Threshold Effect Analysis of Influence of Age on Live Birth Rate in Poor Ovarian Response Patients Treated by Assisted Reproductive Technology
Pregnancy outcome in patients with poor ovarian response (POR) has always been one of the difficult problems in reproductive medicine, but there is few threshold effect analysis of influence of age on live birth rate in POR patients treated by assisted reproductive technology (ART) .
To analyze the threshold effect of influence of age on live birth rate in POR patients treated by ART.
Among 19 185 women who received routine in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and embryo transplantation in Department of Gynaecology and Obstetrics, the First People's Hospital of Shangqiu and Fertility Support Center, the First Affiliated Hospital of Xinjiang Medical University from August 2014 to December 2018, 3 337 patients with POR were selected, and received controlled ovarian stimulation, embryo transplantation by IVF/ICSI and luteal support therapy. The incidence of live birth was analyzed. Univariate and multivariate Logistic analyses were used to analyze the influence of age on live birth in POR patients treated by ART. Moreover, smooth curve fitting and threshold effect analysis were conducted.
Of the 3 337 cases, 1 134 obtained a live birth, the other 2 203 did not, achieving a rate of live birth of 33.98% (1 134/3 337) . Multivariate Logistic analysis result showed that, age was independently associated with live birth in POR patients treated by ART〔OR=0.920, 95%CI (0.902, 0.939) , P<0.01〕. Smooth curve fitting showed that, age was negatively correlated with live birth rate in POR patients treated by ART, but the correlation was not simple linear. Threshold effect analysis results showed that, 32 years old was the threshold for decrease of live birth rate in POR patients treated by ART, namely age did not affect the live birth rate in those ≤32 years old〔OR=1.000, 95%CI (0.998, 1.012) , P=0.38〕, but the live birth rate decreased as age grew in those over 32 years old〔OR=0.800, 95%CI (0.799, 0.823) , P<0.01〕.
Age was an independent influencing factor of live birth in POR patients treated by ART. The live birth rate may decrease as age grows in these patients over 32 years old.
Influence of Two Endometrial Preparation Programs Independent of Endogenous Ovarian Cycle on the Pregnancy Outcome of Thin Endometrial Patients with Freeze-thaw Embryo Transfer
Thin endometrium is one of the crucial reasons leading to the reduction of pregnancy rate in patients. The whole embryo freezing is an important strategy in the process of assisting pregnancy in patients with thin endometrium. However, there are still controversies regarding the choice of subsequent freeze-thaw embryo transfer.
To explore the difference between two endometrial preparation programs〔artificial cycle and gonadotropin releasing hormone agonist (GnRH-a) down regulating artificial cycle〕 independent of endogenous ovarian cycle in patients with thin endometrial.
A retrospective analysis of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) assisted pregnancy treatment was performed in the Reproductive Center of Henan Provincial People's Hospital from December 2016 to July 2019. The whole embryo was frozen due to endometrial thickness less than 7 mm in the month of egg collection, then the clinical data of the freezing-thawing embryo transfer patients were collected by artificial cycle (artificial cycle group, n=409) and GnRH-a down-regulated artificial cycle (GnRH-a down-regulated artificial cycle group, n=103) . Pregnancy results were compared between the two groups of patients.
The average number of transplanted embryos in the artificial cycle group was (1.60±0.49) , while that in the GnRH-a daon-regulated artificial cycle group was (1.66±0.52) , and there was no statistically significant difference between the two groups (P>0.05) . In the artificial cycle group, there were no significant differences in clinical pregnancy rate, implantation rate, abortion rate, ectopic pregnancy rate and multiple pregnancy rate among those with 1, 2 and 3 embryos transferred, respectively (P>0.05) . In the GnRH-a down-regulated artificial cycle group, there were also no significant differences in clinical pregnancy rate, implantation rate, abortion rate, ectopic pregnancy rate and multiple fetus rate among those with 1, 2 and 3 embryos transferred, respectively (P>0.05) .
In patients with thin endometrium thickness (≤7 mm) , two endometrial preparation programs (artificial cycle and GnRH-a) independent of endogenous ovarian cycle had similar results in regulating artificial cycle pregnancy. It is not recommended to use GnRH-a combined with hormone replacement in the endometrial preparation program of conventional thin endometrial patients without special medical history such as endometriosis and repeated implant failure.
Microsatellite Instability and Its Clinical Significance in Endometrial Carcinoma
The role of microsatellite instability in the progression of endometrial cancer, a common cancer in women, has obtained increasing attentions in recent years. However, there are few studies regarding the association of microsatellite instability with clinicopathologic features and prognosis in patients with endometrial cancer.
To investigate the microsatellite instability and its clinical significance in patients with endometrial carcinoma.
A total of 248 endometrial cancer patients who underwent surgery in Shiyan People's Hospital Affiliated to Hubei University of Medicine from January 2015 to December 2020 were selected. Their cancer tissue specimens were collected to detect the expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. Relations of microsatellite instability with clinicopathologic features and prognosis were analyzed.
The rates of lost expression of MLH1, MSH2, MSH6 and PMS2 were 32.6% (78/239) , 22.2% (53/239) , 2.9% (7/239) and 65.7% (157/239) , respectively, in patients with endometrioid adenocarcinoma. For those with endometrial squamous cell carcinoma, the rates of lost expression of MLH1, MSH2, MSH6 and PMS2 were 5/5, 3/5, 5/5 and 4/5, respectively. And rates of lost expression of MLH1, MSH2, MSH6 and PMS2 were 4/4, 2/4, 3/4, and 2/4, respectively, in those with endometrial clear cell carcinoma. The rates of lost expression of MLH1, MSH2, MSH6 and PMS2 varied significantly by the pathological pattern of endometrial carcinoma (P<0.05) . The prevalence of high-level microsatellite instability (MSI-H) , low-level microsatellite instability (MSI-L) and microsatellite stability (MSS) was 19.7% (47/239) , 34.7% (83/239) and 45.6% (109/239) , respectively, in patients with endometrioid adenocarcinoma. The prevalence of MSI-H, MSI-L and MSS was 4/5, 1/5 and 0, respectively, in patients with endometrial squamous cell carcinoma. And that of MSI-H, MSI-L and MSS was 3/4, 1/4 and 0, respectively, in patients with endometrial clear cell carcinoma. The prevalence of MSI-H, MSI-L and MSS differed significantly by the pathological pattern of endometrial carcinoma (P<0.05) . The prevalence of MSI-H, MSI-L and MSS was associated with the depth of myometrial invasion (P<0.05) , but was not associated with age and degree of histologic differentiation of endometrial cancer (P>0.05) . There were no significant differences of Kaplan-Meier curves for overall survival and disease-free survival in endometrial cancer patients with MSI-H, MSI-L and MSS (P>0.05) . Cox proportional hazards regression analysis results showed that the expression of mismatch repair protein was not the independent influencing factor for disease-free survival (P>0.05) , but for overall survival (P<0.05) in patients with endometrial cancer.
Microsatellite instability is correlated with the progression and prognosis of endometrial cancer, so detecting it may have some referential value for clinical prevention and treatment of endometrial cancer.
Clinical Evaluation of High-risk HR-HPV E6/E7 mRNA Detection during Pregnancy
It is necessary to differentiate high-risk human papillomavirus (HR-HPV) infection and cervical lesions during pregnancy using an effective measure, so as to guide personalized diagnosis and treatment and to reduce unnecessary invasive examinations during pregnancy.
To assess the value of HR-HPV E6/E7 mRNA detection in differentiating HR-HPV infection and cervical lesions during pregnancy by comparing efficacy between it and HR-HPV DNA testing.
Participants were healthy women with singleton pregnancy (20-45-years old) selected from Department of Obstetrics and Gynecology of Capital Medical University Xuanwu Hospital during January 2016 to January 2019. All had file creation and underwent regular prenatal examination, and those with abnormal liquid-based cytology and HR-HPV DNA testing results further underwent colposcopy with biopsy taken for pathological examination (serving as a gold standard) , and performed HR-HPV E6/E7 mRNA detection in cervical exfoliated cells collected as samples. Pathologically detected CIN Ⅱand Ⅲ were defined as high-grade cervical lesions.
Of the 1 058 participants, 118 had cytological abnormalities and/or HPV 16 and 18 infections, and 84 of them consented to perform colposcopy with biopsy pathological results successfully obtained. The prevalence of HR-HPV E6/E7 mRNA positivity was lower than that of HR-HPV DNA positivity in women with CINⅠ, normal cervical epithelium or cervicitis detected by pathological examination (P<0.05) . In contrast, the prevalence of HR-HPV E6/E7 mRNA positivity was similar to that of HR-HPV DNA positivity in those with CINⅡ and Ⅲ detected by pathological examination without statistical difference (P>0.05) . In predicting CINⅡ and Ⅲ, the HR-HPV DNA testing had a sensitivity of 89.7% (26/29) , a specificity of 21.8% (12/55) , a positive predictive value of 37.1% (26/69) , and a negative predictive value of 75.0% (12/29) , and the HR-HPV E6/E7 mRNA detection had a sensitivity of 65.5% (19/29) , a specificity of 54.5% (25/55) , a positive predictive value of 43.0% (19/44) , and a negative predictive value 75.0% (25/40) . McNemar's test revealed that HR-HPV E6/E7 mRNA detection had a lower sensitivity but a higher specificity than HR-HPV DNA testing in diagnosing CINⅡ and Ⅲ (P<0.05) .
HR-HPV E6/E7 mRNA detection may have an increased specificity in diagnosing CINⅡandⅢ than HR-HPV DNA testing, so it may be used in HR-HPV positive cases for differentiating HR-HPV infections and cervical lesions to avoid unnecessary invasive examinations during pregnancy.
