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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.

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infertility a clinical dilemma

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

slide2

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
INCIDENCE
  • Female Factor: - 40-45%
  • Male Factor: -25-40%
  • Both: - 10%
  • Unexplained: - 10%.
slide4

HSG – Septate uterus

HSG – Bicornuate uterus

Causes of Infertility

Female

  • 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)

Tubal factor is a common cause of infertility in our country.

slide5

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.

slide6

Infertility

Rise in infertility : -

- increased women employment

- Late marriages

- Preferring weekend sex

- highly stressful job

- Onset of childbearing at later age.

male infertility
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
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
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
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.

slide11

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

insulin resistance hyperinsulinemia
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
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.

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

PCOS- DIAGNOSIS
tubal factor
Tubal Factor
  • Fallopian tube blockage:

Sites : Cornual end, interstitial, isthmus, ampulla, fimbrial end.

fallopian tube blockage
Tubo-Cornual region: -

Tubal spasm

Salphingitis Isthmica nodosa(SIN)

Endometriosis

Polyps

Isthmus: -

Occlusion-Prior sterilization,tubalpregnancy, SIN, T.B. Endometriosis.

Ampulla: -

Intraluminal adhesions, Tubal pregnancy

Infundibulum: -

Hydrosalphinx, phimosis of distal tubal ostium sec to PID.

Intraperitoneal spread: -

Adhesions.

FALLOPIAN TUBE BLOCKAGE
diagnosis
Patency of tube

Laparoscopic chromotubation

Hysterosalphingo

graphy

Falloposcopy

Methylene blue test

Gas hydrotubation

Sonosalphingography

Direct cannulation

Functioning of tubal mucosa

Microsphere migration

Descending tests

Starch & Gold.

DIAGNOSIS
management of tubal block
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

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
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
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
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
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
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
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
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
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.
what is 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.

slide30
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:

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

Indications for IUI
steps involved in coh iui
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
IUI : Complications
  • Uterine cramping -5%
  • Spotting -1%
  • G I upset -0.5%
  • Infection -0.2%
  • OHSS -1%
  • Multiple gestation
  • Ectopic gestation

Artificial Insemination

iui results
IUI Results

751 cycles in 322 couples

Chaffkin L.M.;Nulsen,J.C.,1991

iui failures
IUI Failures
  • Poor responders
  • Hyperstimulation
  • LUF
  • Endometrial problems
  • Insatisfactory semen preparations
slide38

ICSI Procedure

ICSI involves injection of single sperm into the egg

slide39

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

slide40

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.

slide41

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.

slide42

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 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.
slide44

1 2 3 4 5 6 7 8 9

250bp

78bp

100bp

50bp

861bp

285bp

250bp

242bp

50bp

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.

slide45

Cryopreservation

For future fertilisation attempts

slide46

Laparoscopy

Looking inside the abdominal cavity

slide47

Hysteroscopy

Looking inside the uterus

myths about infertility
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
slide50

“The greatest motivational act one person can do for another is to listen.”

Roy Moody

THANK YOU