Zusammenfassung
Neben anatomischen, hormonellen, infektiösen und genetischen Faktoren spielen immunologische
Komponenten beim HA eine wesentliche Rolle. Diese Faktoren sollten daher bei der diagnostischen
Abklärung betroffener Frauen berücksichtigt werden. Während der Schwangerschaft erlaubt
ein subtiles Zusammenspiel einer Vielzahl von immunmodulatorischen Prozessen dem Embryo/Fetus,
der Abstoßungsreaktion durch das mütterliche Immunsystem zu entgehen. Eine Defizienz
in einem oder mehreren dieser Prozesse erhöht das Risiko für einen Spontanabort. Frauen
mit HA zeigen sowohl im Bereich von Autoimmunkomponenten, z. B. dem Antiphospholipidsyndrom,
als auch von Alloimmunkomponenten, z. B. der TH-1/TH-2-Ratio und der asymmetrischen
Antikörper, charakteristische Mängel. Realistische therapeutische Optionen für Frauen
mit HA, vor allem Therapieschemata mit Progesteron, Folsäure, Aspirin, Heparin und
Kortison, sind einsetzbar und durch klinische Studien im Sinne einer Level II evidence
(American College of Obstetricians and Gynecologists [ACOG] 1995) abgesichert.
Summary
Etiologic factors associated with habitual pregnancy loss include uterine anomalies,
luteal phase defects, hyperprolactinemia, hyperandrogenemia, genital infections, and
balanced chromosomal translocations. The diagnostic work-up should be planned accordingly.
Normally the maternal immune system recognizes paternally-derived fetal and placental
antigens and confronts the embryo/fetus with a host defense response. To avoid rejection
of the semiallogenic embryo/fetus, the maternal immune system is suppressed. Imbalances
in the complex immunologic interactions between mother and embryo/fetus increase the
risk for spontaneous abortion. Women with habitual abortion can show characteristic
deficiencies in autoimmune components (e.g., the antiphospholipid syndrome) or alloimmune
components (e.g., TH-1/TH-2 ratio and asymmetrically glycosylated blocking antibodies).
Treatment options based on level-II evidence include progesterone, folate, aspirin,
heparin, and cortisone.
Literatur
- 1
Boklage C E.
Survival probability of human conceptions from fertilization to term.
Int J Fertil.
1990;
35
75-94
- 2
Wilcox A J, Weinberg C R, O'Connor J F, Baird D D, Schlatterer J P. et al .
Incidence of early of pregnancy.
N Engl J Med.
1988;
319
189-194
- 3 American College of Obstetricians and Gynecologists .Early Pregnancy Loss. ACOG
technical bulletin No. 212. Washington DC; American College of Obstetricians and
Gynecologists 1995
- 4 Regan L.
A prospective study of spontaneous abortion. Beard RW, Sharp F Early Pregnancy Loss. London; Springer-Verlag 1988: 23-37
- 5
Coulam C B, Clark D A, Collins J, Scott J R, Sclesselman J J.
A worldwide collaborative observational study and meta-analysis on allogenic leucocyte
immunotherapy for recurrent spontaneous abortion.
Am J Reprod Immunol.
1994;
23
55-72
- 6
Husslein P, Huber J, Wagenbichler P, Schnedl W.
Chromosome abnormalities in 150 couples with multiple spontaneous abortions.
Fertil Steril.
1982;
37 (3)
379-383
- 7
Simpson J L, Elias S, Meyers C M, Ober C, Martin A O.
Translocations are infrequent among couples having repeated spontaneous abortions
but no other abnormal pregnancies.
Fertil Steril.
1989;
51
811-814
- 8
Simpson J L.
Genes, chromosomes, and reproductive failure.
Fertil Steril.
1980;
33
107-116
- 9
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
- 10
Warburton D, Kline J, Stein Z, Hutzler M, Chin A, Hassold T.
Does the karyotype of a spontaneous abortion predict the karyotype of a subsequent
abortion? Evidence from 273 women with two karyotyped spontaneous abortions.
Am J Hum Genet.
1987;
41
465-483
- 11
Foka Z J, Lambropoulos A F, Saravelos H, Karas G B, Karavida A, Agarastos T. et al
.
Factor V Leiden and prothrombin G 20 210 A mutations, but not methylenetetrahydrofolate
reductase C 677 T, are associated with recurrent miscarriages.
Hum Reprod.
2000;
15 (2)
458-462
- 12
Souza S S, Ferriani R A, Pontes A G, Zago M A, Franco R F.
Factor V Leiden and factor II G20210 A mutations in patients with recurrent abortion.
Hum Reprod.
1999;
14
2448-2450
- 13
Brenner B, Sarig G, Weiner Z, Younis J, Blumenfeld Z, Lanir N.
Thrombophilic polymorphisms are common in women with fetal loss without apparent cause.
Thromb Hemost.
1999;
82 (1)
6-9
- 14
Tempfer C B, Moreno R M, Gregg A R.
Genetic Control of Fertility and Embryonic Waste in the Mouse: A Role for Angiotensinogen.
Biol Reprod.
2000;
62 (2)
457-462
- 15
Tho P T, Byrd J R, McDonough P G.
Etiologies and subsequent reproductive performance of 100 couples with recurrent abortion.
Fertil Steril.
1979;
32
389-395
- 16
DeCherney A H, Russell J B, Graebe R A, Polan M L.
Resectoscopic management of muellerian fusion defects.
Fertil Steril.
1986;
45
726-728
- 17
Nagele F, O'Connor H, Davies A, Badawy A, Mohamed H, Magos A.
2500 outpatient hysteroscopies.
Obstet Gynecol.
1996;
88 (1)
87-92
- 18
Kutteh W H.
Recurrent pregnancy loss: an update.
Curr Opin Obstet Gynecol.
1999;
11 (5)
435-439
- 19
Daya S.
Efficacy of progesterone support for pregnancy in women with recurrent miscarriage.
A meta-analysis of controlled trials.
Br J Obstet Gynaecol.
1989;
96 (3)
275-280
- 20
Wouters M G, Boers G H, Blom H J, Trijbels F J, Thomas C M, Borm G F, Steegers-Theunissen R P,
Eskes T K.
Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy
loss.
Fertil Steril.
1993;
60 (5)
820-825
- 21
Ray J G, Laskin C A.
Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption,
pre-eclampsia and pregnancy loss: A systematic review.
Placenta.
1999;
20 (7)
519-529
- 22
Quere I, Bellet H, Hoffet M, Janbon C, Mares P, Gris J C.
A woman with five consecutive fetal deaths: case report and retrospective analysis
of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages.
Fertil Steril.
1998;
69 (1)
152-154
- 23
Touam M, Zingraff J, Jungers P, Chadefaux-Vekemans B, Drueke. et al .
Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous
folinic acid and pyridoxine therapy.
Kidney Int.
1999;
56 (6)
2292-2296
- 24
Berry R J, Li Z, Erickson J D, Li S, Moore C A. et al .
Prevention of neural-tube defects with folic acid in China. China-US-Collaborative
Project for Neural Tube Defect Prevention.
N Engl J Med.
1999;
341 (20)
1485-1490
- 25
Manganiello P D, Yearke R R.
A 10-year prospective study of women with a history of recurrent fetal losses fails
to identify Listeria monocytogenes in the genital tract.
Fertil Steril.
1991;
56 (4)
781-782
- 26
Seoud M, Saade G, Awar G, Uwaydah M.
Brucellosis in pregnancy.
J Reprod Med.
1991;
36 (6)
441-445
- 27
Cook S M, Himebaugh K S, Frank T S.
Absence of cytomegalovirus in gestational tissue in recurrent spontaneous abortion.
Diagn Mol Pathol.
1993;
2 (2)
116-119
- 28
Naessens A, Foulon W, Cammu H, Goossens A, Lauwers S.
Epidemiology and pathogenesis of ureaplasma urealyticum in spontaneous abortion and
early preterm labor.
Acta Obstet Gynecol Scand.
1987;
66 (6)
513-516
- 29
Witkin S S, Ledger W J.
Antibodies to chlamydia trachomatis in sera of women with recurrent spontaneous abortions.
Am J Obstet Gynecol.
1992;
167 (1)
135-139
- 30
Sahwi S Y, Zaki M S, Haiba N Y, Elsaid O K, Anwar M Y, AbdRabbo S A.
Toxoplasmosis as a cause of repeated abortion.
J Obstet Gynaecol.
1995;
21 (2)
145-148
- 31
Quinn P A, Shewchuk A B, Shuber J, Lie K I, Ryan E. et al .
Efficacy of antibiotic therapy in preventing spontaneous pregnancy loss among couples
colonized with genital mycoplasmas.
Am J Obstet Gynecol.
1983;
145 (2)
239-244
- 32
Di Simone N, DeCarolis S, Lanzone A, Ronsisvalle E, Giannice R. et al .
In vitro effect of antiphospholipid antibody-containing sera on basal and gonadotrophin
releasing hormone-dependent human chorionic gonadotrophin release by cultured trophoblast
cells.
Placenta.
1995;
16 (1)
75-83
- 33
Di Simone N, Caliandro D, Castellani S, Ferrazzani S, Decarolis S. et al .
Low-molecular weight heparin restores in-vitro trophoblast invasiveness and differentiation
in presence of immunoglobulin G fractions obtained from patients with antiphospholipid
syndrome.
Placenta.
1999;
14 (2)
489-495
- 34
Kutteh W H.
Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin
and low-dose aspirin is superior to low-dose aspirin alone.
Am J Obstet Gynecol.
1996;
174
1584-1589
- 35
Rai R, Cohen H, Dave M, Regan L.
Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women
with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid
antibodies).
Br Med J.
1997;
314
253-257
- 36
Lim K J, Odukoya O A, Ajjan R A, Li T C, Weetman A P. et al .
The role of T-helper cytokines in human reproduction.
Fertil Steril.
2000;
73 (1)
136-142
- 37
Rhaghupathy R.
Th-1 type immunity is incompatible with successful pregnancy.
Immunol Today.
1997;
18 (10)
478-482
- 38
Nossent H C, Swaak T J.
Systemic lupus erythematosus. VI. Analysis of the interrelationship with pregnancy.
J Rheumatol.
1990;
17 (6)
771-776
- 39
Infante R, Lahita R G.
Rheumatoid arthritis. New disease-modifying and anti-inflammatory drugs.
Geriatrics.
2000;
55 (3)
30-40
- 40
Reinhard G, Noll A, Schlebusch H, Mallmann P, Ruecker A V.
Shifts in the TH1/TH2 balance during human pregnancy correlate with apoptotic changes.
Biochem Biophys Res Commun.
1998;
245 (3)
933-938
- 41
Jenkins C, Roberts J, Wilson R, McLean M A, Shilito J. et al .
Evidence of a TH1 type response associated with recurrent miscarriage.
Fertil Steril.
2000;
73 (6)
1206-1208
- 42
Petrovsky N, Harrison L C.
The chronobiology of human cytokine production.
Int Rev Immunol.
1998;
16 (5 - 6)
635-649
- 43
Reznikoff-Etievant M F, Cayol V, Zou G M, Abuaf N, Robert A. et al .
Habitual abortions in 678 healthy patients: investigation and prevention.
Hum Reprod.
1999;
14 (8)
2106-2109
- 44
Szekeres-Bartho J, Wegmann T G.
A progesterone-dependent immunomodulatory protein alters the Th1/Th2 balance.
J Reprod Immunol.
1996;
31
81-95
- 45
Goldstein P, Berrier J, Rosen S, Sacks H S, Chalmers T C.
A meta-analysis of randomized control trials of progestational agents in pregnancy.
Br J Obstet Gynaecol.
1989;
96 (3)
265-274
- 46
Daya S.
Efficacy of progesterone support for pregnancy in women with recurrent miscarriage.
A meta-analysis of controlled trials.
Br J Obstet Gynaecol.
1989;
96 (3)
275-280
- 47
Orgad S, Loewenthal R, Gazit E, Sadetzki S, Novikov I. et al .
The prognostic value of anti-paternal antibodies and leukocyte immunizations on the
proportion of live births incouples with consecutive recurrent miscarriages.
Hum Reprod.
1999;
14 (12)
2974-2979
- 48
Moncayo R, Moncayo H, Steffens U, Soelder E, Kersting A. et al .
Serum levels of anticardiolipin antibodies are pathologically increased after active
immunization of patients with recurrent spontaneous abortion.
Fertil Steril.
1990;
54 (4)
619-623
- 49
Fraser E J, Grimes D A, Schulz K F.
Immunization as therapy for recurrent spontaneous abortion: a review and meta-analysis.
Obstet Gynecol.
1993;
82 (5)
854-859
- 50
Gentile T, Borel I M, Angelucci J, Miranda S, Margni R A.
Preferential synthesis of asymmetric antibodies in rats immunized with paternal particulate
antigens: Effect on pregnancy.
J Reprod Immunol.
1992;
22 (2)
173-183
- 51
Eblen A C, Gercel-Taylor C, Shields L B, Sanfilippo J S, Nakajima S T, Taylor D D.
Alterations in humoral immune responses associated with recurrent pregnancy loss.
Fertil Steril.
2000;
73 (2)
305-313
- 52
Stricker R B, Steinleitner A, Bookoff C N, Weckstein L N, Winger E E.
Successful treatment of immunologic abortion with low-dose intravenous immunoglobulin.
Fertil Steril.
2000;
73 (3)
536-540
- 53
Christiansen O B, Mathiesen O, Lauritsen J G, Grunnet N.
Intravenous immunoglobulin treatment of women with multiple miscarriages.
Hum Reprod.
1992;
7 (5)
718-722
- 54
Daya S, Gunby J, Clark D A.
Intravenous immunoglobulin therapy for recurrent spontaneous abortion: a meta-analysis.
Am J Reprod Immunol.
1998;
39 (2)
69-76
- 55
Jablonowska B, Selbing A, Palfi M, Ernerudh J, Kjellberg S, Lindton B.
Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind
placebo-controlled study.
Hum Reprod.
1999;
14 (3)
838-841
- 56
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
- 57
Neugebauer R, Kline J, Shrout P, Skodol A, O'Connor P. et al .
Major depressive disorder in the 6 months after miscarriage.
J Am Med Assoc.
1997;
277 (5)
383-388
Dr. Clemens Tempfer
Universitätsklinik für Frauenheilkunde Wien Klinische Abteilung für Gynäkologie und
Geburtshilfe
Währinger Gürtel 18 - 20
1090 Wien
Österreich
Email: E-mail: clemens.tempfer@akh-wien.ac.at
