Departments of 1 Obstetrics and Gynaecology and 2 Immunology, University of Liverpool, Liverpool L69 3BX and 3 Liverpool Womens Hospital, Crown Street, Liverpool L8 7SS, UK
4 To whom correspondence should be addressed. e-mail: squenby{at}liv.ac.uk
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Abstract |
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Key words: case report/natural killer cells/prednisolone/recurrent miscarriage
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Introduction |
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The patient described was found to have the highest number of preimplantation uNK cells within a local study of endometrium from RM patients (n = 21) (Quenby et al., 1999). Following discussion with the patient, prednisolone was prescribed as immunomodulation therapy to attempt improvement in implantation.
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Case report |
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As part of an ethically approved research study, the patient consented to a mid-luteal phase endometrial biopsy that showed the highest recorded level of uNK cells of those studied (Quenby et al., 1999). Thirty-one percent of this patients endometrial cells were uNK cells. The control patients, who had had at least two live births, had 0.29.5% uNK cells in their endometrium and the other recurrent miscarriage patients in the study had 0.222% uNK cells (Quenby et al., 1999
). In light of this information various immunomodulation therapies were discussed, including i.v. immunoglobulin (IVIg) and prednisolone use. The patient decided that a trial of pre-conceptual prednisolone 5 mg/day should be prescribed. Between 1999 and 2001 she suffered three further consecutive losses at 56 weeks of gestation, bringing the total number of losses to 19.
An increased dose of preconceptual prednisolone (20 mg/day) was taken for 6 months prior to conception in May 2002. The prednisolone was stopped at 5 weeks gestation after a home pregnancy test was positive. The pregnancy was monitored with serial ultrasonography and complicated by intrauterine growth restriction and oligohydramnios. A Caesarean section was performed at 32+6 weeks, because of poor growth velocity on serial ultrasonography, with the birth of a female infant weighing 1484 g, in good condition. After observation on the Special Care Baby Unit, baby and mother were discharged home well. At her post-natal visit mother and baby were both well. Bone density measurement of maternal hip and spine showed readings above average for her age.
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Discussion |
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The presence of uNK cells in significant numbers in preimplantation endometrium and the existence of NK cell receptors that can recognize antigens on invading trophoblast (King et al. 2000) mean that uNK cells are considered to have a critical role in implantation. However, the exact role of uNK cells is not yet elucidated. There are two competing hypotheses: either uNK cells are hostile to invading trophoblast or uNK cells may facilitate the implantation of abnormal blastocysts leading to the clinical presentation of RM (Quenby et al., 2002
). The latter interpretation is supported by recent data showing CD56+ NK cells are more numerous in the decidua from chromosomally abnormal miscarriages than in chromosomally normal miscarriages (Yamamoto et al., 1999b
). Differences were detected in the decidual leucocytes from the miscarried tissue of women with unexplained RM and a normal fetal karyotype compared to women with RM and abnormal fetal karyotype (Quack et al., 2001
). As not all this patients 19 miscarriages were karyotyped, we do not know how many losses were of karyotypical normal or abnormal pregnancies. The two miscarriages in which tissue was successfully cultured showed a normal karyotype.
uNK cells have recently been found to express the glucocorticoid receptor and the estrogen receptor 1, thereby raising the possibility of pharmacological manipulation of this cell population (Henderson et al., 2003
). Several immunomodulation therapies are available. IVIg, third-party donor cell immunization, paternal cell immunization, trophoblast membrane infusion and steroids have all been suggested, with conflicting evidence as to their efficacy. A recent meta-analysis of 19 high-quality trials evaluated IVIg, third-party donor cell immunization, paternal cell immunization and trophoblast membrane infusions, and found no evidence of a beneficial effect (Scott, 2003
). However, preimplantation prednisolone for the prevention of RM has not yet been investigated in any trial. Unfortunately we were not able to analyse a second biopsy from this patients endometrium whilst taking predisolone, hence the effect of glucocorticoids on this patients uNK cells cannot be verified. Furthermore the patient had three further miscarriages, following the endometrial biopsy and we do not know how miscarriage or aging affects the uNK cell levels. Hence, this case represents a novel observation of untested significance. We do not recommend the measurement and treatment of uNK cells in recurrent miscarriage accept in the context of an ethically approved study or a well designed randomized controlled trial.
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References |
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Submitted on June 24, 2003; resubmitted on August 7, 2003; accepted on September 4, 2003.