It is always a special pleasure when an opportunity arises to mention favorably a New York City colleague. Such an opportunity presented itself with the recent publication of a study by Kara Goldman, MD, Assistant Professor in the Reproductive Endocrinology and Infertility Division of the Department of Obstetrics and Gynecology at New York University (NYU), who with colleagues in the very prestigious journal Proceedings of the National Academy of Sciences (PNAS) recently published a very interesting study, potentially pointing to a pharmacological solution how the loss of ovarian function from chemotherapies can be prevented [Goldman et al., mTORC1/2 inhibition preserves ovarian function and fertility during genotoxic chemotherapy (2017;114:3186-3191)].
Though this study was conducted in a mouse model (and men are not mice), it strongly suggests that blockage of the so-called kinase mammalian/mechanistic target of rapamycin, (called mTOR) with already existing small molecule inhibitors preserves ovarian follicles during chemotherapy that, otherwise, would be destroyed. To demonstrate this effect, the investigators induced in a mouse model gonadotoxicity by administering cyclophosphamide, while inhibiting mTOR complex 1 with everolimus (RAD001) or mTOR complex 1/2 with the still experimental drug INK128. So treated animals preserved their ovarian reserve when treated with gonadotoxic drugs, as demonstrated by stable primordial follicles, anti-Müllerian hormone levels (AMH) and overall fertility.
These are extremely exiting findings because if such treatment can be confirmed as equally efficient in preserving ovarian function in young women undergoing chemotherapy, other methods of fertility preservation, like oocyte or even ovarian tissue cryopreservation would become unnecessary. Interestingly, Everolimus (Afinitor®, Novartis) is already widely used in cancer treatments (advanced renal and advanced HR+, HER2-Negative breast cancers) and as an immunosuppressant in prevention of organ rejection and, therefore, off-label could be tested very quickly. This study was considered of enough importance to be summarized by Science in its April 21, 2017 issue. We congratulate our NYU colleagues on this accomplishment.
An issue that received considerable attention in the media recently was the length human embryos can be cultured in vitro in the laboratory. Currently worldwide respected limits mandate termination of human embryo cultures not later than 14 days after fertilization. Two in vitro implantation studies of human embryos published in 2016 by the laboratories of Ali Brivanlou, PhD (Rockefeller University, N.Y.) and Magdalena Zernicka-Goetz, PhD (Cambridge University, U.K.), at the time reviewed here, however, challenged these limits, as embryos, completely self-sufficient, appeared to develop up to day-14, and, likely, could have been grown much longer.
A recent paper in the journal eLife by George Church, PhD and co-workers at Harvard University ignited flames of controversy, when actually recommending an even more structured set of guidelines than are currently in place. The Wall Street Journal on March 22, 2017 dedicated almost a full page to the subject with Ali Brivanlou, PhD, representing the contrarian view point. Brivanlou, of course, is also a Senior Visiting Scientist at CHR, and CHR investigators maintain a close collaboration with his Stem Cell and Molecular Embryology Laboratory at Rockefeller University.
This is a part of the May 2017 CHR VOICE.