Pre-implantation endometrial leukocytes in women with recurrent miscarriage

Abstract

Immunohistochemistry was used to investigate the leukocyte populations in the endometrium of women suffering recurrent miscarriage. Mid-luteal phase endometrial biopsies were taken from 22 patients with idiopathic recurrent miscarriage and from nine women with normal obstetric histories. The samples were dated histologically and stained with a panel of monoclonal antibodies to identify leukocytes. The outcome of any pregnancy in subsequent cycles following the biopsy was determined. Similar numbers of cluster designation (CD)3(+) and CD8(+) cells were seen in both groups. However, CD4(+), CD14(+), CD16(+), CD56(+) and MHC class II(+) cells were significantly higher in the recurrent miscarriage group than in the controls. Two patients had B cells (CD22(+)) in their endometrium. No CD57(+) cells were seen in the controls; however, eight of the patients had a few CD57(+) cells present. Only two patients, both from the recurrent miscarriage group, had CD69(+) leukocytes in their endometrium. Patients who had miscarriages following endometrial biopsy had significantly more CD4(+), CD8(+), CD14(+), CD16(+), and CD56(+) leukocytes in their endometrium than either those who had live births or women with proven fertility. A different population of leukocytes was found in the pre-implantation endometrium from recurrent miscarriage patients as compared to those from fertile controls. These differences were accentuated in women who had a miscarriage subsequent to the biopsy compared with those who subsequently had a live birth.

Immune cells in the placental bed

“…All studies of decidua in miscarriage suffer from the criticism of 'cause or result' since samples are collected after clinical presentation and any alteration in leukocyte populations may simply reflect an inflammatory response to pregnancy demise. Nevertheless, macrophage numbers were also increased in luteal phase endometrium from women with a history of recurrent miscarriage, supporting a causative rather than a secondary effect (Quenby et al, 1999).…”

“…For example, increased numbers of CD56+ NK cells have been reported in decidua of women with sporadic miscarriage compared with controls (Zenclussen et al, 2001), although we were not able to confirm this finding in a study of placental bed biopsies from aneuploid and euploid miscarriages from 8 -20 weeks gestation, compared with normal pregnancy (Scaife et al, 2004). Despite the inconsistency of data for decidual and peripheral blood leukocytes, there are several independent reports from different groups of increased numbers of uNK cells, detected using immunohistochemistry, in luteal phase endometrium of both women with unexplained recurrent miscarriage and recurrent implantation failure (Quenby et al, 1999;Clifford et al, 1999;Laird et al, 2005;Tuckerman et al, 2007). Furthermore, it has been suggested that high uNK cell numbers in mid-secretory phase endometrium from women with recurrent miscarriage predicted miscarriage in subsequent pregnancy (Quenby et al, 1999).…”

“…Despite the inconsistency of data for decidual and peripheral blood leukocytes, there are several independent reports from different groups of increased numbers of uNK cells, detected using immunohistochemistry, in luteal phase endometrium of both women with unexplained recurrent miscarriage and recurrent implantation failure (Quenby et al, 1999;Clifford et al, 1999;Laird et al, 2005;Tuckerman et al, 2007). Furthermore, it has been suggested that high uNK cell numbers in mid-secretory phase endometrium from women with recurrent miscarriage predicted miscarriage in subsequent pregnancy (Quenby et al, 1999). A recent larger study did not confirm prediction of pregnancy outcome from uNK cell numbers but treatment details were not provided, interval between uNK cell assessment and subsequent pregnancy was not clear and pregnancy data were only available for a subset of the group (Tuckerman et al, 2007).…”

“…There have been several reports of perturbation of the normal CD8:CD4 ratio (reduced CD8-positive cell numbers) in the nonpregnant endometrium of women who suffer unexplained infertility (Klentzeris et al, 1994) and recurrent miscarriage (Lachapelle et al, 1996;Quenby et al, 1999). In decidua associated with pregnancy loss, several studies have reported no difference in decidual CD3-positive numbers in women with recurrent (Quack et al, 2001) or sporadic (Vassiliadou and Bulmer, 1998b;Scaife et al, 2004) miscarriage compared to normal early pregnancy.…”

The Role of Glucocorticoids in Pregnancy: Four Decades Experience with Use of Betamethasone in the Prevention of Pregnancy Loss

“…Idiopathic recurrent miscarriage has traditionally been associated with alloimmune factors, in which uterine CD56+/16 NK cells have been implicated (Quenby et al, 1999). In vitro studies suggest that pregnancy may result in uterine T-cell activation along the Th-2 pathway, resulting in blocking antibodies which mask trophoblast antigens (Wegmann et al, 1993).…”