In vitro fertilization

from Wikipedia, the free encyclopedia

The in-vitro fertilization (IVF) - Latin for "fertilization in glass" - is a method of artificial insemination . It was developed in the 1960s and 1970s by Robert Edwards , who received the Nobel Prize in Medicine for it in 2010 , and Patrick Steptoe . In Germany this treatment is allowed if one year despite regular, unprotected in a (married) pair long intercourse , the pregnancy is absent or a preimplantation genetic diagnosis (PGD) is displayed.

Process of in vitro fertilization

Sperm and egg retrieval

Checking for errors in the genetic material : If hereditary diseases are suspected, a genetic examination is usually carried out to determine the karyotype - chromosome examination - normal karyotype woman 46 XX, man 46 XY, deviating karyotype e.g. B. in Klinefelter syndrome 47XXY, as well as an examination for serious hereditary diseases (e.g. cystic fibrosis , which is based on defects in certain sections of chromosome 7; azoospermia factor (AZF, in men)).

Downregulation: The administration of certain drugs GnRH analogs / agonists , GnRH antagonists or birth control pills slows down the ovaries' own activity so that more than one egg cell can then be obtained through the hormonal stimulation.

Ovarian stimulation: Hormones (FSH preparations) stimulate several egg cells to mature; According to a British study, the optimal maturation of 15 egg cells is optimal. The woman injects herself with a syringe or a so-called pen follicle-stimulating hormone (FSH) in a fixed dose subcutaneously for approx. 11 days (depending on the follicle growth) . H. under the skin (stomach).

Checking the sperm : Sperm are checked for density / concentration (number), morphology (shape), motility (mobility) and infections (bacteria, chlamydia). Criteria for a normal sperm analysis according to WHO criteria 2010: sperm density 15 million / ml, progressive (linear) motility 32%, normal morphology 4%

Monitoring of follicle growth: From the 6th day of your cycle, the follicles are monitored using ultrasound. The woman's abdominal wall can tighten slightly. On the 9th day of the cycle (ultrasound) it is decided when the egg cells will be removed (depending on the follicle size).

Triggering of the follicle rupture : The follicle rupture (ovulation) is triggered by the hormone HCG .

Follicular puncture : The follicular fluid is punctured transvaginally from the individual follicles, controlled by ultrasound using a rod-shaped transducer equipped with a puncture needle.

Sperm collection: Sperm for fertilization of the egg are usually collected in parallel to the egg puncture by masturbation or a microsurgical procedure (TESE, see below).

fertilization

The egg cells obtained are fertilized. This succeeds with a success rate of approx. 50% to 70%. There are four ways to do this.

Classic in vitro fertilization (IVF)

The egg cells are brought together with the prepared sperm in a test tube. Spontaneous fertilization takes place. This results in a natural selection of the mobile and fast sperm.

Intracytoplasmic Sperm Injection (ICSI)

With intracytoplasmic sperm injection, the sperm is introduced into the egg cell, which is fixed by means of a holding pipette (left), using a pipette (right).

The ICSI is used if the mobility of the sperm cells, sperm antibodies or very low sperm count in the ejaculate is impaired. Another indication is the lack of fertilization during classic in vitro fertilization (see above) despite normal semen parameters. In ICSI, a single sperm is injected into the prepared egg cell under microscopic sight using a micromanipulator. This treatment is also recommended for men who have had a vasectomy, people with an infectious STD (HIV, hepatitis, etc.) and cancer patients whose semen has been compromised after chemotherapy.

A special form is the I ntracytoplasmic M orphologically S elected Sperm- I represents njection (IMSI), wherein the sperm used is selected under a high resolution microscope using morphological criteria. In a prospective study on 446 couples with reduced sperm quality in men and who wanted to have children for at least 3 years after previous ICSI attempts were unsuccessful, the use of IMSI compared to ICSI showed a significantly higher pregnancy rate (29.8% IMSI versus 12.9% % ICSI) and a lower abortion rate (17.4% IMSI versus 37.5% ICSI). Even more recent studies can confirm this trend, although this is controversial, but the assessment of the embryo quality on day 2 is more important on day 5. The selection of sperm without DNA fragmentation and vacuoles as one of the advantages of IMSI is also discussed.

Testicular sperm extraction with ICSI (TESE-ICSI)

The same procedure as for ICSI, but the sperm are not obtained from the ejaculate, but from a testicular biopsy . It is used for occlusion of the efferent seminal passages and in azoospermia, which is not based on occlusion of the efferent seminal passages.

Microsurgical epididymal sperm aspiration (MESA-ICSI)

Also corresponds to the ICSI procedure, whereby the sperm cells are obtained directly from the epididymis using a surgical microscope. Indication is as with the TESE the Verschlussazoospermie (= lack mature as immature sperm in the ejaculate by closure of the seed cell ways normal testicular volume and normal FSH -mirror).

Post-fertilization phase and embryo transfer

Culture of the embryos : zygotes are cultivated in an incubator and subjected to quality control.

Embryo transfer : Ideally, 2 embryos are transferred into the uterus . This happens either on the 2nd day after fertilization (4-cell stage) or on the 5th day after fertilization (blastocyst stage). Excess impregnated egg cells in the pronucleus stage (approx. 16–20 hours after fertilization initially 2 pronuclei - genetic material from sperm and egg cells) or embryos (only allowed as an emergency measure in Germany) can befrozenin liquid nitrogen ( cryopreservation ). In general, no more than two embryos should be transferred before the age of 35, otherwise the risk of multiple births and an associated high-risk pregnancy is high.

Time to wait: 14 days after the follicle puncture, a pregnancy test with a reliable statement (blood sample, HCG determination) can be made.

The success rate of carrying a child to term is around 20–40% and depends to a large extent on the age of the woman at the time of egg retrieval.

If a pregnancy does not occur despite multiple transfers of embryos, this is referred to as “implantation failure”. There are a number of treatment approaches that are designed to improve implantation and the live birth rate. This also includes endometrial scratching . In the cycle before the embryo transfer, the uterine lining is scratched and stimulated with a small pipelle. The effectiveness of the method has not been proven

Legal and ethical problems

Parent combinations

With IVF, it is possible that genetic and social parenthood may fall apart. In extreme cases, it is conceivable that the egg cell of a donor is fertilized with the sperm cell of a donor and the zygote created in this way is used by a surrogate mother . Together with the social parents, (partial) parenthood of up to five people is conceivable.

Such combinations are ethically problematic. In some countries, egg donation and / or surrogacy are therefore prohibited, in many others it is regulated by law. In Poland, the Catholic Church failed in 2009 with an initiative to legally ban IVF. In Germany, both egg donation and surrogacy are prohibited by the Embryo Protection Act. In contrast, sperm donation is permitted, which is being discussed critically in view of the principle of equal treatment . If the partner's sperm is used, it is referred to as “homologous”, when using semen from third (mostly unknown) donors it is referred to as “heterologous” sperm donation.

Generation and transfer of multiple embryos

Another problem concerns the creation of surplus embryos. In order to increase the likelihood of pregnancy, artificial insemination is usually carried out on several egg cells. However, the resulting zygotes are often not all inserted into the woman's uterus. How the “surplus” embryos are dealt with or should be dealt with is an ethical and moral problem that is handled differently in many countries.

For the most part, these embryos are "discarded", ie killed, and a small part used in the context of controversial embryo research: both are forbidden in Germany due to the Embryo Protection Act. Another way to preserve the surplus embryos is cryopreservation , in which the embryos are preserved in liquid nitrogen and stored for later treatment.

In order to counter the problem of the rejection of viable embryos, which is forbidden in Germany, and the creation of embryos "in reserve", impregnated egg cells in the so-called pronuclear stage, i.e. before the merging of the maternal and paternal genes, may be cryopreserved. These impregnated egg cells can later be thawed and develop into embryos that are transferred to the uterus.

Killing of surplus embryos

In the case of a multiple pregnancy with more than three fetuses, there is a risk for the physical (eclampsia, thrombo-embolism) and mental health of the mother as well as for the children, as they have a birth weight of 1250 g (minimum weight for a good prognosis for the physical and mental health) is unlikely to be achieved this way. For this purpose, according to the German Medical Association, every effort should be made to limit the pregnancy to three fetuses. A maximum of three embryos can therefore be used per IVF cycle in Germany. If, despite all caution, e.g. If, for example, a high-grade multiple pregnancy occurs as part of hormone therapy, there is the possibility of multiple reduction through fetocide (intrauterine killing of individual fetuses) of the fetus that is most accessible. In individual cases, a reduction to less than three fetuses would only be possible if there is concrete evidence of a risk to the mother or children.

Social law situation in Germany

Up to 2003 the statutory health insurance companies covered four full treatment cycles, now only three are half covered. The remaining costs must be borne by yourself. The assumption of costs is regulated for patients in the statutory health insurance (GKV) in § 27a SGB V. The prerequisite for the assumption of costs is: The couple must be married, only egg and sperm cells of the spouses may be used; Wife and husband must be 25 years of age before starting treatment; the wife may not have reached the age of 40 at the start of treatment and the husband may not be 50 years old; Before the start of treatment, a treatment plan must be submitted to the health insurance company for approval; additional advice to the spouse about the measures from a doctor who does not carry out the treatment himself, about such treatment and referral of the consulting doctor; there is a reasonable prospect that the selected treatment method will lead to pregnancy; The man or woman must not have been sterilized beforehand (exceptions require the approval of the health insurance company) and an HIV test must be carried out. The assumption of costs is also limited with regard to the number of treatment attempts: for insemination in the spontaneous cycle up to eight times, for insemination after hormonal stimulation up to three times, for in-vitro fertilization up to three times, for intratubar gamete transfer up to twice , for intracytoplasmic sperm injection up to three times.

Social law situation in Austria

For certain indications, the Austrian IVF Fund has been covering 70 percent of the drug and treatment costs for up to four IVF treatments since 2000. The prerequisite is at least one of the following medical indications: bilateral blocked or otherwise permanently inoperable fallopian tubes, endometriosis, polycystic ovaries (polycystic ovaries ( PCO syndrome ) or male sterility or severe male infertility. The couple must live in an upright marriage or cohabitation. At the time of the start of the experiment, the woman must not have reached the age of 40 (40th birthday) and the man may not have reached the age of 50 (50th birthday). If pregnancy occurs up to the eighth week during treatment (heartbeat must be visible on the ultrasound ), then up to four treatment cycles can be used again. Interestingly, in Austria a proven ectopic pregnancy leads to 4 further attempts, but not the abortion before the 8th week of pregnancy. Furthermore, in contrast to Germany, which legally permits ( blastocyst ) culture even under the restrictive conditions of the Embryo Protection Act (ESchG), in Austria the further cultivation of all impregnated egg cells and thus all embryos as well as the subsequent embryo selection is permitted.

Social law situation in Switzerland

In Switzerland, the costs for in vitro fertilization are not covered by the health insurance. Only with the tax return of the woman (of the married couple) is it possible to claim the entire expenses as medical expenses and thus save a small part of the expenses again.

Health and mental problems

The children conceived with the help of VF technologies showed an increased risk of organic malformations and functional changes. These include "malformations of the heart, the musculoskeletal and central nervous systems as well as premature births and low birth weights".

The process of IVF as a very complex treatment in the course of artificial insemination (e.g. compared to insemination ) is a heavy burden for both partners involved.

  • In the psychological area, men and women alike focus on the - possibly long-term - unsuccessful desire for children as well as the pressure to perform. The desire to have children or their fulfillment is supposedly very close. Treatment cycles without pregnancy can lead to depression . In extreme cases, the relationship can break up.
  • In the health sector, women are particularly affected. The necessary hormone treatments with high doses, often lasting for months or years, can lead to mood swings, weight gain, edema, increased risk of heart attack, etc. The removal of the egg cells represents an operation with all associated risks ( infection , damage to internal organs, etc.). The fact that the woman bears most of the physical and medical effort even if the man is childless, can in turn lead to psychological pressure and partnership problems to lead.
  • IVF is not only a psychological burden for those wishing to have children. Psychologists warn of later psychological impairments in children conceived in test tubes. They may have difficulties with their own ancestry if anonymous gamete donation was used for IVF. Parents must expect mental health problems in every fourth child.

Despite this complex of problems, it can sometimes be observed that even if the failure persists, couples repeatedly undertake new treatment - sometimes at their own expense.

Chances of success

The chances of success with IVF depend heavily on various factors, such as: B. the age of the woman, the number of fertilized eggs and the like. The psychological stress involved in measures such as IVF should not be underestimated and can influence the chances of success. In a study at an Israeli clinic, for example, it was observed that the percentage of successful in vitro fertilizations increased from 20% to 36% with visits to clown doctors .

Independent statistical studies are published annually in the German IVF register. Globally, it can be said that IVF is successful for around 40 percent of couples (several IVF cycles are necessary for this). In Germany, around every 80th child is conceived by IVF, and every tenth couple needs medical support in fulfilling their desire to have children .

Studies in the field of epigenetics have shown that children from IVF theoretically have a slightly higher probability of developing genetic disorders. The presumed numbers could partly be reproduced in practice. For example, children conceived by artificial insemination are three to six times more likely to develop the very rare stature syndrome ( Proteus syndrome ) than naturally conceived children. A Swiss study published in March 2012 showed for the first time that children born using artificial insemination have significantly more vascular dysfunction. In 2018, another study on young adults showed that 16% of them were affected by high blood pressure .

economic aspects

In Germany there are around 125 clinics and specialist centers that offer in vitro fertilization. They carry out around 70,000 treatments a year, with a treatment costing around 4,000 euros on average. In 2016 there were already more than 90,000 treatments, and the trend is still rising. In 2007 11,500 children were born after artificial insemination. The worldwide expenditures for in vitro fertilization were estimated at 6 billion euros per year in 2010. Of this, around 2.4 billion euros go to the USA and 300 million euros to Germany, which makes up around 0.1% of all health expenditure in Germany. About a quarter of sales are from fertility drugs; Merck KGaA from Darmstadt is the world market leader in these . In 2009, Merck's fertility business contributed around a tenth of Merck's entire pharmaceuticals business with sales of EUR 600 million. This also makes Merck the only pharmaceutical company for which reproductive medicine plays a significant role.

Costs and financing in Austria

A provider of IVF - and intracytoplasmic sperm injection (ICSI) - in Vienna charges costs of around € 2700 for women under 35 or € 2900 for 35–40 year olds. ICSI is about 10% more expensive in each case. These amounts do not include taxes. The services include advice, medication, and IVF up to the determination or non-determination of pregnancy. (As of November 2018)

If there are certain medical indications, such as removed or non-functional fallopian tubes (except as a result of an intended fallopian tube ligation), since the IVF Fund Act came into force on January 1, 2000 (last amended in 2018), the Federal Ministry of Labor, Social Affairs, Health and Consumer Protection took over (BMASGK) set up IVF funds under certain conditions 70% of the costs. Such co-financed IVF attempts are statistically recorded anonymously in the IVF register, for the year 2017 10,216 attempts.

According to the IVF Fund Act, there are 29 contract centers, 22 private and 7 public, in 6 federal states (not in: Bgld., Ktn., Lower Austria).

Swap two embryos in the same family

According to ORF, which quoted Spiegel, there were two exchanges of two different embryos in the same family in a fertility clinic in Austria. These were discovered in 2014 through a comparison of DNA analyzes between the pregnant mother and the IVF child. The couple, who were in a fertility clinic in Austria in July 1990 and whose treatment resulted in their first daughter, determined by means of a DNA test that it was not their biological daughter. Furthermore, the second treatment, which also took place in Austria in January 1992 with the same doctor and from which a second daughter emerges, is the biological mother of the child, but the father is not the father of the second daughter either. Both children are still looking for their biological parents. The effects of such a mix-up incident are immense, both factually and legally.

See also

Web links

Individual evidence

  1. ↑ nobelprize.org. Retrieved October 4, 2010 .
  2. ↑ Sesh Kamal Sunkara et al .: Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. In: Human Reproduction , online advance publication of May 10th, 2011, doi: 10.1093 / humrep / der106doi: 10.1093 / humrep / der106
    eurekalert.org of May 10th, 2011: “15 eggs is the perfect number needed to achieve a live birth after IVF. "
  3. ↑ Sperm microinjection: What is ICSI and what does it cost? September 11, 2018, accessed on July 5, 2019 (German).
  4. ↑ A. Berkovitz et al .: How to improve IVF-ICSI outcome by sperm selection . In: Reprod Biomed Online , 2006 May, 12 (5), pp. 634-638.
  5. ^ M. Antinori et al .: Intracytoplasmic morphologically selected sperm injection: a prospective randomized trial. R In: Reprod Biomed Online , 2008 Jun, 16 (6), pp. 835-841.
  6. ↑ K. Knez et al .: The IMSI procedure improves poor embryo development in the same infertile couples with poor semen quality: A comparative prospective randomized study . In: Reprod Biol Endocrinol. , 2011, 9, p. 123. C Gonzalez-Ortega et al .: Intracytoplasmic morphologically selected sperm injection (IMSI) vs intracytoplasmic sperm injection (ICSI) in patients with repeated ICSI failure . In: Ginecol Obstet Mex. , 2010, pp. 652-659. Rde C Figueira et al .: Morphological nuclear integrity of sperm cells is associated with preimplantation genetic aneuploidy screening cycle outcomes . In: Fertil Steril. , 2011, 95, pp. 990-993. Comparison of day 2 embryo quality after conventional ICSI versus intracytoplasmic morphologically selected sperm injection (IMSI) using sibling oocytes . In: Eur J Obstet Gynecol Reprod Biol. , 2010 May, 150 (1) :, pp. 42-46. Impact of intracytoplasmic morphologically selected sperm injection on assisted reproduction outcome: a review . In: Reprod Biomed Online , 2009, 19 Suppl 3, pp. 45-55. Review. Can intracytoplasmic morphologically selected sperm injection be used to select normal-sized sperm heads in infertile patients with macrocephalic sperm head syndrome? In: Fertil Steril . , 2010 Mar 1, 93 (4), pp. 347.e1-5.
  7. ↑ A Randomized Trial of Endometrial Scratching before In Vitro Fertilization . PMID 30673547
  8. ^ Poland: Church crusade against artificial insemination . ( Memento of September 13, 2009 in the Internet Archive ) DiePresse.com
  9. ↑ Multiple reduction using fetocide. Statement of the "Central Commission of the German Medical Association for the protection of ethical principles in reproductive medicine, research on human embryos and gene therapy" . ( Memento from September 19, 2010 in the Internet Archive ; PDF; 22 kB) Federal Medical Association , August 7, 1989.
  10. ↑ § 1 Paragraph 1 No. 3 Embryo Protection Act (ESchG)
  11. ↑ Guidelines of the Federal Committee of Doctors and Health Insurance Companies on Medical Measures for Artificial Insemination ("Guidelines on Artificial Insemination")
  12. ↑ ris.bka.gv.at , Federal law that sets up a fund to finance in vitro fertilization (IVF Fund Law)
  13. ↑ Michael von Wolff, Thomas Haaf: In-vitro fertilization technologies and child health. Risks, causes and possible consequences. In: Deutsches Ärzteblatt. Volume 117, Issue 3, January 17, 2020, pp. 23-30.
  14. ↑ Psychologists warn: Many test tube children suffer from their origins. Retrieved on July 5, 2019 (Swiss Standard German).
  15. ^ S. Friedler et al .: The effect of medical clowning on pregnancy rates after in vitro fertilization and embryo transfer (IVF-ET). In: Fertility and Sterility . 2011 ( doi: 10.1016 / j.fertnstert.2010.12.016 doi: 10.1016 / j.fertnstert.2010.12.016 ) fertstert.org
  16. ↑ Laughter may increase the probability of IVF pregnancy, study finds . (Reuters) theguardian.com
  17. ^ Website of the German IVF Register
  18. ↑ Systemic and Pulmonary Vascular Dysfunction in Children Conceived by Assisted Reproductive Technologies . circ.ahajournals.org
  19. ^ Théo A. Meister, Stefano F. Rimoldi, Rodrigo Soria, Robert von Arx, Franz H. Messerli, Claudio Sartori, Urs Scherrer, Emrush Rexhaj: Association of Assisted Reproductive Technologies With Arterial Hypertension During Adolescence. In: Journal of the American College of Cardiology. 72, 2018, p. 1267, doi: 10.1016 / j.jacc.2018.06.060 doi: 10.1016 / j.jacc.2018.06.060 .
  20. ↑ Reproductive medicine: Germany is losing ground in artificial insemination. Retrieved July 5, 2019 .
  21. ↑ Federal Statistical Office . Status 2013, accessed on November 6, 2015.
  22. ↑ Handelsblatt , July 7, 2010, pp. 4–5.
  23. ↑ Costs of the Wunschbaby Institut Feichtinger, Vienna, 2018, accessed November 10, 2018.
  24. ↑ IVF Fund: Help with unfulfilled desire to have children bmgf.gv.at, accessed November 10, 2018 - Links to annual reports 2012–2017.
  25. ↑ IVF Fund Annual Report 2017 (PDF) June 2018, accessed November 10, 2018, p. 27.
  26. ↑ Embryos swapped? Allegations against Zech . vorarlberg.orf.at, July 25, 2016; Retrieved July 25, 2016.
  27. ↑ Reproductive medicine under fire again. May 5, 2017. Retrieved July 25, 2019 .
  28. ↑ Donat Beerli, Donat Beerli: SPERMAPFUSCH: Kristina's new certainty. Retrieved July 25, 2019 .
  29. ↑ Moritz L. Jäschke: Exchanged germ cells and embryos - analysis of reproductive medical incidents: norm context, legal consequences, need for regulation . 1st edition. Mohr Siebeck, Tübingen 2020, ISBN 978-3-16-159182-2 , p. 376 .