Over the last several years a considerable progress has been made in the field of diagnosis and treatment of infertility. Artificial fertilisation methods give people who are unable to conceive a child a chance to have their own baby.
According to the definition offered by WHO infertility is the inability of a sexually active (3 - 4 intercourses a week), non-contracepting couple to achieve pregnancy over a period of one year. It is estimated that around 20% of couples at a reproductive age struggle with infertility, although we still lack exact data for Poland. According to statistical data, the percentage of infertile couples is 16.4% in France and 17% in the United Kingdom. Fertility issues affect men and women equally.
The causes of infertility are varied and multifactoral. In case of women the most common causes include the tubal factor, endometriosis and ovulation problems due to polycystic ovary syndrome. Male infertility is caused by incorrect structure, number and/or motility of sperm. The immunological factor is less common. In case of 10% of couples the cause of infertility remains unidentified – this is called unexplained infertility, or in other words, idiopathic infertility. The Polish Association of Gynaecology estimates that every year 2%, i.e. 24,000 couples, need infertility treatment with the use of assisted reproductive technologies, including in vitro fertilisation. The number continues to grow. The results of infertility treatments are monitored and published on the website of SPiN, i.e. the Fertility and Infertility Section of the Polish Association of Gynaecology.
Assisted reproductive technologies
Assisted reproductive technologies (ART) include a range of methods used to achieve pregnancy with one or more stages of natural conception omitted. The methods are employed in case of patients diagnosed with infertility due to permanent impediment that prevents the conception of a child, or in case of whom the cause of infertility is unexplained.
Intrauterine insemination (IUI) is a simple procedure. The sperm provided by either the woman’s partner or a donor and properly prepared is placed directly in the uterus. The procedure is performed in the case of women with idiopathic infertility, or those who suffer from first- or second-degree endometriosis, or in the case of mild male factor (the amount and motility of sperm not sufficient) and ejaculation problems. Prior to the insemination the patient is subject to tests that evaluate the structure of the reproductive organs, as the procedure will prove ineffective in case of fallopian tube obstruction.
Before the procedure the menstrual cycle of the patient is monitored. In case of young patients who cannot get pregnant due to male factor, the insemination may be based on natural menstrual cycle. In other cases the uterine tubes are stimulated through administration of hormones, as the presence of 2 or 3 ovarian follicles increases the chances of achieving pregnancy. After the day of ovulation is determined the patient presents herself in the clinic. A partner’s semen is prepared in the laboratory and administered with a thin and soft catheter directly inside the uterus. After the procedure the patient lies down for 15 minutes, and then she is free to go home. For the following two weeks she should avoid intense workout and hot baths.
Insemination increases the chances of achieving pregnancy by 10 to 25%. Thanks to preparation and placement of semen directly in the uterus the natural obstacles are eliminated and the sperm’s normal route is shortened. The maximum number of insemination cycles is six. They can be performed on a monthly basis or less often. In women over 35 the number of inseminations is decreased to three. If the intrauterine insemination is unsuccessful, this is an indication for external fertilisation.
In vitro fertilisation is a process whereby an egg cell of a woman and sperm of a man are connected outside the body. The fertilised egg is then implanted in female uterus. The process involves several stages, it requires the performance of initial tests and hormonal stimulation prior to and after the procedure. It is the most effective treatment among the infertility treatment methods. The effectiveness of the method in Poland is estimated to be 35.2%, whereas the European average is 29.9%.
The indications for external fertilisation include low parameters of semen, fallopian tube obstruction, endometriosis (in particular, third- and fourth-degree endometriosis), idiopathic infertility, ineffective treatment with assisted reproductive technology, incapacity to induce ovulation. The method is recommended if one of the partners is a HIV or hepatitis C virus carrier, or if the woman faces cancer treatment that will limit her fertility. Preimplantation genetic diagnosis may spare the couples that comprise genetic carriers who inherited alleles which may cause serious and irreversible changes in the child the difficult decision of abortion.
Before the in vitro procedure commences the partners are subject to a number of tests. The basic test is an ultrasound of the reproductive organ. The level of the following hormones is measured: Anti-Müllerian hormone (AMH), estrone (on the third day of the cycle), TSH, prolactin, testosterone and estradiol. In addition, the woman undergoes a pap smear, blood type test, blood count and both partners undergo a series of virus tests. Sometimes it is necessary to conduct a karyotype test, especially in the case of patients who have genetic defects, men with azoospermia and congenital absence of vas deferens.
External fertilisation procedure
The first stage of the external fertilisation process involves hormonal stimulation that will ensure an adequate number of mature egg cells. The physician selects appropriate stimulation protocol (short or long) based on the results of tests, patient’s age and her health. In the course of the stimulation process the patient is monitored by health professionals and attends obligatory appointments and ultrasounds every two days. This is when the exact date of collection of egg cells is set.
On the day of collection of egg cells both partners must be present at the clinic. The woman must be fasted. The procedure is performed under general anaesthesia. The follicular fluid and the egg cells are collected from the fallopian tubes. The procedure is short – it takes 15 minutes. Afterwards a two-hour patient observation at the clinic is required. During this time the partner produces a semen sample. The man is advised to abstain for 2-3 days prior to the procedure. Then, the egg cells and sperm are mixed in the laboratory. The embryos mature for 2 to 5 days and then one or two are selected and placed inside the uterus. The other embryos are frozen. After the collection the woman is administered drugs that favour the implantation of the embryo. The treatment is continued for 12 days and the patient presents for hCG test that will confirm pregnancy. In the fifth week after the collection the patient undergoes an ultrasound to confirm the presence of a yolk sac.
IVF, ICSI or IMSI?
The egg cell and the sperm are mixed in an embryology laboratory under the watchful eye of embryologists. The process may be conducted in a few different ways. Conventional in vitro fertilisation (IVF) involves spontaneous combination of cells. This is possible only in case of healthy patients who cannot conceive a child due to fallopian tube obstruction.
The intracytoplasmic sperm injection (ICSI) procedure is applied in case of low semen parameters (small number, low motility or defective sperm structure). It is recommended if the semen has to be surgically collected from testicles or epididymis or the fertilisation is done with frozen sperm. The procedure involves direct placement of sperm in egg cells by way of micromanipulation.
The intracytoplasmic morphologically selected sperm injection (IMSI) procedure is even more advanced. The sperm is carefully observed and evaluated prior to injection inside an egg cell. Sperm images enlarged 6,000 times (compared to ICSI – 400 times) show sperm with defective structure and allow for elimination of incorrect genetic material. IMSI increases the chances of achieving pregnancy in couples who struggle with male infertility factor or unsatisfactory response to stimulation in a woman. It increases the effectiveness of external fertilisation up to 55% and reduces the number of miscarriages.
Egg and embryo freezing
After the collection only egg cells with the greatest potential are selected and mixed with sperm. If the number of collected egg cells is large, a part of them are frozen. They are stored for future use or may be donated for adoption.
It is advised that only one or two embryos are placed in the uterus at one time. In some cases three embryos may be placed e.g. in case of women over 40. The other embryos with development potential must be subject to cryopreservation. They may be either stored for future use of the couple, or donated anonymously for adoption. Freezing is an embryo storage method that does not reduce the quality of biological material. In Poland there have been a few cases where embryos stored for years (8-11 years) were used for procedures which proved successful – either biological or adoptive mothers gave birth to babies. The longest storage period of an embryo in history lasted 19 years. The embryo was then implanted and a healthy baby was born. It is an evidence that over the years the potential of the embryo was not lost.
The future of in vitro fertilisation
External fertilisation methods have revolutionised infertility treatment. The procedure has been developed by British physicians - Robert G. Edwards and Patrick Steptoe. Edwards, today a retired Cambridge University professor, was awarded a Nobel Prize, and the Jury announced that his work is a milestone for the development of contemporary medicine. Edwards himself emphasises that the most important thing is our life is to have children.
The first child born thanks to the method is currently 32 years old and has their own children. There are over 4 million people born thanks to in vitro fertilisation in the world. In 2011 in Poland over 15,000 cycles with the use of assisted reproductive technology were performed, and the number continues to grow every year. There are more and more clinics specialising in infertility treatment and technologies that improve the effectiveness of the treatment. In 2013 the Polish Ministry of Health has started a national programme entitled: “Infertility treatment by in vitro fertilisation for 2013-2016”. Thanks to the programme some couples that satisfy certain criteria are able to get a refund of the costs associated with in vitro treatment.