Adalgisa Pietropolli

Purpose: There is limited information on the risk factors for recurrent pregnancy loss (RPL). Methods: In this study, a patient-based approach was used to investigate the possible involvement and relative relevance of a large number of diagnostic factors in 843 women with RPL who underwent an extensive diagnostic workup including 44 diagnostic factors divided into 7 major categories. Results: The rates of abnormalities found were: (1) genital infections: 11.74%; (2) uterine anatomic defects: 23.72%; (3) endocrine disorders: 29.42%; (4) thrombophilias: 62%; (5) autoimmune abnormalities: 39.2%; (6) parental karyotype abnormalities 2.25%; (7) clinical factors: 87.78%. Six hundred and fifty-nine out of eight hundred and forty-three women (78.17%) had more than one abnormality. The mean number of pregnancy losses increased by increasing the number of the abnormalities found (r = 0.86949, P < 0.02). The factors associated with the highest mean number of pregnancy losses were cervical isthmic incompetence, anti-beta-2-glycoprotein-1 antibodies, unicornuate uterus, anti-prothrombin A antibodies, protein C deficiency, and lupus anticoagulant. The majority of the considered abnormalities had similar, non-significant prevalence between women with 2 versus ≥ 3 pregnancy losses with the exception of age ≥ 35 years and MTHFR A1298C heterozygote mutation. No difference was found between women with primary and secondary RPL stratified according to the number of abnormalities detected (Chi-square: 8.55, P = 0.07). In these women, the only factors found to be present with statistically different rates were age ≥ 35 years, cigarette smoking, and genital infection by Ureaplasma. Conclusion: A patient-based diagnostic approach in women with RPL could be clinically useful and could represent a basis for future research.

The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and 661 in normal healthy women. The prevalence of the following complications was observed: threatened miscarriage, miscarriage, cervical insufficiency, chromosomal/genetic abnormalities, fetal anomalies, oligohydramnios, polyhydramnios, fetal growth restriction, intrauterine fetal death, gestational diabetes mellitus (GDM), preeclampsia, placenta previa, abruptio placentae, pregnancy-related liver disorders, and preterm premature rupture of the membranes. The odds ratio and 95% CI for each pregnancy complication considered were determined by comparing women with RPL and normal healthy women. Women with RPL had an overall rate of pregnancy complications higher than normal women (OR = 4.37; 95% CI: 3.353–5.714; p < 0.0001). Their risk was increased for nearly all the conditions considered. They also had an increased risk of multiple concomitant pregnancy complications (OR = 4.64; 95% CI: 3.10–6.94, p < 0.0001). Considering only women with RPL, women with ≥3 losses had a higher risk of pregnancy complications than women with two losses (OR = 1.269; 95% CI: 1.112–2.386, p < 0.02). No differences were found in the overall risk of pregnancy complications according to the type, explained or unexplained, of RPL. Women with secondary RPL had an increased risk of GDM than women with primary RPL. Pregnancy in women with RPL should be considered at high risk.

In the article titled “Uterine Tumor Resembling Ovarian Sex Cord Tumors Type II with Vaginal Vault Recurrence” [1], there is an author name “Adalgisa Pietropolli” missing so that the author order in the author list was incorrect, where Oriana Marrucci,¹ Paola Nicoletti,¹ Alessandro Mauriello,² Simone Facchetti,² Lodovico Patrizi,¹ Carlo Ticconi,¹ Francesco Sesti,¹ and Emilio Piccione¹ should have read Oriana Marrucci,¹ Paola Nicoletti,¹ Alessandro Mauriello,² Simone Facchetti,² Adalgisa Pietropolli,¹ Lodovico Patrizi,¹ Carlo Ticconi,¹ Francesco Sesti,¹ and Emilio Piccione¹.

To determine whether differences are present in the time-to-pregnancy (TTP) between women with unexplained recurrent pregnancy loss (uRPL) and control women, in this case-control, retrospective study, carried out in tertiary university hospitals, the TTP, defined as the months needed to reach pregnancy from when the woman started to try to conceive, was determined in 512 women, 207 of which were diagnosed as having uRPL and 305 were normal healthy control women. The specific TTPs for each pregnancy, stratified by order of pregnancy occurrence, were also determined. Pregnancy rates by time were calculated by using the Kaplan-Meier method to construct the survival curves. The age at which the pregnancies occurred was determined. Comparisons were carried out between women with uRPL and controls. Overall, 1192 pregnancies occurred and were analyzed. Mean TTP in uRPL women was shorter than in controls (P < 0.001) when all the pregnancies were considered. Similarly, it was shorter in the first, second, third, and fifth pregnancy. The pregnancy rates of uRPL women were shorter than that of control women for the first three pregnancies, for which the numbers of subjects allowed the comparisons to be made. These findings were observed despite maternal age of uRPL women was higher than that of control women. TTP is shorter in uRPL than in normal women. This finding clinically supports to the hypothesis that women with uRPL could be, at least in early stages of pregnancy, more fertile or receptive toward the implanting embryo than healthy women.

Recurrent pregnancy loss (RPL) represents an unresolved problem for contemporary gynecology and obstetrics. In fact, it is not only a relevant complication of pregnancy, but is also a significant reproductive disorder affecting around 5% of couples desiring a child. The current knowledge on RPL is largely incomplete, since nearly 50% of RPL cases are still classified as unexplained. Emerging evidence indicates that the endometrium is a key tissue involved in the correct immunologic dialogue between the mother and the conceptus, which is a condition essential for the proper establishment and maintenance of a successful pregnancy. The immunologic events occurring at the maternal–fetal interface within the endometrium in early pregnancy are extremely complex and involve a large array of immune cells and molecules with immunoregulatory properties. A growing body of experimental studies suggests that endometrial immune dysregulation could be responsible for several, if not many, cases of RPL of unknown origin. The present article reviews the major immunologic pathways, cells, and molecular determinants involved in the endometrial dysfunction observed with specific application to RPL.

Objective: To evaluate the effects of chorionic villus sampling (CVS) on placental volume (PV), perfusion, and vasculature in the first trimester of pregnancy. Method: Uterine artery pulsatility index (PI), PV, vascularization index (VI), flow index (FI), and Vascularization Flow Index (VFI) were serially measured in 38 pregnant women who underwent CVS. Thirty-eight women who did not undergo invasive prenatal diagnosis were recruited as controls. Results: CVS was associated with a mild reduction of PI, a reduction of placental VI, FI, and VFI and with an increase in PV detected one week after the procedure. The outcome of pregnancy was similar between women of the two groups. Conclusion: Our findings showed that CVS is associated with mild placental vascular and morphological changes. However, these changes do not seem to be associated with adverse outcome.

Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para-Nonylphenol (p-NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances.

The possible association between allergy and neoplastic disorders has been the subject of many investigations but no general relationship has been determined. Little attention, however, has been paid to the possible role of allergy in the clinical manifestations of these diseases. In this study, the role of allergy in the susceptibility to uterine leiomyomas and in their growth was investigated. Interaction with ACP1, a genetic polymorphism associated with the growth of leiomyomas, has been also considered. Two hundred and three White woman from the population of Rome hospitalized for symptomatic leiomyomas requiring surgical intervention have been studied. One hundred thirty eight healthy women have been considered as controls. Allergy has been evaluated by prick test. T-test for equality of means, analysis of variance and linear correlation analysis has been performed. The level of statistical significance was set at 0.05. The frequency of allergic manifestations in women with leiomyomas does not differ from healthy women. The dimension of leiomyomas is lower in allergic than in non allergic women (p=0.004). The ACP1 *B/*B genotype and allergy cooperate in lowering the dimension of leiomyomas; the proportion of woman with small leiomyomas (<10 percentile) is much higher in allergic women carrying the *B/*B genotype as compared to other women (p<0.001). About 8% of variance of leiomyomas dimension is attributable to the joint effect of ACP1 and allergy. Allergic women with high concentration of ACP1 f isoform (*B/*B genotype) are protected from excessive leyomioma growth. If confirmed in other clinical settings, our observation may have practical importance in identifying women at risk of more severe clinical manifestations.

Previous studies suggest that adenylate kinase locus 1 (Ak1) has an important role in the control of blood glucose level and in the glycation of structural and functional proteins in type 2 diabetes and in the balanced development of feto-placental unit in healthy puerperae (HP). In this study, an attempt was made to investigate the relationship of Ak1 with maternal and neonatal parameters in puerperae with gestational diabetes (GDP) and with preexisting type 1 diabetes (T1DP). This study was carried on 402 HP, 347 consecutive healthy newborns, 102 GDP and 111 T1DP with their newborn infants. Ak1 phenotype was determined by starch gel electrophoresis. Chi-square test of independence was carried out by SPSS program. The analysis of three way contingency table was carried out by a loglinear model. Significant level was 0.05. In T1DP, the frequency of Ak1*2 allele was higher than in GDP and in HP. Serum glucose level was higher in T1DP than in GDP with higher values in carriers of Ak1*2 allele. Neonatal hypoglycemia was more frequent in T1DP than in GDP with a positive association with Ak1*2 allele. The correlation between birth weight (BW) and placental weight (PW) was lower in infants from T1DP than HP. In healthy puerperae the correlation is higher in Ak1 2-1 than in Ak11 phenotype while in diabetic puerperae the pattern is reversed with lower values in Ak12-1 than in Ak11 phenotype. The lowest value of correlation is observed in infants from T1D mothers carrying the Ak1*2 allele. The data confirmed the involvement of Ak1 in glucose metabolism and showed a disturbance of the balance between placental and fetal growth which was more marked in T1DP.