Evaluation of the Therapeutic Effect of Quadrivalent Human Papillomavirus (HPV) Vaccination on Cervical Intraepithelial Neoplasia Lesions.

Cervical cancer is the most common health problem among global young women. Cervical intraepithelial neoplasia (CIN) is a pre-invasive stage of cervical cancer, the major cause of which is human papillomavirus (HPV), and vaccination has a promising effect on reducing the progression of CIN lesions. The current study was a retrospective case control investigation in two centers, Shiraz and Sari Universities of Medical Sciences from 2018 to 2020 to evaluate the effect of quadrivalent HPV vaccination on CIN lesions (I, II, and III). Eligible patients diagnosed with CIN were selected and divided into two groups: one group received HPV vaccine and the control group did not. The patients were followed up after 12 and 24 months. The information about tests (e.g., Pap smear, colposcopy, and pathology biopsy) and history of vaccination was recorded and statistically analyzed. 150 patients were classified into the control group (without HPV vaccination) and the other 150 patients were in the Gardasil group (with HPV vaccination). The patients' mean age was 32 years old. Two groups were not significantly different according to age and CIN grades. Between two groups in 1 and 2 years' follow-up examinations, the high-grade lesions in both Pap smear and pathology were significantly diminished in patients in the HPV vaccinated group in comparison with the control group with p-values 0.001 and 0.004 in 1 year follow-up respectively and 0.00 after 2 years follow-up. HPV vaccination can prevent the progression of CIN lesions in 2-year follow-up examination.

A 5-year experience on perinatal outcome of placenta accreta spectrum disorder managed by cesarean hysterectomy in southern Iranian women.

BACKGROUND: We aimed to investigate the risk factors of placenta accreta spectrum (PAS) disorder, management options and maternal and neonatal outcomes of these pregnancies in a resource-limited clinical setting. METHODS: All women diagnosed with placenta accreta, increta, and percreta who underwent peripartum hysterectomy using a multidisciplinary approach in a tertiary center in Shiraz, southern Iran between January 2015 until October 2019 were included in this retrospective cohort study. Maternal variables, such as estimated blood loss, transfusion requirements and ICU admission, as well as neonatal variables such as, Apgar score, NICU admission and birthweight, were among the primary outcomes of this study. RESULTS: A total number of 198 pregnancies underwent peripartum hysterectomy due to PAS during the study period, of whom163 pregnancies had antenatal diagnosis of PAS. The mean gestational age at the time of diagnosis was 26 weeks, the mean intra-operative blood loss was 2446 ml, and an average of 2 packs of red blood cells were transfused intra-operatively. Fifteen percent of women had surgical complications with bladder injuries being the most common complication. Furthermore, 113 neonates of PAS group were admitted to NICU due to prematurity of which 15 (7.6%) died in neonatal period. CONCLUSION: Our findings showed that PAS pregnancies managed in a resource-limited setting in Southern Iran have both maternal and neonatal outcomes comparable to those in developed countries, which is hypothesized to be due to high rate of antenatal diagnosis (86.3%) and multidisciplinary approach used for the management of pregnancies with PAS.

TGF-ß1 role in uterine leiomyoma and endometrial polyp: an insight to drug-based treatment instead of surgical techniques.

OBJECTIVE: Considering the high prevalence of leiomyoma and endometrial polyps, investigating the contributing factors and determining the pathophysiology of these lesions are essential. Target therapy is now an acceptable method for the treatment of some diseases. We aimed to determine the expression of transforming growth factor (TGF)-ß1 in endometrial polyps and leiomyomas to discover a drug-based method to overcome surgical treatments. METHODS: In this cross-sectional study, 55 patients with leiomyoma and 55 patients with polyps were included. Prepared slides from leiomyoma and adjacent myometrium or polyp lesions and adjacent endometrium were obtained and investigated for TGF-ß1. Then, data were collected and analyzed using SPSS version 22. RESULTS: The mean age of participants was 40.6±5.8 years. Based on their reports, 88.2% (n=97) of patients in the study population had abnormal uterine bleeding with similar distributions among both groups. In contrast, 63.5% of the leiomyoma group did not express TGF-ß1. However, in normal myometrium, 23.6% had the highest degree of TGF-ß1 expression. Polyp tissue did not show staining for TGF-ß1 in any patients. Additionally, 89.1% of non-polypoid endometrium did not express TGF-ß1. Normal tissue had a significantly greater amount of TGF-ß1 compared to leiomyoma and endometrial polyps. CONCLUSION: TGF-ß1 is expressed more prominently in normal myometrium with mostly high-intensity features compared to leiomyoma. Additionally, polyps showed no staining for TGF-ß1, while normal endometrium showed a low-density staining pattern.

Glutathione-dependent enzymes in the follicular fluid of the first-retrieved oocyte and their impact on oocyte and embryos in polycystic ovary syndrome: A cross-sectional study.

BACKGROUND: Oxidative stress and GSH-dependent antioxidant system plays a key role in the pathogenesis of polycystic ovary syndrome (PCOS). OBJECTIVE: We compared glutathione peroxidase (GPx) and glutathione reductase activities and reduced glutathione (GSH) levels in serum and follicular fluid (FF) of the first-retrieved follicle and their impact on quality of oocyte and embryo in PCOS women undergoing IVF. MATERIALS AND METHODS: This cross sectional study was conducted on 80 pairs of blood samples and FF of the first-retrieved follicle from PCOS women, at the Infertility center of Ghadir Mother and Child Hospital. The mean activity of GPx and GR, also GSH levels in the serum and FF were compared to the quality of the first follicle and resultant embryo. RESULTS: Retrieved oocytes included 53 (66.25%) MII, 17 (21.25%) MI, and 10 (12.5%) germinal vesicles; after IVF 42 (52.50%) embryos with grade I and 11 (13.75%) with grade II were produced. The mean values for all three antioxidants were higher in the FF compared to serum (p < 0.001). Also all of the mean measured levels were significantly higher in the FF of the MII oocytes compared to that of oocytes with lower grades (p = 0.012, 0.006 and 0.012, respectively). The mean GPX activity and GSH levels were significantly higher in the serum (p = 0.016 and 0.012, respectively) and FF (p = 0.001 for both) of the high-quality grade I embryos. CONCLUSION: GSH-dependent antioxidant system functions more efficiently in the FF of oocytes and embryos with higher quality.

Introducing an efficient model for the prediction of placenta accreta spectrum using the MCP regression approach based on sonography indexes: how efficient is sonography in diagnosing accreta?

BACKGROUND: For the first time, we aimed to introduce a model for prediction of placenta accreta spectrum (PAS), using existing sonography indices. METHODS: Women with a history of Cesarean sections were included. Participants were categorized "high risk" for PAS if the placenta was previa or low-lying. Sonography indices including abnormal placental lacuna, loss of clear zone, bladder wall interruption, myometrial thinning, placental bulging, exophytic mass, utero-vesical hypervascularity, subplacental hypervascularity, existence of bridging vessels, and lacunar flow, were registered. To investigate simultaneous effects of 15 variables on PAS, Minimax Concave Penalty (MCP) was used. RESULTS: Among 259 participants, 74 (28.5%) were high risk and 43 individuals had PASs. All sonography indices were higher among patient with PAS (p < 0.001) in the high risk group. Our model showed that utero-vesical hypervascularity, bladder interruption and new lacunae have significant contribution in PAS. Optimal cut off point was p = 0.51 in ROC analysis. Probability of PAS for women with lacunae was between 96 and 100% and probability of PAS for women without lacunae was between 0 to 7%, therefore accuracy of the proposed model was equal to 100%. CONCLUSIONS: Using the introduced model based on three factors of abnormal lacuna structures (grades 2 and 3), bladder wall interruption and utero-vesical vascularity, 100% of all cases of PASs are diagnosable. If supported by future studies our model eliminates the need for other imaging assessments for diagnosis of invasive placentation among high risk women with previous history of Cesarean sections.

A KHDC3L mutation resulting in recurrent hydatidiform mole causes genome-wide DNA methylation loss in oocytes and persistent imprinting defects post-fertilisation.

BACKGROUND: Maternal effect mutations in the components of the subcortical maternal complex (SCMC) of the human oocyte can cause early embryonic failure, gestational abnormalities and recurrent pregnancy loss. Enigmatically, they are also associated with DNA methylation abnormalities at imprinted genes in conceptuses: in the devastating gestational abnormality biparental complete hydatidiform mole (BiCHM) or in multi-locus imprinting disease (MLID). However, the developmental timing, genomic extent and mechanistic basis of these imprinting defects are unknown. The rarity of these disorders and the possibility that methylation defects originate in oocytes have made these questions very challenging to address. METHODS: Single-cell bisulphite sequencing (scBS-seq) was used to assess methylation in oocytes from a patient with BiCHM identified to be homozygous for an inactivating mutation in the human SCMC component KHDC3L. Genome-wide methylation analysis of a preimplantation embryo and molar tissue from the same patient was also performed. RESULTS: High-coverage scBS-seq libraries were obtained from five KHDC3Lc.1A>G oocytes, which revealed a genome-wide deficit of DNA methylation compared with normal human oocytes. Importantly, germline differentially methylated regions (gDMRs) of imprinted genes were affected similarly to other sequence features that normally become methylated in oocytes, indicating no selectivity towards imprinted genes. A range of methylation losses was observed across genomic features, including gDMRs, indicating variable sensitivity to defects in the SCMC. Genome-wide analysis of a pre-implantation embryo and molar tissue from the same patient showed that following fertilisation methylation defects at imprinted genes persist, while most non-imprinted regions of the genome recover near-normal methylation post-implantation. CONCLUSIONS: We show for the first time that the integrity of the SCMC is essential for de novo methylation in the female germline. These findings have important implications for understanding the role of the SCMC in DNA methylation and for the origin of imprinting defects, for counselling affected families, and will help inform future therapeutic approaches.