During the period of 2018–2020, we first combined reported low-pass whole genome sequencing and NGS-based STR tests for miscarriage samples analysis. Compared with G-banding karyotyping, the system increased the detection rate of chromosomal abnormalities in miscarriage samples to 56.4% in 500 unexplained recurrent spontaneous abortions. In this study, a total of 386 STR loci were developed on twenty-two autosomes and two sex chromosomes (X and Y chromosomes), which can help to distinguish triploidy, uniparental diploidy and maternal cell contamination and can trace the parental origin of erroneous chromosomes. It is not possible to accomplish this with existing methods of detection in miscarriage samples. Among the tested aneuploid errors, the most frequently detected error was trisomy (33.4% in total and 59.9% in the error chromosome group). In the trisomy samples, 94.7% extra chromosomes were of maternal origin and 5.31% were of paternal origin. This novel system improves the genetic analysis method of miscarriage samples and provides more reference information for clinical pregnancy guidance.

Background: Genetic kidney disease is a major cause of morbidity and mortality in neonates and end-stage renal disease (ESRD) in children and adolescents. Genetic diagnosis provides key information for early identification of congenital kidney disease and reproductive risk counseling. Preimplantation genetic testing for monogenic disease (PGT-M) as a reproductive technology helps prospective parents to prevent passing on disease-causing mutations to their offspring.Materials and Methods: A retrospective cohort of couples counseled on PGT who had a risk to given birth to a child with genetic kidney disease or had a history of prenatal fetal kidney and urinary system development abnormalities from 2011 to 2021. Through a combination of simultaneously screening for aneuploidy and monogenic kidney disease, we achieved reproductive genetic intervention.Results: A total of 64 couples counseled on PGT for monogenic kidney disease in a single reproductive center during the past 10 years, of whom 38 different genetic kidney diseases were identified. The most frequent indications for referral were autosomal recessive disease (54.7%), then autosomal dominant disease (29.7%), and X-linked disease (15.6%). Polycystic kidney disease was the most common diseases counted for 34.4%. After oocyte-retrieval in all of 64 females, a total of 339 embryos were diagnosed and 63 embryos were transferred in succession. Among 61 cycles of frozen-embryo transfer (FET), ongoing pregnancy/live birth rate (OP/LBR) reached 57.38%. The cumulative OP/LBR in our cohort for the 64 couples was 54.69%. In addition, we have carried out expanded carrier screening (ECS) in all the in vitro fertilization (IVF) couples performed PGT covering 7,311 individuals. The carrier frequency of the candidate genes for monogenic kidney diseases accounted for 12.19%.Conclusion: Overall, the customization PGT-M plan in our IVF center is pivotal to decreasing the morbidity and implementing reproductive genetic intervention of genetic kidney disease.

Studies have shown that supplementation with recombinant human GH (rh-GH) during ovarian stimulation (OS) may improve the ovarian response and clinical outcomes of IVF. However, it remains unclear whether GH is associated with the ploidy status of embryos, and therefore, is unable to explain the underlying reason for the effect of GH on IVF outcomes. This study aimed to investigate whether GH supplementation in women with advanced maternal age (AMA) during OS is related to an increased probability of obtaining euploid blastocysts. This was a single center retrospective cohort study. The data of all women aged 38–46 years who underwent their first preimplantation genetic testing for aneuploidy (PGT-A) cycle between January 2021 and June 2022 were reviewed. Patients in the GH group received 4 IU/day subcutaneous GH supplementation from the beginning of OS to the trigger day, and patients in the control group did not. A total of 140 patients in the GH group and 272 patients in the control group were included after 1:2 propensity score matching. The baseline and cycle characteristics between the two groups were similar. The proportion of cycles which obtained euploid blastocysts was significantly higher in the GH group than that in the control group (41.43% vs. 27.21%, P = 0.00). The GH group had a significantly higher euploid blastocyst rate per cohort (32.47% vs. 21.34%, P = 0.00) and mean euploid blastocyst rate per cycle (per biopsy cycle 0.35 ± 0.40 vs. 0.21 ± 0.33, P = 0.00; per OS cycle 0.27 ± 0.38 vs. 0.16 ± 0.30, P = 0.02). However, the benefit of GH was more significant in patients aged 38–40 years, but not significant in patients aged 41–46 years. Pregnancy outcomes were similar between the two groups after embryo transfer. GH supplementation during OS is associated with a significantly increased probability of obtaining euploid blastocysts in women aged 38–40 years, but this benefit is not significant in women aged 41–46 years. Our results explained the underlying reason for the effect of GH on IVF outcomes in existing studies, and might be helpful for AMA patients undergoing PGT-A cycles to obtain a better outcome meanwhile to avoid over-treatment. NCT05574894, www.clinicaltrials.gov.

Fluorescence in situ hybridization analysis of numerical chromosomal abnormalities in the sperm of Robertsonian translocation der (13;14) (q10;q10) carriers has focused on a limited number of chromosomes mainly on chromosome 13, 18, 21, X, and Y. Here, we aimed to expand the analysis to all chromosomes by increasing the number of probes analyzed in fluorescence in situ hybridization. The incidence of numerical abnormalities of all chromosomes (1–22, X, and Y) was determined in sperm from 10 carriers of the Robertsonian translocation der(13;14)(q10;q10) and 10 normozoospermic males to fully assess the effect of translocation-derived chromosome on the segregation of all chromosomes during meiosis. Numerical abnormalities of the two translocated chromosomes were frequently detected in the sperm of der (13;14) translocation carriers, with an average frequency of 14.55% ± 6.00% for chromosome 13 and 13.27% ± 4.14% for chromosome 14. Numerical abnormalities of nontranslocated chromosomes, with an average frequency of 1.77% ± 0.62% (range, 1.16%–3.73%), was lower than that of translocated chromosome. However, the cumulative numerical abnormality of the 22 nontranslocated chromosomes was comparable to that of the two translocated chromosomes. Significantly increased numerical abnormalities in der(13;14) translocation carriers compared with those in normozoospermic males indicates the presence of translocation-derived chromosome disturbances, with translocated chromosomes being most affected; nontranslocated chromosomes were also affected, but to a lesser extent due to a mild interchromosomal effect.