Journal of Assisted Reproduction and Genetics最新文献

Poor ovarian response (POR) significantly impacts the success of assisted reproductive technology (ART), and growth hormone (GH) has been proposed as an adjuvant treatment to improve outcomes in POR patients undergoing in vitro fertilization (IVF). A systematic review and meta-analysis were conducted to evaluate the effectiveness of GH in enhancing pregnancy outcomes, registering a protocol on PROSPERO and searching multiple databases up to September 2023. Twelve systematic reviews/meta-analysis and 20 randomized controlled trials (RCTs) involving 1984 patients were included. Quality assessment was performed using AMSTAR 2, GRADE, and RoB tools. The meta-analysis revealed that GH significantly increased live birth rates [OR=1.80, 95% CI (1.22, 2.64)] and clinical pregnancy rates [OR=1.92, 95% CI (1.51, 2.43)] compared to the control group. Subgroup analysis indicated that administering 5-10 IU/d of GH combined with a long protocol during the middle and late follicular stages maximized these benefits. Despite these promising findings, most outcome indicators exhibited low-quality evidence, highlighting the need for improved research standards to ensure solid evidence supports treatment strategies for POR, thereby promoting reliable application of GH in IVF treatments.

Purpose: To investigate BMAL1 and BMP6 expressive differences in ovarian granulosa cells (OGCs) of patients with polycystic ovary syndrome (PCOS), explore regulatory relationship, assess their impacts on OGC proliferation and apoptosis, and analyze their correlations with ART outcomes of patients.

Methods: A clinical study selected 40 PCOS patients who underwent IVF/ICSI in our hospital from January to October 2022 and 39 controls with male or tubal factor infertility. RT-qPCR and Western blot assessed BMAL1 and BMP6 mRNA/protein levels. The number of oocytes retrieved, 2PN fertilized oocytes, available embryos, and high-quality embryos were compared between groups and analyzed their correlations with BMAL1 and BMP6 expression levels. Cellular experiments were performed by overexpressing or knocking down BMAL1 in KGN cells by plasmid transfection. The dual-luciferase reporter assay was used to identify BMAL1/BMP6 regulatory relationship. CCK-8 and flow cytometry assessed cellular proliferation and apoptosis.

Results: BMAL1 mRNA/protein expression (P < 0.001) in the PCOS group was significantly lower than that in controls, as was the number of high-quality embryos (P = 0.001). Contrastingly, BMP6 (P < 0.001) was significantly higher in the PCOS group. BMAL1 expression levels were negatively correlated with BMP6 (r = - 0.684, P = 0.002) and positively correlated with the number of 2PN fertilized oocytes, available embryos, and high-quality embryos (r = 0.659, P = 0.003; r = 0.623, P = 0.006; and r = 0.738, P < 0.001). Cellular experiments showed that overexpression of BMAL1 significantly decreased relative luciferase activity (P < 0.01). Overexpression of BMAL1 significantly decreased KGN cell apoptosis (P < 0.01) and enhanced proliferation (P < 0.01).

Conclusion: BMAL1 regulates OGCs proliferation and apoptosis by targeting BMP6, thereby influencing ART outcomes in patients with PCOS. This study might provide molecular factors that indicate ART outcomes and therapeutic targets for PCOS.

Trial registration: Registration number: ChiCTR2100052331; registration date: 2021-10-24.

Purpose: This study aimed to monitor the expression of B-cell translocation gene 2 (BTG2) in granulosa cells of patients undergoing IVF/ICSI with respect blastocyst quality outcomes.

Methods: We recruited 181 women undergoing IVF/ICSI cycles for infertility. Granulosa cells were extracted from follicular fluid. BTG2 expression level of granulosa cells were stratified into tertiles (low, middle, and high), and the patients of each tertile were compared for outcome indicators by Kruskal-Wallis analysis. Spearman's correlation analyses were used to evaluate the correlation between BTG2 mRNA levels and outcome indicators. Generalized linear models and generalized additive models with smoothing splines were used to adjust for potential confounders.

Results: Patients in the low BTG2 tertile had higher oocyte retrieval, fertilization, blastocyst formation, and high-quality blastocyst rates than those in the high BTG2 tertile. Patients in the high BTG2 tertile exhibited a downward trend in implantation and clinical pregnancy rates compared to those in the low or middle BTG2 tertiles, whereas the early pregnancy loss rate showed an upward trend, although the difference was not significant. After adjusting for confounding factors, the expression level of BTG2 was negatively correlated with oocyte retrieval, blastocyst formation, and high-quality blastocyst rates. Stratified analysis of AMH > 4 ng/ml showed elevated BTG2 expression was associated with reduced oocyte retrieval, fertilization, cleavage, blastocyst formation, and high-quality blastocyst rates. No differences in these outcomes were observed in patients with AMH ≤ 4 ng/ml.

Conclusion: In women with high AMH levels (> 4 ng/ml) elevated BTG2 expression in granulosa cells was associated with poor quality blastocyst outcomes.

Background: The 12-h ultradian rhythm plays a crucial role in metabolic homeostasis, but its role in ovarian aging has not been explored. This study investigates age-related changes in 12-h rhythmic gene expression across various human tissues, with a particular focus on the ovary.

Methods: We analyzed transcriptomic data from the GTEx project to examine 12-h ultradian rhythmic gene expression across multiple peripheral human tissues, exploring sex-specific patterns and age-related reprogramming of both 12-h and 24-h rhythmic gene expression.

Results: Our findings revealed sex-dimorphic patterns in 12-h rhythmic gene expression, with females exhibiting stronger 12-h rhythms than males. Midlife (ages 40-49) was identified as a critical period for the reprogramming of both 12-h and 24-h rhythmic gene expression. The ovary was notable among other organs due to its high number of genes exhibiting 12-h rhythmic expression and a distinct pattern of rhythmic gene expression reprogramming during aging. This reprogramming involved two gene subsets: one subset adopted de novo 12-h rhythms, while another subset shifted from 24-h rhythms in younger individuals to dual 12-h and 24-h rhythms in middle-aged individuals. Both subsets were primarily associated with angiogenesis.

Conclusions: This study is the first to report age-related reprogramming of 12-h rhythms in human tissues, with a particular focus on the amplification of 12-h rhythms in angiogenesis-related genes in the aging ovary. These findings provide novel insights into the mechanisms structured format of the abstract text underlying ovarian aging and suggest potential therapeutic strategies targeting rhythmic gene expression in the ovary.

Purpose: To evaluate the performance of different embryo transfer (ET) operators in a strictly controlled scenario minimizing potential confounders.

Methods: This single-center retrospective cohort study analyzed vitrified-warmed single euploid top-quality day-5 blastocyst transfers performed in non-obese women at the same IVF center by four equally trained clinicians using a standardized ET technique. These strict inclusion criteria allowed excluding all main confounders on the primary study outcome, namely clinical pregnancy rate (CPR) per ET across different operators. Endometrial preparation protocol, maternal age at transfer, parity, and the embryologist involved were assessed as putative further confounders.

Results: Out of 8663 ETs performed between January 2013 and December 2021, 421 first single euploid top-quality blastocyst transfers were included. No significant difference in ET outcomes was observed among clinicians. Multivariate logistic regression analysis confirmed no association between ET operators and CPR. The experience-defined as the sequential number of previous ETs conducted-did not involve any increase in the CPR.

Conclusions: The ET operator does not affect ET outcomes when subject to the same training and adopting a standardized ET protocol. As the performance does not increase with experience, the initial training is crucial to standardize the procedure across clinicians. In this regard, the CPR per euploid transfer can be considered a valuable Key Performance Indicator (KPI) for quality control purposes. Larger studies are required to build a consensus on competence and benchmark values to achieve.

Purpose: While the literature has addressed the implementation of oncofertility care at developed institutions, minimal advice exists for those seeking to build oncofertility programs in limited resource settings (LRS). Our research offers a promising conversation on establishing oncofertility care in such settings from the perspective of a practitioner working to establish care in Latin America. We propose practices that have the potential to significantly improve access to and quality of care in these challenging settings.

Methods: PubMed was used to identify articles on fertility preservation (FP) in LRS for this narrative review. Eligible articles were published between January 2010 and May 2023, available in English and include two or more key phrases: "oncofertility care," "limited resources," "low-income settings," "limiting access," and "fertility preservation."

Results: As each institution faces a unique profile of medical, financial, geographical, cultural, and legal considerations, it is difficult to generalize an approach to optimizing care. However, the success of many programs is underpinned by collaborative efforts to educate and support healthcare specialists across the globe. National and international clinical guidelines, an unparalleled opportunity to promote the maintenance of a high level of care, do not exist for many Oncofertility practices. It is necessary that future guidelines consider barriers unique to implementing care in LRS as historically, guidelines have not done so, leaving LRS practitioners to deviate from the standard of care without consensus on how to best do so.

Conclusion: It is crucial to consider the unique challenges in low-resource settings when strategizing the expansion of oncofertility efforts, optimizing care, and developing clinical guidelines. Addressing the diverse barriers to care requires multifaceted initiatives at local, national, and international levels.

Purpose: To investigate the impact of first-trimester COVID-19 infection on the perinatal and obstetric outcomes following in vitro fertilization-frozen embryo transfer.

Methods: This retrospective study was conducted at a university-affiliated IVF center. The infection group included women who contracted SARS-CoV-2 during the first trimester following frozen embryo transfer in China's initial pandemic wave that occurred from 7 December 2022 to 7 January 2023. The control group consisted of pregnant women from the pre-pandemic period, considering the widespread incidence of the disease among the Chinese population during such a large outbreak. The primary outcome was perinatal and obstetric parameters.

Results: A total of 346 pregnant women who tested positive for COVID-19 during the first trimester were included in the analysis, while the control group comprised 705 uninfected women (pre-COVID-19 controls). Perinatal outcomes, such as preterm birth, low birthweight, birthweight Z scores, macrosomia, small for gestational age, large for gestational age, and congenital malformations, showed no significant differences between the infected and control groups in both the unadjusted and confounder-adjusted logistic regression models. Additionally, there were no significant differences between the groups concerning obstetric complications, including gestational diabetes mellitus, hypertensive disorders of pregnancy, placenta previa, preterm premature rupture of the membrane, and mode of delivery.

Conclusion: The current study demonstrated that contracting COVID-19 during the first trimester did not adversely impact future obstetric and perinatal outcomes following in vitro fertilization-frozen embryo transfer. This data holds practical significance and offers essential insights for reproductive specialists and obstetricians advising expectant mothers.

Purpose: To evaluate the effect of endometrial scratching on in vitro fertilization (IVF) success rates in women undergoing frozen embryo transfer with preimplantation genetic testing for aneuploidy (PGT-A).

Methods: Biopsy was performed at oocyte retrieval in cases and compared to those who did not undergo scratching (controls). Endpoints included pregnancy loss, total pregnancy, clinical pregnancy rate (CPR), ongoing pregnancy rate/live birth rate (OPR), and the incidence of chronic endometritis (CE).

Results: Women in case and control groups had similar characteristics, such as age, body mass index, and parity. Overall total pregnancy rate was 82.43% following single euploid embryo transfer in cases compared to 85.7% in controls (p = 0.57; OR = 1.27; 95% CI = 0.565 to 2.78). CPR was 73.3% and 76.2% (p = 0.62; OR = 1.18; 95% CI = 0.594 to 2.29), and OPR between groups was 64.8% and 72.3% (p = 0.28; OR = 1.42; 95% CI = 0.74 to 2.7). First trimester loss rate was similar at 16.9%% and 15.5%%, respectively (p = 0.82). Subjects who underwent scratching closer to their frozen embryo transfer (≤ 3 months) had a similar overall pregnancy rate to those with a longer delay between retrieval and frozen embryo transfer (> 3 months 81.4% vs.87.5%; p = 0.56). CE incidence was 10.8% (8 out of 74; 95% CI = 5.5% to 19.9%). The odds of having a second trimester loss were significantly higher in the scratch group compared to controls (p = 0.03; OR = infinity; 95% CI = 1.3 to infinity).

Conclusions: Endometrial scratching before frozen euploid embryo transfer did not influence pregnancy outcome but increased the chances of second trimester loss. CE was a frequent finding in those undergoing endometrial scratching at the time of retrieval.

Objective: To investigate whether gestational diabetes mellitus (GDM) mediates the association between assisted reproductive technology (ART) and preterm birth (PTB), and to examine the interaction and joint effects of ART and GDM on PTB.

Methods: This retrospective cohort study utilized data from 20,721 mothers with singleton live births at Sichuan Jinxin Xinan Women and Children's Hospital from January 2020 to December 2023. The exposures were ART and GDM, and the outcome was PTB. Multivariate logistic regression assessed the separate associations of ART and GDM with PTB. Mediation, interaction, and joint effects were analyzed using R software.

Results: 1,053 (5.08%) women experienced PTB. ART (OR 1.60; 95% CI 1.27-2.03) and GDM (OR 1.51; 95% CI 1.19-1.92) were both associated with increased PTB risk. GDM partially mediated the ART-PTB relationship (PM 2.72%; 95%CI 0.47%-8.86%). No additive interaction was found between GDM and ART for PTB in the general population. However, a significant additive interaction was observed in women aged ≥ 35 years (RERI 1.22; 95%CI 0.27-2.39). Compared to the spontaneous conception (SC)-non-GDM group, the SC-GDM (OR 1.56; 95%CI 1.07-2.29), ART-non-GDM (OR 1.63; 95%CI 1.22-2.18), and ART-GDM (OR 2.42; 95%CI 1.74-3.37) groups had higher PTB risk.

Conclusions: ART was associated with higher PTB risk, partially mediated by GDM. Women undergoing ART who develop GDM may face greater PTB risk than those exposed to only one factor, with a synergistic effect in older pregnancies.