ABSTRACT
Pregnancy and obstetric outcome are the final steps in infertility treatment. Additional
data from recent studies demonstrate an increased risk for pregnancy course and obstetric
outcome. These risks include an increased risk for intrauterine growth retardation,
preeclampsia, and premature birth. Children born after in vitro fertilization and
intracytoplasmic sperm injection (ICSI) have an increased risk for major malformations
compared with spontaneously conceived pregnancies. Patients have to be counseled about
these risks. The question is where these increased risks originate. At present, there
are insufficient data available from pregnancies established following hormonal treatment
or intrauterine insemination cycles. Therefore, the question is still open for debate,
whether either in vitro culture or infertility per se or perhaps other components
of the treatment cycle contribute to this risk. There is some evidence that at least
the ICSI technique or the in vitro culture technique is not the only or most prominent
factor. A long time to pregnancy with subsequent spontaneous pregnancy results in
a similar risk profile as pregnancies following infertility treatment. This article
discusses a possible pathogenetic model for these observations.
KEYWORDS
IVF - ICSI - pregnancy - malformation - imprinting defect
REFERENCES
- 1
Bonduelle M, Liebaers I, Deketelaere V et al..
Neonatal data on a cohort of 2889 infants born after ICSI (1991-1999) and of 2995
infants born after IVF (1983-1999).
Hum Reprod.
2002;
17
671-694
- 2
Hansen M, Kurinczuk J J, Bower C, Webb S.
The risk of major birth defects after intracytoplasmic sperm injection and in vitro
fertilization.
N Engl J Med.
2002;
346
725-730
- 3
Katalinic A, Rösch C, Ludwig M. for German ICSI Follow-Up Study Group .
Pregnancy course and outcome after intracytoplasmic sperm injection (ICSI)-a controlled,
prospective cohort study.
Fertil Steril.
2004;
81
1604-1616
- 4
Ludwig M, Katalinic A.
Malformation rate in fetuses and children conceived after intracytoplasmic sperm injection
(ICSI): results of a prospective cohort study.
Reprod Biomed Online.
2002;
5
171-178
- 5
Ludwig M, Diedrich K.
Follow up of children born after assisted reproductive technologies.
Reprod Biomed Online.
2002;
5
317-322
- 6
Ludwig M, Katalinic A.
Pregnancy course and health of children born after ICSI depending on parameters of
male factor infertility.
Hum Reprod.
2003;
18
351-357
- 7
Ericson A, Kallen B.
Congenital malformations in infants born after IVF: a population-based study.
Hum Reprod.
2001;
16
504-509
- 8
Wennerholm U B, Bergh C, Hamberger L et al..
Incidence of congenital malformations in children born after ICSI.
Hum Reprod.
2000;
15
944-948
- 9
Edwards R G, Ludwig M.
Are major defects in children conceived in vitro due to innate problems in patients
or to induced genetic damage?.
Reprod Biomed Online.
2003;
7
131-138
- 10
Gosden R, Trasler J, Lucifero D, Faddy M.
Rare congenital disorders, imprinted genes, and assisted reproductive technology.
Lancet.
2003;
361
1975-1977
- 11
Hoshi H.
In vitro production of bovine embryos and their application for embryo transfer.
Theriogenology.
2003;
59
675-685
- 12
Sollars V, Lu X, Xiao L, Wang X, Garfinkel M D, Ruden D M.
Evidence for an epigenetic mechanism by which Hsp90 acts as a capacitor for morphological
evolution.
Nat Genet.
2003;
33
70-74
- 13
Marques C J, Carvalho F, Sousa M, Barros A.
Genomic imprinting in disruptive spermatogenesis.
Lancet.
2004;
363
1700-1702
- 14 Ludwig M. Pregnancy and Birth after Assisted Reproductive Technologies. Berlin;
Springer Verlag 2002
- 15
Pezeshki K, Feldman J, Stein D E, Lobel S M, Grazi R V.
Bleeding and spontaneous abortion after therapy for infertility.
Fertil Steril.
2000;
74
504-508
- 16
Wang J X, Norman R J, Wilcox A J.
Incidence of spontaneous abortion among pregnancies produced by assisted reproductive
technology.
Hum Reprod.
2004;
19
272-277
- 17
Helmerhorst F M, Perquin D A, Donker D, Keirse M J.
Perinatal outcome of singletons and twins after assisted conception: a systematic
review of controlled studies.
BMJ.
2004;
328
261
- 18
Schieve L A, Meikle S F, Ferre C, Peterson H B, Jeng G, Wilcox L S.
Low and very low birth weight in infants conceived with use of assisted reproductive
technology.
N Engl J Med.
2002;
346
731-737
- 19
Wang J X, Knottnerus A-M, Schuit G, Norman R J, Chan A, Dekker G A.
Surgically obtained sperm, and risk of gestational hypertension and pre-eclampsia.
Lancet.
2002;
359
673-674
- 20
Vernaeve V, Bonduelle M, Tournaye H, Camus M, Van Steirteghem A, Devroey P.
Pregnancy outcome and neonatal data of children born after ICSI using testicular sperm
in obstructive and non-obstructive azoospermia.
Hum Reprod.
2003;
18
2093-2097
- 21
Pandian Z, Bhattacharya S, Templeton A.
Review of unexplained infertility and obstetric outcome: a 10 year review.
Hum Reprod.
2001;
16
2593-2597
- 22
Basso O, Weinberg C R, Baird D D, Wilcox A J, Olsen J.
Subfecundity as a correlate of preeclampsia: a study within the Danish National Birth
Cohort.
Am J Epidemiol.
2003;
157
195-202
- 23
Henriksen T B, Baird D D, Olsen J, Hedegaard M, Secher N J, Wilcox A J.
Time to pregnancy and preterm delivery.
Obstet Gynecol.
1997;
89
594-599
- 24
Peschka B, Leygraaf J. van d V, Montag M, Schartmann B, Schubert R, Schwanitz G.
Type and frequency of chromosome aberrations in 781 couples undergoing intracytoplasmic
sperm injection.
Hum Reprod.
1999;
14
2257-2263
- 25
Meschede D, Lemcke B, Exeler J R et al..
Chromosome abnormalities in 447 couples undergoing intracytoplasmic sperm injection-prevalence,
types, sex distribution and reproductive relevance.
Hum Reprod.
1998;
13
576-582
- 26
Scholtes M C, Behrend C, Dietzel-Dahmen J et al..
Chromosomal aberrations in couples undergoing intracytoplasmic sperm injection: influence
on implantation and ongoing pregnancy rates.
Fertil Steril.
1998;
70
933-937
- 27
Wu L, de Bruin A, Saavedra H I et al..
Extra-embryonic function of Rb is essential for embryonic development and viability.
Nature.
2003;
421
942-947
- 28
Georgiades P, Watkins M, Surani M A, Ferguson-Smith A C.
Parental origin-specific developmental defects in mice with uniparental disomy for
chromosome 12.
Development.
2000;
127
4719-4728
- 29
Muller F, Dreux S, Lemeur A et al..
Medically assisted reproduction and second-trimester maternal serum marker screening
for Down syndrome.
Prenat Diagn.
2003;
23
1073-1076
- 30
Ghisoni L, Ferrazzi E, Castagna C, Levi Setti P E, Masini A C, Pigni A.
Prenatal diagnosis after ART success: the role of early combined screening tests in
counselling pregnant patients.
Placenta.
2003;
24(suppl B)
S99-S103
- 31
Hui P W, Lam Y H, Tang M H, Ng E H, Yeung W S, Ho P C.
Amniotic fluid human chorionic gonadotrophin and alpha-fetoprotein levels in pregnancies
conceived after assisted reproduction.
Prenat Diagn.
2003;
23
484-487
- 32
Maymon R, Shulman A.
Serial first- and second-trimester Down's syndrome screening tests among IVF-versus
naturally-conceived singletons.
Hum Reprod.
2002;
17
1081-1085
- 33
Wojdemann K R, Larsen S O, Shalmi A, Sundberg K, Christiansen M, Tabor A.
First trimester screening for Down syndrome and assisted reproduction: no basis for
concern.
Prenat Diagn.
2001;
21
563-565
- 34
Liao A W, Heath V, Kametas N, Spencer K, Nicolaides K H.
First-trimester screening for trisomy 21 in singleton pregnancies achieved by assisted
reproduction.
Hum Reprod.
2001;
16
1501-1504
- 35
Wald N J, White N, Morris J K, Huttly W J, Canick J A.
Serum markers for Down's syndrome in women who have had in vitro fertilisation: implications
for antenatal screening.
Br J Obstet Gynaecol.
1999;
106
1304-1306
- 36
Ribbert L S, Kornman L H, de Wolf B T et al..
Maternal serum screening for fetal Down syndrome in IVF pregnancies.
Prenat Diagn.
1996;
16
35-38
Priv. Doz. Dr. Med.
Michael Ludwig
Endokrinologikum Hamburg
Lornsenstrasse 6, 22767 Hamburg, Germany
eMail: Michael.Ludwig@Endokrinologikum.com
