Recurrent spontaneous miscarriage (RSM), affecting 1-2% of women of reproductive age seeking pregnancy, has been a clinical quagmire and a formidable challenge for the treating physician. There are many areas of controversy in the definition, aetiology, investigations and treatment of RSM. This review will address the many factors involved in the aetiology of RSM which is multifactorial in many patients, with antiphospholipid syndrome (APS) being the most recognized aetiological factor. There is no identifiable cause in about 40-60% of these patients, in which case the condition is classified as idiopathic or unexplained RSM. The RSM investigations are extensive and should be undertaken in dedicated, specialized, well-equipped clinics/centres where services are provided by trained specialists. The challenges faced by the treating physician are even more overwhelming regarding the decision of what should be the most appropriate therapy offered to patients with RSM. Our review will cover the diverse modalities of therapy available including the role of preimplantation genetic testing using recent microarray technology, such as single nucleotide polymorphism and comparative genomic hybridization, as well as preimplantation genetic diagnosis; the greatest emphasis will be on the treatment of APS, and there will be important comments on the management of patients presenting with idiopathic RSM. The controversial areas of the role of natural killer cells in RSM, the varied modalities in the management of idiopathic RSM and the need for better-planned studies will be covered as well.

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BACKGROUND:Insulin resistance (IR) plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS), but identification of insulin-resistant individuals is difficult. The homeostasis model assessment (HOMA), a surrogate marker of IR, is available in 2 computational models: HOMA1-IR (formula) and HOMA2-IR (computer program), which differ in incorporated physiological assumptions. This study evaluates the associations of the 2 models as markers of IR, the metabolic syndrome (MS), and PCOS.

Intravenously administered polyspecific IgG is being increasingly used as an immunomodulating therapy with controversial beneficial outcome. The aim of this study was to evaluate the effects of IgG infusion on peripheral T-cell subpopulations in women with recurrent pregnancy loss (RPL). Fifteen women with a history of three previous RPL between 6 and 22 weeks of gestation and positivity for the antiphospholipid antibody syndrome (APS) were randomized to one of two treatment groups: (a) an intravenous immunoglobulin therapy group (RPL-IVIg; 7 patients), 500 mg IVIg/kg/month and (b) a placebo-treated group given multivitamins (8 patients). Control groups comprised either normal pregnant women without APS (10 patients) or non-pregnant women. The T-cell markers were characterized using a monoclonal antibody panel including CD3, CD4, CD8, CD25, CD29, CD38, CD45RA, CD45RO, CD54 and HLA-DR. Analysis was performed with a two-color fluorescent-activated flow cytometer. In the first trimester, the percentage of CD4+CD25+, CD4+CD45RO+, CD8+HLA-DR+, and CD8+CD38+ populations were reduced in the multivitamin group compared to normal pregnant women (p < 0.05) while in the RPL-IVIg group only CD4+CD25+ cells were reduced (p < 0.05). By the second trimester, CD3+CD16+CD56+ was significantly higher in multivitamin- than in IVIg-treated women (p < 0.05). The percentage of CD4+HLA-DR+ was significantly higher in the two RPL groups compared to normal pregnant women (p < 0.05). IVIg therapy in women with RPL was associated with a significant reduction in CD3+CD16+CD56+ and CD4+CD25+. This may contribute to the suppression of immune-mediated processes contributing to premature abortion.

The aims of this study were to determine the aetiological factors and the pattern of recurrent pregnancy loss in Kuwait. Ninety consecutive patients attending the special recurrent miscarriage clinic were studied prospectively. A comprehensive history of all previous miscarriages and pregnancies, past medical and gynaecological events were established. A physical examination was performed. Extensive investigations were performed. Pregnancies which occurred during the study were monitored carefully. The mean age of the patients was 30.46+/-6.04 years. The patients were subdivided into the groups of secondary (57%) and primary (43%) recurrent miscarriages. Eighty-five per cent of all previous miscarriages occurred in the first trimester. The main aetiological factors were uterine anomaly 2.2%, chromosome anomaly (parental) 2.2%, PCOS, infections and other miscellaneous factors 21.1%, positive antiphospholipid antibodies 33.3% and unexplained in 35.6%. The overall live birth rate was 82% and maternal morbidity was low. Positive antiphospholipid antibodies are the most frequently associated cause of recurrent pregnancy loss in Kuwait.

Objective: To investigate the reproductive performance of non-pregnant women with recurrent spontaneous miscarriage (RSM) and the association between RSM and polycystic ovary syndrome (PCOS) in reproductive failure. Subjects and Methods: Fifty non-pregnant women with 3 or more consecutive RSM attending our RSM clinic were evaluated prospectively. Detailed history and physical examination were completed. Extensive laboratory investigations, ultrasonographic, radiological and specialized procedures/tests were performed. Those patients who did not achieve pregnancy within the first 6 months of follow-up had appropriate treatment options implemented. The outcome of any subsequent pregnancies was analyzed. Results: The mean age of the patients was 33.8 ± 4.6 years (range 22–43 years). The aetiological factors associated with RSM were chromosome anomaly, uterine abnormality, antiphospholipid syndrome, PCOS and infections; 40% were ‘unexplained’. Thirty patients (60%) were able to achieve viable pregnancies which progressed to term, resulting in live births. Fourteen of the other 20 patients had high body mass index (BMI) >30 and evidence of PCOS. Of these 20 patients, 13 eventually achieved pregnancies which ended again in first-second-trimester abortions (cause undetermined). The remaining 7 patients (4 with high BMI) who had a combination of male factor/protracted PCOS/ovarian failure did not achieve pregnancies. Conclusion: The association of RSM with PCOS resulted in poor reproductive performance, which may progress to reproductive failure.

The fetal and maternal outcome of pregnancies in patients with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome were virtually identical and quite satisfactory. Intravenous immunoglobulin added to the standard therapy resulted in excellent fetal and maternal outcome, although its definitive role will have to wait for the outcome of randomised trials.

Objective: The objective of this study was to explore the role of insulin resistance in women with recurrent spontaneous miscarriage (RSM). Patients with ≧3 consecutive spontaneous miscarriages were classified as having RSM. Subjects and Methods: Thirty-five non-pregnant women presenting with RSM in our specialized RSM clinic constituted the study population, while 30 non-pregnant, parous, fertile women without RSM served as controls. The study and control patients were matched for age, ethnicity and body mass index (BMI). Blood was extracted from these patients for fasting blood glucose and fasting insulin simultaneously, and a battery of investigations including ultrasonography was performed on all the patients with RSM. Results: There was no significant difference in the mean fasting glucose for the study and control patients (5.5 ± 0.7 vs. 5.3 ± 0.6 mmol/dl) and in the mean fasting insulin (15.0 ± 5.1 and 12.9 ± 2.9 mU/l). There was a significant difference between the mean parity of the study and control patients (0.7 ± 0.7 vs. 1.7 ± 0.5, p < 0.0001) and also the mean number of miscarriages (4.2 ± 1.2 vs. 0.1 ± 0.4, p < 0.0001). There was, however, no significant difference in the insulin resistance of both groups as calculated using the Homeostasis Model Assessment and the fasting glucose insulin ratio of <4.5. Conclusion: Insulin resistance was not significantly associated with RSM in our study. Further studies may be needed.