Supplementary Data from Pamiparib Monotherapy for Patients with Germline <i>BRCA1/2</i>-Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study
Supplementary Figure from Pamiparib Monotherapy for Patients with Germline <i>BRCA1/2</i>-Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study
Objective
To evaluate the dynamics of anti-Mullerian hormone (AMH) of serum and follicular fluid (FF) during controlled ovarian hyperstimulation (COH) and to analyze the relationship between AMH and outcomes of COH.
Methods
A total of 76 eligible IVF/ICSI-ET cycles owing to the tubal or male factors were studied, which were randomly grouped into GnRH-a long protocol and non pituitary down regulation protocol. Serum AMH levels were measured at day 2/3 of previous menstrual cycle (baseline), day 2/3 of menstrual during down regulation, the day of Gn starting, day 5 of Gn stimulation (Gn5), day of hCG administration (dhCG), the day before oocyte retrieval and 3 d after oocyte retrieval. FF was grouped into huge (≥18 mm), middle (14-17 mm) and small (<14 mm) depending on diameters.
Results
Serum AMH level was significantly higher on the day of Gn staring compared with baseline after the GnRH-a. AMH was gradually decreased with exogenous Gn administration during COH. AMH in FF was gradually decreased with follicles diameter increasing. There was the strongest correlation between AMH of Gn5 and number of retrieved oocytes, the number of MII and embryos conditions during COH. AMH in middle FF was significantly related with antral follicle count (AFC), Gn used dosage and number of available embryos.
Conclusions
AMH level is significantly elevated after pituitary down regulation, and this augments the number of recruited follicles and improves follicle synchronization. In addition, we can adjust Gn used dosage depending on AMH level of Gn starting. AMH is gradually decreased with exogenous Gn using. At Gn5 serum AMH level may be a better predictive marker of the outcomes of IVF.
Key words:
Anti-Mulleran hormone (AMH); Non pituitary down regulation; Follicular fluid (FF); Controlled ovarian hyperstimulation (COH)
To report the obstetric outcomes of young patients undergoing abdominal radical trachelectomy (ART) for the treatment of early-stage cervical cancers in China.
Methodology
We retrospectively reviewed 341 patients with stage IA-IB1 cervical cancer who underwent ART between April 2004 and September 2017 in China.
Results
Of the 341 patients underwent ART, 325 had their fertilities preserved. 200 women (61.5%) did not plan to get pregnant after ART, and 85.0% of them were due to childbearing before surgery (55.0%) or unmarried (30.0%). Among 125 women attempted to conceive, 23 women achieved a total of 26 pregnancies. Seventy-four patients had infertility problems, 35 conceived with assisted reproductive technologies, and 13 of them succeeded. Cervical stenosis (22, 25.9%) and fallopian tube obstruction (18, 21.2%) were the most frequently cause of fertility treatment after surgery. Among patients who conceived, 3 patients had first trimester miscarriage and 5 patient had second trimester miscarriage. Two woman elected to have pregnancy termination and 1 were currently pregnant. A total of 15 pregnancies reached the third trimester, and 80% of them ended more than 36 weeks of gestation. Among 13 cases of miscarriages and preterm birth, 7 occurred in patients without cerclage placed. In 10 cases of full-time birth, 8 patients had cerclage placed.
Conclusion
The majority of patients did not attempt to conceive or experienced infertility after ART in China. Assisted reproductive technology should be encouraged to improve the fertility rate. Cerclage is effective in the prevention of miscarriage and pre-term labor.
Abstract Background Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m 5 C) in cervical cancer radiosensitivity. Methods The abundance of RNA modification in radiotherapy-resistant and sensitive CC specimens was quantified by liquid chromatography-tandem mass spectrometry. The essential RNA modification-related genes involved in CC radiosensitivity were screened via RNA sequencing. The effect of NSUN6 on radiosensitivity was verified in CC cell lines, cell-derived xenograft (CDX), and 3D bioprinted patient-derived organoid (PDO). The mechanisms of NSUN6 in regulating CC radiosensitivity were investigated by integrative m 5 C sequencing, mRNA sequencing, and RNA immunoprecipitation. Results We found a higher abundance of m 5 C modification in resistant CC samples, and NSUN6 was the essential m 5 C-regulating gene concerning radiosensitivity. NSUN6 overexpression was clinically correlated with radioresistance and poor prognosis in cervical cancer. Functionally, higher NSUN6 expression was associated with radioresistance in the 3D PDO model of cervical cancer. Moreover, silencing NSUN6 increased CC radiosensitivity in vivo and in vitro. Mechanistically, NDRG1 was one of the downstream target genes of NSUN6 identified by integrated m 5 C-seq, mRNA-seq, and functional validation. NSUN6 promoted the m 5 C modification of NDRG1 mRNA, and the m 5 C reader ALYREF bound explicitly to the m 5 C-labeled NDRG1 mRNA and enhanced NDRG1 mRNA stability. NDRG1 overexpression promoted homologous recombination-mediated DNA repair, which in turn led to radioresistance in cervical cancer. Conclusions Aberrant m 5 C hypermethylation and NSUN6 overexpression drive resistance to radiotherapy in cervical cancer. Elevated NSUN6 expression promotes radioresistance in cervical cancer by activating the NSUN6/ALYREF-m 5 C-NDRG1 pathway. The low expression of NSUN6 in cervical cancer indicates sensitivity to radiotherapy and a better prognosis.