administration or ET.
L-arginin: 6 g/day
Nitroglycerin
IV. New modalities
Granulocyte colony-stimulating factor
Autologous platelet-rich plasma
Endometrial stem cells from bone marrow

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67
5. Unexplained infertility
Prof. aboubakr elnashar
1. DEFINITION
Inability to conceive (before 35 y) after one year of unprotected
intercourse with routine (standard, basic) investigations of
infertility showing no abnormality (RCOG guidelines,1998;
Randolph,2000)
 Inability to conceive
 after one year of unprotected intercourse,
 not explained by anovulation, poor sperm quality, tubal
pathology, or any known cause of infertility (Moll et al, 2018)
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3. EVALUATION
By exclusion
 Consider the following (Moghissi et al,2000)
Was the infertility evaluation
1. Complete?
2. Performed correctly?
3.Interpreted appropriately?
ESHRE (2000)
Tests that have an established association with
pregnancy:
1. Conventional semen analysis
2. Tubal patency tests
3. Tests of ovulation

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69
1. Semen analysis: WHO, 2010
:
:
Lower reference limit
Parameter
1.5 ml
Volume
7.2
pH
15 million/ml
Concentration
39 million/ejaculate
Total sperm number
40% or
PR: 32%
Total motility: (PR+NP)
58% live spermatozoa
Vitality
4% (strict criteria).
Normal forms
Motility: progressive: rapid (a)+ slow (b)
A and b Not used in WHO 2010
Non progressive (c)
2. HSG
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3. Midluteal progesterone
in regular and irregular cycles
{confirm ovulation}
 In irregular prolonged cycles
Depending upon the timing of menstrual periods, conducted
later in the cycle (for example day 28 of a 35-day cycle) and
repeated weekly thereafter until the next menstrual cycle
starts (NICE, 2013)
Hormonal assay (NICE, 2013)
1. Basal FSH and LH
• Only in irregular prolonged cycles
2. Prolactin
Only in
 ovulatory disorder
 galactorrhoea or
 pituitary tumour
3. TSH:
only if symptoms of thyroid disease

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71
4. Ovarian reserve testing
 Woman’s age:
An initial predictor of overall chance of success through
natural conception or IVF
 Predictors of ovarian response to Gnt stimulation
High response
Low response
16 or more
4 or less
Total AFC
3.5 or more
25
0.8 or less
5.5
AMH
ng/ml
pmol/l
Conversion ratio:7
4 or less
8.9 or more
FSH IU/L
Indications:
≥ 35 ys or
< 35 ys
 Endometriosis
 Unexplained infertility
 Single ovary
 Previous ovarian surgery,
 Poor response to FSH,
 Previous exposure to chemotherapy or
radiation
(Iii-b) SOGC, 2011
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 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
 Superovulation with IUI
 IVF. ABOUBAKR MOHAMED ELNASHAR
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
-

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73
Laparoscopy should be omitted in couples with
unexplained infertility
1.Laparoscopy may reveal
minimal or mild endometriosis or
Peritubal adhesions:
Surgery or medical tt has not been proven to improve fecundity.
2. In women with unexplained infertility
laparoscopy did not increase the PR (Badawy et
al, 2010)
Hysteroscopy
Not routine in investigation of infertility
except when an intrauterine lesion is suspected.
Not an initial investigation
unless clinically indicated
{effectiveness of surgical treatment of uterine
abnormalities on improving pregnancy rates has not
been established} (NICE, 2013)
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74
Treatment
By definition: Empiric (ASRM, 2006)
{does not address a specific defect or functional impairment}
Dependent on:
• Resources
• Patients’ age
• Duration of infertility.
The standard protocol is to:
• Progress from simple to complex
• Balance the effectiveness against the cost and side
effects (Ray et al,2012)
 Lines of treatment
I. Expectant management (EM)
II. Ovulation-inducing agents
1. CC:
2. Aromatase inhibitors (AI)
3. Gonadotropins
III. IUI
1. Alone
2. CC or Let
3. GnT
IV. IVF/ICSI
Tubal flushing or perturbation
Fallopian tube sperm perfusion

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75
I. Expectant management (EM)
 Spontaneous PR
After one y: 27.4% (Snick et al.1997)
14.3% (Collins et al. 1995).
9.9% (Gleicher et al., 1996)
After 3y: 60% (Godon & Sperof,2002)
 After 5 y: 80% (Randolph,2000)
Chance of spontaneous pregnancy with EM is low but
never zero.
 Good-prognosis: mean age 33 y,
median duration of infertility 2 y
 EM:
 LBR after 6 months: 27% (Steures et al., RCT, 2006)
 Good prognosis: mean age 32 y
median duration of infertility 2.5 y (Bhattacharya
et al. 2008, RCT)
ABOUBAKR ELNASHAR
11/2/2021
76
 The synthesis model= Hunault model (Hunault et al, 2004)
 Discriminate between those couples who will
conceive naturally and those who will not
 It includes the variables
1. Female age
2. Duration of infertility
3. Type of infertility: primary or secondary,
4. Referral status: referred by
 general practitioner or
 another gynaecologist
5. Percentage motile sperm
Score
Age (Y) 21-25
0
26-31
3
32-35
7
36-37
10
38-39
13
40-41
15
Infertility
Duration(Y)
1
0
2
3
3-4
7
5-6
12
7-8
18
Type of
infertility
2ndry
0
Primary
8
Motility
(%)
60
0
40-59
2
20-39
4
0-19
6
Referral
status
2ndry care
0
Tertiary
care
4
Total
(Hunault et al, 2004, Hum Rep)

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II. Ovulation-inducing agents
1. CC:
Enhances fertility by:
1.Correcting subtle defect in ovarian function
follicular development or
luteal phase defect
2. Increasing the number of follicles (Balen,2003).
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Results:
 No better (and even inferior) LBR than EM
(14% vs 17%) (Bhattacharya et al., 2008)
Number of cycles needed under CC for one
additional pregnancy: 40 compared with placebo
(ASRM, 2006).
No evidence that CC was more effective than no tt
or placebo for LBR or CPR (SR by Hughes et al.;2010)
2. Aromatase inhibitors (AI)
 Mechanism
1. Release of the estrogen negative feedback, increase
GnTR, stimulate ovarian follicle development
2. Increase sensitivity of follicles to FSH. increasing follicle
recruitment in UI (Mitwally & Casper,2000)
 Advantages over CC:
{short half life (45h) & absence of ER depletion}
No effect on
endometrial thickness or
cervical mucous

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79
3. Gonadotropins:
 HMG Vs CC
Significantly higher CPR: 25% Vs 8%
(Karlstro¨m et al., 1993; Echochard et al., 2000 Balasch)
injectable ovulation Vs oral
insufficient evidence to prefer either of the
methods(Cochrane SR,2009)
FSH plus Letrozole:
improved response to FSH:
lower FSH dose &
higher number of mature follicles UI (Mitwally & Casper, 2003)
III. IUI
I. IUI in natural cycle
does not significantly increase PR
(ESHRE, 2009)
No evidence of effect of IUI in natural cycles compared with EM
(Cochrane, 2012)
IUI without stimulation was no better than EM
The evidence does not support the use of IUI as an alternative to EM in the
belief that doing something was better than doing nothing.
(NICE, 2013)
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II. Stimulated IUI
Mechanism
increasing the density of the motile spermatozoa available to these eggs:
increase the monthly probability of pregnancy.
1. IUI with CC
5–7% PR/cycle even after 7 cycles ( ESHRE, 2009)
Not proved to be effective (Hughes et al, 2010)
 Farquhar et al, 2018, lancet
 A pragmatic, open-label, RCT, two-centre trial.
 Unexplained infertility for 2-3 y
 Oral OS IUI is an effective treatment in uexplained
infertility
ABOUBAKR ELNASHAR

11/2/2021
81
2. IUI with Letrozole
can replace CC in patients with UI undergoing
ovulation induction & IUI
(Sammour,2001).
3. IUI with Gnt
ESHRE, 2009
PR: 12%/cycle
Multiple birth rates:13%.
High multiple PR mean that it is no more than a poor substitute for
IVF.
IUI in stimulated cycles may be considered
1. while waiting for IVF or
2. when in women with patent tubes and IVF is not affordable
ESHRE, 2004
UI or stimulated ovary/IUI is indicated as empiric treatment for all categories of UI
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LPS:
significantly improves the outcome
Benefit was restricted to Gnt stimulated cycles.
vaginal progesterone
Dydrogesterone
(Malhotra J , Krishnaprasad, 2016)
IV. IVF
Rationales:
1.To increase the number & quality of oocytes
available for fertilization
2. To facilitate the sperm-oocyte interaction &
enhance fertilization
3. To document the occurrence of fertilization
4. To evaluate embryo quality (Randolph,2000) .
Cycle fecundity rate:
25.7% (ESHRE).

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83
GnT/ IUI Vs IVF for unexplained infertility (Nandi et al,
RCT, 2017)
ABOUBAKR ELNASHAR
Protocol for Management
(Ray et al, 2012)
3
3
2

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