"Breakthrough" ideas presented at the 21st COGI Congress, Frankfurt, May 14-16, 2015

The 21st COGI Congress took place in Frankfurt, May 14-16, 2015. The Congress was dedicated to "Innovation in the field of Reproductive Medicine". Papers presented at the Congress included subjects with Innovative topics that crossed disciplines. Some of the presentations introduced "Breakthrough" ideas in the field. Therefore, we found it adequate to be presented on IVF-Worldwide for educational purposes and to encourage discussions in the field.

 

GnRH-agonist triggering for ovulation induction and freeze-all policy (segmented cycles) is now widely used to avoid the risk of OHSS in high responders and in egg donation program.
Due to the profile of the LH surge an intensive luteal support is needed for fresh embryo transfer.
The FSH surge which accompanies the LH surge after GnRH-agonist triggering, is more physiologic and is responsible for several benefits like more favorable gene expression profile of the cumulus and granulose cells, more mature oocytes, better fertilization rates and higher implantation rates.
We successfully changed in 2011 the treatment conception in the Fertility Center Hamburg and integrated the ovulation induction with GnRH-agonist for all ART patients including a very individualized luteal support and fresh embryo transfer.

We are facing a global menopause epidemics as the populations become older.
Menopause causes a long list of sequelae including osteoporosis, cardiovascular disease and many other diseases.
Only a tiny fraction of the ovarian follicles are utilised for providing fertility and the vast majority undergo degeneration.
It is an option to excise ovarian tissue in the young years without affecting fertility and entrance into menopause.
Frozen/thawed tissue restores ovarian function with good efficacy and for at least several years.

In this talk we integrate a number of discoveries made in recent years: (1) Normal androgen levels are crucial for follicle development at small growing follicle stages, with poor androgen levels causing developmental arrest and apoptosis, and in surviving follicles poor egg quality. The decisive androgen is testosterone, acting via the androgen receptor on granulosa cells by sensitizing granulosa cells to FSH. (2) Androgen production in women is shared between ovaries (theca) and adrenals (zona reticularis). Just as the hyperandrogenemia of PCOS has for decades been recognized as ovarian and/or adrenal in nature, so can hypoandrogenemia be ovarian and/or adrenal in origin; (3) Low functional ovarian reserve (LFOR), whether occurring at young ages (called premature ovarian aging, POA, or occult primary ovarian insufficiency, OPOI) or due to physiologic ovarian aging, is almost universally characterized by relative hypoandrogenemia (and therefore relatively high SHBG).

In women with previous failed IVF due to poor embryo development including fragmentation and arrest, decreased mitochondrial energy production may be a problem. Previous clinical trials of cytoplasmic transfer from healthy donor oocytes into the oocytes of women with poor embryo quality resulted in the births of dozens of healthy children. The beneficial effect of cytoplasm injection could be due to several components of the donor cytoplasm including proteins, mRNA or cytoplasmic organelles. Attention was focused on the mitochondria in the cytoplasm with the discovery that some of the children born from this procedure were heteroplasmic with regard to mitochondrial DNA and cytoplasmic transfer and donor mitochondrial injection were put on hold.

Introduction
The Human Genome Project took almost 13 years to complete and some 3 billion dollars in order to generate the first draft of the human genome, which contains 3 billion base pairs (bp). The project was largely based on Sanger sequencing which is capable of sequencing ~1000bp at a time. In recent years, the introduction of Next Generation Sequencing (NGS) has resulted in a precipitous drop in the price of sequencing. The entire human genome can now be sequenced in a matter of days for close to 1000 USD.. Next Generation Sequencing is also called Massive Parallel Sequencing (MPS) because it allows the simultaneous sequencing in parallel of hundreds of millions DNA fragments. This enables the reconstruction of the entire genome – Whole Genome Sequencing (WGS); the determination of the entire coding sequenced of all genes - Whole Exome sequencing (WES); Complete sequencing of selected genes (NGS Panels); and detection of chromosomal aberrations. NGS has been employed in many areas in Medicine including research, personalized-precision medicine, cancer and more. Some of the most significant and commonly used applications are in the field of Reproductive Medicine:

POI is characterized by high circulating levels of follicular stimulating FSH along with amenorrhea before 40 years of age. They are infertile due to a lack of follicle growth and ovulation; oocyte donation is the only effective treatment option. Residual ovarian follicles in these patients are not responsive to traditional gonadotropin treatments. Recently, we developed a method for activation of dormant follicles by using in vitro culture of ovarian fragments treated with Akt stimulators (IVA).