Jan-Steffen Krüssel

Expression of vascular endothelial growth factor mRNA in human preimplantation embryos derived from tripronuclear zygotes

OBJECTIVE To detect the expression of vascular endothelial growth factor (VEGF) mRNA and/or secretion of VEGF protein by human preimplantation embryos. DESIGN Human preimplantation embryos not suitable for uterine transfer were examined for beta-actin and VEGF mRNA expression. Culture media from normally fertilized and developing preimplantation embryos were assessed for VEGF protein secretion. SETTING Clinics and academic research laboratories at the Departments of Obstetrics and Gynecology at the Stanford University, Palo Alto, California and the Heinrich-Heine-University, Düsseldorf, Germany. PATIENT(S) Couples undergoing IVF by intracytoplasmic sperm injection for various reasons. INTERVENTION(S) Six unfertilized oocytes and 33 pathologically fertilized (tripronucleic, 3PN) preimplantation embryos were examined for VEGF mRNA expression, and 16 embryos were examined for VEGF protein secretion. MAIN OUTCOME MEASURE(S) Embryonic expression of VEGF mRNA and VEGF protein as determined by reverse transcription (RT)/nested polymerase chain reaction (PCR) and ELISA. RESULT(S) VEGF mRNA and protein could not be detected in unfertilized oocytes. However, 30/33 preimplantation embryos did express VEGF mRNA (11/12 10-to-16-cell embryos, 3/4 morulae, 11/12 early blastocysts, 5/5 hatched blastocysts). The VEGF protein level was below the sensitivity of the ELISA. CONCLUSION(S) Production of VEGF may give the embryo the ability to induce neoangiogenesis at the implantation site, thus creating an environment necessary for its survival.

Endometriosis doubles odds for miscarriage in patients undergoing IVF or ICSI

OBJECTIVE To identify and estimate the importance of risk factors on pregnancy loss until the end of the second trimester after clinical pregnancy was achieved by either in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI). STUDY DESIGN Retrospective cohort study including 588 cycles with fresh embryo transfers and 150 cycles with frozen-thawed embryo transfers using logistic regression. RESULTS The rate of miscarriages subsequent to a fresh embryo transfer was significantly increased by a diagnosis of endometriosis (p=0.02), as well as significantly influenced by the age of the female patient at the time of oocyte retrieval (p<0.01) and the serum level of testosterone (p=0.02). The time between freezing and thawing of the pronuclear stages for a frozen-thawed embryo transfer revealed a trend to a higher rate of miscarriages (p=0.06). CONCLUSION Endometriosis significantly decreases the chance of having a baby even with IVF or ICSI.

S2k-Leitlinie: Fertilitätserhaltende Maßnahmen bei onkologischen Erkrankungen

ZusammenfassungOnkologische und nichtonkologische Erkrankungen können die gegenwärtige oder zukünftige Fertilität beeinträchtigen, entweder durch die Krankheit selbst oder durch notwendig chirurgische Eingriffe, hormonelle und/oder gonadotoxische Behandlungen. Sie erfordern damit einen adäquaten fertilitätsprotektiven Ansatz – sprich eine unbedingte Beratung und, wenn die Voraussetzungen gegeben sind, auch eine entsprechende fertilitätsprotektive Therapie. Die Kryokonservierung von Oozyten stellt zumeist die Methode der ersten Wahl bei postpubertären Frauen dar. Metaphase-II-Oozyten-Kryokonservierung mittels Vitrifikation ist dabei die bevorzugte und empfohlene Option. Aber auch der kumulative Nachweis der Wiederherstellung der endokrinen Ovarialfunktion und der daraus resultierenden spontanen bzw. nach orthotoper Transplantation von kryokonserviertem Ovarialgewebe und Einsatz unterstützender assistierter reproduktionsmedizinischer Techniken resultierenden Schwangerschaften und Geburten spricht für diese Methode als offene klinische Anwendung – insbesondere bei präpubertären Mädchen, die nicht minder von keimzellschädigenden Behandlungen betroffen sind als adoleszente oder adulte Patientinnen im fertilen Alter und bei denen keine andere nachweislich wirksame Option zum Fertilitätserhalt derzeit verfügbar ist.AbstractOncological and nononcological diseases can affect current or future fertility, either through the disease itself or through necessary surgery, hormonal and/or gonadotoxic treatments. They therefore require an adequate fertility-protective approach—i. e. counselling is essential and, if the prerequisites are met, an appropriate fertility-protective therapy. Cryopreservation of oocytes is usually the first-choice method for postpubertal women. Metaphase II oocyte cryopreservation by vitrification is the preferred and recommended option. However, cumulative evidence of restoration of ovarian endocrine function and resulting spontaneous pregnancies and births, or after the use of assisted reproductive techniques, after orthotopic transplantation of cryopreserved ovarian tissue also advocates this method as an open clinical application, especially in prepubertal girls who are no less affected by germ cell-damaging treatments than adolescent or adult patients of reproductive age and for whom no other possible option for fertility preservation is currently available.

Concept Paper on the Technique of Cryopreservation, Removal and Transplantation of Ovarian Tissue for Fertility Preservation

The cryopreservation of ovarian tissue with subsequent transplantation of the tissue represents an established method of fertility protection for female patients who have to undergo gonadotoxic therapy. The procedure can be performed at any point in the cycle and thus generally does not lead to any delay in oncological therapy. With the aid of this procedure, more than 130 births to date worldwide have been able to be recorded. The birth rate is currently approximately 30% and it can be assumed that this will increase through the further optimisation of the cryopreservation and surgical technique. The concept paper presented here is intended to provide guidance for managing cryopreservation and transplantation of ovarian tissue to German-speaking reproductive medicine centres.

Possible Reasons for Discontinuation of Therapy: an Analysis of 571 071 Treatment Cycles From the German IVF Registry

Introduction Numerous couples discontinue fertility treatment before achieving the objective, the birth of a child. The aim of this retrospective data analysis is to identify the reasons for early discontinuation of therapy (drop-out). Materials and Methods Retrospective data analysis. With the aid of the German IVF Registry (D·I·R ® ), a total of 122 560 “last cycles” in Germany in the period 2012 – 2015 were identified and the courses were analysed. Results From the named cohort of “last cycles”, 37.3% of the female patients (45 699) gave birth to a child and ended the therapy. The remaining 76 861 discontinued the treatment before having a child. The fertility treatment was conducted due to a purely male indication in 46.27% of cases and in 17.96% the cause lay exclusively with the woman. 4.53% of the drop-outs suffered a miscarriage in the last cycle. 73.56% of the drop-out patients ended the therapy after the lack of a positive pregnancy test. After the third therapy cycle, 67% of the couples ended their treatment. Conclusion The results make it possible to provide couples with individual counselling. They offer an option for preparing for the emotional and physical hurdles.