The role of levonorgestrel intra-uterine system in the management of adenomyosis: A systematic review and meta-analysis of prospective studies.

INTRODUCTION: The levonorgestrel intrauterine system (LNG-IUS) is a long-acting hormone-releasing uterine device that has many non-contraceptive benefits. The study aims to assess the safety and efficacy of LNG-IUS in the management of adenomyosis. MATERIAL AND METHODS: We searched the following bibliographic databases: MEDLINE via PubMed, SCOPUS, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and Google Scholar for the relevant studies which used LNG-IUS in management of patients with clinically or ultrasonographic diagnosed adenomyosis.The main outcome measures are pain score at the end of follow-up, bleeding, symptomatic relief, uterine volume (mL), endometrial thickness (mm) and/or hemoglobin level. RESULTS: Ten prospective studies (patients n = 551) were included. The overall effect estimates showed that the LNG-IUS led to significant reductions in pain score after 12 months (standardized mean difference [SMD[ -3.87, 95% confidence interval [CI] -5.51 to -2.23, P < .001), 24 months (SMD -5.56, 95% CI -9.80 to -1.32, P = .01) and 36 months of insertion (SMD -3.81, 95% CI -4.27 to -3.36, P < .001). Similarly, the Pictorial Blood Assessment Chart (PBAC) showed significant reduction up to 36 months after LNG-IUS insertion (SMD -2.32, 95% CI -2.91 to -1.73, P < .001). The LNG-IUS led to significant reductions in the uterine volume 12 months (SMD -.60, 95% CI -0.88 to -.31, P < .001) and 36 months after insertion (SMD -0.42, 95% CI -0.69 to -0.14, P = .003). CONCLUSIONS: LNG-IUS is a promising and effective option for the management of adenomyosis. Its use effectively reduced the severity of symptoms, uterine volume and endometrial thickness, and improved laboratory outcomes.

Prediction of Neoplastic Transformation of Hydatidiform Mole: Current Evidence.

Gestational trophoblastic disease is not an uncommonly encountered pathology in clinical practice. The rate of post-molar neoplastic transformation is around 5-20% with higher rates after complete versus partial molar pregnancies. Recently, a role for molecular and genetic markers in the prediction of neoplastic transformation has emerged. We read with interest the article by St. Laurent et al. published in this issue of Reproductive Sciences. The authors compared miRNA profiles between complete hydatidiform moles (CHMs) and pre-gestational trophoblastic neoplasia CHM samples at three distinct tropho-miRNA clusters, 14q32, C19MC, and miR-371-3, as well as the expression of the contiguous DLK1, DIO3, and RTL1 genes. They found significant differences in expression of the 14q32 miRNA cluster and a fivefold decrease in protein expression of DIO3 but no difference in DIO3 mRNA expression. We reviewed the literature for similar studies looking at predictive tools for neoplastic transformation. We encourage future randomized controlled trials using these 2 novel risk predictors postulated by St. Laurent et al. to validate and guide future prophylactic chemotherapy for prevention of post-molar GTN.

Early Diagnosis of Classic Homocystinuria in Kuwait through Newborn Screening: A 6-Year Experience.

Kuwait is a small Arabian Gulf country with a high rate of consanguinity and where a national newborn screening program was expanded in October 2014 to include a wide range of endocrine and metabolic disorders. A retrospective study conducted between January 2015 and December 2020 revealed a total of 304,086 newborns have been screened in Kuwait. Six newborns were diagnosed with classic homocystinuria with an incidence of 1:50,000, which is not as high as in Qatar but higher than the global incidence. Molecular testing for five of them has revealed three previously reported pathogenic variants in the CBS gene, c.969G>A, p.(Trp323Ter); c.982G>A, p.(Asp328Asn); and the Qatari founder variant c.1006C>T, p.(Arg336Cys). This is the first study to review the screening of newborns in Kuwait for classic homocystinuria, starting with the detection of elevated blood methionine and providing a follow-up strategy for positive results, including plasma total homocysteine and amino acid analyses. Further, we have demonstrated an increase in the specificity of the current newborn screening test for classic homocystinuria by including the methionine to phenylalanine ratio along with the elevated methionine blood levels in first-tier testing. Here, we provide evidence that the newborn screening in Kuwait has led to the early detection of classic homocystinuria cases and enabled the affected individuals to lead active and productive lives.

The association between pentraxin 3 in maternal circulation and pathological intrauterine fetal growth restriction.

OBJECTIVE: To assess the diagnostic accuracy of maternal serum pentraxin 3 (PTX3) in identifying pathological intrauterine fetal growth restriction (IUFGR) among women presented in the third trimester of pregnancy with a small for gestational age (SGA) fetus. STUDY DESIGN: This case control study was conducted in Ain-Shams University Maternity Hospital, Abbasiya Square, Cairo, Egypt and included women diagnosed at the third trimester of pregnancy as having a SGA fetus. Cases included pregnant women with pathological IUFGR, while women with physiologically SGA fetus were included in the control group. Diagnosis of antenatal SGA fetus was based on the presence of abdominal circumference <10th percentile. Pathological IUFGR was provisionally diagnosed antenatally by the presence of falling percentiles on serial ultrasound scans and then the definitive diagnosis was established postnatally after comprehensive neonatal evaluation. Maternal venous blood samples were collected from the eligible participants, once at the time of enrollment, to assess serum PTX3 levels using enzyme-linked immunosorbent assay (ELISA). Both groups were then followed up till delivery to confirm the diagnosis. RESULTS: Among the 68 pregnant included in the study, PTX3 was found to be significantly elevated in women with SGA fetus due to pathological IUFGR (n=34) than those with physiologically SGA fetus (n=34) [6.5 ng/ml (2.5-11.0) versus 1.2 ng/ml (0.8-2.5) respectively], with a best cutoff value of ≥1.3 ng/ml [sensitivity of 85.3% (95% confidence interval (CI), 68.9-95.0) and a specificity of 73.5% (95% CI, 55.6-87.1)]. Using multivariable binary logistic regression model, amniotic fluid index (AFI) (P=0.010), estimated fetal weight (EFW) (P=0.016), PTX3 level (P=0.041), and umbilical artery pulsatility index (UA-PI) (P=0.027) were all found to be independent diagnostic markers for pathological IUFGR. CONCLUSION: PTX3 is a promising marker that deserves further evaluation as it may differentiate normal and abnormal fetal growth among women presenting at third trimester of pregnancy with a SGA fetus.