• Like
Genetic factors in rpl
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

Genetic factors in rpl

  • 498 views
Published

 

Published in Health & Medicine
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
    Be the first to like this
No Downloads

Views

Total Views
498
On SlideShare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
21
Comments
0
Likes
0

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. Genetic Factors & Recurrent Pregnancy Loss Dr. Raju R Sahetya M.D., D.G.O., D.F.P., F.C.P.S., F.I.C.O.G., OBSTETRICIAN & GYNAECOLOGIST Specialist: Infertility & Maternal Fetal Medicine Hospital Pushpaa Hospital Mumbai, India www.pushpaahospital.com , [email_address] Mobile 9821090102 Honorary Hinduja Hospital * BSES Hospital Mumbadevi Hospital * Hiranandani Hospita
  • 2. Vice President Indian Society for Prenatal Diagnosis & Fetal Therapy (ISPAT) Member Excecutive Council Mumbai Obstetrics & Gynaecology Society (MOGS) Association of Fellow Gynaecologist (AFG) Assciation of Medical Consultant (AMC) Current Position Held MOGS – PNDT & Academic Cell, FOGSI – Sexual Medicine Committee Editorial Board – ISPAT International Journal of Prenatal Diagnosis & AFG Times Rotarian Past President Rotary Club of Bombay Airport
  • 3. “ I OWE TO MY ALMA MATER !”
  • 4. Recurrent Pregnancy Loss
  • 5. possible causes
    • Recurrent miscarriage is a heterogeneous condition that has many possible causes; more than one contributory factor may underlie the recurrent pregnancy losses.
    • each Loss may have had a different or multiple causes.
  • 6. Genetic factors Anatomical factors Endocrine Infective agents Immune factors Inhereted Thrombophilic defect Explained Un-explained Recurent Miscarriage Enviromental factors Body Cervix Paternal karyotyping Cytogenetic Of miscarriage C I Uterine anomalies APS Bacterial Vaginosis
  • 7.
    • 50 % of all conception are lost (includes early abortions).
    • 15-20 % of recognized pregnancies.
    • 70% of these early losses is due to cytogenetic
    • 50% between 8-15 weeks.
    • 5 – 10 % still births.
    Frequency
  • 8. Pregnancy Loss
  • 9.
    • Chromosomal
    • Mendelian Inheritance .
    • Multifactorial.
    Genetic Causes
  • 10.
    • Establish the etiology
    • Investigate the couple
    • Estimate recurrence risk
    • Provide accurate genetic counseling.
    • Discuss reproductive options.
    • Essential as patients have small planned families.
    Aim Of Genetic Evaluation
  • 11.
    • Denovo, paternal or maternal meiotic or post zygotic division or abnormal fertilization.
    • 26 % are trisomies including trisomy 16.
    • 10 % are triploidy , tetraploidy.
    • 10 % are sex chromosomal monosomy (45,X)
    • 2% are unbalanced or double trisomies.
    • .?9% trisomy and still birth
    • Histopathology / morphology insufficient to asses etiology .
    Cytogenetic Abnormalities
  • 12. Karyotype
  • 13.
    • Tissues usually used for karyotype from abortuses .
    • Chorionic Villi from products in normal saline
    • P iece of placenta at cord insertion in normal saline.
    • Fetal cord / cardiac blood, in sodium heparin vaccutainers.
    • No formalin or freezing for preservation
    • S hould reach within 24-36 hours at Room Temperature.  
    Tissue, Collection & Transport
  • 14. Choosing A Centre.
  • 15. NABL ACCREDITED (ISO / IEC – 17025) Accreditations Experienced Medical Geneticist Qualified staff State of the art equipment. Reliable reports Minimum turn around time. Interaction with physician. Choosing the Centre Accessibility
  • 16. Methods Of Study
  • 17.
    • History taking.
    • Genetic counseling
    • Examination of the Fetus, Villi and Placenta.
    • Correlation with CRL and stage ( milestones)
    • Morphology of the villi. ( hydropic, hypoplastic etc.)
    • Review of Ultrasound reports .( Syndrome assignment.)
    • Photography and / or Radiology ( skeletal dysplasias )
    • Karyotype studies and FISH for fetal chromosomal abnormalities.
    • Histopathology studies for infection and vascular insufficiency.
    • Karyotype of the couple - for transmissible chromosomal error.
    • Prenatal Genetic Diagnosis in subsequent pregnancy
  • 18.
    • Medical and Maternal
    • Family
    • Previous and present pregnancy.
    • Antenatal
    • Fetal wellbeing
    • Labor and Postnatal.
    History
  • 19.
    • Level 1 – Obstetrician
    • Discussing causes for Pregnancy Loss
    • Investigations required
    • Role of Geneticist
    • Level 2 – Clinical Geneticist
    • Details about causes in RPL
    • To evaluate, Diagnose and Prognosis
    • Discuss recurrences
  • 20. C E MORPHOLOGY & KARYOTYPE OF VILLI NORMAL-46,XX/46,XY CLUBBING- VARIABLE - - MOLAR- 46,XX / 46,XY HYPOPLASTIC- 45,XO CYSTIC- 69,XXX/XXYTRI-16
  • 21. Exomphalos. Trisomy 18. Holoprosencephaly Trisomy13, 15. Choroid Plexus Cyst Trisomy 18. Nuchal Translucency Trisomy 21.45X. Ventriculomegaly 13,18,21 Cystic Hygroma 45X. Abnormal USG Findings
  • 22. Correlation With Developmental Age
  • 23. Trisomy 18 Monosomy X Triploidy Trisomy 13 Trisomy 21 Fetuses With Visible Malformations
  • 24.
    • FISH (Fluroscent Insitu Hybridization)
      • Permits detection of specific nucleic acid sequences in morphologically preserved chromosomes, cells, and tissues.
      • Specific probes are utilized for the purpose.
    Newer Technique
  • 25. Karyotype FISH Needs viable ,specific tissues Any fetal tissue either fresh, frozen or paraffin block Culture essential Uncultured cells work. Selective growth of maternal decidua Not possible. Screens all chromosomes and used for > 40 yrs now for establishing etiology. Screens for major aneuploidies (13, 18, 21, X and Y) Turn around time 2 weeks Turn around time 2 days Ideal for focal anomalies
  • 26. FISH Newer Techniques
  • 27. Karyotypes & Prognostic Significance
  • 28.
    • DEPENDS ON :
    • Parental age .
    • Advanced maternal age : Trisomic conceptus Monosomy X.
    • Cytogenetic status of the spontaneous abortion.
    • Exponential increase in the rate of trisomy
    • Karyotype of parents (balanced translocations).
    • Leads to deficiencies and duplication of chromosomes in the fetus
    Prognostic Significance of the Abortus karyotype
  • 29. Risk Estimation & Follow Up
  • 30.
    • Parental Karyotype.
    • Prenatal Diagnosis PGD / CVS / Amniocentesis
    • Gamet Donation.
    Follow Up
  • 31. Subsequent Pregnancy CHORIONIC VILLUS SAMPLING 10-11 WEEKS AMNIOCENTESIS 15-17 WEEKS
  • 32.
    • Frequency : 2-3 per 1000.
    • Inheritance : Multifactorial, single gene / chromosomal.
    • Recurrence risk : 9% / 2-3%.
    • Periconceptional folic acid supplement .
    Neural Tube Defects Multifactorial
  • 33.  
  • 34.
    • Genetic Factors more often responsible for RPL
    • Genetic Counseling plays an important role in RPL management.
    • Cytogenetic/FISH and morphological evaluation of products of conception is a valuable tool for assessing a cause of fetal loss.
    • Prenatal Genetic Diagnosis in subsequent pregnancy
    Conclusion
  • 35. Thank you