REVIEW AND COMMENTARY ON RECENT LITERATURE IN REPRODUCTIVE MEDICINE
The staff of THE REPRODUCTIVE TIMES here offers commentaries on recently published articles, primarily chosen for educational values—in the positive but also in the negative—for clinical purposes, and for their potential translational values to clinical medicine when addressing basic science issues.
September 11, 2024. Revised with permission from the September CHR VOICE.
SUBJECT: Drug use and abuse
More on cannabis use
With the rapidly expanding use of cannabis products in the country following most states’ legalization of this “product,” use in pregnancy has also skyrocketed. Unsurprisingly, adverse effects on pregnancy have, therefore, been increasing in parallel. How much of this message is reaching the public through government efforts and/or media has, however, despite increasing number of publications, remained frustratingly low.
Two recent publications are good examples: U.S. investigators looked at self-reported prenatal cannabis use in 316,722 pregnancies and maternal pregnancy outcomes.1 Though overall 6.3% screened positive, only 2.9% self-reported; 0.6% used daily, 0.7% weekly, 1.5% monthly or less, and the rest were unknown. Prenatal use was associated with increased risk of gestational hypertension, preeclampsia, smaller or larger than recommended weight gain, and placental abruption.
As an observational study, cannabis use cannot be considered directly responsible for these findings since outcomes obviously could not be adjusted for confounders, including social confounders. The data, nevertheless, are concerning because they just reaffirm what other studies have shown.
An essay by Megan Brooks after interviewing several experts on the subject for Medscape Medical News concentrated on the effects of current-day high-potency cannabis (no longer the fathers’ and grandfathers’ strength) on the adolescent brain because this age group’s brains have been reported especially vulnerable to cannabis. Yet cannabis use (or should we call it “abuse”) has since 2000 increased by about 254% in the U.S. The consequences in adolescents and young adults are especially concerning because those are also the ages when psychoses for the first time become apparent and cannabis, especially in young males, has been shown to trigger psychotic episodes.2
References
1. Young-Wolff et al., JAMA Internal Medicine 2024;e243270
2. Brooks M. Medscape Medical News. May 13, 2024. https://www.medscape.com/ viewarticle/high-potency-cannabis-tied-im- paired-brain-development-2024a1000935?- form=fpf
SUBJECT: Basic science research
Embryo and endometrial implantation models
Investigators, ethicists, and laypeople have for several years been expressing concerns about the lack of ethical guidelines for an abundance of rapidly evolving laboratory-grown embryo models. Now the U.K. developed and published in July a first code of behavior for the use of human embryo models (see Key-points in BOX I).1
The creation of the Code—its full title being, “Code of Practice for the Generation and Use of Human Stem Cell-Based Embryo Models”—was led by Cambridge Reproduction, an interdisciplinary research center at the University of Cambridge, in partnership with the Progress Educational Trust, a charity, and was funded by the BBSRC, the University of Cambridge Impact and Knowledge Exchange Fund, and UKRI Sciencewise. The complete guideline can be downloaded here. As a brief commentary in Nature magazine noted, countries are grappling with how to regulate research that uses stem-cell-based embryo models. They will be watching the U.K.’s voluntary approach2 (described in this document).
Somewhat related, Chinese investigators, who have made enormous progress in the field, in a reviewed preprint in eLife reported on a human receptive endometrial organoid with the purpose of deciphering
the black box of implantation.3 The journal’s editorial assessment of this preprint was: “This study presents a valuable development of endometrial organoid culture methodology that mimics the window of implantation. Functional validation to demonstrate its robustness is lacking; therefore, the study is considered incomplete. The data may be interesting to embryologists and investigators working on reproductive biology and medicine.”
One question this model and the editorial comment immediately raises is whether the above noted British Code would allow for implantation experiments of artificial human embryos using this implantation model?
References
1. https://www.repro.cam.ac.uk/scbemcode
2. Mallapaty A. Nature 2024;631:259-260
3. Zhang et al., 2024. https://doi.org/10.7554/eLife.90729.2. July 19, 2024
The amazing plasticity of the primitive endoderm
Another amazing paper, this time from Danish investigators, reported that the primitive endoderm of a blastocyst-stage embryo, derived from splitting of the inner cell mass into embryonic epiblast (producing the fetus from the so-called embryonic cell lineage) and primitive endoderm (producing the trophectoderm and placenta from the so-called extraembryonic cell lineage) has so much plasticity and potency that it can regenerate a complete blastocyst which continues post-implantation development.1
This is not only an astonishing finding, but should convince even the most extreme skeptics that a blastocyst-stage embryo can self-correct from having aneuploid cells.
Reference
1. Linnenberg-Agerholm et al Cell 2024;S0092-8674(24)00595-6