A C TA Obstetricia et Gynecologica
AOGS LE TT E R TO THE EDIT O R
Recurrent miscarriage, fact or fiction? Reply on comment by Christiansen
Sir 1. Prof. Christiansen does not share my view that recurrent miscarriage (RM) is not a useful clinical concept (1). However, at one point we seem to agree: the absence of statistical reasons to assume that RM is not a chance event. He writes: Due to all these uncertainties, these kinds of calculation are not useful in proving or disproving whether RM is a specific clinical entity (2). Apparently he changed his view in this regard very recently, because in 2013 he wrote: Since the incidence of RM is greater than would be predicted by chance, it is considered to represent a disease entity defined by a series of events, with a number of possible etiologies (3). 2. In the same publication (3) he writes: It is a generally accepted assumption that sporadic pregnancy losses occurring before an embryo has developed represent a “physiological” phenomenon, which prevents conceptions affected by serious structural malformations or chromosomal aberrations incompatible with life from progressing to viability. This concept is supported by clinical studies in which embryoscopy was used to assess fetal morphology prior to removal by uterine evacuation. Fetal malformations were observed in 85% of cases presenting with early clinical miscarriage [Philipp]. The same study also demonstrated that 75% of the fetuses had an abnormal karyotype. I could not agree more. Early embryonic death is common in many mammals and certainly can be considered as a normal biological phenomenon. But why should that be accepted only for the first miscarriage of a woman, and not for her second or third or sixth miscarriage? Where is the evidence that in recurring miscarriages more normal, euploid, nonmalformed fetuses are being lost than in the first one? We are still waiting for a prospective, observational study of RM patients, with complete biochemical, sonographic, embryoscopic, anatomic and cytogenetic analysis of the subsequent miscarriages. If a subset of women should be found repeatedly losing normal and healthy fetuses, then investigations and intervention trials should be focused on such a group. In all other women no justification exists for attempts to block the natural selection. 3. Prof. Christiansen doubts if the prognosis is as favorable as calculated with the help of tables with observed success rates. He writes:
Among 987 patients with three or more miscarriages referred during 1986–2008, we found that 66.7% had achieved a live birth 5 years and 71.1% 15 years after the first consultation, apparently lower than the percentages in my article. However, the percentages mentioned by Prof. Christiansen are found with the help of the Danish national birth register (4). An unknown percentage of this group may have stopped conceiving, for either voluntary or involuntary reasons. The prediction of the high success rates is only valid in women continuing to conceive, at least two or three times. 4. Prof. Christiansen writes: There is increasing evidence for an association between obstetric and neonatal outcomes in pregnancies among patients with RM and factors that negatively affect placental growth. He uses this observation as an argument to consider RM a clinical entity. However, the reason that such an association has been found is probably that in most epidemiological studies no distinction has been made between early and late miscarriages. Early (first-trimester) miscarriage represents a “physiological” phenomenon: removal of compromised conception products. Miscarriages in the second trimester are more often associated with maternal factors, some of these connected with obstetric complications. In conclusion, thanks to technical developments our knowledge of early pregnancy has considerably improved in recent decades. Most researchers now seem to accept that the vast majority of early miscarriages are abnormal products of conception. However, many of them have far more difficulty in accepting the fact that the same is true for the vast majority of recurrent miscarriages, as the comments of Prof. Christiansen show. His opinion that RM should be viewed as a clinical entity is not supported by solid evidence. His proposal to focus future research on possible high-risk cases, such as women with at least four consecutive miscarriages, can be seen as a step in the right direction. Yet even in those cases a complete analysis of the pregnancy products should precede any intervention trial. Willem Vlaanderen* Vinkenlaan 24, 6581 CK, Malden, the Netherlands *Corresponding Author: Willem Vlaanderen E-mail: [email protected] DOI: 10.1111/aogs.12489
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014) 1331–1332
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Letter to the Editor
References 1. Vlaanderen W. Is recurrent miscarriage a useful clinical concept? Acta Obstet Gynecol Scand. 2014;93:848–51. 2. Christiansen OB. Recurrent miscarriage is a useful and valid clinical concept. Acta Obstet Gynecol Scand. 2014;93:852–7.
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3. Larsen EC, Christiansen OB, Kolte AM, Macklon N. New insights into mechanisms behind miscarriage. BMC Med. 2013;11:154. 4. Lund M, Kamper-Jørgensen M, Nielsen HS, Lidegaard Ø, Andersen A-MN, Christiansen OB. Prognosis for live birth in women with recurrent miscarriage. What is the best measure of success? Obstet Gynecol. 2012;119:37–43.
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014) 1331–1332
Copyright of Acta Obstetricia et Gynecologica Scandinavica is the property of WileyBlackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
AOGS LE TT E R TO THE EDIT O R
Recurrent miscarriage, fact or fiction? Reply on comment by Christiansen
Sir 1. Prof. Christiansen does not share my view that recurrent miscarriage (RM) is not a useful clinical concept (1). However, at one point we seem to agree: the absence of statistical reasons to assume that RM is not a chance event. He writes: Due to all these uncertainties, these kinds of calculation are not useful in proving or disproving whether RM is a specific clinical entity (2). Apparently he changed his view in this regard very recently, because in 2013 he wrote: Since the incidence of RM is greater than would be predicted by chance, it is considered to represent a disease entity defined by a series of events, with a number of possible etiologies (3). 2. In the same publication (3) he writes: It is a generally accepted assumption that sporadic pregnancy losses occurring before an embryo has developed represent a “physiological” phenomenon, which prevents conceptions affected by serious structural malformations or chromosomal aberrations incompatible with life from progressing to viability. This concept is supported by clinical studies in which embryoscopy was used to assess fetal morphology prior to removal by uterine evacuation. Fetal malformations were observed in 85% of cases presenting with early clinical miscarriage [Philipp]. The same study also demonstrated that 75% of the fetuses had an abnormal karyotype. I could not agree more. Early embryonic death is common in many mammals and certainly can be considered as a normal biological phenomenon. But why should that be accepted only for the first miscarriage of a woman, and not for her second or third or sixth miscarriage? Where is the evidence that in recurring miscarriages more normal, euploid, nonmalformed fetuses are being lost than in the first one? We are still waiting for a prospective, observational study of RM patients, with complete biochemical, sonographic, embryoscopic, anatomic and cytogenetic analysis of the subsequent miscarriages. If a subset of women should be found repeatedly losing normal and healthy fetuses, then investigations and intervention trials should be focused on such a group. In all other women no justification exists for attempts to block the natural selection. 3. Prof. Christiansen doubts if the prognosis is as favorable as calculated with the help of tables with observed success rates. He writes:
Among 987 patients with three or more miscarriages referred during 1986–2008, we found that 66.7% had achieved a live birth 5 years and 71.1% 15 years after the first consultation, apparently lower than the percentages in my article. However, the percentages mentioned by Prof. Christiansen are found with the help of the Danish national birth register (4). An unknown percentage of this group may have stopped conceiving, for either voluntary or involuntary reasons. The prediction of the high success rates is only valid in women continuing to conceive, at least two or three times. 4. Prof. Christiansen writes: There is increasing evidence for an association between obstetric and neonatal outcomes in pregnancies among patients with RM and factors that negatively affect placental growth. He uses this observation as an argument to consider RM a clinical entity. However, the reason that such an association has been found is probably that in most epidemiological studies no distinction has been made between early and late miscarriages. Early (first-trimester) miscarriage represents a “physiological” phenomenon: removal of compromised conception products. Miscarriages in the second trimester are more often associated with maternal factors, some of these connected with obstetric complications. In conclusion, thanks to technical developments our knowledge of early pregnancy has considerably improved in recent decades. Most researchers now seem to accept that the vast majority of early miscarriages are abnormal products of conception. However, many of them have far more difficulty in accepting the fact that the same is true for the vast majority of recurrent miscarriages, as the comments of Prof. Christiansen show. His opinion that RM should be viewed as a clinical entity is not supported by solid evidence. His proposal to focus future research on possible high-risk cases, such as women with at least four consecutive miscarriages, can be seen as a step in the right direction. Yet even in those cases a complete analysis of the pregnancy products should precede any intervention trial. Willem Vlaanderen* Vinkenlaan 24, 6581 CK, Malden, the Netherlands *Corresponding Author: Willem Vlaanderen E-mail: [email protected] DOI: 10.1111/aogs.12489
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014) 1331–1332
1331
Letter to the Editor
References 1. Vlaanderen W. Is recurrent miscarriage a useful clinical concept? Acta Obstet Gynecol Scand. 2014;93:848–51. 2. Christiansen OB. Recurrent miscarriage is a useful and valid clinical concept. Acta Obstet Gynecol Scand. 2014;93:852–7.
1332
3. Larsen EC, Christiansen OB, Kolte AM, Macklon N. New insights into mechanisms behind miscarriage. BMC Med. 2013;11:154. 4. Lund M, Kamper-Jørgensen M, Nielsen HS, Lidegaard Ø, Andersen A-MN, Christiansen OB. Prognosis for live birth in women with recurrent miscarriage. What is the best measure of success? Obstet Gynecol. 2012;119:37–43.
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014) 1331–1332
Copyright of Acta Obstetricia et Gynecologica Scandinavica is the property of WileyBlackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
