Modern Methods in Medically Assisted Human Reproduction

The right to child bearing is protected by the constitution in our country as the expression of personal freedom to develop one’s own personality. Within this framework, every man is free to decide whether he wants to have natural descendants, the time in life when he wishes this to happen, the way as well as their number.

And although the said right enjoys adequate constitutional protection, a large number of couples in our country is devastated with sterility problems and hence, having natural descendants constitutes in their case an unfulfilled desire. It is worth mentioning that statistical studies report that nowadays 15% of couples face an infertility problem.

This is the area where a new field of the medical science, the genetic technology, comes in to assist in coping with infertility problems. The advancement of the genetic technology secures new potential for child bearing with revolutionary achievements in the human reproduction procedure, in which sexual contact is not a prerequisite nor is the genetic material necessarily required to come from the person who wishes to have a child. Recent studies show that 40% of infertility cases is woman related, another 40% is man related and the rest 20% is due to unexplained infertility.

The artificial fertilization methods are numerous and vary according to the specific problem that each couple is facing: artificial insemination (homologous or heterologous) is the oldest, the most common and painless method, followed by in vitro fertilization IVF with genetic material of the couple or for lack thereof with donation of genetic material (oocytes or sperm) from third parties, anonymous donors, the gamete intrafallopian transfer (GIFT) , the blastocyte embryo transfer, the intrafallopian transfer of zygotes and surrogacy.

With artificial insemination, the husband’s sperm, which is taken on the day of the wife’s ovulation day, is injected into the woman’s cervix or womb by means of a simple, harmless medical method without spoiling the quality of the sperm and without any harmful effects to the child born as a result of this method. The use of fresh sperm is forbidden when the sperm comes from a donor, given the fact that the donor is obliged by law to undergo specific medical examinations in order to rule out any contagious diseases (such as AIDS or syphilis).

The most common method is by in vitro fertilization. The first successful IVF cycle (egg retrieval, in vitro fertilization and embryo transfer) was performed in 1978 in Great Britain by doctors Patrick Steptoe and Robert Edwards and resulted in the birth of Louise Brown. This success constitutes ever since a milestone, as it has allowed immediate access to human gametes (oocytes and sperm) and therefore to the genetic material that they carry. This jumpstarted a revolutionary cure for sterility problems and led to the development of a new technology called assisted reproduction.

During in vitro fertilization, the sperm of the husband is used (in the homologous system) or the sperm of a selected donor (in the heterologous system) for the fertilization of oocytes of the wife (or another woman in the case of egg donation).

In the event of genetic material of the couple, the stages followed are as follows: the couple undergoes the necessary haematological examinations, which aim to increase as much as possible the successful outcome of this method. Semen is taken from the husband and oocytes from the wife. These are retrieved after a hormonal procedure called ovulation induction, which is achieved due to the over-stimulation of the ovaries (overovulation) in order to secure a larger number of available oocytes than during the normal procedure and therefore increase the chances of a successful of the in vitro fertilization process and enable the cryopreservation of surplus embryos so that they may be used in the future (in case the current attempt fails) and prevent the woman from undergoing a hormonal stimulation all over again. Then, fertilization takes place outside the woman’s vagina inside a special medical tube. More particularly, several hours after the egg retrieval and after the semen has undergone the proper process, it is placed together with the oocytes inside a special culture media. As early as the following day, fertilization process shall be examined (two prenuclei should have been created within the oocytes), while 48 hours after the egg retrieval, the division process has already started in the fertilized oocytes into 2 or 4 cells. Then, 20-60 hours after fertilization and more particularly when the fertilized oocyte reaches 8 or 16 cells, it is implanted in the uterus of the woman so that its development may continue there. The embryo transfer is a simple and painless procedure. Pursuant to the recent law (L. 3305/2005), the number of embryos is now specific: up to three for women up to 40 years old whereas for women over 40, up to four fertilized oocytes.

The method of in vitro fertilization with microfertilization of oocytes offers a significant contribution in couples where men are facing a serious problem in the number or the mobility of sperm or even in total lack of sperm in their semen (azoospermia). It involves a light intervention in the oocytes: sperm is retrieved by means of a micropipette under a very powerful microscope and after the outer lining of the oocytes is opened, the sperm is inserted in the cytoplasm of the oocytes.

The gamete intrafallopian transfer (GIFT) is used with substantial success. It is a procedure mainly used on women who suffer from endometriosis or in case of unexplained infertility. During this procedure, gametes (sperm from the husband or a third donor) are taken and are inserted with immediate laparoscopy inside the two fallopian tubes. A necessary prerequisite for its use is the existence of healthy fallopian tubes as well as proven fertile sperm.

A variation of the above mentioned method is the zygote intrafallopian transfer (ZIFT), where the egg is fertilized in vitro and then is introduced as zygote into the fallopian tubes with laparoscopy. The difference between the two last methods is that ZIFT is performed 48 hours after egg retrieval, after fertilization has been performed in the laboratory and the fertility of the semen has been established.

Another innovative procedure is the transfer of one or more embryos at the blastocyst stage into the uterine cavity. As the embryo advances in the development, after 5-6 days it becomes a blastocyst. A blastocyst has about 150-200 cells whose differentiation into trophoblasts and foetal pole has already begun. The fertilized oocytes reach the uterus through the fallopian tube on the 5th or 6th day as a blastocyst, leaves the zone that encircles it and is implanted in the uterus. With the suitable culture fluids as well as the necessary knowledge, embryos are cultivated for 6 days after egg retrieval, after which time the embryo transfer can be performed.

The dissolution of the zona pellucida of the embryo is also successfully applied by laser whereas in order to avoid any pregnancies of suffering embryos preimplantantion genetic diagnosis is performed. It is a technique that can be applied during the in vitro fertilization which allows the diagnosis of hereditary genetic disorders of genetic origin such as thalassemia as well as chromosomal genetic abnormalities. It is performed on embryos in the time between egg retrieval and embryo transfer; more particularly, one or two cells of the embryo undergo a biopsy on the third day or 5-10 cells during blastocyst stage; then, a genetic analysis is performed on the cells and based on the results, only healthy embryos are selected and transferred to the woman’s body.

A study published in Human Reproduction in July 2005 shows that after a biopsy of blastocysts for the preimplantation diagnosis of beta thalassemia in a couple both of which were heterozygotic for beta thalassemia, as a result of which the first in the world successful birth of a healthy child was achieved.

The surrogacy method has had wide appeal to Greek society as court decisions follow one after the other. This procedure enables women who are incapable of bearing a child themselves to have a child that will carry their own genetic material if they have (if they do not, they resort to unknown donors) with the help of a surrogate mother: the latter is the person who will undertake to carry the embryo and to give up the baby right after its birth to the woman who has been awarded the court authorization. It is worth mentioning here that the doctor cannot go through this procedure unless there is a prior court authorization that will allow it to happen.

Finally, sperm and fertilized oocytes cryopreservation have a very important contribution. In the first case, sperm sustains its viability due to cryopreservation thus enabling the conception of a child in the future, even if future situations may occur that would normally rule it out (e.g. terminal disease or disease which affects irreversibly the fertilising ability of the sperm), while in the second case, a delay in the implantation of the zygote in the woman’s uterus can be achieved. According to recently published studies, the cryopreservation of an embryo facilitates its biopsy and a pre-implantation diagnosis while at the same time the woman can avoid undergoing another hormonal therapy until all existing cryopreserved embryos have been used. As I mentioned in my speech at the 8th Pan-Hellenic Conference of Psychosocial Oncology, modern studies are completely reassuring, proving that there is no correlation between the use of fertility hormones and specific drugs administered during a human infertility therapy and the occurrence of gynaecological cancer.

Finally, a new and much promising area has started to develop: it involves stem cells, with cryopreservation of blastic cells from the umbilical cord and the differentiation of embryonic pluripotent cells into a certain type of tissue. This field is expected to provide solutions to problems that have remained unresolved to this day.

The efforts of doctors are nowadays assisted by two particularly innovative laws, which regulate issues arising from the application of the methods of medically assisted human reproduction. Laws 3089/2002 and 3305/2005 require increased obligations by doctors (written consent before performing any medical procedure, notarized consent in the case of couples living together and single women and prior court decision for surrogacy and posthumous conception).

The intention of these legal measures is to protect the interest of the child to be born as a result of the use of the above mentioned methods. Modern procedures of artificial fertilization: Modern methods for artificial fertilization applied in our country achieve high success rates as high as 50%, which means that one out of two women subjected to an in vitro fertilization method nowadays can become pregnant and make her dream come true. Infertility is a very private matter for the couple who is facing such a problem. This is why it is recommended that any therapeutic method selected must remain private and that a lot of time must be spent for a full and well documented update of the concerned couple. A properly selected therapeutic programme, correct information, trust in the attending physicians as well as full knowledge of all existing methods for medically assisted human reproduction and their potential shall often result in a successful effort of having a healthy baby at the least emotional and psychological cost.