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Problem: While there are several known causes for recurrent pregnancy loss (RPL), about 50% are unexplained (uRPL), and in these cases, an aberrant immune regulation seems to be involved. Although fetally derived trophoblast cells have a key role in immune regulation, it is difficult to study their immune function during pregnancy, and it is not known whether trophoblast function may be an inherent aberration in uRPL or whether it is associated with the outcome of the current pregnancy. Method of study: Chorionic villus sampling (CVS) was performed for clinical indications at 12 weeks of gestation. Superfluous materials, divided in small explants, were cultured for 20‐24 hours, and supernatants (conditioned medium) were collected from 36 women with singleton normal pregnancies, of whom 9 women had a history of RPL. The secreted immune protein profile was measured by proximity extension assay, and the conditioned medium was further used in functional ex vivo models to assess ability to polarize blood monocytes and CD4+ T cells into immune regulatory phenotypes, as detected by flow cytometry. Results: Conditioned medium from chorionic villi, human fetally derived placental tissue, was able to induce a decidual‐type of M2‐like macrophages, as well as an expansion of Treg cells ex vivo, both in women with uRPL and in control women. The preserved immunological properties were confirmed by a maintained immune protein profile in RPL compared with controls. Conclusion: Trophoblasts in an ex vivo model maintain tolerogenic and proteomic profile features in successful pregnancies, despite a previous history of RPL. [ABSTRACT FROM AUTHOR]

UTROSCTs (Uterine Tumors Resembling Ovarian Sex Cord Tumors) are rare neoplasms of unknown etiology usually occurring in middle-aged women. Less than 100 cases of UTROSCT have been reported so far. Although the typical behavior of UTROSCT is benign, metastatic and recurrent cases can occur. Here we describe an extremely rare case of vaginal vault recurrence of UTROSCT occurring 5 years after total hysterectomy with bilateral salpingo-oophorectomy. Though rare, UTROSCT should always be taken into account in the differential diagnosis of uterine masses initially considered leiomyomas. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of this study was to investigate the possible association between recurrent miscarriage (RM) and ectopic pregnancy (EP). Methods: In this case–control retrospective study, the clinical cards of women followed as outpatients in the RM and low‐risk pregnancy offices of the Obstetrics and Gynecology Unit at the Policlinico Tor Vergata University Hospital were carefully reviewed for the occurrence of EP. Results: Overall, 598 women with RM and 2043 normal women without RM (controls) were included in the study. Among these women, 4974 pregnancies were analyzed, in which 2028 miscarriages occurred. The EP rate (3.51%) was significantly higher in RM than in control women (1.51%) [odds ratio = 2.31 (95% confidence interval: 2.3–2.4)]; it was particularly high in women with primary RM (5.11%). However, when EP rates were calculated not by women but by overall pregnancies, no differences could be found between RM and control women. In control women, the absence of a miscarriage in the reproductive history was associated with a lower rate of EP. Conclusions: Women with RM, particularly primary RM, are at increased risk of EP. This increased risk seems to be dependent on the high number of pregnancies occurring in women with RM rather than to specific characteristics of these women. [ABSTRACT FROM AUTHOR]

Problem To investigate whether antinuclear autoantibodies ( ANA) could be related to the outcome of the successive pregnancy in women with unexplained recurrent miscarriage ( uRM). Methods Circulating ANA were measured by indirect immunofluorescence in 86 women with uRM before pregnancy, repeated in the first trimester of the successive gestation and correlated with pregnancy outcome. Results Forty-one women were ANA− and 45 were ANA+ before pregnancy. No relation was found between pre-pregnancy ANA status and the outcome of the successive pregnancy. However, when these women were monitored at 7th week during their pregnancy for ANA, of the 22 ANA+ women who remained ANA+ seven miscarriages (31.8%) were observed, whereas all of the 23 ANA+ women who became ANA− had pregnancies ongoing beyond the 20th week without miscarriage. Conclusions ANA status could have a role in uRM. Disappearance of ANA in early pregnancy could have a favorable prognostic value in the successive pregnancy. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to investigate the gestational age (GA) of pregnancy loss in women with unexplained recurrent miscarriage (RM) and to determine whether the miscarriages occur at similar GA in RM women. Material and Methods This retrospective study was carried out in a university hospital and included 288 women with unexplained RM. The GA at which each miscarriage occurred was carefully determined. Overall, 739 miscarriages were analyzed. Results RM women had miscarriages at a median GA of 7 weeks (range: 3-20). In RM women, 47.2% ( n = 136) experienced miscarriages within a 1-week range of GA and 53.4% ( n = 154) had miscarriages in the same period of fetal development (pre-embryonic, embryonic or fetal). Conclusion Women with unexplained RM tend to have miscarriages at the same GA, which is characteristic for each patient. [ABSTRACT FROM AUTHOR]

Problem To investigate the possible relationship between human papillomavirus ( HPV) infection and recurrent miscarriage ( RM). Methods In this retrospective case-control study, 49 women with unexplained RM (Group 1 - cases) and 475 women without any miscarriage and with at least one pregnancy at term (Group 2 - controls) were checked for cervical HPV infection through Hybrid Capture® II ( HC 2) or polymerase chain reaction ( PCR). Results HPV+ DNA tests were detected in 13 (26.53%) RM women and in 294 (61.89%) control women ( P < 0.001). The prevalence rate in HPV+ DNA tests was significantly different in the 30-39 years age range. No differences between groups were detected in HPV types, nor in the cytological and histological findings. Conclusion Women with RM have a lower prevalence of HPV+ DNA tests than controls. This suggests that immune reactivity potentially leading to RM could be in some way protective against genital HPV infection. [ABSTRACT FROM AUTHOR]

Citation Ticconi C, Giuliani E, Veglia M, Pietropolli A, Piccione E, Di Simone N. Thyroid autoimmunity and recurrent miscarriage. Am J Reprod Immunol 2011; 66: 452-459 Problem To investigate the role of antithyroid autoantibodies (ATA) in recurrent miscarriage (RM). Methods In this case-control study, a total of 160 women with RM and 100 healthy women were investigated for the presence of serum ATA directed against thyreoglobulin (TG-Ab), thyroid peroxidase (TPO-Ab) and TSH receptor (TSHr-Ab), which were determined by either chemiluminescence or radioimmunoassay. Results Antithyroid autoantibodies were detected in 46 (28.75%) women with RM and in 13 (13%) women of the control group ( P < 0.05). The frequencies for TG-Ab and TPO-Ab were higher in RM than in control women. Among the women of RM group, 91.3% of ATA+ women were positive also for other autoantibodies. The majority of study women were euthyroid. Conclusions Antithyroid autoantibodies, particularly TG-Ab, are associated with RM and could be an expression of a more general maternal immune system abnormality leading to RM. ATA could have a role in RM irrespective of thyroid hormone status. [ABSTRACT FROM AUTHOR]

Ticconi C, Rotondi F, Veglia M, Pietropolli A, Bernardini S, Ria F, Caruso A, Di Simone N. Antinuclear autoantibodies in women with recurrent pregnancy loss. Am J Reprod Immunol 2010; 64: 384-392 To investigate the possibility that antinuclear antibodies (ANA) are involved in recurrent pregnancy loss (RPL). Case-control study carried out on 294 women (194 cases and 100 controls) in two University hospitals. The presence, the serum titers and the indirect immunofluorescence (IIF) patterns of ANA were determined in women with RPL and in control women. Antinuclear antibodies at titers ≥ 1:80 were detected in 97 (50%) women with RPL and in 16 (16%) control women. Elevated ANA titers (≥1:180) were detected only in RPL women, whereas all control women had ANA titers no greater than 1:80. No differences could be detected in the IIF patterns between RPL and control women. No differences in ANA positivity could be detected according to the type (primary or secondary) or number (>2 versus ≥3) of losses. ANA could be of some value in identifying women with RPL with potential, although still not fully defined, immune abnormalities. [ABSTRACT FROM AUTHOR]

Aim: To investigate the clinical role of the bone turnover markers type I collagen C telopeptide (CTX), osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) in the assessment of bone status in women with postmenopausal osteoporosis. Methods: Serum CTX (s-CTX), OC and BAP were measured in 200 healthy menopausal women at their initial visit and were correlated with spine and femur bone mineral density (BMD), determined on dual-energy X-ray absorptiometry. The relationship between biochemical markers of bone turnover and age, age at menopause, body mass index (BMI) and BMD was analyzed using linear correlation. A receiver operating characteristic (ROC) curve was constructed for each serum marker versus both femur and vertebral BMD. Results: No correlation was found between serum levels of OC and BAP and vertebral or femur BMD. A statistically significant inverse correlation was found between s-CTX and BMD at spine and femur. S-CTX levels were higher in women with osteoporosis than in women with normal or moderately low (osteopenic) values of BMD. The sensitivity and specificity versus spine BMD were 73.9% and 41.6% for s-CTX, 40.4% and 80.6% for BAP, and 68.3% and 39% for OC, respectively. The sensitivity and specificity versus femur BMD were 76.9% and 40.4% for s-CTX, 23.8% and 88.3% for BAP, and 80.4% and 53.3% for OC, respectively. Conclusions: Determination of s-CTX, BAP and OC is of limited clinical value in the initial evaluation of bone status in menopausal women. [ABSTRACT FROM AUTHOR]

In the present manuscript, we review the recent research investigating the pathogenic association between most studied autoantibodies and recurrent pregnancy loss. Pregnancy loss represents a common obstetric complication occurring in about 15%‐25% of all clinically recognized pregnancies. The recurrence of pregnancy loss identifies a distinct clinical entity, that is recurrent pregnancy loss (RPL), affecting about 2%‐4% of couples. Several factors, including age, chromosomal abnormalities, uterine anomalies, thrombophilic disorders, endocrinopathies, hormonal and metabolic disorders, infections, sperm quality, and lifestyle issues, are involved in RPL. The role of autoantibodies in RPL is only partially determined. In some cases (antiphospholipid antibodies [aPL]), their involvement is well established. In other cases (anti‐thyroid autoantibodies, antinuclear, anti‐transglutaminase, and anti‐endomysial antibodies), it is still debated, despite multiple, although not fully conclusive, evidences strongly suggest a possible involvement in RPL. Further extensive research is needed to definitively confirm or exclude their actual role. [ABSTRACT FROM AUTHOR]