Current treatments for infertility are effective and the results are good. These treatments facilitate pregnancy or may even be the only way to become pregnant. Our clinic provides treatment for heterosexual couples, female couples and for self-sufficient women and infertility treatment after sterilization. Everyone who is considering fertility treatment should make the first appointment with a physician specialized in fertility treatments.
At this visit, the physician will discuss the matter and gain information about the couple or single woman and make the necessary examinations. For female clients, the physician makes a pelvic exam and vaginal ultrasound. Ultrasound is an important aid for infertility treatment, since it facilitates close follow-up of how the treatment works. Most visits to the clinic will involve an ultrasound, which can be performed during menstruation. The ultrasound provides images of the uterus and ovaries. Knowledge of the current situation of these organs is crucial for the managing physician. Of male clients, the structure of the testicles is examined, if needed, and often arrangements are made for the male client to provide a semen sample. With the results of these visits and examinations, the physician and couple agree on a preliminary treatment plan. The goal is to start a long-desired pregnancy as soon as possible.
Ovulation induction (encouragement)
The purpose of encouraging egg release (ovulation induction) with medicines is to support the maturation of 1–2 egg follicles. This treatment is used when the menstrual cycle is not regular or when maturation of the egg follicle does not proceed as it should, e.g., due to the polycystic ovary syndrome (PCOS). Ovulation induction is also often needed in connection with insemination.
The physician prepares a treatment plan: the ovulation inducing-hormones are taken according to plan either as tablets by mouth or as injections under the skin. Usually, a tablet called letrozole is taken by mouth for five days in the beginning of the menstrual cycle. The development of the follicles and the endometrium (inner lining of the uterus) is followed with ultrasound.
Couples longing for pregnancy may run a test to examine if ovulation has occurred (the LH-test). These tests are available at pharmacies. If the couple can make the ovulation test with no problems, this is a valuable aid for determining the time of ovulation. The development of follicles and determining the time of ovulation may, if needed, be checked by ultrasound or by determining the blood concentration of the hormone progesterone. There is also medication available to encourage ovulation.
It is optimal to have intercourse during a few days after the ovulation test has become positive, because the egg cell is susceptible for fertilization for only brief period of time.
Insemination
Insemination is inserting sperm into the uterus through a thin plastic tube. This is often the primary treatment of infertility of unknown cause and of male infertility due to poor sperm production. Self-sufficient women and female couples are inseminated with donated spermatozoa.
Insemination is possible if the woman’s menstrual cycle is natural or hormone-supported. Further requirements are that the uterine tubes (Fallopian tubes, oviducts) are open, and that ovulation takes place. The time of ovulation can be determined by testing the urine for LH (luteinizing hormone) at home. Occasionally, ovulation is encouraged with a hormone injection.
The sperm is processed to isolate healthy spermatozoa on the day of insemination. Dead and poorly moving spermatozoa are “washed away” from the sperm sample. The most mobile and vivacious spermatozoa are introduced into the cavity of the uterus through a thin catheter (tube). Insertion of the insemination catheter does not usually cause pain nor do the spermatozoa ooze out from the uterus. The processed spermatozoa are viable for 1–2 days, and hence insemination must be scheduled close to the time of ovulation.
Before insemination, the parties must sign a consent form, as required by the Act on Assisted Fertility Treatments. The male partner must also provide the lab test results for certain infections: HIV, hepatitis B and hepatitis C.
If the sperm of the male does not contain spermatozoa, insemination may be carried out with donated spermatozoa. In this case, the client may select the donor of the spermatozoa based on the data collected of donors. The collected data are ethnicity, height, eye color and hair color. All donors are registered and examined, as required by the Act on Assisted Fertility Treatments. The Aura Klinikka uses spermatozoa purchased from abroad.
In vitro fertilization (IVF)
The most efficient treatment for infertility is in vitro fertilization (IVF). IVF is used if infertility is due to poor sperm quality of if there is something wrong with the uterine tubes, e.g., if they are blocked, maybe because of sterilization or some infection or inflammation, or if they have been surgically removed, e.g., because of extrauterine (ectopic) pregnancy. IVF is also often required to treat infertility of unknown cause.
The hormone treatment to stimulate the ovaries is always planned individually. Rather that to generate one follicle, the goal is to generate several. The stimulation may be carried out according to a delayed program or – which is more common – an accelerated program. In the delayed program, agonist drugs are used to induce a period of ovarian dormancy before stimulation with injectable hormones. In the accelerated program the stimulation with injectable hormones is given during the first days of the menstrual cycle following a preset treatment plan. Depending on which program is used, the treatment duration totals about 2–4 weeks. The hormones are injected under the skin with a thin needle in the evening. It is easy to carry out the medication and it causes no pain. The nurses will provide detailed injection instructions and they are easily reached for consultations, if needed. The development and growth of the follicles is followed by ultrasound, usually 2 or 3 times, and the hormone dose is adjusted according to the response seen. Once the follicles have reached a size of 18–20 millimeters, an additional hormone injection will release the egg cells into the fluid of the follicles. Then the ova are collected into thin tubes by puncturing the ovary with a thin needle and by aspiration (suction) of the follicular fluid where the egg cells reside. This procedure requires ultrasound guidance and takes 10–20 minutes. During the procedure, a cell biologist in the adjacent laboratory collects the egg cells from the aspired liquid.
During the egg collection process, pain relief is provided by an effective intravenous analgesic and local anesthesia of the back wall of the vagina. If needed, the doctor may prescribe a tranquilizer before the procedure. After the egg cells have been collected, the patient is followed up for about an hour. She will be discharged home as soon as she feels well. It is advisable to rest after the procedure and to avoid physical strain and to drink sufficiently. Sick leave is prescribed as needed. On the day after the puncture for egg retrieval, hormone support therapy starts as prescribed by the physician at Aura Klinikka.
The male partner provides a semen sample on the same day as the egg retrieval. The sample is processed (washed) and the best spermatozoa are isolated for use. If donated spermatozoa are used, they are thawed after egg retrieval and are processed as are non-frozen semen samples. The egg cells and the spermatozoa are placed concomitantly on a Petri dish, and fertilization of the egg cell takes place within about 20 hours.
The egg cells and spermatozoa are kept in a cell culture incubator optimized for the conditions prevailing in the human reproductive system. Fertilization and the development of the embryos are followed in the laboratory for 2 –5 days, after which the best embryo is selected for transfer into the uterus. Additional embryos of good quality are kept frozen (cryopreserved) in liquid nitrogen for transfer of frozen embryos, when needed later. The physician and the couple or the self-sufficient woman discuss and decide on the number of embryos to be transferred into the uterus. Usually, only one embryo is transferred to reduce the risk of multiple pregnancies; the maximum number of embryos to be transferred into the uterus is two. The hormone support treatment continues also after embryo transfer, and a pregnancy test of a urine sample may be taken about two weeks after the transfer.
On average, 30–40% of fresh embryo transfers result in pregnancy. The most important factor affecting the prognosis of pregnancy is the woman’s age.
Before starting the IVF procedure, the parties must sign a consent form, as required by the Act on Assisted Fertility Treatments. The male partner must also provide the lab test results for certain infections: HIV, hepatitis B and hepatitis C.
Intracytoplasmic sperm injection (ICSI)
ICSI is mainly used when the cause for infertility is a low sperm count, when the spermatozoa have poor mobility or when spermatozoa are collected from the testicle tissue. ICSI is also used if IVF has not been successful.
For the woman, the procedure for ICSI and IVF are the same. On the same day as when the egg cells are collected, the male provides a semen sample. The most mobile and vivacious spermatozoa are identified, separated and collected.
If the spermatozoa are collected directly from the testicle tissue, this is usually done on the same day as the follicle puncture.
Fertilization is performed under the microscope: one solitary, highly mobile spermatozoon is injected directly into a mature egg cell. The egg cells fertilized by this technique are kept in a cell culture incubator optimized for the same conditions as those which prevail in the human reproductive system. Fertilization and embryo development are followed in the laboratory for 2–5 days, after which the best embryo is selected for transfer into the uterus. Additional embryos of good quality are kept frozen in liquid nitrogen (cryopreserved) for later transfer of frozen embryos.
The physician and the couple decide together how many embryos are to be transferred into the uterus. Usually, only one embryo is transferred to reduce the risk of multiple pregnancies; the maximum number of embryos transferred into the uterus is two. Hormone support treatment continues also after embryo transfer, and a pregnancy test of a urine sample is made about two weeks after the transfer. On average, 30–40% of fresh embryo transfers result in pregnancy.
Before insemination by the ICSI technique, the parties must sign a consent form, as required by the Act on Assisted Fertility Treatments. Also, the results of blood tests for HIV, hepatitis B and hepatitis C of the individuals undergoing treatment are needed.
Embryo freezing and transfer of frozen embryos
The best of the embryos obtained by IVF or ICSI is selected for fresh embryo transfer and the remaining embryos of high quality may be frozen (cryopreserved) in a container with liquid nitrogen (-196°C). Frozen embryos may later be thawed and used for embryo transfer. Transfer of frozen embryos may be performed for women with a normal or hormone-supported menstrual cycle. The embryo is usually thawed on the day before the transfer. This makes it easier to follow if the embryo is vital and if cell division has started.
More than half of the frozen embryos survive thawing and the likelihood of pregnancy or 20–40%. A separate agreement covering the next 12 months is signed for embryo freezing and preservation. The agreement specifies the fee for this service. If frozen embryos are no longer to be used, they may be destroyed, donated for embryo adoption or handed over for quality control or educational purposes of the clinic. The decision to preserve the embryos and the time when preservation ends are agreed on in writing. Embryos may be kept in liquid nitrogen for years, if needed, but embryos derived from donated gametes are kept for a maximum time of 15 years from the day of donation.
Testicular sperm extraction (TESE)
If the semen of the male partner is completely void of spermatozoa, testicular sperm extraction (TESE) may be the next alternative. A complete lack of spermatozoa from the semen may be due to genetic or structural abnormalities, sterilization, some chronic illness or previous infection or inflammation, some intervention or injury to the testicles. Identification of the reason for the lack of spermatozoa requires often blood testing of some hormones.
Based on a thorough physical examination by the doctor and on hormone values, the doctor can decide it there are possibilities to recover spermatozoa with a needle biopsy or if a more invasive surgical procedure is needed where the testicle tissue is examined under a microscope for identification of suitable sampling sites containing spermatozoa.
A needle biopsy of the testicle may also be done to examine if there are any spermatozoa in the tissue or not. If the biopsy shows the presence of lots of spermatozoa, the sample may be frozen for later treatments. TESE may be used in the same session as ICSI, and in this case the female partner will undergo hormone treatment which will stimulate follicle maturation to take place at the time when the ICSI is performed.
TESE is performed under local anesthesia and, if needed, an intravenous dose of an analgesic may be administered. For collection of spermatozoa from the testicular tissue, a biopsy needle is used. In a separate laboratory, spermatozoa are identified and isolated for ICSI, where a single spermatozoon is injected into the center of the mature egg cell.
Safety
Ovulation is induced (encouraged) with hormones administered according to a schedule set on beforehand, and no negative effects of the hormones on the fetus have been described. When the ovaries are stimulated to produce mature egg cells in IVF, about 2% of the women experience overactivity of the ovaries. This situation is treated by bed rest, which very seldom requires hospital care. Estrogen treatment carries a slight risk of venous blood clots. To avoid such problems, treatments are always individualized, and patients are followed up very carefully all along the treatment
If two embryos have been transferred, a twin pregnancy is possible. A twin pregnancy is always considered to be a risk pregnancy since it is associated with an increased risk of fetal death, premature labor and delivery complications. Also, the two newborns have a higher rate of sickness and death than single newborns. The risk for complications to the mother is also increased. Due to these facts, single embryo transfers are recommended.
Children born through fertility treatments have a slightly higher risk for congenital malformations than the average population. Based on current knowledge, this is assumed to be primarily due to the cause of infertility rather than to the methods used to treat the condition. Information about the health of children born with the help of fertility treatments is continuously collected and the accumulated data indicate that infertility treatment are safe.
There are lifestyle circumstances of the woman and male partner which affect pregnancy initiation and the wellbeing of the fetus and child. Smoking needs to be avoided and alcohol consumption kept to moderation. It is also important to strive for normal weight and to maintain it. If the diet is healthy and balanced, no food supplements are needed. However, a current recommendation is that all women should take supplemental folic acid and start taking it already when planning pregnancy. It is also important to secure that the intake of vitamin D is sufficient.
Results
The likelihood of success for any of the fertility treatments is determined by the cause and duration of infertility, age (specially of the woman), previous pregnancies and the outcome of previous fertility treatments.
An elective transfer of one or two embryos means that the one or two best embryos out of a number of embryos are selected by a biologist for the transfer procedure. If the number of embryos is limited, the pregnancy prognosis will be negatively affected, since the choice is limited.
Clinical pregnancy is defined as an intrauterine pregnancy diagnosed by a physician. Diagnosed extrauterine pregnancies and blighted ova (gestations without an embryo) are also considered to be clinical pregnancies. Biochemical pregnancies and pregnancies miscarried before the early-pregnancy ultrasound should not be included in the result assessments of infertility treatments.
Clinical pregnancy is defined as a pregnancy diagnosed by a physician with ultrasound. Intrauterine, extrauterine and blighted ova are considered clinical pregnancies. Biochemical pregnancies and pregnancies miscarried before the early-pregnancy ultrasound should not be included in the result assessment of infertility treatments.
IVF leads usually to pregnancy after 1–4 well-timed treatment courses. Occasionally, there are indications for several treatments, and this may bring about better results. The rate of clinical pregnancies resulting from IVF using gametes of the spouses and diagnosed by a physician is 20–25%. The corresponding rate when donated spermatozoa are used is 25–30%.
The rate is 30–40% for elective embryo transfers following IVF or ICSI. When frozen embryos are used, the likelihood of pregnancy is 20–30%, when donated fresh egg cells are used, the likelihood is 40–50% and slightly lower when frozen embryos are used.
An important principle when using fresh embryos and frozen embryos is to transfer only one high-quality embryo so that multifetal pregnancies are avoided. Whether there are possibilities to transfer two embryos is considered case-by-case. A measure of high quality is a rate of multifetal pregnancies below 10%.
