Generation of MZ twins Isaac Blickstein, MD Leonardo da Vinci’s Leda and the Swan Tyndareus Leda Zeus King of Sparta Ruler of gods Castor Clytemnestra Helene Pollux JM Thijssen. Twins as monsters: Albertus Magnus theory of the generation of twins and its philosophical context. Bull Med Hist 1987; 61:237-46 Albertus Magnus (ca 1200-80), Albert the Great, doctor universalis Twins are a divine punishment for misbehaving Albertus Magnus: “Therefore it is dangerous that the female moves during sexual intercourse in the way prostitutes are reputed to do, because if at such moment they would conceive, they could generate an awful two-headed monster” Blickstein I. Twin Res 2000 MZ = embryonic accident Axioms related to MZ twinning 1. Same prevalence in different populations 2. Corner’s theory of MZ placentation Example 1: Fusion not Fission Fusion not Fission Fusion not Fission Example 2: DZ MC twins 3a. High malformation rate 3b. Very high perinatal risk •PTD/vPTD •VLBW/ELBW •Brain damage 4. All methods of ART increase MZ splitting Mechanism – Unknown Recurrent MZs: 1/250 X 1/250 = 1/62,500 Familial The potential role of the ELABELA peptide hormone in the generation of MZ twins Bruno Reversade Experimental halving of the embryo (different mares) Involution of a co-dominant axis Evolution of a co-dominant axis Evolution of a co-dominant axis Blastomere herniation theory Cell repulsion theory Anomalies Zygotic •Fetal Trigger splitting •Placental Zygotic Anomalies Infertility treatment splitting Infertility treatment = teratogen* *Fulfilling 5/6 Wilson’s Six Principles of Teratology Unanswered questions Day 3 IVF embryo. Where is the split ? Why some zygotes split and others do not split ? Image: M. Ropacka How do we explain MC triplets ? De Lia, June 5, 2008 How do we explain MZ triplets ? How do we explain MZ quadruplets ? How do we explain MZ quintuplets ? Polyembryony occurs in two mammalian species Nine-banded Armadillo h. Sapiens The theory 1. The ovary (irrespective of race) contains oocytes with an inborn propensity to undergo splitting after fertilization Selection of splitting-prone oocyte is at random OI increases the chance of selection Spontaneous Ovulation induction 1/250 16 12 8 RR 4 0 Spontaneous ART hMG Clomiphene EFPTS, 2004 Blickstein et al, 2003 1. The ovary (irrespective of race) contains oocytes with an inborn propensity to undergo splitting after fertilization Explains why • Similar prevalence of spontaneous MZs in different races • Prevalence increases after all methods of infertility treatment Observations in the Armadillo: • Always produce MZ offspring • Uterus simplex Observations in the Armadillo: • Delayed implantation (3-4 months) • Implantation in predestined uterine locus • The armadillo’s uterus forms a space that allows no more than one blastocyst to implant • In order to produce more offspring (= reproductive fitness) the blastocyst undergoes two binary divisions. 2. The inborn propensity is to undergo to undergo binary splitting Derom, 1986 This explains MZ quadruplets This explains MZ triplets This suggests 3 types of MZ twins This explains MZ twins Singleton, but with characteristics of an MZ twin Bocklage, 1980 Singleton, but with characteristics of an MZ twin Bocklage, 1980 3. The zona pellucida controls the timely hatching Where is the split ? 4. There is no ‘physical’ split as long as the zona pellucida is intact This explains why splits are not seen in ‘regular’ IVF De Lia’s asymmetry configurations Summary: Fertilization of a splitting- prone oocyte may lead to ZP-controlled binary splitting Thank you ! .