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DOI: 10.1055/s-0031-1293208
Is There a Role for Assisted Reproductive Technology in Recurrent Miscarriage?
Publikationsverlauf
Publikationsdatum:
08. Dezember 2011 (online)

ABSTRACT
Unexplained recurrent miscarriage (RM) is a significant health problem for which no effective treatment is available yet. In only 50% of couples with RM a cause can be found. In clinical practice, a frequently asked question is whether assisted reproductive technology (ART) is a treatment option. The scientific rationale and the chances of success for ART in couples with unexplained RM are still controversial. Presently, there is not enough evidence to justify IVF or intrauterine insemination (IUI) as a treatment option. Research on oocyte donation has been reported in one article. It is questionable whether couples with unexplained RM would undergo the potential risks and emotional aspects of ART. There is insufficient data on whether preimplantation genetic diagnosis improves the live birthrate in carriers of a structural chromosome rearrangement with a history of RM. No randomized controlled trials are available for preimplantation genetic screening (PGS) for unexplained RM. A recently published review concluded that the live birthrate for IVF/PGS and natural conception groups appears to be quite similar. Because evidence is lacking, we recommend refraining from ART in couples with recurrent miscarriage.
KEYWORDS
Recurrent miscarriage - assisted reproductive technology - preimplantation genetic screening - preimplantation genetic diagnosis - live birthrates
REFERENCES
- 1
Farquharson R G, Jauniaux E, Exalto N. ESHRE Special Interest Group for Early Pregnancy (SIGEP) .
Updated and revised nomenclature for description of early pregnancy events.
Hum Reprod.
2005;
20
(11)
3008-3011
MissingFormLabel
- 2
Jaslow C R, Carney J L, Kutteh W H.
Diagnostic factors identified in 1020 women with two versus three or more recurrent
pregnancy losses.
Fertil Steril.
2010;
93
(4)
1234-1243
MissingFormLabel
- 3
van den Boogaard E, Kaandorp S P, Franssen M T et al..
Consecutive or non-consecutive recurrent miscarriage: is there any difference in carrier
status?.
Hum Reprod.
2010;
25
(6)
1411-1414
MissingFormLabel
- 4
Kaandorp S P, Goddijn M, van der Post J A et al..
Aspirin plus heparin or aspirin alone in women with recurrent miscarriage.
N Engl J Med.
2010;
362
(17)
1586-1596
MissingFormLabel
- 5
Li T C, Makris M, Tomsu M, Tuckerman E, Laird S.
Recurrent miscarriage: aetiology, management and prognosis.
Hum Reprod Update.
2002;
8
(5)
463-481
MissingFormLabel
- 6
Clark D A, Coulam C B, Daya S, Chaouat G.
Unexplained sporadic and recurrent miscarriage in the new millennium: a critical analysis
of immune mechanisms and treatments.
Hum Reprod Update.
2001;
7
(5)
501-511
MissingFormLabel
- 7
Rai R, Regan L.
Recurrent miscarriage.
Lancet.
2006;
368
(9535)
601-611
MissingFormLabel
- 8
Empson M, Lassere M, Craig J, Scott J.
Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus
anticoagulant.
Cochrane Database Syst Rev.
2005;
(2)
CD002859
MissingFormLabel
- 9
Franssen M T, Korevaar J C, van der Veen F, Boer K, Leschot N J, Goddijn M.
Management of recurrent miscarriage: evaluating the impact of a guideline.
Hum Reprod.
2007;
22
(5)
1298-1303
MissingFormLabel
- 10
Brigham S A, Conlon C, Farquharson R G.
A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage.
Hum Reprod.
1999;
14
(11)
2868-2871
MissingFormLabel
- 11
Clifford K, Rai R, Regan L.
Future pregnancy outcome in unexplained recurrent first trimester miscarriage.
Hum Reprod.
1997;
12
(2)
387-389
MissingFormLabel
- 12
Franssen M T, Korevaar J C, van der Veen F, Leschot N J, Bossuyt P M, Goddijn M.
Reproductive outcome after chromosome analysis in couples with two or more miscarriages:
index [corrected]-control study.
BMJ.
2006;
332
(7544)
759-763
MissingFormLabel
- 13
Franssen M T, Korevaar J C, Tjoa W M et al..
Inherited unbalanced structural chromosome abnormalities at prenatal chromosome analysis
are rarely ascertained through recurrent miscarriage.
Prenat Diagn.
2008;
28
(5)
408-411
MissingFormLabel
- 14
Barber J C, Cockwell A E, Grant E, Williams S, Dunn R, Ogilvie C M.
Is karyotyping couples experiencing recurrent miscarriage worth the cost?.
BJOG.
2010;
117
(7)
885-888
MissingFormLabel
- 15
Ogasawara M, Aoki K, Okada S, Suzumori K.
Embryonic karyotype of abortuses in relation to the number of previous miscarriages.
Fertil Steril.
2000;
73
(2)
300-304
MissingFormLabel
- 16
Carp H, Toder V, Aviram A, Daniely M, Mashiach S, Barkai G.
Karyotype of the abortus in recurrent miscarriage.
Fertil Steril.
2001;
75
(4)
678-682
MissingFormLabel
- 17
Stephenson M D, Awartani K A, Robinson W P.
Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control
study.
Hum Reprod.
2002;
17
(2)
446-451
MissingFormLabel
- 18
Stern J J, Dorfmann A D, Gutiérrez-Najar A J, Cerrillo M, Coulam C B.
Frequency of abnormal karyotypes among abortuses from women with and without a history
of recurrent spontaneous abortion.
Fertil Steril.
1996;
65
(2)
250-253
MissingFormLabel
- 19
Nybo Andersen A M, Wohlfahrt J, Christens P, Olsen J, Melbye M.
Maternal age and fetal loss: population based register linkage study.
BMJ.
2000;
320
(7251)
1708-1712
MissingFormLabel
- 20
Hassold T, Hall H, Hunt P.
The origin of human aneuploidy: where we have been, where we are going.
Hum Mol Genet.
2007;
16 Spec No. 2
R203-R208
MissingFormLabel
- 21
Hook E B, Albright S G.
Mutation rates for unbalanced Robertsonian translocations associated with Down syndrome.
Evidence for a temporal change in New York State live births 1968–1977.
Am J Hum Genet.
1981;
33
(3)
443-454
MissingFormLabel
- 22
Hassold T, Hunt P.
To err (meiotically) is human: the genesis of human aneuploidy.
Nat Rev Genet.
2001;
2
(4)
280-291
MissingFormLabel
- 23
Bellver J, Meseguer M, Muriel L et al..
Y chromosome microdeletions, sperm DNA fragmentation and sperm oxidative stress as
causes of recurrent spontaneous abortion of unknown etiology.
Hum Reprod.
2010;
25
(7)
1713-1721
MissingFormLabel
- 24
Wettasinghe T K, Jayasekara R W, Dissanayake V H.
Y chromosome microdeletions are not associated with spontaneous recurrent pregnancy
loss in a Sinhalese population in Sri Lanka.
Hum Reprod.
2010;
25
(12)
3152-3156
MissingFormLabel
- 25
Recurrent Miscarriage Immunotherapy Trialists Group .
Worldwide collaborative observational study and meta-analysis on allogenic leukocyte
immunotherapy for recurrent spontaneous abortion.
Am J Reprod Immunol.
1994;
32
(2)
55-72
MissingFormLabel
- 26
Clark D A, Chaouat G, Gorczynski R M.
Thinking outside the box: mechanisms of environmental selective pressures on the outcome
of the materno-fetal relationship.
Am J Reprod Immunol.
2002;
47
(5)
275-282
MissingFormLabel
- 27
Quenby S, Nik H, Innes B et al..
Uterine natural killer cells and angiogenesis in recurrent reproductive failure.
Hum Reprod.
2009;
24
(1)
45-54
MissingFormLabel
- 28
Clifford K, Flanagan A M, Regan L.
Endometrial CD56 + natural killer cells in women with recurrent miscarriage: a histomorphometric
study.
Hum Reprod.
1999;
14
(11)
2727-2730
MissingFormLabel
- 29
Lachapelle M H, Miron P, Hemmings R, Roy D C.
Endometrial T, B, and NK cells in patients with recurrent spontaneous abortion. Altered
profile and pregnancy outcome.
J Immunol.
1996;
156
(10)
4027-4034
MissingFormLabel
- 30
Choudhury S R, Knapp L A.
Human reproductive failure I: immunological factors.
Hum Reprod Update.
2001;
7
(2)
113-134
MissingFormLabel
- 31
Barnea E R.
Embryo maternal dialogue: From pregnancy recognition to proliferation control.
Early Pregnancy.
2001;
5
(1)
65-66
MissingFormLabel
- 32
Clark D A.
Is there any evidence for immunologically mediated or immunologically modifiable early
pregnancy failure?.
J Assist Reprod Genet.
2003;
20
(2)
63-72
MissingFormLabel
- 33
Creus M, Calafell J M, Cívico S et al..
Materno-fetal immunogenetic disparity: the biological basis for in vitro fertilization
treatment in patients with unexplained recurrent abortion?.
Am J Reprod Immunol.
2003;
50
(5)
420-426
MissingFormLabel
- 34
Biljan M M, Buckett W M, Taylor C T et al..
Effect of abnormal hypo-osmotic swelling test on fertilization rate and pregnancy
outcome in in vitro fertilization cycles.
Fertil Steril.
1996;
66
(3)
412-416
MissingFormLabel
- 35
Saxena P, Misro M M, Chaki S P, Chopra K, Roy S, Nandan D.
Is abnormal sperm function an indicator among couples with recurrent pregnancy loss?.
Fertil Steril.
2008;
90
(5)
1854-1858
MissingFormLabel
- 36
Gil-Villa A M, Cardona-Maya W, Agarwal A, Sharma R, Cadavid A.
Assessment of sperm factors possibly involved in early recurrent pregnancy loss.
Fertil Steril.
2010;
94
(4)
1465-1472
MissingFormLabel
- 37
Bhattacharya S M.
Hypo-osmotic swelling test and unexplained repeat early pregnancy loss.
J Obstet Gynaecol Res.
2010;
36
(1)
119-122
MissingFormLabel
- 38
Hill J A, Abbott A F, Politch J A.
Sperm morphology and recurrent abortion.
Fertil Steril.
1994;
61
(4)
776-778
MissingFormLabel
- 39
Puscheck E E, Jeyendran R S.
The impact of male factor on recurrent pregnancy loss.
Curr Opin Obstet Gynecol.
2007;
19
(3)
222-228
MissingFormLabel
- 40
Zolghadri J, Tavana Z, Alborzi S, Kazerooni T.
Pregnancy outcome with intrauterine insemination in patients with unexplained recurrent
abortion whose partners have abnormal hypo-osmotic swelling test.
Iran J Med Sci.
2009;
34
(3)
172-176
MissingFormLabel
- 41
Buckett W M, Luckas M J, Aird I A, Farquharson R G, Kingsland C R, Lewis-Jones D I.
The hypo-osmotic swelling test in recurrent miscarriage.
Fertil Steril.
1997;
68
(3)
506-509
MissingFormLabel
- 42
Zegers-Hochschild F, Adamson G D, de Mouzon J International Committee for Monitoring Assisted Reproductive Technology et al.
International Committee for Monitoring Assisted Reproductive Technology (ICMART) and
the World Health Organization (WHO) revised glossary of ART terminology, 2009.
Fertil Steril.
2009;
92
(5)
1520-1524
MissingFormLabel
- 43
Raziel A, Herman A, Strassburger D, Soffer Y, Bukovsky I, Ron-El R.
The outcome of in vitro fertilization in unexplained habitual aborters concurrent
with secondary infertility.
Fertil Steril.
1997;
67
(1)
88-92
MissingFormLabel
- 44
Christiansen O B, Nybo Andersen A M, Bosch E et al..
Evidence-based investigations and treatments of recurrent pregnancy loss.
Fertil Steril.
2005;
83
(4)
821-839
MissingFormLabel
- 45
Walch K T, Huber J C.
Progesterone for recurrent miscarriage: truth and deceptions.
Best Pract Res Clin Obstet Gynaecol.
2008;
22
(2)
375-389
MissingFormLabel
- 46
El-Zibdeh M Y.
Dydrogesterone in the reduction of recurrent spontaneous abortion.
J Steroid Biochem Mol Biol.
2005;
97
(5)
431-434
MissingFormLabel
- 47
Hassold T, Chiu D.
Maternal age-specific rates of numerical chromosome abnormalities with special reference
to trisomy.
Hum Genet.
1985;
70
(1)
11-17
MissingFormLabel
- 48
Remohí J, Gallardo E, Levy M et al..
Oocyte donation in women with recurrent pregnancy loss.
Hum Reprod.
1996;
11
(9)
2048-2051
MissingFormLabel
- 49
Franssen M T, Musters A M, van der Veen F et al..
Reproductive outcome after PGD in couples with recurrent miscarriage carrying a structural
chromosome abnormality: a systematic review.
Hum Reprod Update.
2011;
17
(4)
467-475
MissingFormLabel
- 50
Goossens V, Harton G, Moutou C, Traeger-Synodinos J, Van Rij M, Harper J C.
ESHRE PGD Consortium data collection IX: cycles from January to December 2006 with
pregnancy follow-up to October 2007.
Hum Reprod.
2009;
24
(8)
1786-1810
MissingFormLabel
- 51
Otani T, Roche M, Mizuike M, Colls P, Escudero T, Munné S.
Preimplantation genetic diagnosis significantly improves the pregnancy outcome of
translocation carriers with a history of recurrent miscarriage and unsuccessful pregnancies.
Reprod Biomed Online.
2006;
13
(6)
869-874
MissingFormLabel
- 52
Munné S, Chen S, Fischer J et al..
Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and
older with a history of recurrent miscarriages.
Fertil Steril.
2005;
84
(2)
331-335
MissingFormLabel
- 53
Fischer J, Colls P, Escudero T, Munné S.
Preimplantation genetic diagnosis (PGD) improves pregnancy outcome for translocation
carriers with a history of recurrent losses.
Fertil Steril.
2010;
94
(1)
283-289
MissingFormLabel
- 54
Stephenson M D, Goddijn M.
A critical look at the evidence does not support PGD for translocation carriers with
a history of recurrent losses.
Fertil Steril.
2011;
95
(1)
e1
author reply e2
MissingFormLabel
- 55
Musters A M, Taminiau-Bloem E F, van den Boogaard E, van der Veen F, Goddijn M.
Supportive care for women with unexplained recurrent miscarriage: patients' perspectives.
Hum Reprod.
2011;
26
(4)
873-877
MissingFormLabel
- 56
Gianaroli L, Magli M C, Ferraretti A P, Tabanelli C, Trombetta C, Boudjema E.
The role of preimplantation diagnosis for aneuploidies.
Reprod Biomed Online.
2002;
4
(Suppl 3)
31-36
MissingFormLabel
- 57
Werlin L, Rodi I, DeCherney A, Marello E, Hill D, Munné S.
Preimplantation genetic diagnosis as both a therapeutic and diagnostic tool in assisted
reproductive technology.
Fertil Steril.
2003;
80
(2)
467-468
MissingFormLabel
- 58
Rubio C, Pehlivan T, Rodrigo L, Simón C, Remohí J, Pellicer A.
Embryo aneuploidy screening for unexplained recurrent miscarriage: a minireview.
Am J Reprod Immunol.
2005;
53
(4)
159-165
MissingFormLabel
- 59
Mantzouratou A, Mania A, Fragouli E et al..
Variable aneuploidy mechanisms in embryos from couples with poor reproductive histories
undergoing preimplantation genetic screening.
Hum Reprod.
2007;
22
(7)
1844-1853
MissingFormLabel
- 60
Harper J C, Boelaert K, Geraedts J et al..
ESHRE PGD Consortium data collection V: cycles from January to December 2002 with
pregnancy follow-up to October 2003.
Hum Reprod.
2006;
21
(1)
3-21
MissingFormLabel
- 61
Goossens V, Harton G, Moutou C European Society of Human Reproduction and Embryology PGD Consortium et al.
ESHRE PGD Consortium data collection VIII: cycles from January to December 2005 with
pregnancy follow-up to October 2006.
Hum Reprod.
2008;
23
(12)
2629-2645
MissingFormLabel
- 62
Thornhill A R, deDie-Smulders C E, Geraedts J P ESHRE PGD Consortium et al.
ESHRE PGD Consortium ‘Best practice guidelines for clinical preimplantation genetic
diagnosis (PGD) and preimplantation genetic screening (PGS)’.
Hum Reprod.
2005;
20
(1)
35-48
MissingFormLabel
- 63
Practice Committee of the American Society for Reproductive Medicine .
Preimplantation genetic diagnosis.
Fertil Steril.
2006;
86
(5, Suppl 1)
S257-S258
MissingFormLabel
- 64
Musters A M, Repping S, Korevaar J C et al..
Pregnancy outcome after preimplantation genetic screening or natural conception in
couples with unexplained recurrent miscarriage: a systematic review of the best available
evidence.
Fertil Steril.
2011;
95
(6)
2153-2157
2157
e1-e3
MissingFormLabel
- 65
Christiansen O B, Mathiesen O, Husth M, Lauritsen J G, Grunnet N.
Placebo-controlled trial of active immunization with third party leukocytes in recurrent
miscarriage.
Acta Obstet Gynecol Scand.
1994;
73
(3)
261-268
MissingFormLabel
- 66
Clifford K, Rai R, Watson H, Franks S, Regan L.
Does suppressing luteinising hormone secretion reduce the miscarriage rate? Results
of a randomised controlled trial.
BMJ.
1996;
312
(7045)
1508-1511
MissingFormLabel
- 67
Stephenson M D, Dreher K, Houlihan E, Wu V.
Prevention of unexplained recurrent spontaneous abortion using intravenous immunoglobulin:
a prospective, randomized, double-blinded, placebo-controlled trial.
Am J Reprod Immunol.
1998;
39
(2)
82-88
MissingFormLabel
- 68
Ober C, Karrison T, Odem R R et al..
Mononuclear-cell immunisation in prevention of recurrent miscarriages: a randomised
trial.
Lancet.
1999;
354
(9176)
365-369
MissingFormLabel
- 69
Ramhorst R, Agriello E, Zittermann S et al..
Is the paternal mononuclear cells' immunization a successful treatment for recurrent
spontaneous abortion?.
Am J Reprod Immunol.
2000;
44
(3)
129-135
MissingFormLabel
- 70
Pandey M K, Agrawal S.
Induction of MLR-Bf and protection of fetal loss: a current double blind randomized
trial of paternal lymphocyte immunization for women with recurrent spontaneous abortion.
Int Immunopharmacol.
2004;
4
(2)
289-298
MissingFormLabel
- 71
Scarpellini F, Sbracia M.
Use of granulocyte colony-stimulating factor for the treatment of unexplained recurrent
miscarriage: a randomised controlled trial.
Hum Reprod.
2009;
24
(11)
2703-2708
MissingFormLabel
- 72
Wilding M, Forman R, Hogewind G et al..
Preimplantation genetic diagnosis for the treatment of failed in vitro fertilization-embryo
transfer and habitual abortion.
Fertil Steril.
2004;
81
(5)
1302-1307
MissingFormLabel
- 73
Platteau P, Staessen C, Michiels A, Van Steirteghem A, Liebaers I, Devroey P.
Preimplantation genetic diagnosis for aneuploidy screening in women older than 37
years.
Fertil Steril.
2005;
84
(2)
319-324
MissingFormLabel
Mariëtte GoddijnM.D. Ph.D.
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Academic
Medical Center (Q3-119), University of Amsterdam
P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
eMail: m.goddijn@amc.uva.nl