genetic factors in rpl
TRANSCRIPT
Dr. Raju R SahetyaM.D., D.G.O., D.F.P., F.C.P.S., F.I.C.O.G.,
OBSTETRICIAN & GYNAECOLOGISTSpecialist: Infertility & Maternal Fetal Medicine
HospitalPushpaa Hospital
Mumbai, India
www.pushpaahospital.com, [email protected]
Mobile 9821090102
HonoraryHinduja Hospital * BSES Hospital
Mumbadevi Hospital * Hiranandani Hospita
Vice PresidentIndian Society for Prenatal Diagnosis & Fetal Therapy (ISPAT)
Member Excecutive CouncilMumbai 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
“I OWE TO MY ALMA MATER !”
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.
Geneticfactors
Anatomicalfactors
EndocrineInfective
agents
Immunefactors
InheretedThrombophilic
defect
Explained Un-explained
RecurentMiscarriage
Enviromentalfactors
Body Cervix
Paternalkaryotyping
CytogeneticOf miscarriage
C I
Uterineanomalies
APS
BacterialVaginosis
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.
Pregnancy Loss
Chromosomal Mendelian Inheritance.
Multifactorial.
Establish the etiology
Investigate the couple
Estimate recurrence risk
Provide accurate genetic counseling.
Discuss reproductive options.
Essential as patients have small planned families.
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.
•Tissues usually used for karyotype from abortuses.
Chorionic Villi from products in normal saline
Piece of placenta at cord insertion in normal saline.
Fetal cord / cardiac blood, in sodium heparin vaccutainers.
• No formalin or freezing for preservation
• Should reach within 24-36 hours at Room Temperature.
NABL ACCREDITED (ISO / IEC – 17025)
AccreditationsExperienced Medical GeneticistQualified staff
State of the art equipment.Reliable reports Minimum turn around time.Interaction with physician.
Accessibility
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
Medical and Maternal
Family
Previous and present pregnancy.
Antenatal
Fetal wellbeing
Labor and Postnatal.
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
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
Exomphalos. Trisomy 18.
Holoprosencephaly Trisomy13, 15.
Choroid Plexus Cyst Trisomy 18.
Nuchal Translucency Trisomy 21.45X.
Ventriculomegaly 13,18,21
Cystic Hygroma45X.
Trisomy 18
Monosomy XTriploidy Trisomy 13
Trisomy 21
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.
Karyotype FISHNeeds 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
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
Parental Karyotype.
Prenatal Diagnosis PGD / CVS / Amniocentesis
Gamet Donation.
CHORIONIC VILLUS SAMPLING10-11 WEEKS
AMNIOCENTESIS 15-17 WEEKS
Frequency : 2-3 per 1000.
Inheritance : Multifactorial, single gene / chromosomal.
Recurrence risk : 9% / 2-3%.
Periconceptional folic acid supplement.
Neural Tube Defects
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