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The findings revealed that the first-time use of an LNG-IUS was associated with an increased risk of developing depression in a dose-dependent manner across low, medium, and high-dose options. 

“While the observational nature of the study does not allow for causal conclusions, the identified dose-response relationship adds to the growing body of evidence indicating a link between levonorgestrel exposure and depression risk,” the researchers wrote.

Levonorgestrel, a synthetic progestin commonly used in various contraceptive methods, has been the subject of scrutiny regarding its mental health implications. Søren Vinther Larsen, Psychiatric Center Copenhagen, Mental Health Services in the Capital Region of Denmark, Copenhagen, Denmark, and colleagues compared the risk of developing incident depression among first-time users of low-, medium-, and high-dose levonorgestrel-releasing intrauterine systems.

The national cohort study utilized Danish register data on first-time users of LNG-IUSs aged 15 to 44 between 2000 and 2022. To calculate the 1-year average absolute risks, risk differences, and risk ratios for incident depression—defined as either starting an antidepressant or receiving a depression diagnosis—Cox regression and a G-formula estimator were employed.

The analysis was standardized for factors such as calendar year, age, education level, parental history of mental disorders, endometriosis, menorrhagia, polycystic ovary syndrome, dysmenorrhea, leiomyoma, and postpartum initiation.

The study led to the following findings:

• A total of 149,200 women started using an LNG-IUS, among whom 22,029 started a low-dose one (mean age, 22.9 years), 47,712 a medium-dose one (mean age, 25.2 years), and 79,459 a high-dose one (mean age, 30.2 years).
• The associated subsequent 1-year adjusted absolute risks of incident depression were 1.21%, 1.46%, and 1.84%, respectively.
• For the users of high-dose LNG-IUSs, the risk ratios were 1.52 and 1.26 compared with users of the low- and medium-dose LNG-IUSs, respectively.
• For users of medium-dose LNG-IUSs, the risk ratio was 1.21 compared with users of low-dose LNG-IUSs.

The researchers suggest that clinicians should advise patients that there is a modest yet elevated risk of depression linked to first-time LNG-IUS use. While this association is not causal, it can provide valuable information to help patients make informed choices regarding their contraceptive options.

“These findings should be considered within the context of the limitations inherent to an observational study design, including the potential for residual confounding. When offering personalized contraceptive counseling, it’s important to balance the observed risk differences against potential benefits and other side effects associated with LNG-IUS use,” the researchers concluded.

Reference:

Larsen SV, Mikkelsen AP, Ozenne B, Munk-Olsen T, Lidegaard Ø, Frokjaer VG. Association Between Intrauterine System Hormone Dosage and Depression Risk. Am J Psychiatry. 2024 Sep 1;181(9):834-841. doi: 10.1176/appi.ajp.20230909. Epub 2024 Jul 10. PMID: 38982827.

The American College of Chest Physicians (CHEST) recently released a new clinical guideline on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen processing and handling. Published in the journal CHEST, the guideline contains nine evidence-based recommendations to identify best practices for collection, processing, and handling of EBUS-TBNA specimens.

“Endobronchial ultrasound-guided transbronchial needle aspiration has become the standard for initial lung cancer diagnosis and staging, but there is little guidance available on handling and processing specimens during and after acquisition to help optimize both diagnostic yield and specimen preservation for downstream ancillary testing,” says Christopher Gilbert, DO, MS, FCCP, lead author on the guideline. “In [the panel’s] experience, sample collection varies widely between institutions. This guideline seeks to leverage learned experiences of both pulmonologists and pathologists to standardize the process.”

Evidence of the handling and processing of EBUS-TBNA specimens varies in strength but is satisfactory in some areas to guide clinicians in certain aspects of specimen handling. The guideline authors conclude that additional research in many aspects of specimen handling and processing is needed to help improve the knowledge base.

The recommendations of the guideline include:

• In patients with suspected malignant disease undergoing EBUS-TBNA, we recommend performing four or more needle passes over three or less needle passes. (Strong Recommendation)
• In patients with suspected malignant disease undergoing EBUS-TBNA, we suggest utilizing rapid on-site evaluation over usual care. (Conditional Recommendation)
• In patients with suspected malignant disease undergoing EBUS-TBNA, we suggest using a smaller needle (21 gauge or 22 gauge) over a larger needle (19 gauge). (Conditional Recommendation)

The entire list of recommendations included in the new guideline can be accessed through the CHEST journal website.

Reference:

Gilbert, Christopher R. et al.,Acquisition and Handling of Endobronchial Ultrasound Transbronchial Needle Samples – An American College of Chest Physicians Clinical Practice Guideline, CHEST Journal, DOI:10.1016/j.chest.2024.08.056.

A study led by researchers at the University of Rochester Medical Center found that breast milk provides protection against rotavirus, a common gastrointestinal disease that causes diarrhea, vomiting and fever in infants. Babies whose mothers had high levels of specific antibodies in their breast milk were able to fend off the infection for a longer period than infants whose mothers had lower levels. The findings are expected to drive future research to improve infant health through optimized breastfeeding practices.

Published in the Journal of Clinical Investigation and funded by the Bill and Melinda Gates Foundation, the study also found significant differences in antibody profiles in breast milk between mothers in high-income countries (HICs) and low- and middle-income countries (LMICs). Researchers analyzed human milk samples from 695 women in Finland, the U.S., Pakistan, Peru, and Bangladesh, and measured specific IgA and IgG antibodies, which are common antibodies produced in breast milk, against 1,607 proteins from 30 pathogens.

The research,led by Dr. Kirsi Jarvinen-Seppo, MD, PhD, professor in the Division of Allergy and Immunology at UR Medicine Golisano Children’s Hospital (GCH), tracked antibody levels and kinetics over time to analyze antibody responses to a wide range of respiratory, diarrheal and sepsis pathogens in human milk. The study’s primary aim was to understand the protective properties of these antibodies and how they vary across different geographic and economic regions.

“We would expect to find differences in antibody levels in different countries, due to different diseases circulating among areas of the world, but this is one of the first times that there’s been a head-to-head comparison for dozens of pathogens across several continents,” said Jarvinen-Seppo. “It was encouraging to see such a clear link between higher antibody levels and a delay to rotavirus infection, and this was consistently observed among an independent validation cohort.”

Other notable findings from the study:

• Milk from women in LMICs had higher levels of IgA and IgG antibodies against various intestinal and respiratory pathogens compared to milk from HICs. This difference was particularly notable for pathogens such as Shigella and pneumococcus, which are major contributors to morbidity and mortality in young children.
• Higher body mass index (BMI) was associated with lower antibody levels, which went against expectations.

“The variation in antibody profiles between regions highlights the impact of economic and environmental factors on maternal immunity,” said Jarvinen-Seppo.

In addition to Rotavirus findings, the discovery that a higher BMI was associated with lower antibody counts in breast milk was also unexpected.

“We had anticipated that underweight mothers might have lower antibody levels due to poorer nutritional status,” said Jarvinen-Seppo. “Due to rising obesity rates worldwide, this could be a significant finding, but this is preliminary and additional research is needed since this is the first time this has been measured.”

“While the data on rotavirus protection is compelling, the geographical and BMI-related variations highlight areas where further research is essential. The study sets the stage for additional investigations that could lead to better understanding and interventions for improving infant health globally,” said Jarvinen-Seppo.

Reference:

Dr. Kirsi Jarvinen-Seppo, Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG, Journal of Clinical Investigation, https://doi.org/10.1172/JCI168789.

This retrospective cohort study examined donor oocyte thaw
cycles using cryopreserved oocytes from Donor Egg Bank USA between 2016 and
2021. The study received institutional review board approval. Donor Egg Bank’s
standardized protocols were followed for donor screening, donor stimulation,
oocyte retrieval, oocyte vitrification, and oocyte shipping. Authors included
donor cycles with oocyte lots that were received by 2 different recipients,
with one undergoing fresh blastocyst transfer and one undergoing
cryopreservedthawed blastocyst transfer. The primary outcome was an ongoing
pregnancy, defined as a viable intrauterine pregnancy at the time of referral
to an obstetrician at approximately 8 weeks of gestation. Secondary outcomes
included additional pregnancy and embryonic development outcomes

A total of 1,210 recipient cycles of cryopreserved donor
oocytes were included (605 underwent fresh ET, 605 underwent
cryopreserved-thawed ET). The distribution for the year of oocyte thawing
between the fresh and frozen ET groups was distributed similarly for both
groups. The 2 groups were identical in regard to donor characteristics given
the sibling oocyte study design (mean age 25.5 years, mean body mass index 23.0
kg/m2 , mean antimullerian hormone level 5.9 ng/mL, mean antral follicle count
28.3). The recipients in the 2 groups were similar in age (mean age: 42.2 vs.
42.0 years). Surgically retrieved sperm was used by 2.8% of the fresh ET group
and 1.3% of the cryopreserved-thawed ET group.

There was no statistically significant difference in the
ongoing pregnancy rate between the fresh vs. cryopreserved-thawed ET groups
(51.2% vs. 49.6%; relative risk 0.97 [95% confidence interval, 0.83–1.14]).
Secondary pregnancy outcomes were also similar between the 2 groups.

Prior studies with mixed findings focused on comparing the
use of fresh vs. cryopreserved donor oocytes in fresh ET cycles or comparing
fresh vs. cryopreserved-thawed ET using fresh donor oocytes. Many patients use
cryopreserved donor oocytes because of their greater availability and access,
shorter time to treatment, and greater ease of cycle synchronization.

This study specifically addressed cryopreserved donor
oocytes and the potential impact of a second ‘‘freeze-thaw’’ on these gametes.

The retrospective study design restricts analysis to data
previously collected; the Donor Egg Bank’s data set did not include additional
recipient demographic information or transfer cycle characteristics, which
limits the ability to account for these potential confounders and the
generalizability of the findings. In conclusion, among patients using frozen
donor oocytes, pregnancy outcomes per donor oocyte thaw cycle were comparable
between recipients undergoing fresh ET compared with recipients using sibling
oocytes undergoing cryopreserved-thawed ET. On the basis of these findings,
patients using cryopreserved donor oocytes should not be deterred from subsequent
embryo cryopreservation.

Source: Lauren Barrison, M.D.a Melissa Stratton, B.A.b Wayne
Caswell, M.S; VOL. 122 NO. 3 /FertilitySterilty

https://doi.org/10.1016/j.fertnstert.2024.04.027

Telomeres are stretches of DNA found at the ends of the
chromosomes. They cap and protect the end of a chromosome like the end of a
shoelace. Telomeres are crucial for the survival of all living cells and
telomere length (TL) is the key to controlling lifespan and aging of a cell.
Previous research hinted at the importance of TL in early human development,
suggesting that abnormal shortening may lead to embryo loss and implantation
failure. In this study, authors directly estimated TL in embryos using
sequencing data from preimplantation genetic testing. The study aimed to
determine if embryos with longer TL have a higher chance of successful
implantation after transfer.

The lifetime TL is established in the early cleavage cycles
following fertilization through a recombination-based lengthening mechanism and
starts erosion beyond the blastocyst stage. In addition, a telomerase-mediated
slow erosion of TL in human fetuses has been observed from a gestational age of
6–11 weeks. Finally, an abnormal shortening of telomeres is likely involved in
embryo loss during early development.

Blastocyst samples were obtained from patients who underwent
PGT-A and FET in an IVF center from March 2015 to May 2018. Digitally estimated
mitochondrial copy number (mtCN) and TL were used to study associations with
the implantation potential of each embryo. In total, 965 blastocysts from 232
cycles (164 patients) were available to investigate the biological and clinical
relevance of TL. A WGS-based workflow was applied to determine the ploidy of
each embryo. Data from low-pass WGS-PGT-A were used to estimate the mtCN and TL
for each embryo.

Of the 965 blastocysts originally available, only 216
underwent FET. While mtCN from the transferred embryos is significantly
associated with the ploidy call of each embryo, mtCN has no role in impacting
IVF outcomes after an embryo transfer in these women. The results indicate that
mtCN is a marker of embryo aneuploidy. On the other hand, digitally estimated
TL is the most prominent univariant factor and showed a significant positive
association with pregnancy outcomes (P < 0.01, odds ratio 79.1).

Study combined several maternal and embryo parameters to
study the joint effects on successful implantation. The machine learning
models, namely decision tree and random forest, were trained and yielded
classification accuracy of 0.82 and 0.91, respectively. Taken together, these
results support the vital role of TL in governing implantation potential,
perhaps through the ability to control embryo survival after transfer.

In this study, authors directly estimated TL in embryos
using sequencing data from preimplantation genetic testing. The study aimed to
determine if embryos with longer TL have a higher chance of successful implantation
after transfer. These findings highlight that blastocyst TL is a critical
factor influencing implantation potential, likely because of its role in
controlling embryo survival after transfer. In an attempt to reduce to time to
pregnancy in the in vitro fertilization (IVF) processes, authors studied
various maternal and embryo parameters, including TL, that have a high impact
on successful implantation into an artificial intelligence model suitable for
routine use in IVF clinics. Prioritizing embryos based on implantation
potential is vital in clinical infertility treatment, aiming to reduce twin
pregnancies and shorten waiting times during IVF. The predictive model
developed in this study offers a valuable tool to enhance clinical practice,
providing an optimized approach for individuals facing fertility challenges to
increase their chances of achieving parenthood.

Source: Chien et al.; Human Reproduction Open, 2024,
2024(2), hoae012