DR MUHTEREM BAHÇEGATA TIBBİ GENETİK B.D.

ÜREME GENETİĞİ VE TEKRARLAYAN ART BAŞARISIZLIĞINDA PGT

REPEATED IMPLANTATION FAILURE

For several years, researchers have shown a link between recurrent pregnancy loss (RPL) and many factors including anatomical, autoimmune, endocrine, genetic, and thrombotic anomalies.

Recently, it has been hypothesised that the RPL pathophysiology and early implantation failure may be similar, suggesting that the same factors detrimental to fetal survival may be responsible for implantation failure.

• Aneuploidy rate: 54 %

– Two failed IVF cycles : 40 %– Three failed IVF cycles : 50 %– >5 failed IVF cycles : 67 %

Gianaroli 1997, Magli 1998

REPEATED IMPLANTATION FAILURE

Aneuploidy rate: 54%

– Mosaics

– Monosomies

– PoliploidiesTriploidyTetraploidy

Monosomy/trisomy: 14:4

Gianaroli 1999

REPEATED IMPLANTATION FAILURE

Implantation Rate (IR)

Age group Control PGD IR IR IR increase

35-37 32% (16/50) 33% (11/33) + 1.3%

37.1- 39 24.6% (28/114) 27.9% (26/93) + 3.3%

39.1- 42 14.9% (25/168) 20.4% (20/98) + 5.5%

42.1- 45 7.4% (5/68) 17.1% (6/35) + 9.7%

Total 18.5% 23.9% + 5.4%

13, 15, 16, 18, 21, 22, X, Y

The increase in IR is specifically is clear >37 years of age.Munné et al. ASRM 2001

112 PGD cycles112 control cycles

> 3 failed IVF

PGD Control group group

Cycles 27 27 Age 32.2±2.3 31.7±2.4

Abnormal embryo % 54 % -

Transferred embryo 2.6±0.9 3.2±1.1

Clinical pregnancy rate 25%(5/25) 22% (5/23 )

İmplantation rate 17.3% 9.5%

Spontaneous abortion 4% 20%

Ongoing IR 25% 10.5%

Gianaroli 1999

The differences between the types of chromosomal abnormalities in embryos from couples of the three major PGS referral groups (AMA, RM and RIF) were investigated in great detail. RM and AMA embryos show consistent similarities that would imply a common underlying mechanism in the causation of aneuploidy.

Embryos from the RIF group show a significantly lower incidence of meiotic origin errors and almost universal postzygotic errors implying that mitosis and not meiosis is more error prone in this group.

Preimplantation genetic diagnosis of aneuploidy: were we looking at the wrong chromosomes?

Bahce M, Cohen J, Munne S.

Institute for Reproductive Medicine and Science, Saint Barnabas Medical Center, Livingston, New Jersey 07052, USA.

PURPOSE: Our purpose was to study aneuploidy frequencies of chromosomes 1, 4, 6, 7, 14, 15, 17, 18, and 22 in cleavage-stage embryos. These frequencies were compared to spontaneous abortion data to determine differences in survival rate of their aneuploidies. METHODS: One hundred ninety-four embryos were analyzed with multicolor fluorescence in situ hybridization. Embryos were divided into three maternal age groups: 20 to 34.9 years, (2) 35 to 39.9 years, and (3) 40 years and older. Embryos were also divided into two developmental and morphological groups; arrested and nonarrested embryos. RESULTS: The rate of aneuploidy was 14.51%, 14.10%, and 31.48% for age groups 1, 2, and 3, respectively (P < 0.005). The chromosomes most frequently involved in aneuploidy events were 22, 15, 1, and 17. CONCLUSIONS: The chromosomes most involved in spontaneous abortions are not necessarily the ones causing a decrease in implantation rates with maternal age. Other aneuploidies, such as for chromosomes 1 and 17, may seldom implant or die shortly after implantation.

J Assist Reprod Genet. 1999 Apr;16(4):176-81.

Abnormal embryonic development diagnosed embryoscopically in early intrauterine deaths after in vitro fertilization: A preliminary report of 23 cases

Tom Philipp M.D.a, , , Wilfried Feichtinger M.D.b, Margot I. Van Allen M.D.c, Evica Separovic M.D.d, Angelika Reiner M.D.e and Dagmar K. Kalousek M.D.d

aLudwig Boltzmann Institute of Clinical Gynecology and Obstetrics, Danube Hospital, Vienna, AustriabWunschbaby–Institut für Kinderwunsch, Vienna, AustriacDepartment of Medical Genetics, University of British Columbia, Vancouver, British Columbia, CanadadDepartment of Pathology (Cytogenetics), University of British Columbia, Vancouver, British Columbia, CanadaeDepartment of Pathology, Cytogenetic Laboratory, Danube Hospital, Vienna, Austria

Fertility and Sterility Volume 82, Issue 5 , November 2004, Pages 1337-1342

Summary of embryoscopic and cytogenetic findings identified in 23 patients with missed

abortions in pregnancy by IVF. Case Maternal age (y) Karyotype1 37 46,XY2 38 47,XX,+18 3 32 46,XX 4 35 47,XX,+10 (!!) 5 33 45,X6 36 47,XX,+14 (!!) 7 37 45,X8 40 47,XX,+12 (!!) 9 38 47,XX,+14 (!!) 10 29 46,XX,−14,+t(13q;14q)11 41 47,XY,+9 (!!) 12 35 47,XY,+11 (!!) 13 32 46,XX14 35 47,XY,+15 15 30 46,XY16 42 47,XY,+13 17 40 46,XY18 28 46,XY 19 37 47,XX,+16 20 37 47,XY,+3 (!!) 21 36 47,XY,+1622 33 47,XY,+8 (!!) 23 35 47,XX,+16

%73.91

Age Emb. trans. Pregnancy group cycle %

19-36 219 35.61 (31.96) (91.84)

37-46 143 22.38 (40.63) (143/173)

Reproductive Genetics

Single gene defects*Y microdeletions*Thrombophilia genes*Factor II, V, MTHFR Chromosomal abnormalities*Aneuploidies*Structural abnormalities

NanoChipTM 100-Site Microelectronic Array

1,28 cm2 500.000 samples

5,7 micron

Genomics xx (2007) xxx–xxx