The future pregnancy outcome of 201 consecutive women, median age 34 years (range 22-43), with a history of unexplained recurrent first trimester miscarriage (median 3; range 3-13), was studied. All women and their partners had normal peripheral blood karyotypes; none had antiphospholipid antibodies and none hypersecreted luteinizing hormone (LH). No pharmacological treatment was prescribed and early pregnancy supportive care was encouraged. Women aged < or = 30 years had a subsequent miscarriage rate of 25% (14/57) which rose to 52% (13/25) in women aged > or = 40 years (P = 0.02). After three consecutive miscarriages, the risk of miscarriage of the next pregnancy was 29% (34/119) but increased to 53% (9/17) after six or more previous losses (P = 0.04). A past history of a livebirth did not influence the outcome of the next pregnancy. Supportive care in early pregnancy conferred a significant beneficial effect on pregnancy outcome. Of 160 women who attended the early pregnancy clinic, 42 (26%) miscarried in the next pregnancy compared with 21 out of 41 (51%) who did not attend the clinic (P = 0.002). After thorough investigation, women with unexplained recurrent first trimester miscarriage have an excellent pregnancy outcome without pharmacological intervention if offered supportive care alone in the setting of a dedicated miscarriage clinic.

A total of 500 consecutive women (mean age 32.9 years; SD 5 years) presenting with a history of recurrent miscarriages (median 4; range 3-17) were investigated for the presence of antiphospholipid antibodies (APA), polycystic ovaries (PCO), hypersecretion of luteinizing hormone (LH) and chromosome abnormalities in order to detect an underlying cause of their pregnancy losses. All women had details of their previous reproductive history, investigations and treatment documented: 76% of the women had experienced only early pregnancy losses (miscarriage < 13 weeks gestation); 32% had a history of subfertility; and significant parental chromosome rearrangements were present in 3.6% of couples. An ultrasound diagnosis of PCO was made in 56% of women, 58% of whom were demonstrated to hypersecrete LH, based on early morning urinary LH analysis. Circulating APA were found in 14% of women. An underlying cause of recurrent miscarriage--genetic, endocrine or autoimmune--was found in > 50% of couples. Women in the latter two groups are being recruited to randomized treatment trials which are discussed.

Endometrial natural killer (NK) cells were compared in luteal-phase endometrial samples from women with recurrent miscarriage and from normal subjects. Cryostat sections were labelled using a monoclonal antibody to CD56 using an avidin-biotin complex method and a morphometric study performed. Increased mean numbers of CD56+ cells were documented in the endometrium of women with recurrent early miscarriage only. These findings suggest a possible role for NK cells in the pathogenesis of recurrent early pregnancy loss.

Five hundred consecutive women (median age 33 years; range 19-45) with a history of recurrent miscarriage (median 4; range 3-16) were screened for the presence of antiphospholipid antibodies (APA)-lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACA). The prevalence of persistently positive tests for LA was 9.6% and for immunoglobulin G (IgG) and immunoglobulin M (IgM) ACA was 3.3 and 2.2% respectively. Only seven women (1.4%) were LA and ACA positive. Repeat testing, after an interval of at least 8 weeks, demonstrated that only 65.7% of LA positive, 36.6% IgG ACA positive and 36.0% IgM ACA positive women on initial testing had a second positive test result. The dilute Russell's viper venom time detected the LA significantly more often than either the activated partial thromboplastin time or the kaolin clotting time (P < 0.001). There was no difference in the gestation of previous miscarriages between APA positive and APA negative women. There was no difference in the plasma beta 2-glycoprotein-I concentrations between APA positive and APA negative women with miscarriages and normal women. All women with a history of recurrent miscarriage should be tested for the presence of both LA and ACA. A second confirmatory test should be performed in those with an initial positive test result.