Journal of Assisted Reproduction and Genetics最新文献

Purpose: To assess national trends, characteristics, and delivery outcomes associated with gestational carriers (GC) pregnancies.

Methods: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population was 14,312,619 deliveries between 2017 and 2020. Obstetric characteristics and outcomes associated with GC pregnancies were assessed with inverse probability of treatment weighting propensity score.

Results: There were 1965 GCs (13.7 per 100,000) included for national estimates. The prevalence rate of GC pregnancies increased by 55.0% over a 4-year period from 11.8 to 18.2 per 100,000 deliveries (P-trend < .001). In the weighted model, GCs were more likely to have a multiple gestation pregnancy (14.7% vs 1.8%, adjusted odds ratio [aOR] 7.83, 95% confidence interval [CI] 6.54-9.38, P < .001), placental abruption (3.5% vs 1.1%, aOR 2.98, 95%CI 2.12-4.19), and low-lying placenta (1.6% vs 0.2%, aOR 5.14, 95%CI 3.10-8.52). Among singleton delivery, odds of late-preterm (10.8% vs 6.4%, aOR 1.79, 95%CI 1.44-2.23) and periviable (1.1% vs 0.4%, aOR 2.54, 95%CI 1.32-4.89) deliveries and postpartum hemorrhage (12.2% vs 4.1%, aOR 3.27, 95%CI 2.67-4.00) were increased for GC compared to non-GCs whereas odds of cesarean delivery (23.6% vs 31.6%, aOR 0.59, 95%CI 0.51-0.69) were decreased. These associations were less robust in multi-fetal gestations.

Conclusion: The results of the current nationwide assessment suggest that GC pregnancies are rare but gradually increasing in the United States. This study shows that GC pregnancies have usually favorable pre-pregnancy patient characteristics compared to non-GC pregnancies, with mixed obstetric outcomes including increased odds of preterm delivery, placental abnormalities, and postpartum hemorrhage and decreased odds of cesarean delivery in singleton pregnancies.

Purpose: To investigate any correlation between the outcomes of the first euploid frozen-thawed blastocyst embryo transfer (FBT) and the subsequent euploid FBT derived from sibling oocytes.

Methods: This retrospective study analyzed data from 1051 women who underwent preimplantation genetic testing for aneuploidy and had a euploid FBT. Of these patients, 159 underwent a second transfer. The primary outcome was the live birth rate.

Results: Overall, 159 women who underwent a second euploid FBT were categorized into two subgroups depending on the implantation success of the first FBT. Of these patients, 94 (59.1%) belonged to the nonclinical group, signifying a negative result or a biochemical pregnancy. The remaining 65 (40.9%) patients belonged to the clinical group, indicating either a miscarriage or a live birth. In the binary logistic regression analysis, the live birth outcome during the first euploid FBT was a statistically significant and independent predictor of live birth in the subsequent FBT [odds ratio 4.14, 95% confidence interval (1.184-14.531), p < 0.026). Miscarriages, including those that occurred before intracytoplasmic sperm injection and in the first euploid FBT, reduced the live birth rate by approximately 34% (p < 0.027). No significant difference in the miscarriage rate was found between the two subgroups (19.2% (10/52) vs. 25.4% (14/55), p = 0.38).

Conclusion: The live birth outcome of the second euploid FBT is mainly determined by the live birth outcome of the first. Miscarriages that occurred before in vitro fertilization negatively affect the live birth outcome.

Purpose: The objective is to evaluate the effectiveness and safety of calcium ionophore as an artificial oocyte activation (AOA) method on pregnancy outcomes in different groups of intracytoplasmic sperm injection (ICSI) patients, providing potential evidence to establish consensus on the indications of AOA.

Methods: A systematic comprehensive search was performed in Medline, Embase, the Cochrane Library, and Google Scholar databases. Studies published from January 2014 to June 2024 were searched for analysis. All studies that compared ICSI with AOA-ICSI in routine indications composing impaired fertilization or embryo developmental arrest in previous cycles, or male-factor infertility were included.

Results: Twelve studies were included in the meta-analysis. AOA-ICSI was associated with the increase in the overall fertilization rate (OR 1.99, 95% CI 1.16-3.41) and live birth rate (OR 4.58, 95% CI 1.52-13.80). All secondary outcomes including cleavage, blastocyst, high-quality embryo, implantation, biochemical pregnancy, clinical pregnancy presented superiority or equivalence in AOA-ICSI. And the use of calcium ionophore did not increase the miscarriage rate (OR 0.43, 95% CI 0.08-2.43). In subgroup analysis, AOA-ICSI exhibited a more significant effect on patients with indications of no or low fertilization. However, in patients with non-fertilization factors, no statistically significant improvements were observed in all outcomes.

Conclusion: Calcium ionophore is an effective artificial oocyte activation approach to improving pregnancy outcomes after ICSI, particularly in cases with indications of fertilization factors, providing further support for the application of AOA in specific populations. Further validation is needed to comprehensively establish the safety of AOA.

Trial registration: PROSPERO registration number CRD42024551481.

Oocyte cryopreservation has transformed assisted reproductive technology, providing enhanced flexibility and efficacy in assisted reproductive technology treatments. The shift from traditional slow freezing to vitrification has markedly improved survival rates by preventing ice crystal formation, which can damage cellular structures. Despite these advances, rapid warming of vitrified oocytes remains a challenge due to the unique sensitivity of oocytes to thermal and osmotic stress, which can compromise spindle integrity and developmental competence. Recent studies indicate that using both rapid vitrification and rapid warming protocols may reduce processing time and enhance workflow efficiency, yet the impact of rapid warming on oocytes previously cryopreserved using standard methods is not fully understood. Although promising results have emerged from preclinical and clinical studies using rapid warming on embryos, the applicability to human oocytes requires further research. For oocytes, establishing a universal rapid warming protocol that balances efficiency and safety is essential, especially considering the millions of oocytes already preserved with conventional techniques.

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.