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PubMed2026

Intermediate FMR1 cytosine‒guanine‒guanine repeats do not impair assisted reproductive technology outcomes in a large real-world cohort.

RESEARCH QUESTION: Does the presence of moderately elevated FMR1 cytosine‒guanine‒guanine (CGG) repeat numbers (40-70 repeats), identified through routine pre-pregnancy screening, adversely affect assisted reproductive technology (ART) outcomes in a real-world population? DESIGN: Retrospective cohort study including 760 first ART cycles conducted between 2010 and 2021 at a university-affiliated centre. FMR1 CGG repeat testing was conducted independently of infertility evaluation. Patients were categorized by repeat status in both alleles using two thresholds: 40 or more repeats (primary analysis) and 34 or more repeats (secondary analysis). Ovarian reserve markers, stimulation characteristics, oocyte yield, embryologic outcomes, positive beta-HCG and live birth rates were compared across groups. RESULTS: Among 760 patients, 669 (88%) had no allele of 40 or more repeats, 85 (11%) had one allele of 40 or more repeats and six (0.8%) had two alleles of 40 or more repats. The maximum observed repeat length was 71. Baseline demographics and ovarian reserve markers were similar between groups. No differences were observed in ovarian response, oocyte yield, fertilization or embryo development by FMR1 repeat category. Pregnancy and live birth rates were comparable between controls and patients with one expanded allele. Although elevated pregnancy and live birth rates were observed in patients with two expanded alleles, this subgroup was small, limiting interpretation. Analyses using the 34 or more repeat threshold yielded similar findings. CONCLUSIONS: Moderately elevated FMR1 CGG repeat numbers are not associated with impaired ART outcomes. Standard ART protocols remain appropriate, and FMR1 repeat length alone should not guide treatment modification in the absence of clinical ovarian insufficiency.

Humans↗

PubMed2026

Autophagy activation in granulosa cells as a mechanism of astaxanthin action: evidence from a pilot randomised trial in PMOS-associated infertility.

Astaxanthin (AST) has been reported to influence oxidative stress, endoplasmic reticulum stress, and apoptosis in women with polyendocrine metabolic ovarian syndrome (PMOS), formerly referred to as polycystic ovary syndrome (PCOS), but its effects on granulosa-cell (GC) autophagy remain unclear. Given the central role of autophagy in follicular development, this triple-blind, placebo-controlled pilot randomised trial evaluated whether AST modulates autophagy-related signalling in GCs and how these molecular effects relate to ovarian response. Fifty women with PMOS-related anovulatory infertility were enrolled between November 2023 and September 2024 and received AST (12 mg/day) or placebo for six weeks prior to oocyte retrieval; forty-four completed the study (21 AST, 23 placebo). Primary exploratory endpoints were molecular markers of adenosine monophosphate-activated protein kinase (AMPK)-autophagy signalling, and primary clinical outcomes included ovarian response indicators and cleavage stage embryo quality. AST supplementation increased autophagy-related gene 7 (ATG7) expression, enhanced autophagy flux, reduced apoptosis, and showed a trend toward increased AMPK activation. Before adjustment, AST improved oocyte maturity rate (OMR) and increased mature (metaphase II; MII) oocyte yield. After adjusting for age, body mass index, and anti-mullerian hormone level, total oocyte and MII oocyte yields remained significantly higher with AST, while OMR became non-significant. Among embryology outcomes, both the top-ranking embryo rate and the number of embryos suitable for cryopreservation were significantly higher with AST after adjustment. Pregnancy outcomes were numerically higher but not statistically significant. This pilot trial suggests that AST activates autophagy- and apoptosis-related pathways in GCs and may enhance oocyte competence and embryo quality in PMOS. Larger studies are needed to confirm these mechanistic and clinical effects.

Female↗

PubMed2026

IVM rescue: Effect of growth hormone supplementation combined to autologous cumulus co-culture on GV oocyte maturation and competency.

OBJECTIVE: IVM rescue is based on the in vitro maturation of mainly Germinal Vesicle (GV) oocytes collected from stimulated cycles. The objective was to investigate the effects of growth hormone (GH) and autologous cumulus cells co culture (CC) on oocyte meiosis resumption and maturation after 32 h post cumulus denudation, in order to obtain additional embryos for the couple as a rescue system to increase the changes of cumulative pregnancy. MATERIAL AND METHODS: Our study concerned 300 patients who underwent ICSI cycles, during which a total of 1940 cumulus-complex-oocytes were retrieved, giving 1260 metaphase II stage (MII), 200 at the metaphase I stage, and 480 at the Germinal Vesicle (GV) stage. Mature oocytes were microinjected on the same day of retrieval. Immature GV oocytes were divided into four groups, with the first undergoing in vitro maturation (IVM) without cumulus cells (group 1) and the second undergoing IVM with CC (group 2), the third undergoing IVM without CC and with GH (group 3), the fourth undergoing IVM with CC and with GH (group 4). After 32 h of IVM, the matured oocytes, underwent microinjection, followed by embryonic development monitoring. RESULTS: When comparing the IVM outcomes, we observed a significant increase in oocyte maturation, fertilization rates and the percentage of 8-cell embryos on day 3 across the different study groups (p < 0.001) (Figs. 2-5). Furthermore, all study groups (1-4) exhibited notably blastulation rates, with group 3 demonstrating the most promising clinical outcomes. A preliminary pregnancy rate of approximately 20% was recorded in group 3, suggesting a potential improvement in the developmental competence of oocytes matured under specific conditions. CONCLUSION: The IVM rescue of germinal vesicle oocyte could serve as an additional strategy to increase the chance getting extra embryos to patients. Autologous cumulus cells co-culture combined to GH supplementation to IVM media, appear to play a crucial role to enhance successful meiosis resumption, oocyte maturation and competency to support embryos development when the injected spermatozoa is not carrier of severe genome and epigenomic decays.

Humans↗

PubMed1977

Aberrant left pulmonary artery. Clinical and embryologic factors.

The case of an infant with a pulmonary arterial sling (or aberrant left pulmonary artery) is presented. Associated congenital anomalies found in the original patient and in each of four other patients with this lesion, identified from postmortem files, are noted. The importance of associated anomalies of the respiratory tract is emphasized, since if present, they may affect the outcome after sucessful surgical correction of the vascular lesion. Previous theories of the embryologic origin of the anomalous artery are discussed, and a new theory is presented.

Abnormalities, Multiple↗

PubMedDate not supplied

[Functional laryngectomy using a technic of subperichondrial laryngeal curettage].

A new technique of functional laryngectomy using sub-perichondral curettage of some or all of the soft parts of the larynx is described. This method has an embryological and anatomical basis. It is supported by a score of cases which have had a satisfactory outcome, all the patients operated on having been decannulated. Histopathological research was continued with a view to confirming the function of the perichondrium and the cartilage as a barrier to neoplastic invasion.

Connective Tissue↗

PubMed1992

Absence of effect of adjuvant growth hormone therapy on follicular responses to exogenous gonadotropins in women: normal and poor responders.

OBJECTIVE: To examine the effects of growth hormone (GH) on ovarian responses to exogenous gonadotropins after pituitary desensitization in normal and poor responder patients undergoing in vitro fertilization. DESIGN: A prospective study with comparison of control and GH-treated cycles. PATIENTS: Poor responder patients (n = 10) required > 44 ampules of human menopausal gonadotropin (hMG) to achieve criteria for administration of human chorionic gonadotropin (hCG) on day 0 or cancellation in control cycles, and normal responder patients (n = 10) required < 45 ampules. MAIN OUTCOME MEASURES: Ovarian responses to hMG assessed by duration of stimulation required to achieve first significant estradiol (E2) response and hCG criteria. Total doses and duration of hMG, follicular development and E2 concentrations on day 0, and embryology were also assessed. RESULTS: Growth hormone showed no effect on any of the parameters studied in either patient group. CONCLUSION: Follicular recruitment, E2 secretion by mature follicles, and oocyte yield and quality were uninfluenced by GH treatment.

Adult↗

PubMed1977

Ectopia in unduplicated ureters in children.

The clinico-pathological features and surgical management of 19 unduplicated ectopic ureters in 15 children are presented with special reference to the problems of recognition and treatment and to the underlying embryological and pathological significance of the wide-ranging associated abnormalities. The high incidence of renal and ureteric malformations, both ipsilateral and contralateral, is emphasised, as is also the frequent co-existence of vesical, bladder neck, urethral, genital and anal abnormalities. These associated anomalies modify the presentation of unduplicated ureteric ectopia and may mask its presence. Late recognition is common, but may be avoided by awareness of the problem. Whereas the degree of kidney involvement seems to dictate the choice and priorities of surgical treatment, the lower urinary tract anomalies have more significance as regards continuing disability and these largely determine the outcome in relation to continence.

Anal Canal↗

PubMed1992

Musculoskeletal aspects of prune-belly syndrome. Description and pathogenesis.

OBJECTIVE: To determine the types and prevalence of musculoskeletal involvement in children with prune-belly syndrome, and to analyze the pathogenesis of the syndrome in relationship to the musculoskeletal deformities. DESIGN: A retrospective review of charts and roentgenograms along with a comprehensive review of 188 cases from the literature. SETTING: Tertiary care children's hospital. PARTICIPANTS: Twelve boys treated between 1975 and 1990. MEASUREMENTS/MAIN RESULTS: The prevalence of musculoskeletal involvement in patients was 45%. The involvement can be congenital (eg, clubfeet, limb deficiencies, teratologic hip dysplasia, and vertebral malformations) or developmental (eg, renal osteodystrophy, scoliosis, and pectus excavatum and/or pectus carinatum). The embryologic characteristics of congenital musculoskeletal problems correlate better with the embryologic theory of the prune-belly syndrome (an aberration of mesenchymal development around 6 weeks of gestation) than with the distal urinary tract obstructive theory. CONCLUSION: Since children with prune-belly syndrome are now living into adulthood, these musculoskeletal aspects will become important regarding potential morbidity.

Adolescent↗

PubMed1992

Oxygen as a cause of blindness in premature infants: "autopsy" of a decade of errors in clinical epidemiologic research.

Several intellectual "autopsies" have recently reviewed errors in clinical epidemiologic studies of causation, such as the original claim that amyl nitrite "poppers" caused AIDS. The current autopsy was done to determine why it took more than a decade--1942 to 1954--to end an iatrogenic epidemic in which high-dose oxygen therapy led to retrolental fibroplasia (RLF) in premature infants, blinding about 10,000 of them. The autopsy revealed a museum of diverse intellectual pathology. When first noted, RLF was regarded as neither a new disease nor a postnatal effect. In early investigations, the ophthalmologists did not establish explicit criteria for diagnosis and confused RLF with malformations previously seen in full-term infants. Because the patients were not referred until months after birth, the ophthalmologists assumed that the lesion, which resembled an embryologic structure, must have occurred prenatally. Other events suggesting a prenatal cause for RLF were its strong statistical associations with fetal anomalies, multiple gestations, and maternal infections. Although these events were also associated with prematurity, it was ignored when the RLF cases were compared with controls who were mainly full-term infants. The postnatal timing of RLF was eventually recognized when investigators did cohort studies in premature infants and found that RLF could develop in eyes that were normal at birth. As the search for a cause turned to events occurring after birth, statistical associations were produced for agents such as light, vitamins, iron, vitamin E deficiency, and hypoadrenalism. Each study had its own methodologic flaws: controls were missing for light; co-maneuvers were ignored for vitamins and iron; objective diagnosis was not used for vitamin E deficiency; and the research on hypoadrenalism contained biases in susceptibility and detection as well as problems of a competing outcome event. When the role of oxygen administration was first considered, the statistical association with RLF was stronger for vitamin- and iron-therapy than for oxygen. In addition, many investigators were dissuaded by contradictory evidence from institutions in which RLF was either absent despite high-dose oxygen or persistent despite reduced dosage. The contradictory evidence was later regarded as erroneous because of unsatisfactory delivery systems for the oxygen or failure to check the actual oxygen concentrations. An alternative explanatory hypothesis, rejecting the role of high-dose and long-duration oxygen, was the idea that RLF was due to "relative hypoxia", produced by overly rapid weaning from oxygen therapy rather than the duration of oxygen treatment itself.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗