Dehydroepiandrosterone (DHEA) supplementation in women with low functional ovarian reserve

Conflict statement

We want to point out to readers of this article that The Center for Human Reproduction (CHR) holds a number of patents, which claim therapeutic benefits from androgen/DHEA supplementation of selected infertile women. CHR and some CHR employees, including this author, receive royalty payments from two companies, which have licensed these patents and, therefore, are entitled to use these claims in their marketing efforts. Moreover, Dr. Gleicher is a shareholder in one of these companies, Fertility Nutraceuticals, LLC.

Background

DHEA is the most abundant steroid hormone in our bodies, and is the precursor hormone for all sex hormones. It, in itself, has very low affinity to the androgen receptor (AR) (and mild affinity to the estrogen receptor) and, therefore, is functionally almost inert as an androgen. Moreover, DHEA within minutes from ingestion is metabolized to DHEAS. Both, DHEA and DHEAS, as storage forms, usually are to a degree in balance in the circulation, constantly changing back and forth. Increasing evidence suggests that this allows different organs to take up sufficient DHEA to produce organ-specific testosterone (T)-levels. It appears that, aside from ovaries and adrenals, other organs, for example, liver, endometrium, etc. also have the apparatus to produce T from DHEA. The overwhelming amount of T in the woman comes, however, almost evenly, from ovaries and adrenals.

The apparatus for adding a sulfate group to DHEA to produce DHEAS, however, exists almost exclusively only in the zona reticularis of the adrenals. This is diagnostically important, and is also important when patient under DHEA supplementation are clinically monitored: Since DHEA and DHEAS should be in reasonable balance, DHEA supplementation should result in quick increases in DHEA as well as DHEAS.

If only DHEA rises, the patient likely suffers from deficiency of sulfotransferase enzymes (SULT1A1 and SULT1E1) in the zona reticularis, and DHEA supplementation will, likely, not lead to adequate increases in T. Such patients then need to be directly supplemented with T.

It is also important to note that the zona reticularis shrinks with advancing age and, therefore, DHEAS levels decline as women (and men) are getting older.

Open versus closed systems for vitrification of human oocytes and blastocysts

      Vitrification has resulted in a watershed in human embryology during the past decade. This approach enabled safe and efficient cryopreservation of human oocytes and blastocysts allowing efficient application of ART procedures such as elective single blastocyst transfer (eSET) and preimplantation genetic screening (PGS), and opening new possibilities for patients including preservation of fertility for both medical and nonmedical reasons, and resolving many logistic problems during oocyte donation. However, the path was not smooth, and continuous concerns are risen re. Safety issues including long term consequences, potentially toxic cryoprotectant components, and first of all, dangers of disease transmission mediated by liquid nitrogen. Vitrification methods are commonly divided in two categories: open systems allow and closed systems eliminate direct contact with liquid nitrogen – consequently open systems are safe, and closed systems are unsafe.

Universal warming protocol: comments on EM 233, issues 5-6-7 and EM 234

Nowadays, human oocytes/embryos are cryopreserved via slow freezing (SF) or vitrification (VIT). Due to the high survival rate guaranteed by VIT, this procedure is increasingly applied worldwide. Nevertheless, to date, perhaps millions of SF oocytes/embryos have already been stored in IVF cryobanks. The aim of this study was to evaluate a rapid warming protocol for SF human oocytes based on the standard warming procedure for VIT in order to optimize the SF survival rate and reduce costs by using the same solutions for both SF and VIT warming. Between December 2012 and January 2013, 216 SF oocytes donated for research were randomized for the rapid thawing (RT) conventionally used for SF oocytes, or rapid warming (RW) as for VIT protocols.

Preimplantation Sequencing: a new era for PGD/PGS?

Embryology has been again in the focus of news with the birth of a child after genome sequencing from a biopsied embryo was born. The birth was announced at the ESHRE, London, July 2013 as last minute, unpublished achievement, and has become a major sensation, breaking news in TVs, front page reports in leading journals all over the world.

Although achievement was respectable, the reported priority was not entirely justified. Just in the previous abstract in the conference proceedings (that was available in printed form at the time of announcement; Li et al, Clinical application of massively parallel sequencing on chromosomal abnormalities detection of human blastocysts. Hum Reprod 2013, 28 (Suppl. 1): i26) BGI Shenzhen, China, in collaboration with CITIC Xiangya Hospital, Changsha, China has reported 7 babies after PGS with whole genome sequencing, and the number of births is growing exponentially. Maybe China is still far away for the Western world, but - getting closer...

Risk and Safety Management (RSM) in Infertility and ART: A Proactive Recipe

(1)Université Paris Descartes, Paris Sorbonne Cité – Assistance Publique Hôpitaux de Paris, CHU Cochin, Department of Obstetrics and Gynecology, Division of Reproductive Medicine, Paris, France. (3)Department of Obstetrics and Gynecology, Division of Reproductive Medicine, Hopitaux Universitaires de Genève, Genève Switzerland. (4)Department of Biomedicine, Research Group on Gynecological Endocrinology, University Hospital, University of Basel, Basel, Switzerland
Address for correspondence: Dom de Ziegler, MD This email address is being protected from spambots. You need JavaScript enabled to view it.

Summary

     It has become commonplace to proffer that medicine lags behind other industries when it comes to safety records. These are indeed deplorable in medicine worldwide, even if significant efforts have been deployed for curbing the mega-mistakes – wrong patient, wrong side, wrong organ – notably, by implementing checklists and other aviation-derived products.

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