[Analysis of related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes with mosaic embryo transfers].

Objective: To explore the related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes of mosaic embryo transfer in preimplantation genetic testing for aneuploidy (PGT-A) based on next generation sequencing (NGS) technology. Methods: A retrospective study was performed to analyze the clinical data of patients in 745 PGT-A cycles from January 2019 to May 2023 at Chongqing Health Center for Women and Children, including 2 850 blastocysts. The biopsy cells were tested using NGS technology, and the embryos were divided into three groups based on the test results, namely euploid embryos, aneuploid embryos and mosaic embryos. The influence of population characteristics and laboratory-related parameters on the detection rate of mosaic embryo were analyzed, and the pregnancy outcomes of 98 mosaic embryo transfer cycles and 486 euploid embryo transfer cycles were compared during the same period, including clinical pregnancy rate and live birth rate. Results: Among the embryos tested (n=2 850), the number and proportion of euploid embryos, aneuploid embryos and mosaic embryos were 1 489 (52.2%, 1 489/2 850), 917 (32.2%, 917/2 850) and 444 (15.6%, 444/2 850), respectively. Among mosaic embryos, 245 (55.2%, 245/444) were segmental mosaic embryos, 118 (26.6%, 118/444) were whole-chromosome mosaic embryos, and 81 (18.2%, 81/444) were complex mosaic embryos. NGS technology was performed in 4 genetic testing institutions and the detection rate of mosaic embryo fluctuated from 13.5% to 27.0%. The distributions of female age, level of anti-Müllerian hormone, PGT-A indications, ovulation-inducing treatments, gonadotropin (Gn) dosage, Gn days, inner cell mass grade, trophectoderm cell grade, genetic testing institutions and developmental stage of blastocyst were significantly different among the three groups (all P<0.05). Multi-factor analysis showed that the trophectoderm cell grade and genetic testing institutions were significantly related to the detection rate of mosaic embryo; compared with the trophectoderm cell graded as A, the detection rate of mosaic embryo was significantly increased in the trophectoderm cell graded as B-(OR=1.59, 95%CI: 1.04-2.44, P=0.033); compared with genetic testing institution a, the detection rate of mosaic embryo was significantly higher (OR=2.89, 95%CI: 2.10-3.98, P<0.001) in the testing institution c. The clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: 51.0% vs 65.2%, P=0.008; live birth rate: 39.4% vs 53.2%, P=0.017). After adjustment for age, PGT-A indications, trophectoderm cell grade and days of embryo culture in vitro, the clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: OR=0.52, 95%CI: 0.32-0.83, P=0.007; live birth rate: OR=0.50, 95%CI: 0.31-0.83, P=0.007). Conclusions: The trophectoderm cell grade and genetic testing institutions are related to the detection rate of mosaic embryo. Compared with euploid embryos transfer, the clinical pregnancy rate and live birth rate with mosaic embryos transfer are significantly reduced. For infertile couple without euploid embryos, transplantable mosaic embryos could be recommended according to the mosaic ratio and mosaic type in genetic counseling to obtain the optimal pregnancy outcome.

[Impact of trigger timing of gonadotropin-releasing hormone antagonist regimen for infertility patients of various ages].

Objective: To investigate the impact of trigger timing of gonadotropin- releasing hormone (GnRH) antagonist regimen for infertility patients of various ages. Methods: This was a retrospective study, 1 529 infertility patients who receiving GnRH antagonist regimen in Chongqing Health Center for Women and Children from January 2017 to December 2018 were divided into the advance trigger group and the standard trigger group, and further divided into three subgroups according to age:<35 years, 35-40 years,>40 years. The number of retrieved oocytes and transplantable embryos, the clinical pregnancy rate and the live birth rate among patients in the advance trigger group and standard trigger group in various age subgroups were compared. Results: (1) The gonadotropin (Gn) days among the three age subgroups were significantly shorter in the advance trigger group compared to the same-aged standard trigger group (all P<0.01), but only in the 35－40 years and >40 years subgroups, the Gn doses in the advance trigger group [(2 702±551) and (2 780±561) U] were significantly less than those in the standard trigger group (all P<0.01). In the <35 years subgroup, the number of oocytes retrieved and transplantable embryos of the advance trigger group (6.6±4.8 and 2.6±2.7) were significantly less than those of the standard trigger group (all P<0.01), but there was no difference in the number of top-quality embryos (P=0.580); however, in the 35－40 years and >40 years subgroups, there were no significant differences between advance and standard trigger groups in terms of the afore mentioned 3 indicators (all P>0.05), only the numbers of top-quality embryos in the advance trigger group (0.6±1.0 and 0.6±0.9) were significantly higher than those in the standard trigger group (all P<0.01). (2) In the <35 years and 35－40 years subgroups, no significant differences were noted between the advance trigger group and standard trigger group with regard to the clinical pregnancy rate and live birth rate (all P>0.05); but in the >40 years subgroup, the clinical pregnancy rate of the advance trigger group was significantly higher than that of the standard trigger group [33.0% (30/91) vs 19.2% (25/130), P=0.020], and there was no statistical difference in the live birth rate (P=0.064). (3) Multivariate logistic regression analysis showed that trigger timing was an independent predictor of clinical pregnancy rate in the >40 years subgroup (OR=0.334, 95%CI: 0.119-0.937, P=0.037), but not an independent predictor of live birth rate (P>0.05). Conclusions: Advance trigger in the GnRH antagonist protocol for infertility patients >40 years old could effectively reduce Gn times and Gn dosage, increase the number of top-quality embryos, and improve the clinical pregnancy rate. Therefore, compared with patients ≤40 years of age, patients >40 years might benefit more from advance trigger.

[Retrospective analysis of outcomes of selectively or spontaneously reduced multiple pregnancies out of 6 917 in vitro fertilization-embryo transfer pregnancy cycles].

Objective: To analyze the effects of fetal reduction in early pregnancy on obstetric and neonatal outcomes of spontaneously or selectively reduced multiple pregnancies produced by in vitro fertilization-embryo transfer (IVF-ET). Methods: Retrospective study of 6 917 clinical pregnancies from IVF-ET cycles, including 754 multiple pregnancies divided into two groups according to the remaining fetus number: reduced singleton group (n=599) and reduced twin group (n=155); and maternal and neonatal outcomes of two groups were compared to primary singleton group (n=3 589) and primary twin group (n=2 574). Results: The rate of pregnancy complication [9.85%(59/599) versus 6.21%(223/3 589)], preterm birth [19.37%(116/599) versus 10.73%(385/3 589)], low birth weight [9.71%(56/577) versus 4.57% (152/3 324)], perinatal death [0.69%(4/577) versus 0.12%(4/3 324)] and malformation [2.95%(17/577) versus 1.02%(34/3 324)] in reduced singleton group were significantly higher than those in primary singleton group (all P<0.01). There were no significant differences between reduced twin group and primary twin group (all P>0.05). In reduced singleton group, birth defect rate was 2.95%, which was higher than those of the other three groups (P<0.05), in this group spontaneous pregnancy reduction accounted for 89.3% (535/599). Conclusions: (1) The rate of pregnancy complication, preterm birth, low birth weight, perinatal death and malformation in reduced singleton group are still higher than primary singletons, suggesting embryo reduction only is a compensated method in multiple pregnancies. Limiting the number of embryos transferred is the essential solution. (2) The rate of birth defect in spontaneous pregnancy reduction group is higher, so prenatal examination should be reinforced in this group.

Time of insemination culture and outcomes of in vitro fertilization: a systematic review and meta-analysis.

BACKGROUND Conflicting results have been reported regarding the technique of brief insemination used in IVF. The aim of this meta-analysis was to determine if better clinical outcomes of IVF are associated with a brief co-incubation of gametes than with a standard overnight co-incubation. METHODS A computerized search was conducted of the published literature of four databases, using search terms related to gamete, time of co-incubation and outcome measure. Eligible studies compared outcomes of IVF with a brief co-incubation of gametes to that of a control group of standard insemination and reported rates of live birth (primary outcome), normal fertilization, polyspermy, good quality embryos, implantation, clinical pregnancy or ongoing pregnancy (secondary outcomes). A total of 11 studies were included in the meta-analysis. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for the data. Statistical heterogeneity was tested using Cochran Q and I² values. RESULTS Brief co-incubation of gametes was associated with significantly higher rates of clinical pregnancy (RR: 1.84, 95% CI: 1.24-2.73) and ongoing pregnancy (RR: 1.73, 95% CI: 1.27-2.33) than standard insemination. Brief co-incubation of gametes was associated also with a significantly higher rate of implantation (RR: 1.80, 95% CI: 1.43-2.26) than standard insemination. However, the rates of normal fertilization (RR: 0.98, 95% CI: 0.93-1.02), good quality embryos (RR: 1.24, 95% CI: 1.0-1.53) and polyspermy (RR: 0.84, 95% CI: 0.7-1.01) were not significantly different with brief co-incubation of gametes compared with standard insemination. CONCLUSIONS Reduced gamete exposure time may be associated with beneficial outcomes. Drawbacks inherent to the quality of several studies limit the quality of the available evidence. Adequately powered randomized controlled studies need to be performed to evaluate the efficacy of brief insemination.

[Biological effects of diagnostic ultrasound on embryo in first trimester of pregnancy].

Biological effects of diagnostic ultrasound on the embryo during first trimester of pregnancy were studied. Normal pregnant women asked for induced abortion with gestational age of 6-8 weeks were recruited. Embryo in uterus were exposed to the diagnostic ultrasound for 5, 10 and 30 minutes respectively. Surgical evacuations were performed 5, 15, 24 and 48 hours after exposure and chorionic villi were obtained. The villi were determined for 4 lysosomal enzymes, malondialdehyde (MDA), and superoxide dismutase (SOD); and sister chromatid exchange and the ultrastructure of the villi were studied as well. In comparison to normal non-exposure group, the results showed various degrees of changes in lysosomal enzymes, MDA, SOD and ultrastructure of the villi in those exposed to ultrasound 10 and 30 minutes, and most significant changes were observed in the latter group. These included the hyperreaction of lipid peroxides; increased activities of some lysosomal enzymes; reduced SOD activity; and vesiculation and aberration of some mitochondrion, also transformation or disappearance of some microvilli in ultrastructure.