Reproduktionsmedizin in Deutschland

The legal basis of reproductive medicine is the Embryo Protection Act (EPA). According to this law, without exception, in vitro fertilization can only be performed to achieve pregnancy in the woman from whom the ovum was harvested. During the course of a single cycle only as many embryos may be developed as will be transferred to the woman up to a maximum of three (“rule of three”). Preimplantation genetic diagnosis and egg donation are prohibited. Safety standards for handling gametes and embryos are governed by the Transplantation Law. The EPA is incomplete. Enactment of a law on reproductive medicine is required which provides comprehensive regulation of the medical technology used for assisted fertilization and the subsequent problems involved. The EPA allows for advancements in scientific knowledge and techniques of reproductive medicine only to a limited extent. The so-called eSET/eDET as practiced in other countries is not permitted due to the“rule of three.” This rule, however, is in fact interpreted partly in opposition to the explicit wording and intended purpose of the regulation and from a legal standpoint is no longer considered definitive. The validity of the rule of three has to be elucidated by the legislature. Preservation of gametes, pronuclei, and embryos as well as the prerequisites for their destruction also need to be regulated, especially when eSET/eDET or comparable procedures of morphological evaluation and selection are applied before transfer since surplus embryos regularly accumulate. A law on reproductive medicine would have to define the modalities for documenting the source of the donated sperm, regulate the child’s right to access information on its biological heritage, and clarify the validity of the rule of three.     

Infektionen in der Reproduktionsmedizin

Infectious diseases may play an important role in human reproduction: They can cause male/female infertility/sterility. ART (assisted reproductive techniques) can facilitate/induce infectious diseases. Infectious diseases can complicate a pregnancy arising from ART. Official guidelines for ART postulate that before treatment certain infectious diseases such as hepatitis and/or HIV should be excluded in both partners. This article addresses the above-mentioned issues and highlights that some of the potential infectious risk factors are theoretical risks rather than real clinical problems.     

Infektionen in der Reproduktionsmedizin

Infectious diseases play an important role in human reproduction:

they can cause male/female infertility/sterility,

ART (assisted reproductive therapy) can facilitate/induce infectious diseases,

infectious diseases can complicate a pregnancy arising from ART,

official guidelines for ART postulate that before treatment certain infectious diseases such as hepatitis and/or HIV should be excluded in both partners.

This article addresses the above mentioned issues and highlights that some of the potential infectious risk factors are rather theoretical risks than real problems.     

HIV-Infektion in der Reproduktionsmedizin

Responsibility conscious HIV discordant couples require interdisciplinary medical advice and support at the fulfillment of her child wish on the base of a thorough diagnosis of infertility reasons as well as psychological support also focusing on social circumstances. In HIV infection of the man motile spermatozoa can get separated out of the ejaculate and can be used for IUI, IVF or ICSI after detection using a highly sensitive proof method. The standards reached today could dispel legal and medical doubts largely against thus treatment. One of the most important aims in HIV revealed reproductive treatment is to avoid multiple pregnancies and in consequence a maternal-fetal transmission. In case of unstable infection course, restricted anti-retroviral therapy options or resistance development, other co-morbidity as well as pre-existent obstetrical or gynecological risks the woman is to be discouraged from any treatment to fulfill the desire of an own child.     

Epigenetische Aspekte der Reproduktionsmedizin

Background

Assisted reproductive techniques (ART) are associated with an increased risk for perinatal problems and congenital malformations. In addition, imprinting diseases such as Beckwith–Wiedemann syndrome (BWS) and Angelman syndrome (AS) seem to occur more frequently after ART.

Objective

The aim of the present work is to describe the epigenetic and phenotypic effects of ART in humans and animal models.

Materials and methods

Results from basic studies in humans and animal models are summarized and discussed.

Results

The incidence of imprinting diseases in humans after ART is definitely increased. The causal relationship with the ART themselves and/or the infertility/subfertility of the couples has not yet been clarified. ART-induced epigenetic effects on imprint establishment in oocytes and epigenetic reprogramming after fertilization are more frequently observed in animal models than in humans.

Conclusion

Previous work in humans and animal models have provided important evidence on the epigenetic effects of ART and were essentially limited to the occurrence of imprinting diseases and the methylation analysis of imprinted genes, respectively. Further studies based on modern genome-wide analysis techniques are required in animal models and humans particularly focusing on children from ART pregnancies to better characterize and mechanistically understand the effects of ART on health outcome and the epigenome.     

GnRH-Analoga in der Reproduktionsmedizin

In 1997 the Nobel prize for medicine was awarded for the discovery of the GnRH molecule and its mechanisms. By altering natural GnRH synthetic GnRH analogues can be manufactured which have a higher affinity and a longer half-life. These GnRH analogues can be subdivided into GnRH antagonists and GnRH agonists. These medications can be used where suppression of gonadotrophins and sexual hormones is an important principle of the therapy, e.g. breast cancer. GnRH analogues have been established as the standard medication for suppression of LH levels for ovarian stimulation for IVF/ICSI. Various protocols are available for ART with GnRH analogues.     

Informationstechnologie in der Reproduktionsmedizin

Software solutions in the field of reproductive medicine in Germany are numerous despite the relatively specialized subject area. But an all-around solution combining the usual items, such as quality assurance and a billing system, is still lacking. The programming costs for such a solution are still too high to satisfy all the aspects desired by the 122 currently existing in vitro fertilization centers in Germany.     

Die Finanzierung der Reproduktionsmedizin

Co-payments to the extent of 50% of the costs of assisted reproductive techniques (ART) have applied to members of the German statutory health insurances since 2004. This regulation led to a significant decrease in demand for ART. Court decisions confirmed that this is in accordance with German constitutional law. However, there is an ongoing public and political debate on the purpose and justice of limiting coverage in the area of assisted reproduction. Two federal states (Sachsen and Sachsen-Anhalt) introduced tax-financed support for couples undergoing fertility treatment. In a national survey, patients, expert groups and the general public were interviewed regarding their views on the financing of ART. According to the majority of respondents, co-payment by patients is appropriate; however, this should be limited to 15%?C20% of costs, considerably less than patients presently have to pay. The respondents had different opinions on whether to raise medical insurance premiums in order to increase benefits in ART. Reducing services in other areas of healthcare in favour of reproductive medicine was generally rejected, as was egg sharing and money-back guarantees as special financing models in the area of assisted reproduction. The potential for saving in the field of ART was considered low.     

Fehlbildungen nach assistierter Reproduktionsmedizin

New follow-up studies indicate a slightly increased risk of malformations after assisted reproductive techniques (ART). Even if study results vary a lot and the absolute risk for congenital malformations in ART children is small, couples must be properly informed. It is undisputed that parents after in vitro festilization (IVF) or intracytoplasmatic sperm injection (ICSI) have a greater risk to father a child with malformations because of underlying sociodemographic and anamnestic risk factors. Couples have also to be counseled that ICSI-children have a greater risk for chromosomal anomalies compared with naturally conceived children. This is due to transmitted chromosomal anomalies (1–4%), which are already existent in parents (predominantly fathers), or due to de-novo chromosomal anomalies, originating mostly of bad sperm quality (2.1% when the sperm count is <20 Mio./ml). The health of children after assisted reproductive medicine must be systematically documented in follow-up studies to draw clear conclusions regarding the safety of these techniques. The importance of the risk factor “sterility” itself and the significance of epigenetic changes are still unclear.     

Moderne Aspekte der Reproduktionsmedizin

Zusammenfassung Moderne Aspekte der Reproduktionsmedizin betreffen neben der In-vitro-Fertilisation (IVF) oder der intrazytoplasmatischen Spermieninjektion (ICSI) auch v. a. die ovarielle Stimulation. Technisch scheint sich seit Einführung der IVF bzw. ICSI kaum mehr eine Neuerung von ähnlich weitreichender Bedeutung ergeben zu haben. Die Effektivität favorisierter Verfahren wie des "assisted hatching" oder der Übertragung von Eizellplasma von einer Spenderin ist noch nicht bewiesen, bzw. ihre möglichen Auswirkungen sind kritisch zu bewerten. Bei der ovariellen Stimulation konnte die Behandlung durch die GnRH-Antagonisten und v. a. die rekombinanten Gonadotropine optimiert und vereinfacht werden. Wichtig sind sich abzeichnende definierte Risiken für nach reproduktionsmedizinischen Maßnahmen geborene Kinder, die zukünftig mit in der Beratung der Paare berücksichtigt werden müssen. Die Zukunft lässt erwarten, dass v. a. genetische Untersuchungen helfen werden, das Erkennen von Risikogruppen und die Therapien weiter zu verbessern. Allerdings wird hier das Embryonenschutzgesetz in Deutschland wie in der Vergangenheit dazu führen, dass viele Forschungsansätze nicht verwirklicht werden können. Abstract Modern aspects of reproductive medicine involve besides in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) especially ovarian stimulation. In the last 5 years no technical improvement similar in importance to IVF or ICSI seems to have been developed. Techniques such as assisted hatching or the ooplasmic transfer to oocytes with lower quality could not demonstrate their superiority or have not been proven to be really safe for the offspring. GnRH antagonists and recombinant gonadotropins are very important because they have made ovarian stimulation much easier and more convenient and successful for the patients. Recent studies have shown defined risks for children born after procedures of reproductive medicine. Even if these may be associated with infertility itself, these data have to be imparted to couples waiting for a treatment cycle. In the future there might be more involvement of genetic aspects in reproductive medicine helping to identify high-risk groups and to improve treatment. The Embryo Protection Law, however, will - as it did in the past - prevent that Germany has a chance to keep up with embryonic research in the European and extra-European countries.     

Reproduktionsmedizin in der BRD

Assisted reproductive techniques (ART) require continuous reflection in terms of their implications. The legal discussion centers on the Embryo Protection Law (EPL), which is intended to prevent misuse of ART. A revision of the EPL to a Law on Reproductive Medicine is urgently needed including clarification for interpreting the “three-embryo limit” (EPL, paragraph 1, numbers 3 and 5) to preclude higher-order multiple pregnancies and permission to select embryos for elective single/double embryo transfer. Judicial regulations are also necessary pertaining to the legal conditions for the status of ART, requirements for providing patients with information and counseling, integration of quality assurance into a central federal agency using the German IVF Registry along the lines of the Human Fertilisation and Embryology Authority (HFEA) in the UK, and especially dealing with “orphaned” embryos. The current discussion on amending the Stem Cell Law with postponement of the deadline and past rejection of a legal debate on preimplantation diagnostics are based on the status of the embryo: protecting the human dignity and life of the embryo from fertilization onward is categorically stipulated (§8).     

Kontroversen in der Reproduktionsmedizin

Despite substantial scientific and clinical efforts, in vitro fertilization (IVF) per treatment cycle is still relatively unsuccessful over the last 3 decades and the pregnancy rate per transfer is less than 30%. In this article the various approaches to increase the efficiency of IVF procedures will be presented and discussed as well as the use of metformin for polycystic ovarian syndrome (PCOS), assisted hatching using various methods, aneuploidy screening of oocytes and embryos, blastocyst transfer and adjuvant acupuncture. Under the criteria of evidence-based medicine meta-analyses and when available also Cochcrane analyses are reported and critically discussed.