Read some fun facts from its 20-year successful existence
When Louise Brown was born in July 1978 – the world’s first-born baby after in vitro fertilization – a new, better era of assisted reproduction began. Soon, the method celebrated one success after another. Patrick Steptoe and Robert Edwards, the pioneers of the method, suddenly gave many couples a real chance to have their own child – something they had previously only been dreaming about.
Of course, little Louise was not the first attempt at conceiving a baby after IVF. Available sources indicate that before the first success, more than 100 similar IVF cycles had failed. If we put it into very simplified figures, then since 1978, when the success rate of IVF was 1%, we have practically reached almost 60% today, a success rate that most quality centres declare. IVF has thus become the most successful method to treat infertility.
The beginnings of assisted reproduction in Slovakia
In the early 1990s, the foundations were laid for the first Centre for Assisted Reproduction in Slovakia, namely at the gynecological and obstetric clinic of the Faculty of Medicine University of P.J. Šafárik and Luis Pasteur Faculty Hospital on Moyzesova street in Košice. The founder of the centre for assisted reproduction was MUDr. Miroslav Herman, PhD., who considers himself to be one of the pioneers of assisted reproduction in Slovakia. And it was exactly MUDr. Herman who established and opened Gyncare Centre for Assisted Reproduction in Košice in 2001. He has worked in the centre until this very day.
Since the early days, Gyncare has been the leader in the field.
Already at that time, Gyncare was fully equipped and offered all the contemporary state-of-the-art assisted reproduction methods. This included conventional in vitro fertilization, direct fertilization of an egg with sperm – intracytoplasmic sperm injection (ICSI), assisted hatching – cutting of the embryo shell for easier nesting in the uterus, prolonged embryo culture, surgical collection of sperm, cryopreservation (freezing) of embryos and sperm, intrauterine insemination by sperm of the partner or a donor.
In 2021, Gyncare is celebrating 20 years of its existence. In those 20 years, however, neither Gyncare nor assisted reproduction as such have been resting on their laurels. Although it might seem that everything important had already been invented and tested by the time the centre was founded, it is far from truth. The most recent 20 years brought an incredible journey for assisted reproduction as such and although the news no longer come up with such bombastic headlines as in the case of Louise Brown, the method brings couples ever higher chances of having their own baby.
What can we consider to be the greatest discoveries in the field of assisted reproduction in those 20 years of Gyncare’s existence?
Ultrasound diagnostic procedures
Improving the quality of ultrasound devices significantly facilitated the entire in vitro fertilization treatment process. Vaginal ultrasound (a probe inserted into the vagina during the examination) enabled more accurate and easier monitoring of the ovaries during hormonal stimulation and egg retrieval through the vagina. The new ultrasound devices delivery high accuracy in helping determine the ovarian reserve, the blood supply to the uterus and its mucosa, enabling evaluation of the ovarian response to hormonal stimulation almost independently. They significantly facilitate the treatment overall.
Simplified hormonal stimulation
Initially, hormonal treatment within the scope of IVF was a complicated and stressful process for the woman. However, we have seen some really profound changes in this field, too. Most drugs today are administered in the form of subcutaneous injections, which is much more acceptable for the woman than injections into a muscle. Much of the medication is already prepared in the form of single-dose injections or cartridge pen needles, thus eliminating the stress of incorrect dosage. The whole treatment is now highly standardized, so 1 to 2 check-ups are usually sufficient during the whole ovarian stimulation phase, whereas in the past, this would require as many as three check-ups per week. The introduction of the so-called short antagonist protocol in a relatively high percentage of patients means a reduction in hormonal treatment from 4-5 weeks to 8-10 days. This is very important in terms of time schedules as well as general comfort of the patient undergoing the treatment.
ICSI and sperm selection
Sperm microinjection means that individual sperms are injected into the egg using a specially modified microscope. This procedure brought new possibilities to a high percentage of infertile couples. It is applied in most cases of male infertility, where mere conventional addition of sperms would lead to relatively low success of treatment. However, it is also used in women of higher reproductive age, women with endometriosis, unexplained infertility and in cases of low egg counts. On the other hand, this method is criticized as it eliminates natural selection of sperms and the embryologist practically becomes the person who decides on the sperm used for fertilization. Therefore, in recent years, a number of selection methods have been introduced to help embryologists select the optimal sperm, thus helping the couples increase their chances of having a baby. These methods include preselected sperm ICSI (PICSI), ICSI of a morphologically optimal sperm (IMSI), and today probably the most widely used process of magnetic sperm separation (MACS) and the use of chip-based microfluid sperm sorting (MSS). It is therefore likely that for some time, assisted reproduction will continue in the direction of the best possible selection of sperms thus further improving the results in the field.
Single embryo transfer (SET)
The long-term decline in the number of embryos transferred to the uterus also provides clear evidence of the increasing success of IVF. While in the early days of Gyncare, we usually transferred 2-3 embryos into the uterus, nowadays the transfer of a single optimal embryo represents an almost standard procedure. Only very rarely, we transfer two embryos into the uterus, and there should always be a particular reason for doing so. We can agree to this process, for example, in the case of repeated unsuccessful transfers, in older patients, in the case of not entirely optimal embryonic division, etc. However, the long-term average number of transferred embryos has been at 1.2, which means that in the vast majority of patients we simply transfer a single embryo. This reduces the risk of multi-fetal pregnancies to a minimum. Today, multi-fetal pregnancies are considered a failure of assisted reproduction. When 2 embryos are transferred to the uterus, both embryos are nested in up to 25% of cases. Pregnancy with twins comes with a much greater risk, there is a much higher danger of premature birth and pregnancy complications, so we try to avoid this alternative as much as we possibly can.
Embryo culture conditions
However, what has changed the most in those 20 years is precisely the aspect that remains invisible to the eyes of patients and the general public. We are talking about the culture conditions for embryos, which are very important for the process of fertilization and for a timely division of embryos after fertilization, that is, at the time when they are taken care of by our embryologists in the laboratory. In the early days of assisted reproduction, embryologists often had to work in makeshift conditions. Today, all these processes are standardized, and the risk of error is therefore minimized.
Media are special solutions in which embryos are cultured in a laboratory. They are enriched with a number of substances, nutrients and growth factors that are very important for early embryonic development. Today, assisted reproduction centres no longer produce these media in makeshift conditions, but buy them ready-made from reputable companies with a safety certificate. Culture media are instrumental for embryonic development and represent one of the most important factors for the overall success of the whole centre. 20 years ago, the standard procedure was to transfer the embryos to the uterus on the 2nd or 3rd day after fertilization as the laboratory conditions were no longer sufficient to support further embryonic division. Today’s media are able to ensure optimal embryonic division up to the 6th day of their development. Such extended embryo cultivation has an advantage especially if we have a higher number of dividing embryos. This is because a large part of the embryos stops in their division between the 3rd and 4th day of division, when the embryonic genome is initiated. The prolonged cultivation thus prevents the transfer of embryos, which would spontaneously stop their division, thus reducing the number of unnecessary embryo transfers.
Incubators have also changed significantly during those 20 years of Gyncare’s existence. The incubator is a special chamber which maintains the conditions (temperature, humidity, pressure) similar to those in female body. Large cabinet incubators were once used, in which the embryos of all patients were stored in separate dishes. Today, chamber incubators have almost become a standard, where each couple have a dedicated chamber for their embryos. The advantage in this case is that the incubator is opened only when the embryologist needs to check the embryo division of a particular couple. The incubator thus provides more stable surroundings and smaller fluctuations of the conditions. The top range is represented by the camera-equipped incubators. The camera takes a photo of every single embryo once in 20-30 minutes and the computer then combines these photos into a video loop. For embryos, this delivers two basic advantages: Firstly, we do not have to remove them from the incubator where they remain during the whole period of culture and secondly, the embryologist can evaluate the division of each embryo in reverse and choose the best one for transfer.
Storage of frozen embryos
The development of cryopreservation (freezing) techniques represents one of the major milestones of assisted reproduction as such. It was cryopreservation that brought the possibility of elective transfers of a single embryo, delayed transfers in case of the risk of hyperstimulation syndrome, preimplantation genetic diagnosis, maintaining of fertility in cancer patients, but also the so-called “social freezing” (cryopreservation of eggs in women who postpone their pregnancy for any reason). Today, the success rate of thawed embryo transfers is the same as the success rate of fresh transfers. In some categories of patients it is even higher. In most cases, we preserve cells and embryos using the rapid freezing process called vitrification.
Preimplantation genetic diagnostic procedures
Genetics in general has progressed significantly over the last 20 years. And this also applies to genetics in relation to IVF. Before the embryos are transferred to the uterus, we are able to directly examine not only the number of chromosomes, but basically every genetic disease that occurs in the patient’s family. Testing for the number of chromosomes comes important in patients with repeated failed hatching of the embryo in the uterus, in older patients, in whom these so-called aneuploidies are much more frequent, but e.g. also in young patients with recurrent miscarriages. Then, we also look for specific problems (translocations, mutations) in those patients in whom the genetic problem has been confirmed in one of the parents.
Is there anything that has deteriorated in those 20 years?
Well, we should not be overly positive, there unfortunately is. Over the past 20 years, the age breakdown of patients in reproductive medicine centres – including Gyncare – has deteriorated significantly. While patients over the age of 40 were once highly rare, today they account for more than 25% of clients in our centre. And patients around the age of 50 are not uncommon anymore. However, assisted reproduction is not a cure for age. While the success rate of assisted reproduction is relatively high before the age of 40, it declines very rapidly afterwards. At around 40, the success rate of treatment with own eggs is somewhere around 15%. After the age of 43, we are somewhere in the neighbourhood of 7%, and after the age of 45, successful pregnancies after IVF worldwide are actually reported only in the form of case studies. This trend has led to stagnation – even a slight decline -in the average success rate of IVF in recent years. Therefore, in the older age categories of patients, we often need to resort to the use of donor eggs and the percentage of cycles with donated eggs continues to increase.
That is why reproductive health experts have repeatedly pointed out in recent years that if a woman does not have the conditions to have children in her optimal age, she should think about the possibility of preserving her own eggs for future use – i.e. she should consider the so-called social freezing.
The possibilities of assisted reproduction are really vast at the moment. Gyncare is truly proud to be able to help more than 90% of all infertile couples who consult us with their problem. And while this journey is not always easy or short, our common goal – a healthy baby – makes it totally worth it.