Advertisement

Risk factors in miscarriage: a review

      Abstract

      Miscarriage is one of the most frequent problems in human pregnancy. The most widely accepted definition is that proposed by the World Health Organization (WHO) in 1977. The incidence among clinical pregnancies is about 12–15% but including early pregnancy losses it is 17–22%. The only two etiologic factors recognized by all authors are uterine malformations and parental balanced chromosomal rearrangements. There have been many other suggested risk factors. In this revision we discuss these.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      References

      1. WHO recommended definitions, terminology and format for statistical tables related to the perinatal period. Acta Obstet Gynecol Scand 1977;56:247–53.

        • Zinaman M.J
        • Clegg D.E
        • Brown C.C
        • O’Connor J
        • Selevan S.G
        Estimates of human fertility and pregnancy loss.
        Fertil. Steril. 1996; 65: 503-509
        • Ellish N.J
        • Saboda K
        • O’Connor J.O
        • Nasca P.C
        • Stanek E.J
        • Boyle C
        A prospective study of early pregnancy loss.
        Hum. Reprod. 1996; 11: 406-412
        • Plouffe Jr., L
        • White E.W
        • Tho S.P
        • et al.
        Etiologic factors of recurrent abortion and subsequent reproductive performance of couples: have we made any progress in the past 10 years?.
        Am. J. Obstet. Gynecol. 1992; 167: 313-321
        • Bunker M.L
        • McWilliams M
        Caffeine content of common beverages.
        J. Am. Diet. Assoc. 1979; 74: 28
      2. Mirkin ML, Singh S. Placental transfer of pharmacologically active molecules. In: Mirkin BL, editor. Perinatal pharmacology and therapeutics. New York: Academic Press, 1976. p. 1–69.

        • Knutti R
        • Rothweiler H
        • Schlatter C
        The effect of pregnancy on the pharmocokinetics of caffeine.
        Arch. Toxicol. 1982; 5: 187-192
        • Elmazar M.M.A
        • McElhatton P.R
        • Sullivan F.M
        Studies on the teratogenic effects of different preparations of caffeine in mice.
        Toxicology. 1982; 23: 57
        • Domı́nguez-Rojas V
        • de Juanes-Pardo J.R
        • Astasio-Arbiza P
        • Ortega-Molina P
        • Gordillo-Florencio E
        Spontaneous abortion in a hospital population: are tobacco and coffee intake risk factors?.
        Eur. J. Epidemiol. 1994; 10: 665-668
        • Srisuphan W
        • Bracken M.B
        Caffeine consumption during pregnancy and association with late spontaneous abortion.
        Am. J. Obstet. Gynecol. 1986; 154: 14-20
        • Mills J.L
        • Holmes L.B
        • Aarons J.H
        • et al.
        Moderate caffeine use and the risk of spontaneous abortion and intrauterine growth retardation.
        JAMA. 1993; 269: 593-597
        • Menon K.M.J
        • Gunaga K.P
        Role of cyclic AMP in reproductive processes.
        Fertil. Steril. 1974; 25: 732
        • Wethersbee P.S
        • Lodge J.R
        Caffeine: its direct and indirect influence on reproduction.
        J. Reprod. Med. 1977; 19: 55-63
        • Anton A.H
        Catecholamines during pregnancy and their effects on the fetus.
        Pediatr. Adolesc. Endocrinol. 1979; 5: 110-125
        • Harlap S
        • Shiono P.H
        Alcohol, smoking, and incidence of spontaneous abortion in the first and second trimester.
        Lancet. 1980; 2: 173-176
        • Sandhal B
        Smoking habits and spontaneous abortion.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 1989; 31: 23-31
        • Brent R.L
        • Beckmann D.A
        The contribution of environmental teratogens to embryonic and fetal loss.
        Clin. Obstet. Gynecol. 1994; 37: 646-670
        • Kline J
        • Levin B
        • Kinney A
        • Stein Z
        • Susser M
        • Warburton D
        Cigarette smoking and spontaneous abortion of known karyotype.
        Am. J. Epidemiol. 1995; 141: 417-427
        • Jones K.L
        • Smith D.W
        • Ulleland C.N
        • Streissguth A.P
        Patterns of malformation on offspring of chronic alcoholic mothers.
        Lancet. 1973; 1: 1267
      3. Ribas, J. Enfermedades maternas coexistentes o que complican la gestación. Alcohol. In: González Merlo J, Del Sol JR, editor. Obstetricia. Barcelona: Salvat, 1988:417.

        • Abel E.L
        Maternal alcohol consumption and spontaneous abortion.
        Alcohol Alcohol. 1997; 32: 211-219
        • Anokute C.C
        Epidemiology of spontaneous abortion: the effects of alcohol consumption and cigarrette smoking.
        J. Nat. Med. Assoc. 1986; 78: 771-775
        • Parazzini F
        • Tozzi L
        • Chatenoud L
        • Restelli S
        • Luchini L
        • La Vecchia C
        Alcohol and risk of spontaneous abortion.
        Hum. Reprod. 1994; 9: 1950-1953
        • Chasnoff I.J
        • Burns W.J
        • Schnoll S.H
        • Burns K.A
        Cocaine use in pregnancy.
        N. Engl. J. Med. 1985; 313: 666-669
        • Sherman W.T
        • Gautieri R.F
        Effect of certain drugs on perfused human placenta. Norepinephrine release by bradykinin.
        J. Pharm. Sci. 1972; 61: 878-883
        • Woods J.R
        • Plessinger M.A
        • Clark K.E
        Effect of cocaine on uterine blood flow and fetal oxygenation.
        JAMA. 1987; 257: 957-961
        • Lederman R.P
        • Lederman E
        • Work Jr., B.A
        • McCann D.S
        The relationship of maternal anxiety, plasma catecholamines and plasma cortisol to progress in labor.
        Am. J. Obstet. Gynecol. 1978; 132: 495-500
        • Greenland S
        • Richwald G.A
        • Honda G.D
        The effects of marijuana use during pregnancy: a study in a low risk home delivery population.
        Drug Alcohol Depend. 1983; 11: 359
        • Little B.B
        • Snell L.M
        • Klein V.R
        • Gilstrap L.C
        • Knoll K.A
        • Breckenridge J.D
        Maternal and fetal effects of heroin addiction during pregnancy.
        J. Reprod. Med. 1990; 35: 159
        • Stirrat G.M
        Recurrent miscarriage I: definition and epidemiology.
        Lancet. 1990; 336: 673-675
      4. Regan LA. A prospective study of spontaneous abortion. In: Beard RW, Sharp F, editors. Early pregnancy loss: mechanism and treatment. London: RCOG, 1988. p. 23–37.

        • Levin A.A
        • Schoenbaum S.C
        • Monson R.R
        • Stubblefield P.G
        • Ryan K.J
        Association of induced abortion with subsequent pregnancy loss.
        JAMA. 1980; 243: 2495-2499
        • Infante-Rivard C
        • Gauthier R
        Induced abortion as a risk factor for subsequent fetal loss.
        Epidemiology. 1996; 7: 540-542
        • Hogue C.J.R
        • Cates W
        • Tietze C
        The effects of induced abortion on subsequent reproduction.
        Epidemiol. Rev. 1982; 4: 66-94
        • Hakim R.B
        • Gray R.H
        • Zacur H
        Infertility and early pregnancy loss.
        Am. J. Obstet. Gynecol. 1995; 172: 1510-1517
        • Smith K.E
        • Buyalos R.P
        The profound impact of patient age on pregnancy outcome after early detection of fetal cardiac activity.
        Fertil. Steril. 1996; 65: 35-40
        • Berry C.W
        • Brambati B
        • Eskes T.K.A.B
        • et al.
        The Euro-Team Pregnancy (ETEP) protocol for recurrent miscarriage.
        Hum. Reprod. 1995; 10: 1516-1520
        • Abdullah H.I
        • Burton G
        • Kirkland A
        • et al.
        Age, pregnancy, and miscarriage: uterine versus ovarian factors.
        Hum. Reprod. 1993; 8: 1512-1517
        • Hansen J.P
        Older maternal age and pregnancy outcome: a review of the literature.
        Obstet. Gynecol. Surv. 1986; 41: 726-742
        • Vidal F
        • Giménez C
        • Rubio C
        • et al.
        FISH preimplantation diagnosis of chromosome aneuploidy in recurrent pregnancy wastage.
        J. Assist. Reprod. Genet. 1998; 15: 310-313
        • Van Assche E
        • Bonduelle M
        • Tournaye H
        • et al.
        Cytogenetics of infertile men.
        Hum. Reprod. 1996; 11: 1-24
        • Byrne J.L
        • Ward K
        Genetic factors in recurrent abortion.
        Clin. Obstet. Gynecol. 1994; 37: 693-704
        • Simpson J.L
        Genes, chromosomes, and reproductive failure.
        Fertil. Steril. 1980; 33: 107-116
        • Simpson J.L
        • Meyers C.M
        • Martin A.O
        • et al.
        Translocations are infrequent among couples having repeated spontaneous abortions but no other abnormal pregnancies.
        Fertil. Steril. 1989; 51: 811-814
        • Ohno M
        • Maeda T
        • Matsunobu A
        A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi.
        Obstet. Gynecol. 1991; 77: 394-398
        • Grimbizis G.F
        • Camus M
        • Tarlatzis B.C
        • Bontis J.N
        • Devroey P
        Clinical implications of uterine malformations and hysteroscopic treatment results.
        Hum. Reprod. Update. 2001; 7: 161-174
      5. American Fertility Society. The American Fertility Society classifications of adnexal adhesions, tubal occlusion secondary to tubal ligation, tubal pregnancies, Müllerian anomalies and intrauterine adhesions. Fertil. Steril. 1988;49:944–55.

        • Patton P.E
        Anatomic uterine defects.
        Clin. Obstet. Gynecol. 1994; 37: 705-721
        • Burchell R.C
        • Creed F
        • Rasoulpour M
        • Whitcomb M
        Vascular anatomy of the human uterus and pregnancy wastage.
        Br. J. Obstet. Gynecol. 1978; 85: 698-706
      6. Vanrell JA. Alteraciones anatómicas uterinas del útero como causa de infertilidad. In: Vanrell JA, Calaf J, Balasch J, Viscasillas P. Fertilidad y esterilidad humanas. 1a, editors. Barcelona: Masson-Salvat, 1992. p. 429–51.

        • Fedele L
        • Zamberletti D
        • Vercelli P
        • Dorta M
        • Candiani G.B
        Reproductive performance of women with unicornuate uterus.
        Fertil. Steril. 1987; 47: 416-419
        • O’Leary J.L
        • O’Leary J.A
        Rudimentary horn pregnancy.
        Obstet. Gynecol. 1963; 22: 371-375
        • Heinonen P.K
        Unicornuate uterus and rudimentary horn.
        Fertil. Steril. 1997; 68: 224-230
        • Heinonen P.K
        • Saarikoski S
        • Pystine P
        Reproductive performance of women with uterine anomalies.
        Acta Obstet. Gynecol. Scand. 1982; 61: 1157-1160
        • Buttram V.C
        Muellerian anomalies and their management.
        Fertil. Steril. 1983; 40: 159-163
        • Blum M
        Prevention of spontaneous abortion by cervical suture of the malformed uterus.
        Int. Surg. 1977; 62: 213-215
        • Musich J.R
        • Behrman S.J
        Obstetric outcome before and after metroplasty in women with uterine anomalies.
        Obstet. Gynecol. 1978; 52: 63-68
        • Porcu G
        • Cravello L
        • D’Ercole C
        • et al.
        Hysteroscopic metroplasty for septate uterus and repetitive abortions: reproducitve outcome.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 2000; 88: 81-84
        • Fayez J.A
        Comparison between abdominal and hysteroscopic metroplasty.
        Obstet. Gynecol. 1986; 149: 66-73
        • Hickock L.R
        Hysteroscopic treatment of the uterine septum: a clinician’s experience.
        Am. J. Obstet. Gynecol. 2000; 182: 1414-1420
        • Schenker J.G
        • Margalioth E.J
        Intrauterine adhesions: an updated appraisal.
        Fertil. Steril. 1982; 37: 593-610
        • Valle R.F
        • Sciarra J.J
        Intrauterine adhesions: hysteroscopic diagnosis, classification, treatment, and reproductive outcome.
        Am. J. Obstet. Gynecol. 1988; 158: 1459-1470
        • Berger M.J
        • Goldstein D.P
        Impaired reproductive performance in DES-exposed women.
        Obstet. Gynecol. 1980; 55: 25-27
        • Kaufman R.H
        • Adam E
        • Binder G.L
        • Gerthoffer E
        Upper genital tract changes and pregnancy outcome in offspring exposed in utero to diethylstilbestrol.
        Am. J. Obstet. Gynecol. 1980; 137: 299-308
        • Buttram V
        • Reiter R
        Uterine leiomyomata: etiology, symptomatology and management.
        Fertil. Steril. 1981; 36: 433-447
        • Hasegawa I
        • Takakuwa K
        • Tanaka K
        The roles of oligomenorrhoea and fetal chromosomal abnormalities in spontaneous abortions.
        Hum. Reprod. 1996; 11: 2304-2305
        • Fritz M.A
        Inadequate luteal function and recurrent abortion: diagnosis and treatment of luteal phase deficiency.
        Semin. Reprod. Endocrinol. 1988; 6: 129-143
        • Sagle M
        • Bishop K
        • Ridley N
        • et al.
        Recurrent early miscarriage and polycystic ovaries.
        Br. Med. J. 1988; 297: 1027-1028
        • Regan L
        • Owen E.J
        • Jacobs H.S
        Hypersecretion of luteinising hormone, infertility and miscarriage.
        Lancet. 1990; 336: 1141-1144
        • Okon M.A
        • Laird S.M
        • Tuckerman E.M
        • Li T.C
        Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endomertial function.
        Fertil. Steril. 1998; 69: 682-690
        • Mills J.L.M
        • Simpson J.L.L
        • Driscoll S.G
        • et al.
        Incidence of spontaneous abortion among normal women and insulin dependent diabetic women whose pregnancies were identified within 21 days of conception.
        N. J. Engl. J. Med. 1988; 319: 1617-1623
        • Rossen B
        • Miodovnick M
        • Combs C.A
        • Khoury J
        • Siddiqi T.A
        Preconception management of insulin-dependent diabetes: improvement of pregnancy outcome.
        Obstet. Gynecol. 1991; 77: 846-849
        • Nilsson I.M
        • Astedt B
        • Hedner U
        • Berezin D
        Intrauterine death and circulating anticoagulant, antithromboplastin.
        Acta Med. Scand. 1975; 197: 153-159
        • Branch D.W
        Immunological disease and fetal death.
        Clin. Obstet. Gynecol. 1987; 30: 295-311
        • Rai R
        • Regan L
        Antiphospholipid antibodies, infertility and recurrent miscarriage.
        Curr. Opin. Obstet. Gynecol. 1997; 9: 279-282
        • Simpson J.L
        • Carson S.A
        • Chesney C
        • et al.
        Lack of association between antiphospholipid antibodies and first trimester spontaneous abortion: a prospective study of pregnancies detected within 21 days of conception.
        Fertil. Steril. 1998; 69: 814-820
        • Wagenknecht D.R
        • McIntyre J.A
        Changes in β2-GPI antigenicity induced by phospholipid binding.
        Thromb. Hemost. 1993; 69: 361-365
        • Vermylen J
        • Arnout J
        Is the antiphospholipid syndrome caused by antibodies directed against physiologically relevant phospholipid–protein complexes?.
        J. Lab. Clin. Med. 1992; 120: 10-12
        • Bevers E.M
        • Galli M
        • Barbui T
        • et al.
        Lupus anticoagulant IgGs (LA) are not directed to phospholipids only but to a complex of lipid-bound human prothrombin.
        Thromb. Haemost. 1991; 66: 629-632
        • Shoenfeld Y
        • Meroni P.L
        The β2-GPI and antiphospholipid antibodies. Workshop report.
        Clin. Exp. Rheumatol. 1992; 10: 205-209
        • Branch D.W
        • Silver R
        • Perangelli S
        • Van Leeuwen I
        • Harris E.N
        Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome.
        Obstet. Gynecol. 1997; 89: 549-555
        • Ordi J
        • Detarsio G
        Concepto y manifestaciones clı́nicas del sı́ndrome antifosfolı́pido.
        Rev. Iberoamer. Tromb. Hemostasia. 1997; 10: 93-98
        • Branch D.W
        • Silver R.M
        • Blackwell J.L
        • Reading J.C
        • Scott J.R
        Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience.
        Obstet. Gynecol. 1992; 80: 614-620
        • Hughes G.R.V
        The antiphospholipid syndrome: 10 years on.
        Lancet. 1993; 342: 341-344
        • Reverter J.C
        Mecanismos trombóticos de los anticuerpos antifosfolı́pidos.
        Rev. Iberoamer. Tromb. Hemostasia. 1997; 10: 105-109
        • Rand J.H
        • Xiao-Xuan W
        • Andree H.A.M
        • et al.
        Pregnancy loss in the antiphospholipid–antibody syndrome. A possible thrombogenic mechanism.
        N. Engl. J. Med. 1997; 337: 154-160
        • Weschler B
        • Huong Du L.T
        • Piette J.C
        Is there a role for antithrombotic therapy in the prevention of pregnancy loss?.
        Haemostasis. 1999; 29: 112-120
        • Iijima T
        • Tada H
        • Hidaka Y
        • Mitsuda N
        • Murata Y
        • Amino N
        Effects of autoantibodies on the course of pregnancy and fetal growth.
        Obstet. Gynecol. 1997; 90: 364-369
        • Bermas B.L
        • Hill J.A
        Proliferative responses to recall antigens are associated with pregnancy outcome in women with a history of recurrent spontaneous abortion.
        J. Clin. Invest. 1997; 100: 1330-1334
        • Coulam C.B
        Immunologic tests in the evaluation of reproductive disorders: a critical review.
        Am. J. Obstet. Gynecol. 1992; 167: 1844-1851
        • Scott J.R
        • Branch D.W
        Potential alloimmune factors and immunotherapy in recurrent miscarriage.
        Clin. Obstet. Gynecol. 1994; 37: 761-767
        • Mohapeloa H
        • Christiansen O.B
        • Grunnet N
        HLA-DR typing of women with recurrent late spontaneous abortion and unsuccessful cervical cerclage.
        Hum. Reprod. 1998; 13: 1079-1082
        • Balasch J
        • Coll O
        • Martorell J
        • Jove I.C
        • Gaya A
        • Vanrell J.A
        Further data against HLA sharing in couples with recurrent spontaneous abortion.
        Gynecol. Endocrinol. 1989; 3: 63-69
        • Tamura M
        • Takakuwa K
        • Arakawa M
        • Yasuda M
        • Kazama Y
        • Tanaka K
        Relationship between MLR blocking antibodies and the outcome of the third pregnancy in patients with two consecutive spontaneous abortion.
        J. Perinat. Med. 1998; 26: 49-53
        • Cowchock F.S
        • Smith J.B
        Predictors for live birth after unexplained spontaneous abortions: correlation between immunologic test results, obstetric histories, and outcome of next pregnancy without treatment.
        Am. J. Obstet. Gynecol. 1992; 167: 1208-1212
        • Orgad S
        • Loewenthal R
        • Gazit E
        • Sadetzki S
        • Novikov I
        • Carp H
        The prognostic value of antipaternal antibodies and leukocyte immunizations on the proportion of live births in couples with consecutive recurrent miscarriages.
        Hum. Reprod. 1999; 14: 2974-2979
        • Maejima M
        • Fujii T
        • Yamashita T
        • et al.
        Immunotherapy before and during pregnancy outcome in women who suffer from recurrent abortion and did not benefit from immunotherapy before pregnancy.
        Am. J. Reprod. Immunol. 1998; 39: 12-15
        • Vives A
        • Balasch J
        • Yagüe J
        • Quinto L
        • Ordi J
        • Vanrell J.A
        Type-1 and type-2 cytokines in human decidual tissue and trophoblast from normal and abnormal pregnancies detected by reverse transcriptase polymerase chain reaction (RT-PCR).
        Am. J. Reprod. Immunol. 1999; 42: 361-368
        • Fukui K
        • Yoshimoto I
        • Matsubara K
        • Hori R
        • Ochi H
        • Ito M
        Leukocyte function associated antigen-1 expression on decidual natural killer cells in patients with early pregnancy loss.
        Mol. Hum. Reprod. 1999; 5: 1083-1088
        • Deutsch J.A
        Pregnancy sickness as an adaptation to concealed ovulation.
        Riv. Biol. 1994; 87: 277-295
        • Venditelli F
        • Manciet-Labarchede C
        • Tabaste J.L
        • Malinas Y
        Lesions traumatiques de lúterus gravide et de son contenu: aspects medico-legaux.
        Rev. Fr. Gynecol. Obstet. 1994; 89: 393-400
        • Akhtar M.A
        • Mulawkar P.M
        • Kulkarni H.R
        Burns in pregnancy: effect on maternal and fetal outcomes.
        Burns. 1994; 20: 351-355
        • Juntunen K
        • Kirkinen P
        • Kauppila A
        Natural interpregnancy intervals of fertile couples: a longitudinal survey of grand grand multiparous women.
        Fertil. Steril. 1994; 62: 722-725
        • Bateman B.G
        • Felder R
        • Kolp L.A
        • Burkett B
        • Nunley W.C
        Subclinical pregnancy loss in clomiphene citrate treated women.
        Fertil. Steril. 1992; 57: 25-27
        • Hakim R.B
        • Gray R.H
        • Zacur H
        Infertility and early pregnancy loss.
        Am. J. Obstet. Gynecol. 1995; 172: 1510-1517
        • Ransom M.X
        • Bohrer M
        • Blotner M.B
        • Kemmann E
        The difference in miscarriage rates between menotropin-induced and natural pregnancies is not surveillance related.
        Fertil. Steril. 1993; 59: 567-570
        • Ben-Rafael Z
        • Dor J
        • Mashiach S
        • Blankstein J
        • Lunenfeld B
        • Serr D.M
        Abortion rate in pregnancies following ovulation induced by human menopausal gonatropin/human chorionic gonadotropin.
        Fertil. Steril. 1983; 39: 157-161
        • Ford J.H
        • McCormac L
        Pregnancy and lifestyle study: the long-term use of the contraceptive pill and the risk of age-related miscarriage.
        Hum. Reprod. 1995; 10: 1397-1402
        • Glass R.H
        • Golbus M.S
        Habitual abortion.
        Fertil. Steril. 1978; 29: 257-261
        • Holder W.R
        • Knox J.M
        Syphilis in pregnancy.
        Med. Clin. North Am. 1972; 56: 1151-1160
        • Sifakis S
        • Ergazaki M
        • Sourvinos G
        • Koffa M
        • Koumantakis E
        • Spandidos D.A
        Evaluation of Parvo B19, CMV and HPV viruses in human aborted material using the polymerase chain reaction technique.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 1998; 76: 169-173
        • D’Ubaldo C
        • Pezzotti P
        • Rezza G
        • Branca M
        • Ippolito G
        Association between HIV-1 infection and miscarriage: a retrospective study. DIANAIDS Collaborative Study Group. Diagnosi Iniziale Anomalie Neoplastiche AIDS.
        AIDS. 1998; 12: 1087-1093
        • Lewis R
        • Laverson W.H
        • Birnbaum S
        Malaria associated with pregnancy.
        Obstet. Gynecol. 1973; 42: 696-700
        • Aldridge L.M
        • Tunstall M.E
        Nitrous oxide and fetus. A review and the results of a retrospective study of 175 cases of anesthesia for insertion of Shirodkar suture.
        Br. J. Anaesth. 1986; 58: 1348-1356
        • Mazze R.I
        • Fujinaga M
        • Baden J.M
        Halothane prevents nitrous oxide teratogenicity in Sprague–Dawley rats, folinic acid does not.
        Teratology. 1988; 38: 121-127
        • Borja Aburto V.H
        • Hertz Picciotto I
        • Rojas López M
        • Farias P
        • Rı́os C
        • Blanco J
        Blood lead levels measured prospectively and risk of spontaneous abortion.
        Am. J. Epidemiol. 1999; 15: 590-597
        • Giacoia G.P
        Reproductive hazards in the workplace.
        Obstet. Gynecol. Surv. 1992; 47: 679-687
        • Gerhard I
        • Waibel S
        • Daniel V
        • Runnebaum B
        Impact of heavy metals on hormonal and immunological factors in women with repeated miscarriages.
        Hum. Reprod. Update. 1998; 4: 301-309
        • McMartin K.I
        • Chu M
        • Kopecky E
        • Einarson T.R
        • Koren G
        Pregnancy outcome following maternal organic solvent exposure: a meta-analysis of epidemiologic studies.
        Am. J. Ind. Med. 1998; 34: 288-292
        • Xu X
        • Cho S.I
        • Sammel M
        • et al.
        Association of petrochemical exposure with spontaneous abortion.
        Occup. Environ. Med. 1998; 55: 31-36
        • 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: 152-154
        • Foka Z.J
        • Lambropoulos A.F
        • Saravelos H
        • et al.
        Factor V Leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriage.
        Hum. Reprod. 2000; 15: 458-462
        • Martinelli P
        • Troncone R
        • Paparo F
        • et al.
        Coeliac disease and unfavourable outcome of pregnancy.
        Gut. 2000; 46: 332-335