Menstrual abnormalities effects on clinical features and in vitro fertilization pregnancy outcomes in women with polycystic ovarian syndrome.

BACKGROUND: The diagnostic criteria and phenotypes in polycystic ovary syndrome are heterogeneous. Currently, it is unclear how to assess a patient's prognosis based on the onset time of menstruation disturbance. Evidence on this topic is scarce and has mainly focused on menstrual patterns. OBJECTIVE: This study aimed to assess the association between the onset time of menstrual disturbance and clinical features and in vitro fertilization pregnancy outcomes in patients with polycystic ovary syndrome. STUDY DESIGN: Our study was a secondary analysis of data collected as part of a randomized controlled trial conducted to compare live birth rates between fresh embryo transfer and frozen embryo transfer in 1508 individuals with polycystic ovary syndrome. Here, 1500 participants were classified into 2 groups according to the onset time of menstrual disturbance: immediately after menarche (early group) and after at least 1 year of regular menstruation (late group). We compared the prepregnancy clinical features, variables of ovarian stimulation, pregnancy outcomes after the initial cycle of embryo transfer, and perinatal and neonatal complications in the 2 groups. RESULTS: Compared with the late group, the early group had more antral follicles (32.00 [range, 27.25-39.50] vs 28.00 [range, 24.00-36.00]; P<.001), an elevated level of antimüllerian hormone (7.02 ng/mL [range, 3.60-11.47] vs 5.66 ng/mL [range, 3.65-8.92]; P=.024), a higher level of baseline luteinizing hormone (10.01±5.93 vs 8.51±5.53 IU/l; P<.001) and luteinizing hormone-to-follicle-stimulating hormone ratio (1.51 [range, 1.00-2.32] vs 1.45 [range, 0.92-2.13]; P<.001), lower levels of fasting glucose (5.47 mmol/L [range, 5.11-5.73] vs 5.50 mmol/L [range, 5.17-5.76]; P<.001), and insulin at 2 hours after 75-g oral glucose tolerance test (56.85 µU/mL [range, 34.63-94.54] vs 59.82 µU/mL [range, 33.56-94.67]; P=.027), a higher level of high-density lipoprotein (1.26 mmol/L [range, 1.04-1.37] vs 1.21 mmol/L [range, 1.07-1.45]; P=.006). During in vitro fertilization, the early group had a higher level of peak estradiol (4596.50 pg/mL [range, 2639.25-6321.00] vs 3954.00 pg/mL [range, 2378.75-6113.50]; P=.013), and luteinizing hormone (2.52 IU/L [range, 1.40-4.21] vs 1.93 IU/L [range, 0.91-3.32]; P=.010) on the day of human chorionic gonadotropin trigger. There was no statistically significant difference observed in the number of oocytes and embryos, the rates of pregnancy and live birth, and the risks of obstetrical and neonatal between the 2 groups. CONCLUSION: An early onset of menstrual disturbance in patients with polycystic ovary syndrome may be associated with slightly more severe reproductive features and slightly milder metabolic features. Nonetheless, the outcomes of in vitro fertilization and the initial cycle of embryo transfer were comparable between the 2 groups.

The difference in early trimester fetal growth between singletons after frozen embryo transfer and fresh embryo transfer.

BACKGROUND: Frozen embryo transfer resulted in a higher birthweight and an increased risk of macrosomia than fresh embryo transfer. However, the mechanism was still unclear. When the impact of frozen embryo transfer on fetal growth began was unknown. Crown-rump length at 11-13 weeks had been regarded as a good indicator of fetal growth in the first trimester and had been used for gestational age calculation in women with uncertain last menstrual periods. OBJECTIVE: To evaluate the association between frozen embryo transfer and early fetal growth, particularly the crown-rump length, then fresh embryo transfer. The secondary objective was to investigate the potential correlation between crown-rump length and birthweight. STUDY DESIGN: This was a retrospective cohort study conducted at the Reproductive Medical Center of Shandong University. A total of 4949 patients who obtained singleton pregnancy after frozen embryo transfer and 1793 patients who got singleton pregnancy after fresh embryo transfer between January 1, 2017 and December 31, 2022 were included. The primary outcome was the crown-rump length measured via ultrasound at 11-13 weeks gestation. The secondary outcomes were perinatal outcomes, including birthweight and the risk of large for gestational age, small for gestational age, macrosomia, low birthweight, and premature delivery. Multivariable linear regression models were used to adjust for potential confounders of crown-rump length. RESULTS: A total of 6742 live singleton births after frozen embryo transfer or fresh embryo transfer were included in this study. In the univariable analysis, the frozen embryo transfer group had a larger crown-rump length (5.75±0.53 cm vs 5.57±0.48 cm, P<.001) and an increased risk of larger-than-expected crown-rump length (13.5% vs11.2%, P=.013) than the fresh embryo transfer group. After adjusting for confounders in multivariable linear regression models, frozen embryo transfer was still associated with a larger crown-rump length (regression coefficient, 3.809 [95% confidence intervals, 3.621-3.997], P<.001). When subgrouped by fetal gender, the crown-rump length of the frozen embryo transfer group was larger than the fresh embryo transfer group in both male and female fetuses. In addition, the crown-rump length was consistently larger in the frozen embryo transfer group than the fresh embryo transfer group in subgroups of the peak estradiol levels. The comparisons among different crown-rump length groups showed that smaller-than-expected crown-rump length was associated with increased risks of small for gestational age (6.3% vs 3.0%, P<.001) and preterm delivery (9.6% vs 6.7%, P=.004) than normal crown-rump length. CONCLUSION: Frozen embryo transfer was associated with a larger crown-rump length than fresh embryo transfer, suggesting that the effect of frozen embryo transfer on fetal growth may begin in the early trimester. Suboptimal fetal growth in the first trimester may be associated with low birthweight and premature delivery.

Topical delivery of chemotherapeutic drugs using nano-hybrid hydrogels to inhibit post-surgical tumour recurrence.

Residual microtumours after surgical resection leading to tumour relapse is one of the major challenges for cancer therapy. Herein, we developed a nano-hybrid oligopeptide hydrogel for topical delivery of a chemotherapeutic drug, docetaxel (DTX), to inhibit the post-surgical tumour recurrence. This nano-hybrid hydrogel (DTX-CTs/Gel) was prepared by encapsulating DTX in cell-penetrating peptide-modified transfersomes followed by embedment in an oligopeptide hydrogel. The obtained DTX-CTs/Gel showed paintable and injectable properties, and could support prolonged retention at the administrated sites after topical administration. DTX-CTs released from the hydrogel presented high skin and tumour penetration capabilities, and increased the accumulation of DTX in the cancer cells leading to enhanced cell death. We showed that the topical delivery of DTX using DTX-CTs/Gel efficiently slowed down the tumour relapse in post-surgical mouse melanoma and breast tumour models.

Formation Mechanism and Biomedical Applications of Protease-Manipulated Peptide Assemblies.

Exploiting enzyme-catalyzed reactions to manipulate molecular assembly has been considered as an attractive bottom-up nanofabrication approach to developing a variety of nano-, micro-, and macroscale structures. Upon enzymatic catalysis, peptides and their derivatives transform to assemblable building blocks that form ordered architecture by non-covalent interactions. The peptide assemblies with unique characteristics have great potential for applications in bionanotechnology and biomedicine. In this mini review, we describe typical mechanisms of the protease-instructed peptide assembly via bond-cleaving or bond-forming reactions, and outline biomedical applications of the peptide assemblies, such as drug depot, sustained release, controlled release, gelation-regulated cytotoxicity, and matrix construction.