Journal of Assisted Reproduction and Genetics最新文献

Purpose: To evaluate the difference in the number of euploid blastocysts and cumulative live birth rate (LBR) between dual and human chorionic gonadotropin (hCG) triggers in poor and normal ovarian responders undergoing preimplantation genetic testing (PGT) cycles.

Methods: This retrospective cohort study was enrolled from July 2018 to December 2021 and followed up until June 2024 at a single reproductive medical center. Overall, 1040 in vitro fertilization (IVF)-PGT and 784 frozen-thawed embryo transfer (FET) cycles were assessed. Dual (triptorelin acetate 0.2 mg and recombinant hCG [rhCG] 250 µg) or hCG (rhCG 250 µg) trigger was used for oocyte maturation in the gonadotropin-releasing hormone antagonist protocol and PGT cycles. We assessed the embryo outcomes and FET cumulative pregnancy outcomes.

Results: The number of oocytes retrieved (10.17 ± 5.22 vs 10.27 ± 5.14, P = 0.789), MII oocytes (8.24 ± 4.26 vs 8.28 ± 4.05, P = 0.888), blastocysts (2.16 ± 1.50 vs 2.12 ± 1.49, P = 0.729), euploid blastocysts (1.06 ± 1.14 vs 1.09 ± 1.23, P = 0.726), and the rate of cumulative LBR (24.9% vs 24.9%, P = 1.000) in the dual trigger group were comparable with those in the hCG group. The trigger method was not correlated with higher LBR based on logistic regression analysis (odds ratio[OR] = 1.040 [0.778-1.392], P = 0.790).

Conclusion: For poor and normal ovarian responders, the dual trigger, compared with the hCG trigger, did not improve the PGT embryo outcomes and FET cumulative pregnancy outcomes.

Purpose: To identify the benefit of extending embryo culture until day (D)7 based on patients and cycle characteristics.

Methods: A retrospective cohort study was conducted including 25,120 blastocysts from 5278 PGT-A autologous cycles between 2017 and 2022. A theoretical cumulative live birth rate (CLBR) was calculated by binomial density function. An increase of ≥ 5% in theoretical CLBR was considered a tangible benefit when obtaining ≥ 1 euploid D7 blastocyst and ≤ 3 euploid blastocysts from D5/D6. A predictive model was built considering the number of embryos eligible for extended culture until D7, number of blastocysts already biopsied on D5/D6, and patient's age.

Results: Euploidy rates decreased for blastocysts biopsied on D5, D6, and D7 (55.6%, 39.7%, and 27.1%, P < 0.001, respectively). The probability of tangible benefit was increased with more embryos available for extended culture until D7, was decreased with higher D5/D6 blastocysts already biopsied and for older patients. The overall AUC of the final model in the validation sets was 0.75 (95% CI 0.72-0.78). Based on the predictive model, in poor cycles (< 1% tangible benefit), the benefit rate from extended culture was 0.3% and for moderate, good, and best cycles (1-10%, 10-20%, and ≥ 20% tangible benefit) were 4.4%, 14.0%, and 29.3%, respectively. An application of the predictive model is available online for external testing: https://artfertilityclinics.shinyapps.io/WET-D7/ .

Conclusion: The predictive model provides a decision-making tool to objectively identify cycles that would benefit from extending embryo culture until D7.

Purpose: To understand factors influencing patient satisfaction with genetics education and psychosocial support in an IVF clinic without a genetic counselor (GC), and how the role of a GC may fill gaps in care using a mixed-method cross-sectional study.

Methods: Previous IVF patients (n = 133) completed a survey assessing satisfaction with genetics education and psychosocial support and decisional conflict about genetic testing. Kruskal-Wallis tests were used to compare satisfaction level to demographic and clinical variables. Spearman's correlation was used to analyze decisional conflict. Focus groups with 12 total participants expanded on themes identified in survey responses. Thematic analysis was performed using interpretive description.

Results: Participants reported satisfaction with their genetics education experience (78.9% somewhat or extremely satisfied). Satisfaction with genetics education was associated with satisfaction with information received about genetic testing results (H = 21.3, p < 0.01) and confidence using results in future decisions (H = 9.9, p < 0.01). Participants desired thorough pre-test and post-test counseling regarding genetic testing and directive guidance. Decision conflict about genetic testing was low (mean of 22.3, range 0-100). Satisfaction with genetics education was inversely correlated with decisional conflict (r_s = - 0.42, p < 0.05). In-person GC visit scored highest among proposed education methods (mean score of 84.1).

Conclusions: Patients felt satisfied with genetics education and psychosocial support provided by clinical providers. Gaps in care included misconceptions regarding genetic testing, a desire for more thorough counseling about genetic testing options, more directive guidance, and increased psychosocial support through external sources such as support groups.

Purpose: Complex chromosomal rearrangements (CCRs) often remain unidentified as they are rarely observed in the general population. Females with CCRs are generally recognized on the identification of an affected child with multiple congenital anomalies (MCA) or having a history of repeated pregnancy loss/bad obstetric history (RPL/BOH). In contrast, males with CCRs are diagnosed primarily due to infertility. This study aimed to carry out a systematic epidemiological analysis of CCRs in one of the largest series from the Indian population. In addition, a review of the literature on female CCR carriers experiencing RPL/BOH has been compiled in an attempt to identify the genomic landscape of breakpoints, commonly involved chromosomes, and the breakpoint regions.

Methods: A total of 8560 healthy individuals with normal physical and mental well-being and had no history of any obvious genetic disorder at the time of presentation were referred for chromosome analysis in view of RPL/BOH between 1994 and 2024. Of them, 8158 had a normal chromosome complement whereas, 402 (4.7%) showed chromosomal aberrations. CCRs were detected in seven individuals, i.e., one partner in each of seven couples with structural rearrangements, all of whom were females. Comprehensive characterization of CCR was carried out using various molecular cytogenetic techniques.

Results: Seven CCR carriers had a total of 25 pregnancies: 20 leading to miscarriages (80%), one leading to the birth of an abnormal child (4%), two medically terminated pregnancies (8%) due to abnormal antenatal findings, and the remaining two were healthy (8%). A total of 13 different chromosomes with 24 non-recurring breakpoints were identified in these cases. Chromosome (#) 2 showed four breaks (16.7%), followed by #1, #4, #6, and #13 with three breaks each (12.5% each), while one break each (4.2% each) was seen on the remaining eight chromosomes (#3, #5, #8, #11, #14, #15, #17, and #21). Type I and type IV CCRs were observed in five (71.4%) and one case (14.3%), respectively, along with a "not a true" CCR (14.3%) in the present study group. Overall, the prevalence of CCRs in couples with RPL/BOH was 0.16%.

Conclusions: To the best of our knowledge, this is the first study on the epidemiology of CCRs in couples with RPL/BOH of Indian origin. The incidence of CCRs in couples experiencing RPL/BOH in the present cohort was found to be 0.16% with type I CCR being the most predominant of all types, which is congruent with observations from non-Hispanic white and South East Asian populations. The uniqueness and rarity of each CCR pose a challenge in genetic and reproductive counseling.

Purpose: Oocyte aging is a significant factor in the negative reproductive outcomes of older women. However, the pathogenesis of oocyte aging remains unclear. This study aimed to identify the hub genes involved in oocyte aging via bioinformatics methods.

Methods: The oocyte aging datasets GSE155179 and GSE158802 were obtained from the GEO database and analyzed as the training set. The GSE164371 dataset was then defined as the validation set. Differentially expressed genes were analyzed via the limma package and weighted gene coexpression network analysis, and intersected with cellular senescence-associated genes from the Cell Senescence database. The hub genes were identified via three machine learning algorithms, namely, support vector machine recursive feature elimination, random forest, and least absolute shrinkage and selection operator logistic, which were also confirmed via the validation set. Finally, a microRNA-mRNA‒transcription factor regulatory network and single-gene gene set enrichment analysis were performed to clarify the pathogenesis of oocyte aging.

Results: A competing endogenous RNA network of GSE155179 and GSE158802 with 124 mRNAs, 31 long noncoding RNAs, and 31 miRNAs was constructed. Two modules with 814 genes were considered the key modules of oocyte aging. PDIK1L, SIRT1, and MCU were subsequently identified as hub genes; on the basis of these hub genes, a regulatory network of oocyte aging with 8 miRNAs, 3 mRNAs, and 227 TFs was ultimately constructed.

Conclusions: This study contributes to a deeper understanding of oocyte aging and may aid in the development of therapeutic approaches to improve reproductive outcomes in older women.

Purpose: This study is to evaluate the effectiveness of a PPOS protocol in poor prognosis patients undergoing IVF with DuoStim and PGT-A versus the conventional protocol with GnRH antagonist.

Methods: Retrospective cohort study encompassing 444 couples obtained matching one PPOS-DuoStim with two antagonist-DuoStim cycles at a private IVF center between 2020 and 2023 (average maternal age: 40 years, average cumulus-oocyte complexes collected after the first stimulation: 5). The study was powered to exclude a two-sided different euploid blastocyst rate per MII oocytes (EBR per MII) in the two groups (alpha = 0.05, power = 0.9, effect size = 0.3). All cycles involved ICSI, blastocyst stage PGT-A, and single vitrified-warmed euploid transfers. We compared all embryological and clinical outcomes within each group (first vs. second stimulations), and among the two study arms (first stimulation vs. first stimulation; second stimulations vs. second stimulation; overall). The overall EBR per MII was the primary study outcome. The cumulative-live-birth-rate per concluded cycles (CLBR) was the main secondary outcome.

Results: In the second stimulations, we obtained a greater number of COCs and MIIs in both antagonist- and PPOS-DuoStim groups. No difference was observed for all embryological and clinical outcomes when comparing the two stimulations within each group. All embryological and clinical outcomes were comparable also between the two groups, including the EBR per MII. To date, 285 and 121 antagonist- and PPOS-DuoStim cycles were concluded. The CLBR was comparable between the groups: 26% vs. 29%.

Conclusions: PPOS-DuoStim holds potential for being an efficient, patient-friendly, and possibly cost-effective approach that does not compromise treatment efficacy. Future investigations must explore PPOS effect on follicular recruitment, neonatal, and long-term outcomes.

Purpose: To assess the impact of sperm source on cumulative live birth rate (CLBR) after oocyte thaw in autologous oocyte cryopreservation (AOC) patients.

Methods: A retrospective cohort study of autologous oocyte thaw patients at an urban academic fertility center from 2006 to 2021. Patients were stratified by sperm source [partner sperm (PS) vs. donor sperm (DS)]. The primary outcome was CLBR per patient. Secondary outcomes were the oocyte survival rate and usable embryo rate. Statistics included Mann-Whitney U, Kruskal-Wallis, Fisher's exact, chi-square, two-sample t-tests, and multiple logistic regression (p < 0.05).

Results: A total of 653 patients were included; 455 (69.7%) used PS and 198 (30.3%) used DS. Time from the first AOC to the first thaw did not differ among DS and PS users (56.8 vs. 54.0 months, p = 0.20). PS users were younger at AOC (37.9 vs. 38.5 years, p < 0.001) and thaw (42.3 vs. 43.1 years, p < 0.001). There were equivalent overall CLBRs (39.9% PS vs. 40.6% DS, p = 0.85) and CLBRs in patients < 35 years at AOC (51.2% PS vs. 100% DS, p = 0.18), 35-37 years at AOC (45.9% PS vs. 60.4% DS, p = 0.10), 38-40 years at AOC (35.4% PS vs. 35.2% DS, p = 0.93), 41-42 years at AOC (28.9% PS vs 14.3% DS, p = 0.21), and > 43 years at AOC (12.5% PS vs 16.7% DS, p = 0.83) among PS and DS users. There were no significant differences in the oocyte survival (79% PS vs 80.5% DS, p = 0.08) or the proportion of patients with usable embryos (27.3% vs 27.8%, p = 0.70) between PS and DS groups.

Conclusions: In AOC patients, CLBR, oocyte survival rate, and usable embryo rate did not differ based on sperm source.

Purpose: To explore whether a 25 mg subcutaneous progesterone daily rescue daily improves the reproductive outcomes in patients with low serum progesterone (P₄) levels (7-10 ng/mL), measured one day before true natural cycle (t-NC) frozen embryo transfer (FET).

Methods: A cohort study of 192 women undergoing t-NC warmed blastocyst transfer. Patients were stratified into three different groups based on serum P₄ levels on the FET-1 day: patients who had serum P₄ levels of 7-10 ng/mL and underwent rescue progesterone administration (rescue group), patients with serum P₄ levels of 7-10 ng/mL without progesterone administration (non-rescue group), and patients with serum P₄ > 10 ng/mL on FET-1 day (control group). The primary outcome was possible differences in live birth rate (LBR) between groups.

Results: The LBRs for the serum P₄ 7-10 ng/mL without rescue, 7-10 ng/mL with rescue, and > 10 ng/mL (control) groups were 41%, 46%, and 52%, respectively (p = 0.61). The estimated adjusted probability of live birth for serum P₄ 7-10 ng/mL without rescue, 7-10 ng/mL with rescue, and > 10 ng/mL (control) groups were also comparable: 43.5% (95% CI, 20.0-70.4%), 49.8% (95% CI, 28.1-71.6%), and 57.4% (95% CI, 44.0-69.8%), respectively.

Conclusion: Serum P₄ levels higher than 7 ng/mL seem to secure LBRs in patients undergoing t-NC FET. A rescue policy consisting of a daily subcutaneous 25 mg progesterone dose in patients with serum P₄ levels 7-10 ng/mL does not further enhance LBRs when compared to those patients with similar serum P₄ levels without rescue.

Background: Zona pellucida (ZP) plays an important role in oocyte development and fertilisation, as well as in early embryo development. However, there is currently no exploration of systematic categorising and clinical treatment measures for patients with abnormal ZP, especially the fast and easy method that can be used clinically.

Methods: In this study, 185 patients with abnormal ZP (ZPA) and 222 patients with normal ZP (ZPN) were enrolled and analysed.

Results: Patients with ZPA exhibited altered hormone levels and lower laboratory outcomes in in vitro fertilisation (IVF), such as reduced MII rate, cleavage rate, high-quality embryo rate, and blastocyst formation rate compared to ZPN group. ZPA patients were sub-categorised into ZPA-A/B/C/D group according to the status of oocyte polar body and the width of perivitelline space (PVS). There are also differences in the degree of sperm binding to ZP derived from different ZPA patients and the elasticity of the oocyte membrane. ZPA subgroup analysis revealed further disparities in various IVF parameters and pregnancy outcomes. In addition, by performing different treatments on oocytes derived from ZPA patients, we found that ZP assisted hatching before the first oocyte cleavage on D1 of embryonic development in the ZPA-A/B groups and before blastocyst expansion on D4 of embryonic development in the ZPA-C/D groups were beneficial to improve embryonic development.

Conclusion: The degree of the impact on clinical outcomes is correlated with the types of ZPA, and laser-assisted hatching of the ZP helps to improve embryonic development in patients with ZPA.

Purpose: This study aimed to analyze the current status of women's perception of social support levels, psychological resilience, anxiety, and depression levels during IVF-ET, as well as investigate the influence of perceived social support and psychological resilience on the anxiety and depression levels of women undergoing IVF-ET and the mediating role of psychological resilience in this process.

Methods: In this study, a convenience sampling method was used to administer a questionnaire survey among 433 women undergoing IVF-ET. Then, multivariate linear regression models were applied to identify factors influencing anxiety and depression. Lastly, mediation effect analysis was conducted to explore the mediating role of psychological resilience.

Results: The incidence of anxiety and depression was 42% and 46.4%, respectively. The mean score of the Perceived Social Support Scale (PSSS) indicated a high to moderate level of support, while the mean score of the Conner-Davidson Resilience Scale (CD-RISC) suggested moderate psychological resilience. Perceived social support was positively correlated with psychological resilience, and both were negatively correlated with anxiety and depression. Perceived social support and psychological resilience were identified as influencing factors of anxiety and depression (P < 0.001). Moreover, there was a partial mediating effect of psychological resilience between perceived social support and both anxiety and depression (P < 0.01).

Conclusions: These results highlight the need for healthcare providers to assess patients' levels of psychological resilience and perceived social support when developing mental health interventions in order to mitigate the risk of anxiety and depression and concomitantly enhance fertility outcomes.