Reply to ‘Recurrent miscarriage and embryonic loss’
Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Kita-ku N15 W7, Sapporo 060-8638, Japan
Email: yhideto{at}med.hokudai.ac.jp
Sir,
Thank you for the opportunity to reply to Dr Check's letter in which he recommends progesterone therapy rather than high-dose intravenous immunoglobulin (HIVIg) therapy in order to reduce risks of early pregnancy loss, i.e. embryo loss, because the former is less expensive.
It has been widely acknowledged that HIVIg therapy, but not low or medium dose of immunoglobulin, as immunomodifier is beneficially effective in several diseases such as idiopathic thrombocytopenia, Kawasaki disease, and Guillain-Barré syndrome. From 1993, we have applied the HIVIg treatment (20 g/day, 5 days) in severe cases of women with recurrent miscarriage (RM) of unexplained aetiology (Yamada et al., 1998
; Morikawa et al., 2001). Thirty-seven women who experienced four or more RM have received the HIVIg treatment so far: and HIVIg has been started at 4–5 weeks of gestation in all of the women. Twenty-seven of the 37 pregnancies ended in live births, and the remaining 10 in first trimester miscarriages. By karyotypic analyses, it was found that seven miscarriages had abnormal fetal chromosome karyotypes, one normal karyotype, and two resulted in unsuccessful karyotyping. One miscarriage with normal chromosome karyotype was embryo loss; one of two miscarriages with unknown karyotype was embryo loss, and the other was fetal loss at 9 weeks of gestation. Excluding the seven pregnancies with abnormal fetal chromosome karyotypes, the HIVIg therapy was effective in 90% (27/30) women with severe RM. Prior to the index pregnancy with the HIVIg therapy, 18 of the 37 RM women had experienced miscarriages despite progesterone therapy.
Morikawa et al. (2004) demonstrated that embryo loss pattern was predominant in miscarriages with normal chromosome karyotype (MsNK) among RM women, and recommended early commencement of some therapies for RM to reduce risks of embryo loss. In this study, among RM women with explained or unexplained RM we experienced 42 MsNK of which 27 underwent progesterone therapy during the index pregnancies. Sixteen of these 27 pregnancies with progesterone therapy ended in embryo loss, and the remaining 11 in fetal loss (embryo loss rate 59.3%). Among women with unexplained RM, seven of 12 MsNK with progesterone therapy were embryo loss (embryo loss rate 58.3%). These embryo loss rates were higher than that (45.7%) in MsNK of controls. Thus, predominance of embryo loss pattern could not be reversed by progesterone therapy in our study.
If RM women carry luteal insufficiency, we agree with Dr Check's opinion that embryo loss rate can be reduced by progesterone therapy. However, in our experience, progesterone therapy that is likely to be a popular therapy for unexplained RM could not effectively prevent embryo loss as mentioned above. As progesterone is less expensive than immunoglobulin, progesterone can be the first-line therapeutic option in mild cases of unexplained RM. If failed, HIVIg would be the next therapeutic option in severe cases of unexplained RM.
References
Morikawa M, Yamada H, Kato EH, Shimada S, Kishida T, Yamada T, Kobashi G and Fujimoto S (2001) Massive intravenous immunoglobulin treatment in women with four or more recurrent spontaneous abortions of unexplained etiology: down-regulation of NK cell activity and subsets. Am J Reprod Immunol 46, 399–404.
Morikawa M, Yamada H, Kato EH, Shimada S, Yamada T and Minakami H (2004) Embryo loss pattern is predominant in miscarriages with normal chromosome karyotype among women with repeated miscarriage. Hum Reprod 19, 2644–2647.
Yamada H, Kishida T, Kobayashi N, Kato EH, Hoshi N and Fujimoto S (1998) Massive immunoglobulin treatment in women with four or more recurrent spontaneous primary abortions due to unexplained aetiology. Hum Reprod 13, 2620–2623.
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