Journal of Assisted Reproduction and Genetics最新文献

Purpose: The repercussions and outcomes of the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised concerns about potential adverse effects on the male reproductive system. Telomeres are crucial in maintaining the integrity and stability of genomic DNA, and viral infections can induce changes in telomere biology. In this study, the repercussions of SARS-CoV-2 infection in male reproductive health were analyzed.

Methods: This case-control study enrolled subjects who donated blood and semen samples. Fifty-six men with and 56 without prior COVID-19 infection, ages 18-45 years, were included. Semen analysis and hormonal levels were evaluated. The presence of SARS-CoV-2 RNA in semen and the sperm telomere length were assessed by quantitative polymerase chain reaction and associated with clinical and laboratory data. To reduce interference factors, known variables that influence telomere length were analyzed independently.

Results: Sperm telomere length was significantly diminished in the COVID-19 positive group with a mean difference of 0.635 compared to the negative group (p = 0.041). Most individuals in the COVID-19 positive group were clinically classified as asymptomatic/mild illness, and all samples were collected more than 90 days after recovery. No statistically significant differences were observed between the groups in terms of clinical data, semen parameters, and serum levels of follicle-stimulation hormone, estradiol, and testosterone. Persistent or subgenomic SARS-CoV-2 RNA was not detected in the semen samples.

Conclusion: This study revealed that SARS-CoV-2 infection reduced sperm telomere length without alterations in semen parameters or hormonal levels. These results provide further evidence that SARS-CoV-2 infection can induce genomic alterations in human sperm.

Background: This study aimed to investigate the optimal follicular diameter at the initiation of luteal-phase ovarian stimulation (LPOS) protocol after natural ovulation to achieve better laboratory outcomes.

Methods: This retrospective cohort study analyzed 286 in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles in patients who began the LPOS protocol after natural ovulation. Patients were categorized into three groups based on follicle diameter at initiation: small diameter follicles (SDF, < 5 mm, n = 74), medium diameter follicles (MDF, 5.0-7.9 mm, n = 140), and large diameter follicles (LDF, ≥ 8 mm, n = 72). Linear regression analysis was used to assess the relationship between initial follicle diameter and laboratory outcomes.

Result: Significant differences were noted in anti-Müllerian hormone (AMH), body mass index (BMI), and initial gonadotropin (Gn) dose among the groups. Primary outcomes included oocyte retrieval rate (SDF vs. MDF vs. LDF: 0.92 ± 0.88 vs. 0.68 ± 0.48 vs. 0.58 ± 0.54, p = 0.004), mature oocyte retrieval rate (0.78 ± 0.74 vs. 0.58 ± 0.43 vs. 0.51 ± 0.50, p = 0.01), and 2PN rate (0.58 ± 0.68 vs. 0.44 ± 0.40 vs. 0.36 ± 0.43, p = 0.03) in the SDF group were significantly higher than those in the MDF and LDF groups. Multivariate regression analysis, adjusting for potential confounders such as age, AMH levels, baseline follicle-stimulating hormone (FSH) levels, BMI, and initial Gn dosage, revealed negative correlations between the initial follicle diameter and oocyte retrieval rate (p = 0.02), mature oocyte retrieval rate (p = 0.02), and 2PN rate (p = 0.04).

Conclusions: Oocyte retrieval rate, mature oocyte retrieval rate, and 2PN rate decreased significantly with increasing follicle diameter at the initiation of LPOS. The optimal laboratory outcome was achieved with an initial follicle diameter of less than 5 mm.

Purpose: Use of assisted reproductive technology (ART) could lead to abnormal pubertal development in children. We compared pubertal development in children conceived using ART to non-in vitro fertilization fertility treatment (NIFT) and unassisted (UA) conception.

Methods: Children from the Developmental Epidemiological Study of Children through Reproductive Technology (DESCRT) were assessed for pubertal development according to the standardized protocol. Tanner staging (breast, testes, and pubic hair development) was compared between ART, NIFT, and UA-conceived children. Differences were analyzed using Wilcoxon rank-sum test, Pearson's chi-squared test, and Fisher's exact test. Multivariable logistic regression was used to assess association between method of conception and pubertal development.

Results: The sample included 290 children (164 boys and 126 girls) at median age 6 years (range 4 to 18 years); 229 were conceived using ART compared to a combined reference group of 29 conceived via NIFT and 32 via UA. Statistical analyses adjusted for children's age, height, and weight showed statistically non-significant trends wherein boys conceived via ART tended to be in later Tanner stages for pubarche (OR = 2.33, 95% CI 0.44-12.21) and gonadarche (OR = 4.27, 95% CI 0.44-41.99), and girls tended to be in later stages for pubarche (OR = 4.29, 95% CI 0.40-45.62) and thelarche (OR = 2.23, 95% CI 0.35-14.03) compared to the reference group.

Conclusion: As ART becomes more widespread, developmental concerns become increasingly prominent. While results were statistically non-significant, we observed a trend toward differences in pubertal development between ART-conceived children and those conceived without assistance or NIFT.

Purpose: Spermatozoa centriolar defects can result in abnormal zygote functions. Recently, a method to quantify spermatozoa centriolar defects was developed named Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC). However, whether spermatozoa centriolar defects identified by FRAC can result in abnormal zygote functions was not tested.

Methods: Here, we quantified spermatozoa centriolar defects using FRAC, and zygote centriole function was assessed by imaging Nucleolus Precursor Body (NPB) polarization which was based on the pattern of NPB polarization. Data was analyzed at couple and embryo levels. Subjects were divided into two groups: seven couples and 62 embryos with normal spermatozoa centrioles versus eight couples and 78 embryos with abnormal spermatozoa centrioles (140 embryos from 15 couples in total).

Results: Patterned NPB polarization was statistically significant in both couple- and embryo-level analyses (p < 0.0001 and p = 0.0024). These results suggest that the abnormal spermatozoa centrioles identified by FRAC may correlate with abnormal zygote centrosome function via NPB polarization scoring.

Conclusions: This study provides a foundation for more extensive studies to test for FRAC's utility in assessing spermatozoa centriole quality.

Purpose: Dimethyl sulfoxide (DMSO) alters DNA methylation in vitrified-warmed embryos and potentially affects subsequent development. This study aimed to examine possible countermeasures against DMSO-induced demethylation.

Methods: In vitro-produced bovine embryos (8-cell stage) were vitrified using a combination of DMSO and ethylene glycol (EG) or propylene glycol (PG) + EG. After warming, the lipid content and expression levels of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), DNMTs, and TETs were examined. In addition, RNA-sequencing was performed on blastocysts derived from the vitrified embryos. Furthermore, the effect of supplementation with a vitrification medium containing DMSO and N-acetyl-L-cysteine (NAC, 5 mM) on the levels of 5mC in embryos was examined.

Results: Vitrification decreased the levels of 5mC and increased the levels of 5hmC in 8-cell stage embryos. Low levels of 5mC persisted until the blastocyst stage in the DMSO group but increased in the PG group. The expression level of TET3A was higher in the DMSO group than in the fresh group, but not in the PG group. Both cryoprotectants reduced the lipid levels in post-warmed 8-cell stage embryos. The addition of NAC ameliorated DMSO-induced demethylation at both the 8-cell and blastocyst stages. RNA-seq analysis revealed that PG-specific pathways included ribosomes and mitochondria and that both DMSO and PG affected cGMP-PGK, MAPK, Wnt, and insulin secretion-related signaling. The K-medoids method predicted that DMSO affected cell adhesion molecules and that MAPK signaling was affected the most.

Conclusions: PG and NAC may antagonize DMSO-induced demethylation; however, PG exerts adverse effects on embryos.

Purpose: Many national recommendations have been made regarding practice patterns of assisted reproductive technology utilization (intracytoplasmic sperm injection (ICSI), preimplantation genetic testing (PGT), and blastocyst stage embryo transfer). This study seeks to assess individual clinic changes in practice behaviors from 2014 to 2020 in response to national guidelines.

Methods: This retrospective cohort study examined data from individual clinics using the Society of Assisted Reproductive Technology Clinical Outcome Reporting System (SART-CORS) database. Each clinic was weighed individually and equally regardless of clinic volume to avoid skewing national data with larger-volume clinics. The trends of ICSI, PGT, and blastocyst stage embryo transfer were examined across five age groups (< 35, 35-37, 38-40, 40-42, and > 42).

Results: ICSI usage from 2014 to 2020 increased in all age groups (p < 0.001). In 2020, more than half the clinics in this study utilized ICSI in ≥ 90% of IVF cycles (per oocyte retrieval). Utilization of prolonged embryo culture increased in all age groups across the seven years of this study, with a more extensive adoption of this practice in patients ≤ 40 years (p < 0.001). Between 2014 and 2020, PGT usage increased by 3-4 times across all age groups (p < 0.001). By 2020, PGT was performed after egg retrievals in approximately 40 to 50% (mean) of patients < 42 years old.

Conclusions: Nationally, the application of all three reproductive technologies (ICSI, PGT, and blastocyst stage transfer) has drastically increased. The authors suspect that these technology expansions are interrelated and may be associated with the rise of rates of PGT.

Purpose: Obesity is increasingly at the center of modern international healthcare systems. This is a position statement of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) aimed at evaluating the impact of female overweight on infertility in order to improve fertility outcomes, including Assisted Reproductive technology (ART) treatments.

Methods: The SIFES-MR writing group for this position statement was composed by Italian reproductive physicians, embryologists, and scientists with expertise in fertility evaluation, assisted reproduction technologies, and laboratory quality management. The positions stated are based on consensus by the authors, who met over a six-month period. The consensus emerged after thorough review of pertinent literature and standards concerning the impact of female overweight, complemented by extensive dialogue and discussion among the authors. Additionally, input from society members was considered, leading to revisions and eventual approval by the SIFES-MR governing council.

Results: An increasing number of women affected by overweight and infertility accessing to ART treatments are expected in the future. A comprehensive counseling since the first access to infertility care is mandatory and should promote weight restoration, with the aim to improve the likelihood of spontaneous unassisted conception. Careful preconceptional evaluation of obese women is strongly encouraged for counseling purpose and comorbidities should be corrected by a multidisciplinary approach before spontaneous or medically assisted conception. Indeed, female obesity is responsible for high-risk pregnancies, with potential consequences in infants and during childhood. When in vitro fertilization is indicated, the risk of venous thromboembolism exacerbated by controlled ovarian stimulation should be assessed.

Conclusions: Before IVF, different therapeutic approaches and expectant management to reduce overweight could be offered, and the age-related algorithm herein proposed by SIFES may represent an interesting tool for a better personalization of infertility care in these women. The treatment of infertility cannot ignore the correct management of female overweight, given the serious consequences that this condition can have on the outcomes of pregnancies and future generations. IVF specialists should tailor access and modalities of IVF treatment to this class of high-risk women.

Purpose: Reporting a rare viable delivery of a 45,X/46,XY mosaicism female with complete gonadal dysgenesis (CGD) after receiving hormone replacement therapy (HRT), oocyte donation, and overcoming multiple pregnancy complications.

Methods: An infertile female presenting with primary amenorrhea was recruited. Comprehensive genetic evaluation including SRY and AZF gene testing, chromosome karyotyping, fluorescence in situ hybridization (FISH), CNV-seq, and whole-exome sequencing (WES) was performed. This patient was treated with HRT and oocyte donation and received appropriate treatment during pregnancy.

Results: The patient showed a hypoplastic uterus and absent bilateral ovaries via ultrasound detection. She was identified to be a 45,X/46,XY mosaicism through CNV-seq analysis of peripheral blood, saliva, urine, and buccal cells. And further gonadal pathology further confirmed a diagnosis of CGD. Following successful management of multiple pregnancy complications, she delivered a healthy full-term infant.

Conclusions: This is the second case around the world and the first case in China of 45,X/46,XY mosaic female with CGD who experienced a successful pregnancy via occytes donation.And we provided a detailed examination and treatment process for a series of complications in this case, especially the management of threatened miscarriages and preterm labour.

Purpose: To assess the long-term outcomes of MR-guided focused ultrasound (MRgFUS) for treating uterine fibroids, focusing on re-intervention rates, pregnancy outcomes, and the onset of menopause over a 7-year follow-up period.

Materials and methods: We conducted a historical cohort study of 99 women with symptomatic uterine fibroids who underwent MRgFUS between 2013 and 2020 at a single tertiary medical center. Data collection included patient demographics, treatment details, and follow-up interviews. Re-intervention rates were evaluated using Kaplan-Meier curves and Cox regression analysis to identify predictors of further treatments, with a specific focus on age-related differences.

Results: Over a median follow-up of 6.1 years, 33.1% of women required re-intervention for persistent fibroid symptoms. The median patient's age was 43 years old. Women aged ≤ 43 years had significantly higher re-intervention rates than those aged 44 + years (47.5% vs. 16.7%, p = 0.005). Multivariable Cox regression identified age as the sole significant predictor of re-intervention (HR_{44+vs. <43} 0.303 95% CI 0.128-0.714, p = 0.006). Sixteen women conceived after MRgFUS, resulting in 21 pregnancies, with 72.2% live births and a spontaneous miscarriage rate of 22.2%. The mean age of menopause was 51.4 years, similar to global averages.

Conclusions: MRgFUS is a practical, noninvasive option for treating symptomatic uterine fibroids. Older women show lower re-intervention rates. Pregnancies post-MRgFUS are possible, and the procedure does not appear to affect the onset of menopause. Age remains a crucial predictor for further re-intervention.

Purpose: Clomiphene citrate (CC) is often utilized as an adjunct in in vitro fertilization (IVF) protocols during the first 5 days of stimulation for endogenous FSH release. However, due to its antiestrogenic mechanism of action, CC may also effectively prevent the LH surge, and hence premature ovulation, if continued until the day of trigger. The objective of this study was to evaluate a "long CC" protocol, in which CC is continued throughout the entire cycle in-lieu of GnRH antagonist, and to compare IVF outcomes with a standard 5-day CC + GnRH antagonist protocol in patients with diminished ovarian reserve (DOR) undergoing IVF with high-dose gonadotropins.

Methods: This is a retrospective cohort study of all CC-based IVF cycles at a single institution between 9/2020 and 9/2022. Mild stimulation protocols were excluded. The long CC group received CC throughout the entire cycle without GnRH antagonist. The CC + GnRH antagonist group received CC for the first 5 days of stimulation followed by GnRH antagonist when the lead follicle reached 14 mm. The primary outcome was mature oocyte yield.

Results: There were 361 cycles (77%) in the long CC group and 108 (23%) in the 5-day CC + GnRH antagonist group. Age and AMH levels were similar between the two groups. There was no significant difference in mature oocyte yield between the long CC and 5-day CC + GnRH antagonist groups (median 5 (IQR 5) vs. 4.5 (IQR 5), respectively, (P = 0.922)). MII oocytes/AFC did not differ (0.69 vs. 0.56, respectively, P = 0.16). Premature ovulation occurred in 0.3% of cycles in the long CC group vs. 3.0% of cycles in the 5-day CC + GnRH antagonist group (P = 0.019).

Conclusions: In DOR patients undergoing IVF, a long CC protocol is an effective and patient-friendly approach associated with non-inferior oocyte yield.