ART CENTER

Report
Infertility—A Clinical
Dilemma……
Dr.Kundan V.Ingale.
MBBS, DGO, DNB(Mumbai)
Obstetrician & Gynecologist
Consultant in Assisted Reproduction &
Genetics
LOKMANYA HOSPITAL, CHINCHWAD
LOKMANYA HOSPITAL, PRADHIKARAN
Introduction

Traditionally, infertility is defined as the inability to
conceive for one year.

Worldwide, 10 to 14% of couples in the
reproductive age group (20-40) face difficulty in
conceiving

90% of infertility is treatable with advances in
medicines and clinical procedures

Line of treatment includes medical and surgical
intervention, Assisted Reproduction Techniques
(ART) or a combination of these modalities.
Infertility is an extraordinarily common medical problem.
INCIDENCE
• Female Factor: - 40-45%
• Male Factor: -25-40%
• Both: - 10%
• Unexplained: - 10%.
Causes of Infertility
Female
HSG – Septate uterus

Anovulation (accounts for 25% of infertility)

Tubal factors (accounts for 25% - 40%of infertility)

Uterine & cervical factor (accounts for 10% of infertility)

Immunological cases, age and other factors (accounts for
25% of infertility)
HSG – Bicornuate uterus
Tubal factor is a common cause of infertility in our country.
Causes of Infertility
Male

Low sperm count

Low motility

Poor sperm morphology

Other factors such as



stress
varicocoele
chromosomal abnormality
Both female and male factors contribute to infertility.
Infertility
Rise in infertility : - increased women employment
- Late marriages
- Preferring weekend sex
- highly stressful job
- Onset of childbearing at later age.
Male Infertility






Volume: 2-5ml
pH: 7.2-7.8
Liquefaction time: within 40 mins.
Sperm Count: -20-120 million/ml (WHO
Criteria)
Sperm motility: >50% after ½ hour.
Sperm Morphology: >50% normal.
Abnormal Semen
Parameters.

Oligospermia: - sperm count <20 million/ml
 Mild: -10-20 million/ml
 Moderate: -5-10million/ml
 Severe: -<5 million/ml.
 Azoospermia: - Absence of single sperm in
ejaculate.
 Asthenospermia: -Sperm motility <50%
 Teratospermia: - <4% normal sperms
associated with poor fertility prognosis.
POLYCYSTIC OVARIAN
SYNDROME

Heterogeneous complex
condition –
Hyperandrogenemia and
chronic anovulation.
 Associated with Hirsuitism ,
Hyperinsulinemia & insulin
resistance.
 Commonest cause of
anovulation.
 50% patient of PCOS need
assistance in reproduction.
Epidemiolgy of PCOS.

Affect 5-10%of all reproductive age group
women.

50% women attending infertility cilinics.

50% women with recurrent miscarriages.
PCO – LEADING CAUSE OF INFERTILITY.
Abnormal Estrogen
Clearance / Metabolism
Inability of H-P axis to
respond to adequate &
timely feedback signals
LOW FSH
Persistently Elevated
Estrogen
Increased Estrogen
secretion
Chronic
anovulation
High LH/Inadequate
LH surge
Gonadal
Extragonadal
(Ovary&
Adrenal)
(Adipose tissue)
Intrinsic follicular
weakness / Impaired
follicular-Gonadotropin
interaction.
Failed local ovarian
autocrine / paracrine factor
INSULIN RESISTANCE &
HYPERINSULINEMIA

Causes:  Peripheral target tissue resistance.
Decreased insulin receptor number
Decreased insulin binding
Post-receptor failure
 Decreased hepatic clearance.
 Increased pancreatic sensitivity.
INSULIN RESISTANCE – OBESE & NON-OBESE WOMEN.
PCO – THE SIGN
Hyperplastic theca cells
Luteinized due to LH
Partial suppressed FSH
New Follicular growth
Follicular atresia
Repeated follicular atresia &
anovulation
Thickened stroma
PCO
PCO : Sign , not a disease.
PCOS- DIAGNOSIS
MAJOR
 Chronic anovulation
 Hyperandrogenemia
 Clinical
signs of
Hyperandrogenemia.
MINOR
 Insulin resistance
 Perimenarchal onset of
hisuitism and obesity
 Elevated LH and FSH
ratio
 Intermittent
anovulation assoc with
Hyperandrogenemia
Tubal Factor

Fallopian tube
blockage:
Sites : Cornual end,
interstitial, isthmus,
ampulla, fimbrial end.
FALLOPIAN TUBE
BLOCKAGE
 Tubo-Cornual
region:  Ampulla: Tubal spasm
Intraluminal adhesions,
Salphingitis Isthmica
Tubal pregnancy
nodosa(SIN)
 Infundibulum: Endometriosis
Hydrosalphinx, phimosis of
Polyps
distal tubal ostium sec to
 Isthmus: PID.
Occlusion-Prior
 Intraperitoneal spread: sterilization,tubal
Adhesions.
pregnancy, SIN, T.B.
Endometriosis.
DIAGNOSIS
 Functioning of
of tube
tubal mucosa
– Laparoscopic
chromotubation
– Microsphere
– Hysterosalphingo
migration
graphy
– Descending tests
– Falloposcopy
Starch & Gold.
– Methylene blue test
– Gas hydrotubation
– Sonosalphingography
– Direct cannulation
 Patency
MANAGEMENT OF TUBAL
BLOCK
 Proximal
tubal disease: -Tubal cannulation
IVF
 Mid tubal disease: - Tubal reconstruction
Microsurgery/IVF
 Fimbrial / distal tubal disease: - Fimbrioplasty
 Peritubal disease: -Adhesiolysis/IVF
 T-O mass / multiple tubal block: -IVF/ICSI
Assisted Reproductive
Techniques
•Intrauterine insemination (IUI)
•In Vitro
Fertilization (IVF)
•Intracytoplasmic sperm Injection (ICSI)
•Laser Assisted hatching (LAH)
•Pre-implantation genetic diagnosis.(PGD)
•In vitro Maturation
•Donor oocyte programme.
IUI : Stimulation protocols
 Natural
cycle
 Stimulated cycle
CC
CC+HMG
CC+HMG/FSH+hCG
FSH/HMG+hCG
GnRHa + FSH/HMG + hCG
 Follicle monitoring
 Timing of IUI
Success rate is high if more then one egg is produced.
Clomiphene Citrate
Occupies the Estrogen
receptor
Concentration of Estrogen
receptor is reduced
No Negative feedback HPO axis is
blind to Estrogen
GnRH secretion activated
FSH & LH pulse
frequency increased
Maturation of follicles
Results with Clomiphene
Citrate

70% Ovulation rate
 40% Pregnancy rate
 5% have multiple pregnancy
 60% conceive during first three cycles.
If there is no pregnancy in 6 cycles, alternative therapy to be
chosen.
IUI with Gonadotropin
treatment

Gonadotropins : contain naturally occurring
pituitary hormones (FSH & LH)
 Daily injections: creates higher than normal
levels of FSH, simulating the ovaries to produce
multiple follicles and multiple eggs.
 Transvaginal sonography: to check the growing
follicles.
Subcutaneous self injection into the thigh or abdomen.
Gonadotropins : Indications
Indications:
-Failure to respond to antiestrogen therapy



At least 3 cycles of C.C. and no ovulation
Dose: 0-200mg/day for 7 days.
At least 6 Ovulatory cycles and not conceived.
-Side effects to antiestrogen therapy irrespective
of ovulation
-Two or more miscarriage after C. therapy.
Step Up protocols
 Ovulation
in PCO pts remains a
challenge
 OHSS, multiple pregnancy & LUF’s are
a problem.
 Allows right amount of FSH to connect
the hormonal imbalance within the
PCOS ovary.
 Fewer follicles per cycle
 Safer successful ovulation induction
 OHSS reduced.
Step Down Protocols
Principle :
Activating pre-Ovulatory follicles and limiting the
number of growing follicles by hormonal therapy.
Advantages:
Reduced risk of OHSS & multiple pregnancy.
Disadvantages:
Needs tight monitoring.
Increased cancellation cycles.
Metformin in PCO patients
 In
cases diagnosed to have insulin
resistance.
 1500mg/day
 Given
till pregnancy achieved.
for at least 2 mths prior to ovulation
induction programme.
INTRAUTERINE INSEMINATION
(IUI)
What is IUI?

Direct placement of
processed highly
motile, concentrated
sperm, washed free of
seminal plasma and
other debris, into the
uterus as close to the
ovulated oocytes as
possible.
 Reduces distance of
travel
Artificial insemination.
IUI
The Goal is to place as many active,
well-formed sperms as close to the
ovulated eggs as possible, thereby
increasing their chances of meeting.
Indications for IUI
Female factor:
Male Factor:
Anatomic defects
Cervical factors
Ovulatory dysfunction
Unexplained infertility
Minimal endometriosis
Antisperm antibodies in cervix
Psychological & Psychogenic
sexual dysfunction
Anatomic defects of the penis
Sexual or ejaculatory dysfunction
Retrograde ejaculation
Impotency
Immunological increased viscosity
Oligoasthenoteratozoospermia
Azoospermia
Steps involved in COH & IUI
Monitoring of a natural or stimulated cycle:
so that the time of ovulation is apparent
Preparation of Sperm wash:
From either male partner or donor
Procedure of Insemination:
Sperm sample is then inserted into woman’s
uterus via a catheter through the cervix.
IUI : Complications

Uterine cramping
 Spotting
 G I upset
 Infection
 OHSS
 Multiple gestation
 Ectopic gestation
Artificial Insemination
-5%
-1%
-0.5%
-0.2%
-1%
Efficacy of superovulation &
IUI
Treatment
Intracervical
insemination
No.of pregnancies Pregnancy
rate/couple
23
10
Intrauterine
insemination
42
18
Super ovulation &
Intracervical
insemination
Super ovulation &
intrauterine
insemination
44
19
77
33
IUI Results
751 cycles in 322 couples
Treatment
Fecundity/Cycle
COH
6.3%
IUI
3.4%
COH + IUI
19.6%
Chaffkin L.M.;Nulsen,J.C.,1991
IUI Failures
 Poor
responders
 Hyperstimulation
 LUF
 Endometrial problems
 Insatisfactory semen preparations
INTRACYTOPLASMIC SPERM
INJECTION
(ICSI)
ICSI Procedure
ICSI involves injection of single sperm into the egg
Success Rates
If 4 good quality embryos
are produced following ICSI
and the age of the woman is
< 37 years, the pregnancy
rates are 45%
The hallmark to success is good quality embryos
Intra Cytoplasmic Sperm Injection (ICSI)

Revolutionary treatment for patients with severe
male factor infertility

Fertilisation rate of mature eggs injected with
immobilised sperm reached levels comparable to
those obtained in conventional IVF

Also used to treat couples experiencing failure or
low fertilisation rates under conventional IVF
conditions
The advent of ICSI has revolutionised male factor fertility.
Phases of IVF Cycle

Pituitary suppression (Down regulation)
Done with Day 21 Lupride inj followed by
stimulation with HMG or r-FSH.

Ovarian stimulation
Fixed regimen - Step up and Step Down

Egg retrieval
34-36 hours after ovarian trigger
One cycle is spread over a period of 25-30 days.
Phases of IVF Cycle

Fertilisation by ICSI

Embryo transfer

Luteal phase and pregnancy
One cycle is spread over a period of 25-30 days.
Donor Programme

Donor sperms : – azoospermia

Donor oocyte : – Premature ovarian failure
– Advanced maternal age with poor ovarian
reserve

Donor embryo : – Severe male as well as female factor.
Preimplantation genetic Diagnosis (PGD)
1 2 3 4 5 6 7 8 9
The Micromanipulator
250bp
FISH -Trisomy 18, X, Y
78bp
100bp
50bp
PCR - Cystic Fibrosis  F 508 Mutation
Cleavage stage Embryo Biopsy
861bp
285bp
250bp
FISH - Polyploidy
242bp
50bp
Polar Body Biopsy
PCR -  Thalassemia
PGD - Earliest form of prenatal diagnosis.
Cryopreservation
For future fertilisation attempts
Laparoscopy
Looking inside the abdominal cavity
Hysteroscopy
Looking inside the uterus
Myths about infertility
 Timing
of intercourse
 Frequency of intercourse
 Certain coital positions improve chances of
conception
 Orgasm, libido, stress & tension
 IUI improves chances of conception
 Drugs to improve sperm count
 Cold baths, loose pants
 Unexplained infertility
Assisted Reproduction mimics human reproduction
Getting close to nature
“The greatest motivational
act one person can do for
another is to listen.”
Roy Moody

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