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Background: Infertility is one of the most important and underappreciated reproductive health problems in developing countries. Currently, in vitro fertilization and embryo transfer is the most effective treatment strategy for infertility. In a frozen-thawed cycle, single-blastocyst transfer can not only ensure relatively higher pregnancy and live birth rates but also effectively reduce the risk of maternal and neonatal complications. In frozen-thawed cycles, progesterone is initiated to promote the final phase of endometrial preparation prior to embryo transfer. However, the optimal duration of exposure to progesterone has remained inconclusive. Therefore, we designed a randomized controlled trial (RCT) to compare the effects of different prolonged progesterone transformation times (P+6 and P+7) on the pregnancy outcomes of D6 single blastocyst transfer in a frozen-thawed cycle. Methods: This is a single-center, prospective, randomized controlled clinical trial involving 900 patients with single blastocyst transfer in the frozen-thawed cycle, aged from 20 to 38 years, with less than three transfers, and with HRT-cycle single D6 blastocyst transfer in the current cycle. Participants will be randomly assigned (1:1) into two parallel groups: the transfer of day 6 blastocysts on the 7th day of progesterone supplementation and the transfer of day 6 blastocysts on the 6th day of progesterone supplementation. The primary outcome measure is the clinical pregnancy rate. Secondary outcome measures include the miscarriage rate and live birth rate. Discussion: This is the first randomized controlled trial to compare the transfer of day 6 blastocysts on the 6th and 7th day of progesterone supplementation. The results of this study will provide evidence for whether to prolong the duration of exposure to progesterone prior to embryo transfer. Trial registration: ClinicalTrials.gov, ID: NCT04938011. Registered on 19 June 2021. [ABSTRACT FROM AUTHOR]

Objective: To minimize twin birth rate by establishing an elective single cleavage embryo transfer strategy based on a twin live birth prediction model from fresh double cleavage embryos transfer (cleavage DET) patients.Methods: A total of 2478 patients underwent fresh cleavage DET in Nanjing Tower Hospital were enrolled to establish the twin live birth prediction model by logistic regression analysis and the cutoff value was calculated by ROC curve. Another 300 fresh cleavage DET patients and 550 cleavage single-embryo transfer (SET) patients were selected to testify the sensitivity, specificity and usefulness of this model.Results: The twin live birth probability (TLBP) = eX/(eX + 1), e is a natural logarithm, X = -1.763 - (0.319 × female age) + (0.329 × endometrial thickness) + (0.282 × the number of transferred top embryos) - (0.314 × previous transfer times), and the cutoff value of TLBP was 24.2%. The sensitivity of this model for predicting twin live birth was 75.6%, while the specificity was 52.5% in the external validation of 300 DET patients. Furthermore, the validation of 550 SET patients showed that the live birth rate of TLBP value positive patients was significantly higher than that in negative patients (54.3% vs. 35.5%, p < .001). When adopted an elective single cleavage embryo transfer strategy, the patients with a positive TLBP value choose SET, while still undergo DET who with a negative TLBP value, the live birth rate would maintain as 56.7%; however, the twin birth rate would significantly decline to 7.4%.Conclusion: Female age, endometrial thickness, the number of transferred top embryos and previous embryo transfer times were critical variables for the twin live birth prediction model. An elective single cleavage embryo transfer strategy according to this model can maintain the relatively high live birth rate, meanwhile get the acceptable low twin birth rate. [ABSTRACT FROM AUTHOR]

Background: Gestational trophoblastic disease (GTD) usually affects young women of childbearing age. After treatment for GTD, 86% of women wish to achieve pregnancy. On account of the impacts of GTD and treatments as well as patient anxiety, large numbers of couples turn to assisted reproductive technology (ART), especially in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). But few studies have investigated whether a history of GTD affects the outcomes of IVF/ICSI in secondary infertile patients and how it occurs. We investigate whether a history of GTD affects the IVF/ICSI outcomes and the live birth rates in women with secondary infertility. Methods: This retrospective cohort study enrolled 176 women with secondary infertility who underwent IVF/ICSI treatment at the reproductive medical center of Nanjing Drum Tower Hospital from January 1, 2016, to December 31, 2020. Participants were divided into the GTD group (44 women with GTD history) and control group (132 women without GTD history matched from 8318 secondary infertile women). The control group and the study group were matched at a ratio of 3:1 according to patient age, infertility duration, number of cycles and body mass index (BMI). We assessed retrieved oocytes and high-grade embryos, biochemical pregnancy, miscarriage, ectopic pregnancy, gestational age at delivery, delivery mode and live birth rates. Result(s): We found a significantly reduced live-birth rate (34.1% vs 66.7%) associated with IVF/ICSI cycles in patients with a GTD history compared to those without a GTD history. The biochemical pregnancy and miscarriage rates of the GTD group were slightly higher than those of the control group. In addition, there was a difference in gestational age at delivery between the GTD and control groups (p < 0.001) but no differences in the mode of delivery (p = 0.267). Furthermore, the number of abandoned embryos in the GTD group was greater than that in the control group (p = 0.018), and the number of good-quality embryos was less than that in the control group (p = 0.019). The endometrial thickness was thinner (p < 0.001) in the GTD group. Immunohistochemistry (IHC) showed abnormal endometrial receptivity in the GTD group. Conclusion(s): The GTD history of patients undergoing IVF/ICSI cycles had an impact on the live-birth rate and gestational age at delivery, which might result from the thinner endometrium and abnormal endometrial receptivity before embryo transfer. [ABSTRACT FROM AUTHOR]

Purpose: To study the association between the numbers of oocytes retrieved and the cumulative live birth rates (LBR) in women aged 35-40 years undergoing long GnRH agonist IVF/ICSI cycles.Methods: A total of 931 women aged 35-40 years who underwent their first cycle of IVF/ICSI treatment between January 2010 and December 2013 at Nanjing Drum Tower Hospital were identified and reviewed. The main endpoint of this study was the cumulative LBR after one complete oocyte retrieval, which included fresh and all subsequent frozen-thaw embryo transfer cycles. Odds ratios (OR) and 95% confidence interval (CI) for live birth were estimated by multivariate logistic regression analysis. Furthermore, all the women were divided into four groups based on the number of oocytes retrieved: 0-4, 5-9, 10-14 or ≥15 oocytes group. Variables were then compared among groups.Results: We found that 634 out of the 931 patients (68.1%) achieved at least one live birth. The number of oocytes retrieved was an independent predictive factor for live birth, with OR 1.20 (95% CI 1.15-1.26) when adjusted for age (years), duration of infertility and Gn (gonadotrophin) doses. The cumulative LBR in the four different oocyte groups was 35.6, 68.8, 83.4 and 89.2%, respectively. When the 1-4 oocytes group was issued as a reference, the ORs for cumulative LBR gradually increased to 3.66, 6.74 and 11.77 in other three oocytes groups, respectively. The moderate-severe ovarian hyperstimulation syndrome (OHSS) rate was dramatically increased in the ≥15 oocytes group (6.9%) when compared to that in the 10-14 oocytes group (0.8%), while the cumulative LBR only increased 5.8% (from 83.4 to 89.2%).Conclusions: The ideal number of oocytes retrieved in women aged 35-40 years is 10-14 oocytes, which achieves a high cumulative LBR while maintaining an acceptable low OHSS rate. [ABSTRACT FROM AUTHOR]

Objective: The aim of this retrospective cohort study was to assess the effect of subchorionic hematoma (SCH) on pregnancy outcomes in IVF/ICSI patients.Methods: We retrospectively analyzed 1097 pregnancies achieved by in vitro fertilization and embryo transfer (IVF-ET) or frozen-thawed embryo transfers (FETs) between January 2013 and June 2013 at the IVF center of Nanjing Drum Tower Hospital. The prevalence of SCH was 12.1% in this group (133/1097). We compared the pregnancy outcomes between the SCH group and non-SCH group, while the risk factors for SCH were also evaluated.Results: There was no significant difference between SCH group and non-SCH group with regard to patients' age, spouse's age, endometrial thickness, miscarriage rate (5.6% versus 6.2%, p > 0.05), second trimester fetus loss rate (5.6% versus 7.7%, p > 0.05) or live birth rate (89.5% versus 86.1%, p > 0.05). While the birth weight in singleton pregnancy in SCH group was significant lower (3207.8 ± 595.7 g versus 3349.2 ± 59.7 g, p = 0.03). SCH was more common in fresh embryo transfer patients than that in FET patients (16.6% versus 5.1%, p < 0.01), fresh embryo transfer was a high risk for SCH with OR 3.67, 95% CI: 2.28-5.90.Conclusion: We concluded that SCH was associated with lower birth weight in singleton pregnancy, but SCH did not increase pregnancy loss rate in IVF/ICSI patients, and fresh embryo transfer may contribute to SCH onset. [ABSTRACT FROM AUTHOR]

Objective: Dose an elevated serum progesterone (P) level on the human chorionic gonadotropin (hCG) trigger day have a negative effect on clinical pregnancy outcomes for embryos transferred at different stages of development in long-acting gonadotropin-releasing hormone agonist (GnRHa) in vitro fertilization-embryo transfer (IVF-ET) cycles?Study Design: This was a noninterventional, retrospective, observational, single-centre cohort study. A total of 1951 patients received long-acting GnRHa for pituitary downregulation in IVF-ET cycles at Nanjing Drum Tower Hospital from January 2018 to December 2020. The serum P levels on the day of hCG administration were measured, together with other cycle parameters, to explore the relationship between P levels and the clinical pregnancy rate (CPR) of different embryos transferred.Results: When the serum P level on the hCG day was higher than 1.5 ng/mL, the CPR did not decrease significantly. There was no correlation between the CPR of cleavage-stage embryo transfer and the serum P level on the hCG day. In addition, the interaction analysis suggested that the CPR of patients undergoing blastocyst transfer decreased as serum P levels on the hCG day increased. Progesterone levels on the day of hCG administration were closely related to the CPR of blastocyst transfer rather than cleavage-stage embryo transfer.Conclusion: An increased serum P level on the day of hCG administration did not affect the CPR of cleavage-stage embryo transfer, but it reduced the CPR of blastocyst transfer cycles. [ABSTRACT FROM AUTHOR]

Can a non-invasive embryo transfer strategy provide a reference for embryo selection to be established? Chromosome sequencing of 345 paired blastocyst culture medium and whole blastocyst samples was carried out and a non-invasive embryo grading system was developed based on the random forest machine learning algorithm to predict blastocyst ploidy. The system was validated in 266 patients, and a blinded prospective observational study was conducted to investigate clinical outcomes between machine learning-guided and traditional non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) analyses. Embryos were graded as A, B or C according to their euploidy probability levels predicted by non-invasive chromosomal screening (NICS). Higher live birth rate was observed in A- versus C-grade embryos (50.4% versus 27.1%, P = 0.006) and B- versus C-grade embryos (45.3% versus 27.1%, P = 0.022) and lower miscarriage rate in A- versus C-grade embryos (15.9% versus 33.3%, P = 0.026) and B- versus C-grade embryos (14.3% versus 33.3%, P = 0.021). The embryo utilization rate was significantly higher through the machine learning strategy than the conventional dichotomic judgment of euploidy or aneuploidy in the niPGT-A analysis (78.8% versus 57.9%, P < 0.001). Better outcomes were observed in A- and B-grade embryos versus C-grade embryos and higher embryo utilization rates through the machine learning strategy compared with traditional niPGT-A analysis. A machine learning guided embryo grading system can be used to optimize embryo selection and avoid wastage of potential embryos. [ABSTRACT FROM AUTHOR]