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									GENETICS OF PREGNANCY LOSS




Mohamed. A. Sabry, MBBCh, DHCG, MSc, MD (UK)
• Cytogenetic abnormalities

• Recurrent abortion

• Exogenous factors

• Multiple pregnancies

• Second and third trimester fetal loss

• Abnormal uterine environment
• Cytogenetic abnormalities

• Recurrent abortion

• Exogenous factors

• Multiple pregnancies

• Second and third trimester fetal loss

• Abnormal uterine environment
• Chromosomal abnormalities are detected
  in 70% of all spontaneous losses (versus
  0.7% of newborns)
•   Autosomal trisomies
•   Monosomy X
•   Triploidy
•   Tetraploidy
•   Unbalanced structural chromosomal
    abnormalities
• Autosomal trisomies (Autosomal
  monosomies are almost never seen)
  – Detected in 50% of chromosomally abnormal
    fetuses
  – Most autosomal trisomies are lost in the Ist
    trimester
  – The most common trisomies seen are trisomy
    16 (severely lethal), trisomies 15 and 22

• Chromosome X monosomy is detected in
  20% of all 1st trimester losses
• Triploidy
  accounts for 15% of cytogenetically
  abnormal abortuses
  – due to dispermy (fertilization of ovum with 2
    sperm)
  – Rarely due to diploid sperm (fertilization of
    ovum with one sperm containing 2n
    chromosomes)
  – More rarely due to 2 maternal + 1 paternal
    sets of chromosomes (complete maternal
    non-disjunction at meiosis I or meiosis II
    and retention of polar body)
  – Gestational age at abortion: Ist trimester
    mostly
MOLAR PREGNANCY
(HYDATIDIFORM MOLE)
(Overgrowth of placental tissues at the expense of embryonic tissues)

                            Partial hydatidiform    Complete hydatidiform mole
                                      mole
  Evidence of fetal parts            +                            -

      Trophoblastic                  +                           ++
        hyperplasia
     Association with                -                + (should be followed-up)
         malignancy
      Chromosomal                 Triploid             Diploid (duplication of
        constitution                                            paternal
                                                      Haploid complement with
                                                        homozygosity at all loci)
• Tetraploidy
  – Due to failure of post-conceptual cell cleavage
  – 5% of abortus specimens
  – Always has XXXX or XXYY sex chromosome
    complement
  – Abortion occurs at 1st trimester
  – Rarely, may be associated with a live birth
• Unbalanced structural chromosomal
  abnormalities
  – 2% of karyotyped spontaneous abortion
    • 50%% de novo
    • 50% inherited (greatly increased recurrence risk)
• Cytogenetic abnormalities

• Recurrent abortion

• Exogenous factors

• Multiple pregnancies

• Second and third trimester fetal loss

• Abnormal uterine environment
• 1-2% of couples experience 3 or more consecutive spontaneous
  pregnancy losses
• Most common causes for recurrent losses:
   – Luteal phase inadequacies (Progesterone deficit)
   – Anatomic defects in the mother (Uterine, cervical, Polycystic ovaries)
   – Parental chromosomal abnormalities (small proportion)
       • Balanced chromosomal rearrangements in one of the parents:
            – More common in the female partner
            – reciprocal or Robertsonian tanslocations
                 » NB: Carriers of chromosomes 21;21 Robertsonian translocations will lose
                    half of their pregnancies as a result of monosomy 21 , while all of their live-
                    born children will have Down's syndrome
       • Chromosomal inversion
            – Common human inversions, [inv(9)(p12q13) and inv(2)(p11q12)] are unlikely to be
              associated wit either pregnancy loss or abnormal offspring.
       • sex chromosome mosaicism (low-level).
   – Genetic factors
       • X-linked dominant disorders.
       • Skewed X-chromosome inactivation (more than 90% activation of the same
         parental chromosome as opposed to the 50% expected by chance).
       • Autoimmune disorders (Antiphospholipid antibodies, which lead to a higher
         incidence of thrombotic events)
       • Vascular deficiency
                  » Factor XII deficiency
                  » Factor V (Factor V Leiden mutations) and prothrombin mutations
                  » Hyperhomocysteinemia
   – Underlying maternal disease (e.g. Maternal hypertension, Systemic
     lupus erythematosus, Insulin dependant diabetes…)
• Cytogenetic abnormalities

• Recurrent abortion

• Exogenous factors

• Multiple pregnancies

• Second and third trimester fetal loss

• Abnormal uterine environment
• Exogenous factors
 (Teratogens & Teratogenic maternal infections)

• Multiple pregnancies

• Second and third trimester fetal loss
 (Maternal Hypertension, Renal disease…)

• Abnormal uterine environment
 (Oligohydramnios, Polyhydramnios)

								
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