Study question It has been established that radiotherapy can increase the risk of adverse pregnancy outcomes. However, there is currently no consensus on the effective sterilizing dose for adulthood uterine radiotherapy. Summary answer Uterine fertility preservation methods should be guided by the age of the patient receiving radiotherapy and the actual dose of radiation exposure to the uterus. What is known already Many experts have suggested that a high dose of radiation to the uterus is a reason to counsel patients against future pregnancy. There are major limitations to the current literature regarding off-target radiation damage to the uterus. One study reported a relative risk of 9.1 for stillbirth and neonatal death after 10 Gy doses. Study design, size, duration Case report and review of the literature before December 2020 Participants/materials, setting, methods A case report of a 36-year-old female with three cancers and received repeated high-dose radiotherapy of 66 Gy and 50 Gy to the pelvis. We used a dose-volume histogram, the most widely used tool to calculate the radiation distribution within a volume of interest of the patient during radiotherapy. We determined that her uterus may have received the highest uterine radiation dosage for full-term live birth in current literature. Main results and the role of chance Due to iatrogenic ovarian failure, she could only use donor eggs. After endometrium preparation for 18 days, the endometrium reached 8.7 mm with a triple-line appearance. We transferred two cleavage-staged embryos and one of them implanted successfully. The course of the pregnancy was uneventful. Finally, the patient gave birth to a healthy baby via Cesarean section at 38 5/7 weeks of gestation. Limitations, reasons for caution It should be noted that the success of our case may not apply to all patients with cancer after they have received RT. We should inform patients about the increased risk of preterm birth, low birth weight infants, uterine rupture, and neonatal death. Wider implications of the findings: The patient’s age and the dose of RT exposure to the uterus are important factors for the prognosis of a future pregnancy. More well-designed studies will be needed to allow future standard guidelines for uterine fertility preservation. Trial registration number TMU-JIRB N20204149
Study question Is cervical secretion gene methylation profile different between receptive and non-receptive endometrium and associated with implantation outcome in frozen-embryo transfer (FET) cycle? Summary answer The combination of candidate genes methylation profiles obtained from cervical secretion showed significant associations with pregnancy outcomes. What is known already Implantation failure remains a black box in reproductive medicine, and the exact mechanism of how endometrial receptivity is regulated is still unknown. Epigenetic modifications play a role in the gene expression pattern and may alter the endometrial receptivity in the human endometrium. Cervical secretion containing various implantation-related cytokines, and the gene methylation change can be used as a non-invasive molecular source that reflects the endometrium condition. Study design, size, duration In this retrospective case-control study, sixty-two women who entered the FET cycle (30 pregnant and 32 non-pregnant women) were enrolled. Participants/materials, setting, methods Cervical secretion was collected before embryo transfer from women enrolled in multicenter university-affiliated reproductive units. The DNA methylation status of six candidate genes was measured using quantitative methylation-specific PCR (qMSP). The correlation between methylation change and the pregnancy outcome was analyzed. Main results and the role of chance The candidate genes were selected from that associated with implantation with literature review and the original genome-wide DNA methylation data from NCBI GEO DataSets (GSE90060) which processed using bioinformatics analysis. Six candidate genes whose CpG-level methylation analysis with β-value statistically higher in receptive endometrium than in a pre-receptive endometrium were selected. All six candidate genes showed different degrees of correlation with the pregnancy outcomes. Among them, PRKAG2 methylation changes showed the highest correlation with the pregnancy outcome. A logistic regression model was used to evaluate the performance of a single gene or a combination of genes for implantation prediction. The results showed a statistically significant association between the methylation status of a combination of genes (PRKAG2, KRS1, HAND2) and the pregnancy outcome (p = 0.008), resulting in an optimal AUC of 0.7 (95% CI: 0.57 - 0.81) for implantation prediction. Limitations, reasons for caution The results obtained from a relatively small cohort size. A larger study and further comprehensive methylome investigations are warranted. Wider implications of the findings: This study is the first proof-of-concept study that cervical secretion methylation profile is associated with implantation outcome in a FET cycle, and showed potential as a non-invasive method for implantation prediction. Trial registration number non applicable
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