Assisted reproductive technology (ART)
The cause of infertility in a couple may be a reproductive function disorder in women (80% of couples) or in men (45%), or combined in about one-third of infertility couples, the cause lying in both women and in men.
For a long time, infertility has been a problem that, in best cases, could be detected, but was nearly impossible to solve. The lack of effective treatments led to the fact that no more than three out of ten infertile couples with reproductive disorders could expect to have their own child.
Only the introduction into clinical practice of assisted reproduction techniques, based on in vitro (“outside the body”) fertilization since 1978, when Louise Brown was given birth in the UK, led to the conclusion that a fundamental solution of the infertility problem was finally found. The chance of pregnancy rate per one attempt with assisted reproductive technology has risen to 30-40%, compared to 8-25% in natural conception.
Modern ART counts more than 10 methods, the number of which is constantly increasing. Its practical application depends of the country’s law or tradition. The most popular and effective techniques include:
- extracorporeal fertilization — IVF, (“conception in vitro” with subsequent transfer of embryos into the uterus);
- Intracytoplasmic Sperm Injection — ICSI (for male infertility, “forced” in vitro connection of the spermatozoon and the egg);
- surrogacy (obtained with IVF/ICSI: embryos of the genetic mother are carried by another woman);
- preimplantation diagnosis of hereditary and genetic diseases (held at the embryonic stage to eliminate hereditary diseases in children and to avoid medical abortion later in pregnancy);
- use of donor germ cells (in the absence of own eggs and sperm capable of fertilization);
- cryopreservation (freezing of embryos and gametes for subsequent use).
A large interpretation of ART includes hormonal stimulation of ovulation, which is used for endocrine infertility, as well as for the age-related decline of individual reproductive capabilities and allows conceiving in a “natural” way. The necessity for hormonal stimulation is enhanced by the increase of “postponed births” to a later period, which often exceeds the age limit of early physiological decline of ovarian reserve (27 years).
In many cases, the cause of infertility lies in the physical impossibility of male and female sex cells to meet in the woman’s genital tract (for example, the so-called tubal factor infertility — a pathology of the fallopian tubes, when they are impassable for oocytes). In this case, a woman is fully capable to bear and give birth to a child. Consequently, the task of doctors is to “organize a meeting” between the egg and the spermatozoa. The resulting embryo is thus returned to its “rightful place” — into the expectant mother’s uterus, where pregnancy will develop in the most common way. This procedure is called extracorporeal fertilization or “conception in vitro”. It is important to note that children resulted from IVF are not different from “normal”, naturally conceived children; as such, this method of conception does not have any negative impact on the health and development of the unborn baby.
IVF is carried out in several stages:
- Stimulation of ovulation — for a successful in vitro fertilization procedure, it is necessary to obtain a few mature eggs. This is achieved by means of hormonal stimulation of the woman’s body. The purpose of hormonal stimulation is, firstly, provision of oocytes suitable for conception, and secondly — preparing the endometrium for the embryo’s reception. The whole process is under constant ultrasound control.
- Follicle puncture — once the follicles reach maturity, the next stage of preparation for IVF follows with their extraction. Typically, this procedure is carried out in a transvaginal procedure (through the vagina under ultrasound guidance). The resulting oocytes are placed in a special culture medium, where they will meet with the spermatozoa. In turn, the sperm (obtained from the husband in parallel with obtaining oocytes) is also involved in the preparatory process.
- Fertilization in vitro — the eggs and the spermatozoa are placed in a test-tube, where the long-awaited fecundation takes place. Then, the fertilized eggs are placed in an incubator. The entire process takes place in a specially equipped laboratory under the supervision of embryologist specialists. Embryologist keep track of how embryos develop and whether or not they show any morphological deviations. Typically, embryonic “in vitro” development continues from 2 to 5 days. When the embryo is ready to be implanted in the uterus, the transfer is made.
- Embryo transfer — pregnancy after embryo transfer occurs 3-5 days after fertilization. As a rule, no more than two embryos are allowed to fertilize. This reduces the risk of multiple pregnancies. The remaining embryos are cryopreserved. For successful embryo implantation, women should further maintain the hormone therapy. Pregnancy is defined in two weeks through a blood test for HCG — human chorionic gonadotropin.
Conception is certainly not always successful, since the procedure itself is not an easy process. As practice shows, the best IVF is not always the first on the account. There are cases when pregnancy after conception in vitro was obtained on the fourth or even the tenth attempt.
Intracytoplasmic Sperm Injection (ICSI) is a procedure used in at least one of the following situations:
- decreased sperm count;
- decreased motility of the spermatozoa in the sperm;
- large quantity of abnormal spermatozoa in the sperm;
- the sperm contains anti-sperm antibodies;
- undiagnosed pathology of the spermatozoa or egg cells;
ICSI procedure is performed under a microscope. To manipulate the egg and the sperm, glass microtools are used. Microtools are attached to the micromanipulator — a device that allows the embryologist to translate large hand movements (via joysticks) into the microscopic motion of tools. Doctors then attempt to select the fastest and most normal (from a morphological point of view) spermatozoon for ICSI, by immobilizing it with a microneedle, then holding the egg and piercing its membrane to injects the spermatozoon inside it.
Surrogacy — is a method of assisted reproductive technology, whereby the woman voluntarily agrees to become pregnant in order to carry and give birth to a child, who will be later given to his genetic parents. The latter will be legally regarded as the child’s parents, despite the fact that the child was carried and delivered by a surrogate mother.
Pregnancy by surrogacy is recommended for patients with multiple IVF failures, habitual miscarriage, uterus absence, severe somatic disorders when pregnancy is contraindicated. The requirements for surrogacy are: excluded infections, physical well-being and good health. Embryo transfer can be performed in spontaneous or prepared hormonal cycles.
Preimplantation genetic diagnosis (PGD) is the diagnosis of the human embryo’s genetic diseases before its implantation in the uterus. Typically, a biopsy of one of the embryo’s blastomeric cells is performed at the cleavage stage (4-10 blastomeres). Preimplantation genetic diagnosis is considered an alternative method of prenatal diagnosis. Its main advantage is that no selective interruption of pregnancy is made, and that the childbirth probability without genetic disease is high. Thus, PGD is an additional procedure to the assisted reproductive technology and requires in vitro fertilization (IVF).
PGD is also performed in couples with an increased risk of congenital anomalies in children, who carry chromosomal or monogenic aberrations. These cases include couples where the mother’s age exceeds 35 years; where the father is above 39 years has severe spermatogenesis abnormalities; in married couples with recurrent pregnancy loss; in married couples with repeated unsuccessful IVF attempts.
Treatment using donor germ cells is applied by couples that, for whatever reason, do not have their own gametes. The donor is individually selected on the basis of resemblance, such as hair and eye color.
The egg donation program does not allow use of the donor eggs for multiple recipients; the patient receives all obtained eggs from a single selected donor. The number of eggs varies depending on the donor’s response to stimulation. Donor eggs are fertilized with the sperm of the spouse — either fresh or frozen. Egg donors are selected carefully, usually from healthy women aged between 18 to 34 years.
Sperm donors are chosen from healthy volunteers, who, as confirmed by regularly scheduled examinations, do not carry any genetic or infectious diseases.
All samples are quarantined for six months and are used only after proven safe by test results.
Donor sperm from sperm banks may also be used in insemination and IVF treatments. Treatment of donor sperm is very popular among single women who want to become mothers.
Cryopreservation (freezing of embryos and semen)
Often in the course of IVF treatment and ICSI techniques more embryos are developed than can be planted into the uterus at a time. Good quality embryos or germ cells may be frozen and stored for a long period of time in liquid nitrogen. Freezing of embryos makes it possible to attempt pregnancy repeatedly without further hormonal stimulation. Before frozen embryos are transferred, the endometrium is stimulated with oral medications. Frozen embryos are thawed the day before they are transferred into the uterus, but not all of them survive the freezing and thawing.
As practice in some countries shows, the resources for increasing birth rate cannot be ignored in modern, unfavorable demographic situations. Contraceptive revolution has allowed those who did not accept “spontaneous” parenthood to avoid it with a sufficient degree of reliability. The logic of society’s equilibrium poses the emergency of spreading and strengthening institutions that are opposite to contraception: reproductive technologies that allow couples to have their own children in spite of biological obstacles.