Male factor infertility impacts the rate of mosaic blastocysts in cycles of preimplantation genetic testing for aneuploidy.
ABSTRACT: PURPOSE:In this study, we tested the hypothesis that, in PGT-A cycles, decreased semen quality is associated with increased rates of mosaic blastocysts. METHODS:In a retrospective analysis, three hundred and forty PGT-A cycles are divided into study groups according to semen quality. Cycles were initially divided into two groups, discerning couples with absence of male factor of infertility (non-male factor: NMF; N?=?146 cycles) from couples with a male factor of infertility (MF; N?=?173 cycles). Couples with severe male factor (SMF) infertility (n?=?22) were assessed separately. Embryos were cultured to the blastocyst stage and chromosomally assessed by array comparative genomic hybridization (aCGH). The study did not involve specific interventions. RESULTS:The reproductive outcome of MF and NMF groups did not indicate statistically significant differences. However, while no differences were found between MF and NMF groups in terms of euploid or aneuploid blastocysts rates, a significantly higher rate of mosaic blastocysts was observed in the MF group (3.6% vs. 0.5%, respectively; P?=?0.03). A similar pattern of results was observed in the SMF group when compared with those of the other PGT-A cycles taken together (no SMF). In particular, a significantly higher rate of mosaic blastocysts was observed in the SMF group (7.7% and 1.8%, respectively; P?=?0.008). CONCLUSIONS:The study outcome strongly suggests that compromised semen quality is associated with increased rates of mosaic blastocysts analysed in PGT-A cycles. Sperm assessment appears therefore as an important factor in the determination of embryo development and for a more precise prognostic assessment of PGT-A cases.
Project description:PURPOSE:This paper aims to investigate the efficacy of IVF with preimplantation genetic testing for aneuploidy (PGT-A), using only best-scoring blastocysts from young (??35 years) infertile patients undergoing single blastocyst frozen embryo transfers (FET). METHOD:In this randomized controlled trial (RCT) registered 29 March 2017, 302 infertile patient-couples eligible to participate underwent autologous ICSI blastocyst freeze-all cycles. Two-hundred and twenty patient-couples satisfied the inclusion criteria (i.e., female age???35 years, two-day 5 ??2BB blastocysts) and were randomized to either the PGT-A (PGT-A group, n?=?109) selection arm or morphology score (morphology group, n?=?111) selection arm. In both arms, the highest ranking (by morphological score) blastocysts were selected for FET. RESULTS:Of the 109 best-scoring blastocysts that underwent PGT-A, 80 were predicted to be euploid (73.4%) and were transferred in FET (euploid subgroup). There was no statistical difference in LB rate between the euploid subgroup and morphology group (56.3% vs 58.6%, odds ratio 0.91 (95% CI 0.51-1.63), p?=?0.750). In a multiple logistic regression, the transfer of euploid blastocysts was not found to be a significant predictor of LB when adjusting for female age, infertility duration, antral follicle count, and blastocyst quality, with the independent odds expressed as 0.91 (95% CI 0.50-1.66, p?=?0.760). CONCLUSION:In young (??35 years) infertile patients with at least two ??2BB blastocysts, PGT-A blastocyst selection does not result in an enhanced LB rate, with the evidence suggesting that the effectivity of PGT-A may be limited by the effectivity of TE biopsy. TRIAL REGISTRATION:ClinicalTrials.gov ID: NCT03095053.
Project description:<h4>Purpose</h4>The purpose of this study is to summarize the clinical outcomes of apparently balanced chromosome rearrangement (ABCR) carriers in preimplantation genetic testing (PGT) cycles by next-generation sequencing following microdissecting junction region (MicroSeq) to distinguish non-carrier embryos from balanced carriers.<h4>Methods</h4>A retrospective study of 762 ABCR carrier couples who requested PGT for structural rearrangements combined with MicroSeq at the Reproductive and Genetic Hospital of CITIC-Xiangya was conducted between October 2014 and October 2019.<h4>Results</h4>Trophectoderm biopsy was performed in 4122 blastocysts derived from 917 PGT-SR cycles and 3781 blastocysts were detected. Among the 3781 blastocysts diagnosed, 1433 (37.9%, 1433/3781) were balanced, of which 739 blastocysts were carriers (51.57%, 739/1433) and 694 blastocysts were normal (48.43%, 694/1433). Approximately 26.39% of cycles had both carrier and normal embryo transfer, and the average number of biopsied blastocysts was 6.7. In the cumulative 223 biopsied cycles with normal embryo transfer, all couples chose to transfer the normal embryos. In the 225 cycles with only carrier embryos, the couples chose to transfer the carrier embryos in 169/225 (75.11%) cycles. A total of 732 frozen embryo transfer cycles were performed, resulting in 502 clinical pregnancies. Cumulatively, 326 babies were born; all of these babies were healthy and free of any developmental issues.<h4>Conclusion</h4>Our study provides the first evaluation of the clinical outcomes of a large sample with ABCR carrier couples undergoing the MicroSeq-PGT technique and reveals its powerful ability to distinguish between carrier and non-carrier balanced embryos.
Project description:PURPOSE:The aim of our study was to evaluate the impact of severe male infertility (SMF) on the chromosomal status of embryos and any possible correlation between chromosomal status and embryo morphokinetics in younger women using data obtained from comprehensive preimplantation genetic tests. METHODS:The trial was conducted in an ART and Reproductive Genetics Centre between 2011 and 2018. A total of 326 cycles in cases with SMF where the female partner's age was ??35 years were evaluated. SMF is defined as sperm concentration below 5 mil/ml (million per milliliter) and divided into three subgroups according to sperm concentrations: 1-5 mil/ml, <?1mil/ml and testicular sperm. The control group of 190 cycles had normal sperm parameters. RESULTS:Significantly lower chromosomal euploidy rates were found in the testicular sperm group compared with the normal sperm controls when the female age was ??35 years. In SMF, statistically significantly affected chromosomes were 2, 10, 11, 17, 21 and sex chromosomes. The mosaicism and abnormal morphokinetic development rates were higher in the SMF group than in control group, and this difference was significant when testicular sperm was used. CONCLUSION:Lower euploidy rates, higher mosaicism rates and a higher incidence of abnormal morphokinetic development were observed in cases with testicular sperm with female partners ??35 years compared with normal sperm controls. These findings suggest that PGT-A may be advisable in severe male infertility cases. Furthermore, the correlation between morphokinetics and chromosomal status was greatly reduced or absent in these most severe forms of male infertility, thus the need for new morphokinetic models.
Project description:PURPOSE:Surplus cryopreserved affected/aneuploid blastocysts may be obtained after in vitro fertilization (IVF) treatments with preimplantation genetic testing (PGT). These embryos are considered not suitable for transfer and may be discarded. Currently, in Italy, an embryo disposition decision (EDD) is not allowed and the frozen/vitrified blastocysts (even if affected/aneuploid) should be kept cryopreserved indefinitely. In this peculiar clinical, social, and legislative scenario, we aimed at assessing the attitudes of the patients towards the fate of these embryos, in case the local regulation would be changed and allow an EDD regarding the surplus affected/aneuploid embryos obtained after PGT. METHODS:A questionnaire with multiple answers was submitted to 832 patients who obtained affected/aneuploid embryos during a PGT cycle at our private IVF center. They were asked to choose between three putative options with related reasons: everlasting cryopreservation (only option currently available); discard or donate them to research. RESULTS:Overall, 149 patients (18%; 85 women and 64 men) answered the questionnaire. Among them, 84% (n?=?126) would choose to donate their affected/aneuploid blastocysts to research, 9% (n?=?13) would discard them and only 7% (n?=?10) would keep them cryopreserved indefinitely. CONCLUSIONS:Donation of the affected/aneuploid blastocysts is the option chosen from most of the respondents (84%; 15% of the eligible patients). These patients are motivated from the altruistic will of incentivating the progress in IVF and/or stem cell research and supporting future couples to limit/solve their infertility/health issues.
Project description:PURPOSE:We developed and applied a universal strategy for preimplantation genetic testing for all cystic fibrosis gene mutations (PGT-CF) based on next-generation sequencing (NGS). METHODS:A molecular protocol was designed to diagnose all CF mutations at preimplantation stage. The detection of CF mutations was performed by direct gene sequencing and linkage strategy testing 38 specific SNPs located upstream and inside the gene for PGT-CF. Seventeen couples at risk of CF transmission decided to undergo PGT-CF. Trophectoderm cell biopsies were performed on day 5-6 blastocysts. PGT for aneuploidy (PGT-A) was performed from the same samples. Tested embryos were transferred on further natural cycles. RESULTS:PGT was performed on 109 embryos. Fifteen CF mutations were tested. PGT-CF and PGT-A were conclusive for respectively 92.7% and 95.3% of the samples. A mean of 24.1 SNPs was informative per couple. After a single embryo transfer on natural cycle, 81.3% of the transferred tested embryos were implanted. CONCLUSIONS:The present protocol based on the entire CFTR gene together with informative SNPs outside and inside the gene can be applied to diagnose all CF mutations at preimplantation stage.
Project description:BACKGROUND:Assisted reproductive technology (ART) insurance mandates resulted in improved access to infertility treatments like intracytoplasmic sperm injection (ICSI). Our objective was to examine whether ART insurance mandates demonstrate an increased association with ICSI use. METHODS:In this retrospective cohort study, clinic-specific data for 2000-2016 from the Centers for Disease Control (CDC) were grouped by state and subgrouped by the presence and extent of ART state insurance mandates. Mandated (n?=?8) and non-mandated (n?=?22) states were compared for ICSI use and male factor (MF) infertility in fresh non-donor ART cycles with a transfer in women <?35?years. Clinical pregnancy (CPR), live birth (LBR) rates, preimplantation genetic testing (PGT), elective single-embryo transfer (eSET) and twin birth rates per clinic were evaluated utilizing Welch's t-test. Pearson correlation was used to measure the strength of association between MF and ICSI; ICSI and CPR, and ICSI and LBR over time. Results were considered statistically significant at a p-value of <?0.05, with Bonferroni correction used for multiple comparisons. RESULTS:From 2000 to 2016, ICSI use per clinic increased in both mandated and non-mandated states. ICSI use per clinic in non-mandated states was significantly greater from 2011 to 2016 (p?<?0.05, all years) than in mandated states. Clinics in mandated states had less MF (30.5?±?15% vs 36.7?±?15%; p?<?0.001), lower CPR (39.8?±?4% vs 43.4?±?4%; p?=?0.02) and lower LBR (33.9?±?3.5% vs 37.9?±?3.5%; p <?0.05). PGT rates were not significantly different. ICSI use in non-mandated states correlated with MF rates (r?=?0.524, p?=?0.03). A significant correlation between ICSI and CPR (r =?0.8, p?<?0.001) and LBR (r =?0.7, p <?0.001) was noted in mandated states only. eSET rates were greater and twin rates were lower in mandated compared with non-mandated states. CONCLUSIONS:There was greater use of ICSI per clinic in non-mandated states, which correlated with an increased frequency of MF. In mandated states, lower ICSI rates per clinic were accompanied by a positive correlation with CPR and LBR, as well as a trend for greater eSET rates and lower twin rates, suggesting that state mandates for ART coverage may encourage more selective utilization of laboratory resources.
Project description:<h4>Purpose</h4>To investigate the associations of previous pregnancy failures, including implantation failures (IFs), biochemical pregnancy losses (BPLs), and early (EMs) and late miscarriages (LMs), with blastocyst aneuploidy and pregnancy outcomes after PGT-A.<h4>Methods</h4>This study included 792 couples who underwent PGT-A after multiple pregnancy failures. Subgroup analyses were used to compare the blastocyst aneuploidy rate (BAR), implantation rate (IR), early miscarriage rate (EMR), and live birth rate (LBR). Multiple linear and logistic regression models were used to evaluate the associations. The control group comprised couples with ??2 IFs, ??1 BPL, ??1 EM, and no LM.<h4>Results</h4>Notably, a history of ??4 IFs was significantly associated with an increase in aneuploid blastocysts (42.86% vs. 33.05%, P?=?0.044, B?=?10.23 for 4 IFs; 48.80% vs. 33.05%, P?=?0.002, B?=?14.43 for ??5 IFs). Women with ??4 prior EMs also harbored more aneuploid blastocysts (41.00% vs. 33.05%, P?=?0.048; B?=?9.23). Compared with the control group, women with ??4 prior EMs had a significantly higher EMR (6.58% vs. 31.11%, P?<?0.001, OR?=?6.49) and a lower LBR (53.49% vs. 34.18%, P?=?0.007, OR?=?0.56) after euploid transfer. Moreover, a history of LM(s) was associated with adverse pregnancy outcomes after PGT-A (OR for EM?=?3.16; OR for live birth?=?0.48). However, previous BPLs and 2 EMs were not associated significantly with blastocyst aneuploidy and pregnancy outcomes after PGT-A.<h4>Conclusion</h4>A history of high-order IFs or EMs and existence of LM(s) were significantly associated with blastocyst aneuploidy and adverse pregnancy outcomes after PGT-A, whereas no such associations were observed with BPLs or 2 EMs.
Project description:Background:Huntington disease (HD) is an autosomal dominant late-onset neurodegenerative disease caused by an unstable cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (HTT) gene. Preimplantation genetic testing (PGT) is a diagnostic procedure available for these individuals, because they carry a high risk of transmitting this genetic condition to their offspring. Methods:Information about 15 HD couples referred for PGT and 21 cycles performed from 2009 to 2018 was collected retrospectively. PGT provide direct testing of embryos obtained after intracytoplasmic sperm injection, using polymerase chain reaction multiplex as the genetic testing protocol. Results:PGT for HD was performed in 15 couples, with no history of previous attempts, in a total of 21 cycles. The mean number of biopsied embryos per cycle was 4.9. The amplification efficiency in blastomeres was 87.4%. From the 90 amplified embryos, 32 were normal and suitable for transfer. The mean number of transferred embryos per couple was 1.2.Overall, 3 positive human chorionic gonadotropin tests were obtained in 3 couples, resulting in 2 clinical pregnancies. The 2 ongoing clinical pregnancies had normal evolution, and culminated in 2 deliveries, resulting in the birth of 2 healthy children. Conclusions:PGT for HD is considered an effective and safe reproductive option for couples who are at risk of transmitting HD, when proper genetic and reproductive counseling is warranted.
Project description:Spermatid specific thioredoxin-3 (SPTRX3 or TXNDC8) is a testis/male germ line specific member of thioredoxin family that accumulates in the superfluous cytoplasm of defective human spermatozoa. We hypothesized that semen levels of SPTRX3 are reflective of treatment outcome in assisted reproductive therapy (ART) couples treated by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Relationship between SPTRX3 and treatment outcome was investigated in 239 couples undergoing ART at an infertility clinic. Sperm content of SPTRX3 was evaluated by flow cytometry and epifluorescence microscopy, and correlated with clinical semen analysis parameters, and data on embryo development and pregnancy establishment. High SPTRX3 levels (>15% SPTRX3-positive spermatozoa) were found in 51% of male infertility patients (n?=?72), in 20% of men from couples with unexplained, idiopathic infertility (n?=?61) and in 14% of men from couples previously diagnosed with female-only infertility (n?=?85). Couples with high SPTRX3 produced fewer two-pronuclear zygotes and had a reduced pregnancy rate (19.2% pregnant with >15% SPTRX3-positive spermatozoa vs. 41.2% pregnant with <5% SPTRX3-positive sperm; one-sided p<0.05). The average pregnancy rate of all 239 couples was 25.1%. Live birth rate was 19.2% and lowest average SPTRX3 levels were found in couples that delivered twins. Men with >15% of SPTRX3-positive spermatozoa, a cutoff value established by ROC analysis, had their chance of fathering children by IVF or ICSI reduced by nearly two-thirds. The percentage of SPTRX3-positive spermatozoa had predictive value for pregnancy after ART. Gradient purification and sperm swim-up failed to remove all SPTRX3-positive spermatozoa from semen prepared for ART. In summary, the elevated semen content of SPTRX3 in men from ART couples coincided with reduced incidence of pregnancy by IVF or ICSI, identifying SPTRX3 as a candidate biomarker reflective of ART outcome.
Project description:BACKGROUND:Balanced complex chromosome rearrangements (BCCR) are balanced chromosomal structural aberrations that involve two or more chromosomes and at least three breakpoints. It is very rare in the population. The objective is to explore the difference of influence of three types of BCCR on early embryonic development and molecular karyotype. RESULTS:Twelve couples were recruited including four couples of three-way rearrangements carriers (group A), three couples of double two-way translocations carriers (group B) and five couples of exceptional CCR carriers (group C). A total of 243 oocytes were retrievedin the seventeen preimplantation genetic testing (PGT) cycles, and 207 of these were available for fertilization. After intracytoplasmic sperm injection, 181oocytes normally fertilized. The rates of embryos forming on day3 in three groups were 87.88, 97.78 and77.14%, which was significantly different (P?=?0.01). Compared with group B, the rate of embryo formation was statistically significantly lower in group C (P?=?0.01). Furthermore, the rates of high-quality blastocysts in three group were 14.71, 48.15 and 62.96%, respectively, which was significantly different (P?=?0.00). Compared with group B andC, the rate of high-quality blastocysts in group A was statistically significantly lower (P?=?0.00;P?=?0.00). Comprehensive chromosome analysis was performed on 83 embryos, including 75 trophectodermcellsand 8 blastomeres. Except 7 embryos failed to amplify, 9.01%embryos were diagnosed as euploidy, and 90.91% were diagnosed as abnormal. As for group A, the euploid embryo rate was 10.71%and the abnormal embryo rate was 89.29%. In group B,the euploid embryo rate was 3.85%, the abnormal embryo rate was 96.15%. The euploid embryo rate was 13.04%, the abnormal embryo rate was 86.96% in group C. There were no significant differences among the three groups (P?=?0.55). CONCLUSIONS:The lowest rate of high quality blastocysts has been for three-way rearrangements and the lowest rate of euploidy has been for double two-way translocations, although no significant difference. Different types of BCCR maybe have little effect on the embryonic molecular karyotype. The difference of influence of BCCR on early embryonic developmentandmolecular karyotypeshould be further studied.