INVASIVE PROCEDURES

by

DR J JEEBODH

AIM OF PRESENTATION

• Briefly discuss options available for prenatal diagnosis

• Briefly discuss therapeutic options• Procedure/technique• Complications• Limitations

DIAGNOSTIC

• Amniocentesis

• Chorionic villus sampling

• Cordocentesis and other methods of FBS

• Fetal tissue biopsies

• Coelocentesis

• Fetoscopy

AMNIOCENTESIS

Removal of fluid containing fetal cells and biochemical products from amniotic cavity

Cells in amniotic fluid are desquamated from fetal skin & sloughed from GIT,urogenital & resp tract and amnion

INDICATIONS

• CHR and DNA analysis• Biochemistry• Fetal infection• Lung maturity• Chorioamnionitis• Obstetric cholestasis• Therapy

PROCEDURE• Performed more than 15weeks & up to 18 weeks• Consent and counselling• Sonar• Transabdominal approach• Asepsis• Direct and continuous ultrasound guidance• 22 gauge spinal needle • Avoid fetus , placenta and cord

EARLY AMNIOCENTESIS

• Less than 15 weeks• Only 10 to 12 ml• Success between 12 to 14 weeks ?95%• Fewer cells to culture• Advantages• Complications : More than post midtrimester

amnio, failure rate, fetal loss

COMPLICATIONS

• Fetal loss• Pregnancy complications – abdo pain, amniotic

fluid leakage , vaginal bleeding• Chronic leakage• Orthopaedic abnormalities• Fetal trauma• Rhesus alloimmunisation

PREDISPOSING FACTORS TO SPONTANEOUS ABORTIONS POST AMNIOCENTESIS

1. History of previous spontaneous or induced abortion

2. Bleeding in current pregnancy

3. Age > 40 yrs

4. 3 or > 1st trimester abortions

5. 2nd trimester miscarriage or TOP

6. Obstetrician/operator experience

AMNIOCENTESIS & TWINS

• Single needle technique better than double • Needle into proximal sac – aspirate• Advanced into 2nd sac through membrane under

direct vision• Concerns• DO NOT USE DYES• Fetal loss risk

CVS AND PLACENTAL BIOPSY

• Chorion frondosum or placental tissue sampled • Alternative to amniotic fluid and FBS for prenatal

diagnosis of genetic disorders• Villi excellent source of DNA• Tissue obtained consists of syncytiotrophoblast

(outer non-dividing cells) and cytotrophoblast (rapidly dividing cells)

Cytogenetic results in 48hours & final culture in 7d

INDICATIONS FOR CVS

• Maternal age at 35 yrs or more at conception

• Previous child with aneuploidy • Parent who is a carrier of a balanced

translocation or other CHR abnormalities• Autosomal recessive disease• Women who are carriers of sex – linked

disease

PROCEDURE

• Between 11 to 14 weeks• Transabdominal or transcervical (less frequently)• Needle into placenta under continuous

simultaneous ultrasound guidance• Placental biopsies done in 2nd and 3rd trimesters

COMPLICATIONS

• PROCEDURE RELATED Miscarriage Limb reduction

Risk of late termination

• DIAGNOSIS RELATED More cytogenetic ambiguous results Mosaicism & other variants(1%) – false negative

results

CVS AND LIMB DEFICIENCES

• Risk and severity of limb deficiency appear to be associated with timing of CVS

• Overall risk for transverse limb deficiences 0.03% - 0.1% (1 in 3000 to 1 in 1000)

• Less than 10 weeks : 0.2% & more proximal limb deficiences and orofacial defects

• At or greater than 10 weeks : 0.07% & most limited to digits

• Possible mechanism some form of vascular disruption

CVS AND TWINS

• Loss rate similar to amnio• Concerns• Techniques to reduce contamination• Advantages• Disadvantages

FETAL BLOOD SAMPLING

DIAGNOSTIC CHR abnormalities DNA abnormalities / single gene defects Fetal anaemia Fetal thrombocytopaenia Fetal hypoxia / acidosis Fetal infection THERAPEUTIC Anaemia , thrombocytopaenia , drug administration ,

fetacide

PROCEDURE OPTIONS

SAMLING SITE 1. Fetal heart 2. Fetal intrahepatic vessels 3. Umbilical cord (cordocentesis) -Easiest site to puncture is

1cm from cord insertion into placenta (avoid free loop)

-More than 20 weeks : 5ml -Less than 20 weeks : caution

with volume removed

COMPLICATIONS

• FETAL

- bleeding or haematoma

- fetal bradycardia

- Chorioamnionitis

- Placental abruption

- Amniotic fluid leakage or ROM

- Death

- Disability in survivors

- Transmission of maternal infection

• MATERNAL- Alloimmunisation- Chorioamnionitis- Maternal trauma- Possibilty of emergency delivery

Post procedure pregnancy loss rate :1%• Tranfusion carries higher procedure related risk than blood

sampling• Operator skill important

COELOCENTESIS

• Earlier than CVS• Coelomic space between amniotic membrane and

uterine cavity• Under re-evaluation • 1 to 2.5ml of amniotic fluid (vol by 9 weeks ±5 to

6ml)• Cells mostly haemopoetic in origin• 90% of cells viable before 7 weeks• 95% success at 7 weeks

FETAL TISSUE BIOPSIES

• Need for diagnosis of disorders not amenable to molecular approaches

• Indications are possible or potentially lethal or severely handicapping conditions in fetus affecting skin, liver, muscle & occasionally for diagnosis of fetal tumours

• Options : fetoscopic directed biopsies ,ultrasound guided aspiration or ‘tru-cut’ technique

FETAL SKIN BIOPSIES

• Only a few major dermatological disorders associated with CHR abnormalities or enzyme defects detectable on either amniotic fluid or chorionic villi

• Ultrasound visualisation useless in majority of serious cutaneous abnormalities

• Actual visualisation of skin and histology only way to make diagnosis

• Obtained under direct visualisation using fetoscopy or ultrasound guidance

• Heal with no scar formation• Complications : ROM ,bleeding , infection , miscarriage

FETAL LIVER BIOPSIES

• Successfully used for prenatal diagnosis of : - ornithine transcarbamylase deficiency - carbamyl phosphate synthetase deficiency - Von Gierke’s disease - Primary hyperoxaluria type 1

• Needle or coring biopsy instrument inserted into RUQ of fetal abdomen

FETAL MUSCLE BIOPSIES

• Majority of DMD currently diagnosed by molecular analysis of the gene using CVS

• Either through detection of deletion mutation or by linkage analysis

• Is possible that deletion mutation not found• Muscle biopsy allows finding of dystrophin• Complications : nerve damage & bleeding• ONLY USE IF INDICATED • EXPERIENCED OPERATOR

• Other organs : lung , kidney• Tumours• Most indications DO NOT outweigh risk• Risk of pregnancy wastage relatively high• Biopsy when yield exceeds risk• Complex analysis of specimens

THERAPEUTIC INVASIVE PROCEDURES

• Rhesus isoimmunisation• Platelet disorders• Drugs • Multiple pregnancy reduction and selective termination• Fetal shunts• Relief of polyhydramnios• Therapeutic amnioinfusion• Open fetal surgery• TTTS• Fetoscopy

MULTIFETAL PREGNANCY REDUCTION AND SELECTIVE TERMINATION

• Obstetric outcome of triplets & higher numbers of fetuses significantly compromised

• First trimester procedures for fetal number: MFPR

• 2ND Trimester procedures for fetal abnormalities : selective termination

MFPR

• Transvaginal aspiration or transabdominal KCL• Embryo selection

- exclude abnormalities or aneuploidy - choice based on ease of approach - avoid embryo closest to cervix

• Timing – 9 to 12 weeks

SELECTIVE TERMINATION OF ABNORMAL TWIN

• Case selection critical • If placenta shared ,demise of one twin potentially

places surviving co–twin at increased risk• KCL only in dichorionic twins• Umbilical cord ligation or occlusion in

monochrionic twins• Risk of fetal loss

TTTS MANAGEMENT

• Expectant• Medical no benefit• Serial amniodrainage• Septostomy with /without amniodrainge• Selective fetocide – ligation of umbilical cord/

cord coagulation, cord embolisation• Laser occlusion – fetoscopic directed laser

ablation of vascular anastomoses

FETOSCOPIC LASER ABLATION

• Cause-orientated approach• Fetal complications• Maternal complications• Fetal survival• Risk of neurological sequelae

FETAL SHUNTS

• Can perform antenatal drainage of pathological collections of fluids in fetus

• Direct needling or shunting• In theory, drainage of abnormal fluid collections

possible from fetal abdo,brain,chest,renal tract• Pleural effusions – pleuroamniotic shunt• Vesicoamniotic shunts in obstructive uropathy or

to decompress a dilated urinary tract

BLOOD TRANSFUSIONS

• Intraperitoneal(less preferred) or intravascular• INTRAPERITONEAL

- blood absorbed via lymph vessels - 10% of cells absorbed each day by non-hydropic fetus - absorption in hydropic fetus poor - disadvantages : slow correction of HB,increased risk of trauma, can obstruct cardiac return, lower survival rates than intravascular

BLOOD TRANSFUSIONS CONTINUED

• INTRAVASCULAR - Umbilical vein - 22 gauge needle - at insertion or free loop

volume determined by Hct and gest ageWhen to transfuse? Hct < 30 % ( <25th percentile

for GA) ORVol = (weeks in gestation – 20) x 10ml

THERAPEUTIC AMNIOCENTESIS

• Transabdominal • Decrease amniotic fluid under sonar guidance• Prolong gestation & improve survival• Aim : DVP <8cm or AFI normal range• Complication rate 1.5% - PROM,

chorioamnionitis, abruptio, membranous detachment

• Maximum 3litres• TNT patch

AMNIOINFUSION

• INDICATION : Improve visualisation of fetal anatomy or severe oligohydramnios / anhydramnios

• FLUIDS: physiological solution- N/S, RL,5% gluc

• VOL: Minimum needed to improve visualisation

• COMPLICATIONS

CONCLUSION

• Risk of HIV transmission• Counseling – Procedure related risks,

complications, limitations• Individually tailored risk assessment before

procedure

THANK YOU