Reproductive biomedicine online最新文献

Research question: How does diminished ovarian reserve (DOR) affect euploid blastocyst rates, and how many embryos need to be biopsied for women with or without DOR to achieve one euploid embryo?

Design: A retrospective study was conducted at a single reproductive centre, involving 694 women (126 with and 568 without DOR) undergoing 803 preimplantation genetic testing for aneuploidies (PGT-A) cycles from 2016 to 2024. DOR was defined as a concentration of anti-Müllerian hormone below 1.1 ng/ml and/or an antral follicle count of less than 7. Participants were stratified by age into three groups: <35, 35-39 and >39 years. Euploidy rates and pregnancy outcomes were compared between the DOR and non-DOR groups. Cumulative euploid embryo acquisition was analysed.

Results: DOR patients showed comparable euploidy rates to their non-DOR counterparts. The number of embryos required to obtain a euploid embryo was a: for age <35 years, a mean of 1.6 embryos for the DOR group and 1.7 for the non-DOR group; for age 35-39 years, a mean of 1.9 and 2.3 embryos, respectively; and for age >39 years, a mean of 7.2 and 4.2 embryos, respectively. In women over aged 39 years, the mean number of euploid embryos obtained remained low even after two retrievals for both groups. Pregnancy outcomes after euploid embryo transfer were similar between the two groups.

Conclusions: Participants with DOR had similar euploidy rates and pregnancy outcomes to non-DOR patients. Limited embryo quantity, rather than inferior oocyte quality, thus remains the predominant challenge for individuals with DOR.

Micro- and nanoplastics (MNP) are pervasive pollutants, detected in every ecosystem. Human exposure is extensive, and their capacity to cross biological barriers and accumulate in tissues raises growing concerns about reproductive health and pregnancy outcomes. Research has shown the presence of MNP in human placenta, fetal meconium and amniotic fluid, confirming their ability to reach the fetal compartment, potentially increasing risks for fetal development. In women, MNP have also been detected in follicular fluid, although their specific effects remain to be determined. In-vitro studies have reported MNP-induced placental vascular damage, whereas murine models suggest impaired ovarian function, reduced oocyte quality and decreased pregnancy rates after MNP exposure. In men, MNP have been identified in testicular tissue and semen. Animal studies report decreased sperm count and quality, likely because of oxidative stress, hormonal disruption and inflammation. Various techniques are available for detecting MNP in biological tissues. Mass and Raman spectroscopy are among the most widely used, each offering specific advantages and limitations. Interpreting experimental data also requires caution, as many in-vitro and in-vivo models use unrealistically high doses of pristine polymers lacking environmental additives, potentially limiting the relevance of their findings to real-world exposures.

Research question: Are endocrine-disrupting chemicals (EDC) in follicular fluid associated with assisted reproductive technology (ART) outcomes among women undergoing ART treatment?

Design: This prospective cohort study involved 176 women who underwent ART treatment in China. The concentrations of 76 EDC, across five categories, in follicular fluid were quantified. Generalized linear models (with and without restricted cubic splines to account for non-linear relationships) and Bayesian kernel machine regression (BKMR) models were utilized.

Results: Fifteen EDC exhibited significant negative associations with at least one conventional IVF/intracytoplasmic sperm injection (ICSI) outcome. Notably, mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) was consistently associated with reductions in all conventional IVF/ICSI outcomes, including the numbers of retrieved oocytes, mature oocytes, two pronuclear zygotes, blastocysts and high-quality embryos. Similarly, 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH) was negatively associated with all conventional IVF/ICSI outcomes except the number of blastocysts. No significant negative associations were observed between individual EDC and pregnancy outcomes, including the live birth rate. BKMR model analyses revealed that combinations of EDC were significantly associated with reductions in the numbers of retrieved oocytes and mature oocytes, and the probability of biochemical pregnancy. Among EDC combinations, phthalates (PAE) and bisphenol S (BPS) were identified as dominant contributors to adverse conventional IVF/ICSI outcomes and the biochemical pregnancy rate, respectively. Stratified and interaction analyses further indicated that stronger associations with conventional IVF/ICSI outcomes were observed among women aged ≤33 years.

Conclusions: Elevated concentrations of EDC in follicular fluid were associated with adverse ART outcomes, both as individual compounds and in combination. MECPP, BHT-COOH, PAE and BPS were identified as key EDC. Moreover, the associations were modified by age, with stronger adverse effects observed in younger women.

Fertility rates are decreasing globally, and the Nordic countries currently have fertility rates of 1.3-1.5 per woman. The objectives of this scoping review, covering the Nordic welfare states since 1970, were to explore women's and men's parenthood intentions, their assessment of important circumstances for family building and their fertility knowledge. Overall, 24 quantitative studies and 6 qualitative studies were included. Across studies, the majority of both women and men expressed a desire to have children, while 0-14% did not wish to do so. Among those having parenthood intentions approximately 85% wanted to have two or three children. Parenthood intentions did not decline during the 50-year period of the empirical studies. Hence, as fertility rates are substantially decreasing, the gap between parenthood intentions and actual birth rates is widening. Since 2006, 12 of the included studies explored study participants' fertility knowledge. All studies except one reported uncertain fertility knowledge, either overestimating or underestimating the probability of spontaneous pregnancy, or overestimating the success rate after IVF treatment. There is an urgent need for cross-disciplinary and structural efforts to bridge the increasing gap between desired and actualized parenthood.

Research question: Does refreshment of single-step culture medium on Day 3 impact blastocyst formation and ploidy rates in embryos cultured in benchtop dry incubators?

Design: This randomized sibling oocyte study was performed between July 2021 and October 2023 including 177 patients who underwent preimplantation genetic testing for aneuploidy (PGT-A). Following intracytoplasmic sperm injection, 3016 metaphase II (MII) oocytes were randomized equally to two culture conditions: (a) medium refreshment on Day 3 (R-D3) or (b) medium refreshment on Day 5 (R-D5). All embryos were cultured in single-step medium in a benchtop dry incubator. No embryo assessments were performed between fertilization check and Day 5. Post-insemination outcomes and ploidy rates were compared between the groups.

Results: Fertilization rates were similar between R-D3 and R-D5 (OR 0.89, 95% CI 0.75-1.07; P = 0.212). No significant differences in total usable blastocysts (OR 0.88, 95% CI 0.75-1.02; P = 0.091), euploid blastocysts (OR 0.95, 95% CI 0.80-1.13; P = 0.561) or mosaic blastocysts (OR 1.06, 95% CI 0.72-1.56; P = 0.771) per inseminated MII oocyte were observed. Similar results were observed per two pronuclei (2PN) embryo. However, R-D5 was associated with lower odds of Day 5 blastulation (OR 0.80, 95% CI 0.66-0.98; P = 0.032) and high-quality blastulation per inseminated MII oocyte (OR 0.82, 95% CI 0.68-0.98; P = 0.027), although this was not significant when analysed per 2PN embryo. Sensitivity analyses did not identify interactions between treatment group and cycle characteristics.

Conclusion: Omitting the refreshment of single-step medium on Day 3 does not compromise the viability of euploid embryos to blastocyst stage, but does lead to a slight reduction in the number of morphologically high-quality blastocysts.

Research question: Does the synergistic interaction between blastocyst-stage embryo transfer and vitrification in assisted reproductive technology increase the risk of adverse neonatal outcomes, specifically elevated birth weight z-scores and a higher incidence of clinically concerning large for gestational age (LGA) or macrosomia in offspring?

Design: In this cohort study, multivariable regression analyses were conducted to examine the association between embryo transfer strategies (fresh versus frozen; cleavage versus blastocyst stage) and the birth weight z-score of singletons, as well as the incidence of LGA and macrosomia among 42,190 singleton live births from the Center for Reproductive Medicine at Peking University Third Hospital between 2012 and 2022.

Results: Compared with cleavage-stage embryo transfer, newborns resulting from blastocyst-stage transfers had significantly higher birth weight z-scores (P < 0.001), LGA (P < 0.001) and macrosomia (P = 0.013). Frozen embryo transfer (only vitrified-warmed) was associated with increased birth weight z-scores (P = 0.001), LGA (P = 0.004) and macrosomia (P = 0.007), compared with fresh embryo transfers. A significant synergetic effect of blastocyst transfer and vitrified-warmed transfer concerning the LGA was found (relative excess risks due to interaction = 0.24; 95% CI 0.06 to 0.42; P = 0.022 for multiplicative interaction term) on the additive and multiplicative scales.

Conclusions: Blastocyst stage and embryo vitrification were associated with elevated birth weight z-scores and an increased likelihood of LGA, with evidence of a synergistic effect. These findings support the importance of personalized clinical decision-making in the use of vitrified-warmed cleavage-stage transfer, particularly in the absence of clear medical indications.

Research question: What effect does the use of a rapid warming method of vitrified embryos have on survival and pregnancy?

Design: A comparison of two different warming embryos protocols: long protocol (group 1, n = 486) and a new fast protocol (group 2, n = 413) for blastocyst and cleavage stage frozen embryo transfers at two IVF centres: Assisted Reproductive Technology Centre, Careggi University Hospital Firenze and IVF Unit, 'Cervesi' Hospital Cattolica. Total pregnancy rate was considered primary outcome, and embryo survival rate, clinical pregnancy rate, miscarriage rate, ongoing pregnancy rate and mean time required for warming procedure were considered secondary outcomes.

Results: The same embryo survival rate was observed in the two groups. Total and clinical pregnancy rates seemed to be higher, but not statistically different, in group 2 compared with group 1 (29.5% versus 26.7% and 27.6% versus 22.6%, respectively). Conversely, a statistically significant reduction in miscarriage rate was found in group 2 compared with group 1 (18.0% versus 32.3%, P = 0.009). Similarly, a significant increase in pregnancy rate at 26 gestational weeks or over was observed in group 2 compared with group 1 (66.9% versus 80.3%, P = 0.016). Finally, a difference in time required for warming procedures was found in favour of group 2.

Conclusions: The use of the fast warming protocol is a valid alternative to the classic warming protocol, and allows a reduction in the time needed to carry out the procedure and the workload of embryologists in an IVF laboratory.