Infertility

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InfertilityA Clinical Dilemma

• Dr.Kundan V.Ingale.
• MBBS, DGO, DNB(Mumbai)
• Obstetrician Gynecologist
• Consultant in Assisted Reproduction Genetics

LOKMANYA HOSPITAL, CHINCHWAD LOKMANYA HOSPITAL,
PRADHIKARAN
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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.
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INCIDENCE

• Female Factor - 40-45
• Male Factor -25-40
• Both - 10
• Unexplained - 10.

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Causes of Infertility

• Female
• Anovulation (accounts for 25 of infertility)
• Tubal factors (accounts for 25 - 40of
  infertility)
• Uterine cervical factor (accounts for 10 of
  infertility)
• Immunological cases, age and other factors
  (accounts for 25 of infertility)

Tubal factor is a common cause of infertility in
our country.
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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.
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Infertility
Rise in infertility - - increased women
employment - Late marriages - Preferring
weekend sex - highly stressful job - Onset of
childbearing at later age.
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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 gt50 after ½ hour.
• Sperm Morphology gt50 normal.

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Abnormal Semen Parameters.

• Oligospermia - sperm count lt20 million/ml
• Mild -10-20 million/ml
• Moderate -5-10million/ml
• Severe -lt5 million/ml.
• Azoospermia - Absence of single sperm in
  ejaculate.
• Asthenospermia -Sperm motility lt50
• Teratospermia - lt4 normal sperms associated
  with poor fertility prognosis.

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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.

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Epidemiolgy of PCOS.

• Affect 5-10of all reproductive age group women.
• 50 women attending infertility cilinics.
• 50 women with recurrent miscarriages.

PCO LEADING CAUSE OF INFERTILITY.
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Abnormal Estrogen Clearance / Metabolism
Inability of H-P axis to respond to adequate
timely feedback signals
LOW FSH
Chronic anovulation
Persistently Elevated Estrogen
Increased Estrogen secretion
Intrinsic follicular weakness / Impaired
follicular-Gonadotropin interaction.
High LH/Inadequate LH surge
Gonadal (Ovary Adrenal)
Extragonadal (Adipose tissue)
Failed local ovarian autocrine / paracrine factor
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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.
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PCO THE SIGN
Partial suppressed FSH
Hyperplastic theca cells
New Follicular growth
Luteinized due to LH
Follicular atresia
Repeated follicular atresia anovulation
Thickened stroma
PCO
PCO Sign , not a disease.
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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

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Tubal Factor

• Fallopian tube blockage
• Sites Cornual end, interstitial, isthmus,
  ampulla, fimbrial end.

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FALLOPIAN TUBE BLOCKAGE

• Tubo-Cornual region -
• Tubal spasm
• Salphingitis Isthmica nodosa(SIN)
• Endometriosis
• Polyps
• Isthmus -
• Occlusion-Prior sterilization,tubal pregnancy,
  SIN, T.B. Endometriosis.

• Ampulla -
• Intraluminal adhesions, Tubal pregnancy
• Infundibulum -
• Hydrosalphinx, phimosis of distal tubal ostium
  sec to PID.
• Intraperitoneal spread -
• Adhesions.

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DIAGNOSIS

• Functioning of tubal mucosa
• Microsphere migration
• Descending tests
• Starch Gold.

• Patency of tube
• Laparoscopic chromotubation
• Hysterosalphingo
• graphy
• Falloposcopy
• Methylene blue test
• Gas hydrotubation
• Sonosalphingography
• Direct cannulation

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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

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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.

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IUI Stimulation protocols

• Natural cycle
• Stimulated cycle
• CC
• CCHMG
• CCHMG/FSHhCG
• FSH/HMGhCG
• GnRHa FSH/HMG hCG
• Follicle monitoring
• Timing of IUI

Success rate is high if more then one egg is
produced.
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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
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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.
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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.
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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.

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Step Up protocols

• Ovulation in PCO pts remains a challenge
• OHSS, multiple pregnancy LUFs 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.

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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.

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Metformin in PCO patients

• In cases diagnosed to have insulin resistance.
• 1500mg/day till pregnancy achieved.
• Given for at least 2 mths prior to ovulation
  induction programme.

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INTRAUTERINE INSEMINATION(IUI)
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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.
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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.

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Indications for IUI

• Female factor
• Anatomic defects
• Cervical factors
• Ovulatory dysfunction
• Unexplained infertility
• Minimal endometriosis
• Antisperm antibodies in cervix
• Psychological Psychogenic sexual dysfunction

• Male Factor
• Anatomic defects of the penis
• Sexual or ejaculatory dysfunction
• Retrograde ejaculation
• Impotency
• Immunological increased viscosity
• Oligoasthenoteratozoospermia
• Azoospermia

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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 womans
  uterus via a catheter through the cervix.

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IUI Complications

• Uterine cramping -5
• Spotting -1
• G I upset -0.5
• Infection -0.2
• OHSS -1
• Multiple gestation
• Ectopic gestation

Artificial Insemination
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Efficacy of superovulation IUI
Treatment No.of pregnancies Pregnancy rate/couple
Intracervical insemination 23 10
Intrauterine insemination 42 18
Super ovulation Intracervical insemination 44 19
Super ovulation intrauterine insemination 77 33
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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
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IUI Failures

• Poor responders
• Hyperstimulation
• LUF
• Endometrial problems
• Insatisfactory semen preparations

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INTRACYTOPLASMIC SPERM INJECTION(ICSI)
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ICSI Procedure
ICSI involves injection of single sperm into the
egg
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Success Rates
If 4 good quality embryos are produced following
ICSI and the age of the woman is lt 37 years, the
pregnancy rates are 45
The hallmark to success is good quality embryos
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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.
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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.
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Phases of IVF Cycle

• Fertilisation by ICSI
• Embryo transfer
• Luteal phase and pregnancy

One cycle is spread over a period of 25-30 days.
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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.

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Preimplantation genetic Diagnosis (PGD)
The Micromanipulator
FISH -Trisomy 18, X, Y
PCR - Cystic Fibrosis ? F 508 Mutation
Cleavage stage Embryo Biopsy
FISH - Polyploidy
Polar Body Biopsy
PCR - ? Thalassemia
PGD - Earliest form of prenatal diagnosis.
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Cryopreservation
For future fertilisation attempts
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Laparoscopy
Looking inside the abdominal cavity
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Hysteroscopy
Looking inside the uterus
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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

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Assisted Reproduction mimics human reproduction
Getting close to nature
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The greatest motivational act one person can do
for another is to listen. Roy Moody
THANK YOU