Fertility and sterility最新文献

Objective: To determine if the use of preimplantation genetic testing for aneuploidy (PGT-A) increased after the Dobbs decision leak on May 2, 2022, and after the Dobbs final ruling on June 24, 2022, compared with before the Dobbs decision.

Design: Retrospective cohort study.

Subjects: Patients who underwent in vitro fertilization (IVF) within a large fertility network geographically distributed across six states from June 2021 through June 2023. Preimplantation genetic testing for aneuploidy cycles were defined as cycles with at least one embryo biopsied.

Exposure: In vitro fertilization cycles were grouped by cycle start date. Cycles starting between May 3, 2022 and June 24, 2022 were considered post-Dobbs leak. These were compared with cycles starting within the year leading up to the leak and those starting within the year after the final ruling.

Main outcome measures: Percentage of cycles utilizing PGT-A, defined as the number of IVF cycles utilizing PGT-A divided by the total number of IVF cycles during the study period. We stratified by age, socioeconomic status, and state abortion access legislation.

Results: We analyzed 9,371 IVF cycles before Dobbs, 1,581 IVF cycles after Dobbs leak, and 11,536 IVF cycles after Dobbs final ruling, totaling 22,488 IVF cycles. Age, body mass index, antimüllerian hormone, parity, and number of embryos obtained per cycle were similar across time periods, but differences existed among race and infertility diagnoses. There were no differences in the primary outcome of the percentage of cycles utilizing PGT-A between study time periods (57.2% pre-Dobbs, 56.8% post-Dobbs leak, 56.2% post-Dobbs final ruling); a finding which remained when adjusting for confounders. There was no association between the Dobbs decision and PGT-A use in subgroups stratified by age and socioeconomic status. A slight decrease in PGT-A use was noted in states with protective abortion legislation after the Dobbs final ruling (risk ratio, 0.96; 95% confidence interval, 0.93-0.99), with overall PGT-A use higher in states with restrictive policies (66.8%) than protective states (52.4%) across all time periods using Guttmacher's Institute's protective vs. restrictive classifications.

Conclusion: There is no association between Dobbs decision timing and patients' pursuit of PGT-A, but PGT-A use was more common in restrictive states across all included time periods.

Objective: To study the biological origin of chromosomal abnormalities in embryos reported as mosaic following next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) and to assess the accuracy of current NGS-based methods in distinguishing meiotic from mitotic errors.

Design: Retrospective cohort study utilizing single nucleotide polymorphism (SNP) genotyping and Karyomapping to identify meiotic aneuploidy in clinically reported mosaic embryos.

Subjects: A total of 146 embryos from 87 patients who underwent IVF cycles with NGS-based PGT-A between 2018 and 2020 at The Evewell, London, UK.

Exposure: Embryos underwent clinical NGS-based PGT-A to identify chromosomal abnormalities. Haplotype-based methods such as SNP-based genotyping and Karyomapping were performed on the same amplified material used for NGS-based PGT-A to determine the origin of the chromosomal errors.

Main outcome measures: The proportion of embryos reported as mosaic by NGS that contained meiotic errors, and the distribution of meiotic versus mitotic origin among chromosomal abnormalities identified in the mosaic range.

Results: Of the 141 embryos identified as mosaic following NGS-based PGT-A, 32.6% (n=46/141) contained an error of meiotic origin, challenging their classification as 'mosaic embryos'. In total, 191 individual chromosomal errors were reported in the mosaic range by NGS-based PGT-A. Of those, 29.3% (56/191) errors (both below and above the 50% copy number threshold) were found to be of meiotic origin. The majority (94.6%) of meiotic errors were maternal in origin. Embryos with multiple chromosomal abnormalities were significantly more likely to have at least one meiotic error. Higher intermediate copy number values correlated with an increased probability of an error being of meiotic origin.

Conclusion: This study presents the first direct evidence that a third of embryos reported as mosaic (both low- and high-level mosaic) by NGS-based PGT-A contain meiotic errors, highlighting the potential misclassification of aneuploid embryos as mosaic by current NGS-based PGT-A methods which cannot accurately distinguishing between meiotic and mitotic errors. SNP genotyping provides essential information for accurately determining the origin of chromosomal abnormalities and should be integrated with NGS-based copy number analysis to enhance diagnostic accuracy. Further studies are needed to refine mosaicism classification and to better understand its true implications in IVF treatment.

Objective: To demonstrate a novel holding pipette, designed to prevent sliding during the biopsy procedures, and evaluate its performance by comparing the biopsy results of using the novel holding pipette and the conventional holding pipette.

Design: Using images and videos to present the sliding that may occur during biopsy procedures and introduce the mechanism of a novel pipette for reducing the sliding occurrence and demonstrate its step-by-step application in blastocyst biopsy employing the flicking method.

Subjects: Embryos (blastocysts).

Intervention: Different biopsy protocols: using the novel holding pipette (beveled design) or conventional holding pipette for mechanical blunt dissection.

Main outcome measures: Occurrence rate of sliding, dissecting time, successful biopsy rate and blastocyst cryosurvival rate, and clinical pregnancy rate.

Results: Compared with the conventional holding pipette, the novel holding pipette significantly reduced the occurrence rate of sliding and the time required for dissecting. The occurrence rate of sliding decreased from 9.00% to 1.00% (95% confidence interval [CI], 0.02-0.45); the dissecting time decreased from 25.80 to 8.03 seconds (95% CI, 16.44-19.09); the successful 1-time dissecting rate increased from 90.00% to 99.00% (95% CI, 2.54-47.72). There were no significant differences in the successful biopsy rate (conventional, 99.11%; novel, 99.53%), blastocyst cryosurvival rate (conventional, 98.99%; novel, 99.34%), and clinical pregnancy rate (conventional, 55.78%; novel, 64.90%) between the two methods.

Conclusion: The application of the novel holding pipette significantly reduced the occurrence rate of sliding and dissecting time but had no adverse effect on biopsy results, cryosurvival, and pregnancy outcomes. Moreover, aside from the innovative beveled design, no other alterations were introduced, preserving the unvarying holding efficacy and making it applicable for intracytoplasmic sperm injection procedures.

Objective: To compare adverse perinatal outcomes between naturally conceived and pregnancies conceived by assisted reproductive technologies (ARTs) according to underlying male, female, or unexplained infertility.

Design: Registry-based study.

Subjects: All singleton births in Norway between 2000 and 2021 recorded in the national birth registry.

Exposure: We compared ART pregnancies with underlying male (N = 9,957), female (N = 10,031), mixed (N = 3,287), or unexplained (N = 7,178) infertility with naturally conceived pregnancies (N = 1,210,709). Information on underlying causes of infertility was reported from fertility clinics.

Main outcomes and measures: We compared the birthweight and pregnancy length using robust linear regression, and the risk of pre-eclampsia, cesarean section, stillbirth, preterm birth, low birth weight, small-for-gestational age and transfer to neonatal unit using logistic regression, adjusting for parental age, maternal parity, cohabitation, country of birth, and year of delivery.

Results: Pregnancy length and birthweight were lower in all ART groups compared with the naturally conceived. The shorter pregnancy length was less pronounced in ART deliveries resulting from male infertility (adjusted difference -1.24 days; 95% confidence interval [CI]: -1.43 to -1.05) than in ART deliveries resulting from female infertility (adjusted difference -1.92 days; 95% CI: -2.12 to -1.73). Similarly, the lower birthweight in ART deliveries was less pronounced in those resulting from male (adjusted difference -29 grams; 95% CI: -39 to -18) than those resulting from female (adjusted difference -49 grams; 95% CI: -59 to -39) infertility. We also observed a higher risk of most adverse perinatal outcomes in all ART groups, with the magnitude being lower for ART deliveries resulting from male infertility.

Conclusion: The increased risk of adverse perinatal outcomes in pregnancies conceived by ART was less pronounced if used for male infertility than for female infertility. This suggests that the risks in ART pregnancies are a combination of underlying factors related to female infertility and ART procedures. However, whether underlying male infertility also increases the risks cannot be excluded.

Objective: To study whether self-reported psychological stress was associated with impaired semen parameters and reproductive hormones.

Design: An observational study including men aged 18-55 years who attended the Massachusetts General Hospital Fertility Clinic.

Subjects: A total of 718 men who attended the clinic provided semen and serum blood samples and completed the short version of the Cohen Perceived Stress Scale (PSS-4).

Exposure: Scores from completed the short version of the PSS-4 were used to quantify perceived psychological stress.

Main outcome measures: The World Health Organization semen analysis parameters, including ejaculate volume, sperm count, concentration, motility, and morphology, were ascertained. Further analysis of sperm DNA damage was performed using the Comet Assay. Serum concentrations of luteinizing hormone, follicle stimulating hormone, prolactin, inhibin, testosterone, and estrogen were measured. Linear regression models were used to evaluate associations between self-reported stress and testicular function outcomes, adjusting for age, body mass index, abstinence time, year of semen sample collection, and time to blood sampling. Parameters with skewed distributions were natural log-transformed for analysis where appropriate to minimize the influence of outliers.

Results: Compared with the lowest quartile of PSS-4 scores, men in the highest had significantly lower adjusted mean total sperm count, 118 mil/ejaculate (95% confidence interval [CI]: 101-139) vs. 153 mil/ejaculate (95% CI: 133-175) and lower adjusted mean normal morphology count, 5.97 mil/ejaculate (95% CI: 4.73-7.55) vs. 9.13 mil/ejaculate (95% CI: 7.43-11.0). Higher perceived stress showed consistent trends with lower mean levels of sperm concentration, total motile count, percentage of normal sperm morphology, and number of cells with high DNA damage in adjusted models. No associations were observed between self-reported stress and other outcomes of sperm DNA damage and reproductive hormone concentrations.

Conclusion: Greater perceived stress was negatively associated with certain semen quality parameters and spermatic cell DNA damage, whereas no associations were found for additional markers of sperm DNA damage or reproductive hormone levels.

Objective: To estimate the total number of infants born globally between 1978 and 2018 after assisted reproductive technology (ART). Estimates are based on epidemiological data systematically and uniquely collected by the International Committee for Monitoring Assisted Reproductive Technologies over 40 years.

Design: The International Committee for Monitoring Assisted Reproductive Technologies has been reporting global results from country and regional registries since 1991. These observational cohort reports were collated and analyzed to obtain the number of infants born. Because reporting of outcomes is inconsistent, and clinics, countries, and regions report incompletely, sporadically, or not at all, statistical estimates were used to estimate the additional number of infants born from nonreporting clinics, countries, and regions. Upper and lower estimates were based on assumptions about the number of births from nonreporting clinics.

Subjects: Patients starting an ART cycle between 1978 and 2018. All clinics reporting their outcomes to national and regional registries, or directly to the International Committee for Monitoring Assisted Reproductive Technologies.

Exposure: Assisted reproductive technologies.

Main outcome measures: The total number of infants born from ART annually from 1978 through 2018, including the estimated number from nonreporting clinics, countries, and regions.

Results: The global lower and upper estimates of infants born from ART from 1978 through 2018 are 9,829,668 and 13,019,331.

Conclusion: Ten million and up to 13 million or more infants have been born from ART in the 40 years since the first ART-conceived infant was born in 1978. This large number of infants born from both conventional and innovative applications of ART confirms that ART has helped millions of people realize parenthood, is now mainstream medicine, has had a significant societal impact, including novel family formation, and highlighted inequities regarding reproductive rights and access to care.