Efficacy and Safety of 5-Aminolevulinic Acid Photodynamic Therapy for Treating Cervical and Vaginal Intraepithelial Neoplasia.

Persistent HPV infections may cause cervical and vaginal intraepithelial neoplasia (CIN and VaIN). Traditional methods might destroy the structure and function of the cervix. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive targeted therapy. This study aims to evaluate the efficacy and safety of ALA-PDT for CIN and VaIN and the clearance of HPV. A retrospective study of 303 patients who confirmed CIN or VaIN and received ALA-PDT was conducted. All the patients were followed up at six and twelve months after treatment and then annually thereafter. The effect was evaluated through HPV genotyping, a cytology test, and colposcopy-directed biopsy if necessary. After ALA-PDT, the remission rates for CIN 2, CIN 3, VaIN 2, and VaIN 3 were 90.6%, 88.5%, 87.3%, and 77.8%. For CIN 1, the remission rate at the six-month follow-up was 93.1%. The total HPV clearance rates were 72.5% at the six-month follow-up and 85.7% at the 12-month follow-up. The most common adverse event was vaginal discharge. No severe adverse effect was observed. ALA-PDT is an effective and safe treatment for all grades of CIN and VaIN and is helpful in clearing HPV with minimal side effects. This treatment may not influence fertility and delivery.

Efficacy and safety of photodynamic therapy mediatied by 5-aminolevulinic acid for the treatment of vaginal high-grade intraepithelial lesions.

BACKGROUND: Vaginal high-grade squamous intraepithelial lesion (HSIL) (vaginal intraepithelial neoplasia [VAIN] grade 2-3) is clinically, a precancerous lesion condition with an estimated progression rate of 10%-20%. Therefore, treatment is recommended. Because traditional treatments have limited effects, high expense and complications, here we evaluated the efficacy and safety of topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT). METHODS: This study consisted of 56 female patients diagnosed with vaginal HSIL. A 20% 5-ALA jelly formation was topically applied to the vaginal wall, followed by 635 nm PDT at 7-14 days intervals. Cytology, human papillomavirus (HPV) genotyping, colposcopy, and pathology were assessed after treatment. RESULTS: Among the 56 patients in our study, 47 (83.9%) had VAIN 2 and 9 (16.1%) had VAIN 3. 35 patients underwent three courses of PDT treatment, 19 experienced six courses, and two experienced nine courses. The total pathological regression rate was 87.5%, and the HPV clearance rate during the 6-month follow-up was 41.9%. Lesions located in the vaginal stump after hysterectomy seem to be difficult to treat. 9%(4/44) and 23%(7/30) patients had recurrent disease during the 6-month and 1-year follow-up time point. The most common adverse event was increased vaginal discharge, other side effects include abdominal pain, vulvar pruritus, and vaginal bleeding. No severe adverse effect was observed during the treatment. CONCLUSION: Photodynamic therapy mediatied by 5-aminolevulinic acid is an effective and safe treatment for vaginal HSIL with minimal side effects.

Efficacy and safety of photodynamic therapy mediated by 5-aminolevulinic acid for the treatment of cervical intraepithelial neoplasia 2: A single-center, prospective, cohort study.

BACKGROUND: Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (5-ALA) is a minimally-invasive treatment for cervical intraepithelial neoplasia (CIN). The present study was carried out to investigate the effect of 5-ALA-PDT on CIN2 and the factors influencing outcome of 5-ALA-PDT. METHODS: Patients diagnosed as CIN2 who met the inclusion criteria were enrolled in this study sequentially from January 2019 to April 2020. Patients were treated by PDT or cryotherapy according to their intentions. The primary endpoint was pathological regression. The secondary endpoint was HPV clearance. Affecting factors of the efficacy of PDT and adverse events were also assessed during treatment. RESULTS: A total of 210 patients were enrolled, including 97 patients in PDT group and 101 patients in cryotherapy group, with 12 patients excluded. There was no statistical difference in population characteristics. The pathological regression rate in PDT group was 92.0% (80/87), compared with 81.4% (79/97) in cryotherapy group (P < 0.05). The HPV clearance rate was 64.4% (56/87) in PDT group and 57.8% (56/97) in cryotherapy group (P = 0.36). The main side effects of PDT were abdominal pain (24.1%, 21/87) and increased vaginal secretions (23.0%, 20/87). On univariate analysis, the risk for lesions persisting at 6 months after PDT was increased by recurrent genital tract inflammation (P = 0.004), smoking or passive smoking (P = 0.020), and multicentric lesions (P = 0.020). CONCLUSION: PDT can be a safe and efficient treatment for CIN2. Risk factors for persisting HSIL after PDT include recurrent genital tract inflammation, smoking or passive smoking, and multicentric lesions.

The Prognostic Value of DNA Methylation, Post-Translational Modifications and Correlated with Immune Infiltrates in Gynecologic Cancers.

BACKGROUND: To depict the prognostic landscape of gynecological cancers from the perspective of DNA methylation, alternative splicing (AS) and polyadenylation (APA) events and investigate their correlation with immune infiltrates. METHODS: Methylation and RNA-seq data and corresponding clinical information regarding gynecologic cancers were used to explore the relationships between changes in DNA methylation, AS and APA events and gynecologic cancer prognosis. QRT-PCR and multiple bioinformatics tools were employed to construct a gene interaction network and explore immune infiltrates. RESULTS: Only the mRNA levels of CIRBP and INPP5K were simultaneously significantly decreased in gynecologic cancers and negatively associated with overall survival, which verified by qrt-PCR. We also identified that CIRBP or INPP5K DNA methylation, AS and APA events are prognostic indicators of gynecologic cancers. The activation of T cells might be the main signaling pathway by which these genes modulate cancer progression. CIRBP/INPP5K expression is positively associated with immune infiltration and is a major risk factor of survival, especially among uterine corpus endometrial carcinoma (UCEC) patients. CONCLUSION: According to these findings, the DNA methylation, AS and APA events of CIRBP and INPP5K may serve as important prognostic biomarkers and targets in gynecological cancers by modulating T cell infiltration.

Risk of preterm delivery in singletons conceived by in vitro fertilization.

To evaluate the preterm delivery and other obstetrics complications similar in singleton pregnancies achieved through IVF compared to spontaneous pregnancies. Retrospective case-control study included 1663 women with singleton pregnancies following IVF-ICSI (study group) and 3326 women with singleton spontaneous pregnancies (control group) who delivered between January 2015 and January 2018 at the Peking University Third Hospital. The control group matched 1:2 by age, BMI, parity, and gravidity. Maternal outcomes included preterm delivery and complications. There was significantly higher incidence of gestational diabetes, hypertensive disorders, and placenta previa in IVF-ICSI pregnancies versus controls (p < .05). IVF-ICSI resulted in significantly higher rate of preterm birth than in spontaneous pregnancies (p < .05) and the difference remained significant for deliveries that occurred before 28, 32, and 34 weeks gestation (p < .05). Multivariate logistic regression analysis revealed that female-factor infertility, hypertensive disorder, placenta previa, and PROM were significant prognostic factors associated with increased risk of prematurity. IVF-ICSI is associated with increased risk of obstetric complications including preterm delivery in singleton pregnancies. Female-factor infertility is an independent prognostic factor for preterm birth. This information is important for patient counseling and helps to refine the recommendation to optimize maternal health before embarking on fertility treatments.

Risk of miscarriage in women with endometriosis undergoing IVF fresh cycles: a retrospective cohort study.

BACKGROUND: Endometriosis is thought to affect the effectiveness of ART by an increased risk of miscarriage. We aimed to investigate the impact of endometriosis in women achieving singleton pregnancies through IVF fresh cycles and risk of miscarriage. METHODS: This retrospective cohort study included all women undergoing a first IVF cycle and achieving singleton pregnancies after fresh embryo transfer in a tertiary university hospital reproductive medical center between January 2008 and June 2016. Women with endometriosis were compared with women with no endometriosis. Women in the endometriosis group were all with a history of laparoscopy or laparotomy for endometriosis and/or with ovarian endometrioma. The control group was matched 1:2 according to age and study period. RESULTS: Among the cohort, we identified 1006 women with endometriosis as study group and 2012 unaffected women matched in a 1:2 ratios as control group. The miscarriage rate between women with and without endometriosis was similar (22.4 and 20.1%, P = 0.085). The odds ratio after adjusting for the risk factors for miscarriage was 1.14 (95% confidence interval 0.95-1.37). In the study group, the women with and without endometrioma did not show a significant risk of miscarriage, (19.8 and 23.8%, P = 0.152, OR 0.79, 95% CI 0.58-1.09). The miscarriage rate in women with endometrioma ≥30 mm (37.3 ± 7.1 mm) and < 30 mm (19.3 ± 5.5 mm) was not significantly different, (24.7 and 18.5%, P = 0.229, OR 1.44, 95% CI 0.79-2.63). After adjustment for risk factors for miscarriage, the presence of endometrioma and the size of endometrioma, regression model confirmed no significant increase for the risk of miscarriage in the subgroup analyses. CONCLUSIONS: The risk of miscarriage did not statistically increase in women with endometriosis who achieved pregnancy through IVF fresh cycles.

Endometrial miR-543 Is Downregulated During the Implantation Window in Women With Endometriosis-Related Infertility.

BACKGROUND: Differentially expressed microRNAs (miRNAs) and their target mRNAs may lead to alterations in normal physiological status of the tissues and initiate pathological processes. The aim of this study was to investigate the expression of the most relevant miRNAs in the eutopic endometrial tissue during the window of implantation in women with endometriosis-related infertility. METHODS: In the study, 76 infertile women with a regular menstrual cycle were recruited from the Center for Reproductive Medicine, Peking University Third Hospital between January 2014 and June 2016. We performed a combined messenger RNA and miRNA microarray and bioinformatics analysis of eutopic endometrium in 6 women with and without endometriosis-related infertility at the time of implantation window. Quantitative real-time polymerase chain reaction arrays were utilized to examine the expression levels of selected miRNAs (from 35 patients with endometriosis and 35 disease-free individuals at different menstrual stages). RESULTS: Five differentially expressed miRNAs (miR-142-5p, miR-146a-5p, miR-1281, miR-940, and miR-4634) were significantly upregulated, whereas miR-543 was significantly downregulated in the eutopic endometrium during the window of implantation in patients with endometriosis. Further analysis showed that miR-543 was significantly upregulated at the peri-implantation phase compared with that at proliferative phase in the endometrium of disease-free patients (P < .05). However, the expression level of miR-543 was significantly decreased in patients with endometriosis (P < .05), especially downregulated at the window of implantation phase (P < .05). CONCLUSIONS: miR-543 plays an important role during embryo implantation process and is associated with endometrial receptivity. Downregulation of miR-543 may affect embryo implantation, resulting in the pathogenesis of endometriosis-related infertility.

Frozen-Thawed Embryo Transfer Cycles Have a Lower Incidence of Ectopic Pregnancy Compared With Fresh Embryo Transfer Cycles.

OBJECTIVE: To evaluate the risk of ectopic pregnancy of embryo transfer. DESIGN: A retrospective cohort study on the incidence of ectopic pregnancy in fresh and frozen-thawed embryo transfer cycles from January 1st, 2010, to January 1st, 2015. PATIENTS: Infertile women undergoing frozen-thawed transfer cycles or fresh transfer cycles. INTERVENTION: In-vitro fertilization, fresh embryo transfer, frozen-thawed embryo transfer, ectopic pregnancy. MAIN OUTCOME MEASURES: Ectopic pregnancy rate and clinical pregnancy rate. RESULT: A total of 69 756 in vitro fertilization-embryo transfer cycles from 2010 to 2015 were analyzed, including 45 960 (65.9%) fresh and 23 796 (34.1%) frozen-thawed embryo transfer cycles. The clinical pregnancy rate per embryo transfer was slightly lower in fresh embryo transfer cycles compared with frozen-thawed embryo transfer cycles (40.8% vs 43.1%, P < .001). Frozen-thawed embryo transfer is associated with a lower incidence of ectopic pregnancy per clinical pregnancy, compared with fresh embryo transfers (odds ratio = 0.31; 95% confidence interval = 0.24-0.39). Female age and body mass index have no influence on ectopic pregnancy. In the frozen-thawed embryo transfer cycles, blastocyst transfer shows a significantly lower incidence of ectopic pregnancy (0.8% vs 1.8%, P = .002) in comparison with day 3 cleavage embryo transfer. CONCLUSION: The risk of ectopic pregnancy is lower in frozen-thawed embryo transfer cycles than fresh embryo transfer cycles, and blastocyst transfer could further decrease the ectopic pregnancy rate in frozen-thawed embryo transfer cycles.