SCREENING TESTS FOR GENETIC ABNORMALITIES IN IVF AND TWIN PREGNANCIES.

SCREENING TESTS FOR GENETIC ABNORMALITIES IN IVF AND TWIN PREGNANCIES.

Basis of Higher risk of genetic abnormalities in IVF Pregnancies: –

There is higher risk of having genetically abnormal fetus in IVF pregnancy as usually maternal age is advanced for IVF Pregnancy.

Formation of ova for the mother to be, happens for her when she herself was in her mother’s womb.

So, the age of ova in years is equivalent to her own in years while the age of sperm is only 90-120 days.

Precaution before starting testing:-

We must know that in this pregnancy, the ova (egg) used, was it hers or donor’s. All the calculations should be according to that. This rule is called “Risk Priori”.

How to determine Gestation age accurately:-

  1. Measuring CRL (Crown Rump Length) at NT (Nuchal Translucency) scan, at 11-13 weeks.
  2. Early Sonography in which heart beat(Cardiac activity) is seen.
  3. IVF Fresh cycle- egg retrieval date is taken or ET MINUS (-) 14 Days which means date of Embryo Transfer-14 days.
  4. In IVF Frozen Embryo cycle – Date of embryo transfer Minus (-) 17 days is taken to arrive at LMP( Date of last menstrual period ) as embryo is at least 3-5 days old.

Sonography markers like- NT-Nuchal Translucency and NB – Nasal Bone are not affected by mode of conception whether it is spontaneous on IVF

NIPT- Non Invasive Prenatal Testing –is also not affected by mode of conception .In this technique fragments of fetal DNA are extracted from mother’s blood sample.

This fraction is multiplied and analysed for chromosomal anomalies.

It is very good screening test but it is not diagnostic.

-Limitation is that it does not pick up structural abnormalities.

WHY SCREENING FOR GENETIC ABNORMALITIES IN IVF PATIENTS IS COMPLICATED?

  1. Advanced maternal age in itself is a high risk factor.
  2. If patient has undergone ICSI-Intra Cytoplasmic Sperm Injection The procedure itself has inherent increased risk of genetic abnormalities.
  3. Multiple pregnancies like twins or triplets may make the matter more complex.
  4. If clinical situation is of vanishing twin with empty sac –Double marker (Bio chemical test) can be done if correction factor is applied. If vanishing twin has measurable CRL and dead fetus- only ultrasound should be done for genetic abnormalities.
  5. As it is a precious pregnancy, acceptance on patient’s part for screening and invasive test is low.

Double marker measures two hormones

  • PAPP-A (Placenta Associated Plasma Protein- A)
  • Beta HCG

In down syndrome, the findings of double marker are :-

PAPP-A- Reduced

Beta HCG – High

IVF Pregnancies also show similar pattern-

The reasons are:

In IVF we use hyper stimulation protocols which results in some hormonal change like

Increased Inhibit A Level,

Decreased IGF- (Insulin like growth factors)

Increased Beta HCG Levels.

Because of interplay of these hormones even if pregnancy is normal, the values of PAPPA and HCG may mimic that of down’s syndrome.

To avoid that, a correction factor is applied while calculating value of double marker for an IVF Pregnancy.

In Twin Pregnancy there may be masking effect of abnormal twin hence double marker is not a good screening test for twins.

 

Genetic Sonogram (Ultrasound)- This mode of testing is not affected by type of conception whether it is a normal spontaneous conception or an IVF pregnancy.

TAKE HOME MESSEGE FOR SCREENING TESTS FOR TWINS :-

  • Chorionicity – whether there are two placental or one,should be determined by ultrasound.
  • NT, NB Scan along with DV-Ductus Venosus and TR-Tricuspid Regurgitation
  • NIPT may be done.

TAKE HOME MESSAGE FOR SCREENING TESTS FOR IVF PREGNANCY ARE: –

  • NT,NB along with DV,TR
  • NIPT

 

Double marker should be sent to only those labs that have sophisticated algorithms for correction factor for

-Type of conception

-Donor age

-Frozen or Fresh cycle

-Multiple pregnancies

-Chorionicity