Abnormal genes & recurrent miscarriage -a malady

8) Telomeres are the caps on either sends  of chromosomes.  In males with increasing age telomere damage is common.AS such if at the time of conception the age of father is > 40 yrs some gengtic diosrders , autism & behaviour disorders can ensue. But such  telomeric  deletions may also yield to  recurrent  pregnancy loss.

 As we have  mentioned earlier   the amount of genetic  material  content in the embryo is crucial  DNA k imbalance  can be present  in mosaic  or nonmosaic   pattern and some are worse than others  . In general   terms loss of chromosomal   material produces   more important effects   on the growth   of the conceptus than an excess of  material  autosomal monosomies  and trisomies normally   lead to an abortion due to self   destruction of the embryo   Few full trisomies    and many partial   chromosomal   aneuploidies are  associated   with survival of    the fetus  Nevertheless  these babies   carry    a phenotype of   widespread dysmorphogenesis and malformation of internal  organs and limb.

9) Unbalanced Gestations in Carriers of Structural Chromosome  Rearrangements

In this   part of the chapter we will focus on the partial   imbalances   that can lead to abortion  especially those that are carried  by the parents    and can be   the cause of RPL   approximately 2-4%  of RPL are  associated with parental balanced  structural chromosome rearrangements commonly balanced   reciprocal translocations or Robertsonian translocation . A translocation   is a chromosome  abnormality caused by the breakage and rearrangement  of two non homologues   chromosomes. When this structural rearrangement   ends up    with a cell containing the right amount of genetic   material . It is    called balanced   reciprocal   translocation   other  structural     abnormalities   such as chromosomal   inversions,   insertions are associated    with RPL . In the end    we can face a healthy     couple with a    history  of RPL    and discover by   performing  a karyotype   test that one of them is the  carrier    of a balanced  translocation inversion insertion   or deletion This patient could produce    unbalanced   gametes  resulting  in   abnormal    embryos with terminal chromosome    duplications  and deletion   leading     to an abortion  also   embryos   with  full aneuploidies In these cases for further pregnancies  preimplantation genetic   testing can be performed after IVF, with   Trophoectodrm  biopsy at blastocyst stage to   test  the chromosome  conte4nt of the embryos   before replacing    them back to the uterus   with this approach   the risk of a further miscarriage    and unbalanced offspring decrease   to a percentage   similar   to that  of general   population

4) Male  Carriers of Chromosome Y Micro deletions

Micro deletions of the chromosome Y long arm are the most frequent molecular   genetics of severe   male infertility , mainly   by presence of   severe oligozoospermia and non obstructive azoospermia  Nowadays   these genetic    alterations could be screened   as routine   which is important since  they are present  in approximately in 9% of the oligo azoospermia males.

At the molecular   level   Y chromosome  micro deletions affect at least three regions known   as azoospermia factor    these  three regions  are essential   for a   successful spermatogenesis. Different   micro deletions have deleterious  effects  in different  aspects   of male fertility . It is of note though   the AFZ cv 2/64   deletions since men carrying   them produce    a higher percentage   of nullisomy for the sex    chromosome   and NY   disomy  . Once  these findings wee published  a link between male   carriers of Y  chromosome    deletions and RPL   was suggested  . In fact Dewan et al in 2006  observed that in couples  with RPL  a significant percentage   of the  males   had chromosome Y  micro deletions . Another   study   carried out by Agarwal et al in 2015   stated that in couples suffering  RPL  32.5% of males  were carriers of chromosome Y  micro deletions  and after excluding  the female  factor  in 13. 5%   of the cases. Interestingly the most  frequent   micro deletion was the AZFc The incidence of    chromosome Y   micro deletion   is different in different  population    since is linked  to chromosome  Y  haplogroups  . In fact venkatesh et al   did not  detect   any micro deletion  in a population of RPL  in New Delhi.

Nevertheless taking  in account  the population  that we are  working  with  this novel data    suggests   that micro deletions in chromosome Y   could be the cause  of RPL  so the study    of these   chromosomal   abnormalities   could be offered to couples with idiopathic abortion .

11) De novo  Duplications / Deletions from Couples with Normal  Karyotype “What is that ?Sporadic early  pregnancy loss    occurs  in   10-15%  clinically recognized  gestations. As  we have  mentioned   earlier  must of the cases of miscarriages are    due to full chromosomal   trisomies  or monosomies. Nevertheless  in some cases   the  cause of these   abortions could be submicroscopic  chromosomal changes like    duplications and / or   deletions  . The problems is that these structural  abnormalities  could  appear    de novo. This    mens that even though   parents   have a perfectly normal karyotype the embryos could carry   a dup/ del. In these cases the recurrence  risk would be  similar   to general    population  With   the introduction  by pre implantations genetic  testing  for aneuploidies for aneuploidy   screening   also in couples  with normal    karyotype  small dup /del   have been  indentified   in per implantation   embryos  also/ The introduction  of more accurate  techniques like array comparative genomic hybridization and Next   Generation seque3ncing enable the clinicians   the possibility  of  detecting   these small changes in the embryo  before    transfer   in IVF   couples