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Infertility

Infertility is a significant reproductive health issue affecting couples of reproductive age, with biological, psychological and social dimensions.

What is infertility?

Infertility is a significant reproductive health issue affecting couples of reproductive age, with biological, psychological and social dimensions. Infertility is not merely a condition affecting the female or male reproductive system; it should be approached as a situation requiring a joint assessment of the couple.

Based on data from the World Health Organisation (WHO) for the period 1990-2021, it is estimated that approximately 1 in 6 adults will experience infertility at least once in their lifetime. When assessed by age, it has been reported that infertility rates are lowest (approximately 3%) among women aged 20-24 and highest (approximately 5.5%) among women aged 35-39.

How is infertility diagnosed?

The evaluation process for infertility begins when pregnancy is not achieved despite 12 months of unprotected sexual intercourse in women under 35, and 6 months in women aged 35 and over. Furthermore, in women aged 40 and over, those with irregular menstrual cycles, a history of endometriosis, inflammatory diseases, abdominal surgery, or reproductive system abnormalities (all known risk factors for infertility) or in cases where there are known male-related causes, the evaluation process may begin earlier. According to the International Glossary of Reproductive Medicine, couples who have never achieved pregnancy before are defined as having primary infertility, whilst couples who have achieved pregnancy at least once are defined as having secondary infertility.

How is infertility assessed?

When assessing the causes of infertility, it is important to evaluate both partners. From this perspective, causes can be categorised as female-related, male-related, or mixed (affecting both partners). In a study conducted by the World Health Organisation (WHO) on 8,500 couples wishing to have a baby, it was reported that in 37% of couples the cause was female-related, in 8% male-related, and in 35% due to factors affecting both the man and the woman. In cases where no cause can be identified following standard examinations and tests, the condition may be defined as unexplained infertility, which accounts for approximately 18-28% of couples.

What are the causes of infertility?

In a large-scale study, the causes of infertility included: Male-related causes (26%), Ovulation disorders (21%), Tubal issues (14%), Endometriosis (6%), Sexual problems (6%), Cervical issues (3%), and Unexplained infertility (18–28%).

As women age, the percentage of women experiencing age-related infertility increases. In addition, other factors that may reduce fertility, such as the presence of fibroids, fallopian tube-related conditions and endometriosis, also increase with age.

A detailed assessment of both the woman and the man is essential for couples seeking to conceive a child. In this context, the female assessment involves a detailed medical history followed by a physical examination, after which ovarian reserve and ovulation function, fallopian tube function, and uterine factors are evaluated. Similarly, in the male assessment, following a detailed medical history and physical examination, a semen analysis is carried out, and where necessary, a urological assessment is performed.

How is infertility treated?

Following all assessments, a treatment plan is devised by evaluating the findings for both the woman and the man, taking into account the couple's age and how long they have been trying to conceive.

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The IVF Process

IVF treatment consists of four stages. These stages can be listed as follows: 1. Assessment of the couple, examination, diagnostic tests and determination of the treatment protocol: During the assessment of the couple, the patient's symptoms, medical history and family history are reviewed, and factors related to the cause of infertility are investigated. An ultrasound scan is performed to examine the structure of the reproductive organs, the uterus and the ovaries, and to identify any diseases or changes in neighbouring organs, investigating their relationship to infertility. If a problem is identified that hinders treatment or reduces the chances of success, steps are taken to resolve this issue first. During the ultrasound scan, an assessment of 'ovarian reserve' is carried out, which plays a significant role in selecting the treatment to be administered in the future and in determining the likelihood of treatment success. In addition, with a view to preparing for pregnancy, the presence of certain hormonal, metabolic and viral diseases that could adversely affect pregnancy, as well as the patient's immune status, is investigated. 2. Stimulation of the ovaries with medication: This constitutes the most important stage of the treatment. The treatment regimen to be administered during ovarian stimulation is determined based on the patient's age, the appearance of the ovaries on ultrasound, hormone test results, and, in patients who have previously undergone IVF, the response to treatment in the previous cycle. The physician's experience in determining this treatment directly influences the outcome. 3. Egg retrieval: Under anaesthesia, guided by transvaginal ultrasound, eggs are aspirated from the follicles containing the egg cells using a fine needle and removed from the body. 4. Embryo transfer: The best 1 or 2 embryos (fertilised eggs) are selected from those monitored in the laboratory and transferred into the uterus using a thin catheter. This procedure is similar to a routine examination and does not require anaesthesia.

The ideal time to start the egg stimulation process in IVF treatment is on the second or third day of the period. However, this is not an absolute requirement. Under certain specific conditions, ovarian stimulation medication can be started at any stage of the menstrual cycle.

Ovarian stimulation typically lasts approximately 8 to 14 days, although in some cases it may be shorter or longer. The growth of follicles that may contain eggs is monitored via ultrasound. Monitoring will require 4-5 visits to the IVF clinic during the course of treatment. In addition to ultrasound scans, hormone monitoring may also be carried out in some women. These hormones include oestrogen, progesterone and LH, and in some cases FSH. Once the follicles have reached the desired size, maturation injections (known as HCG or GnRH analogues) are administered to bring the eggs inside them to full maturity, and, barring certain special circumstances, the oocyte pick-up procedure is usually performed 34-38 hours later.

The oocyte pick-up (OPU) procedure is usually performed under local anaesthesia and takes approximately 15-30 minutes, depending on the number of follicles. If the ovarian response is limited and a small number of eggs are anticipated, the procedure may also be performed under local anaesthesia whilst the patient is awake. Following the procedure, you can return home after approximately 1-2 hours of observation and monitoring.

Once the oocyte pick-up has been completed, fertilisation with sperm takes place. The embryos are then monitored in the laboratory in special culture media for 3-5 days, or in some cases for 6-7 days. If there are any remaining high-quality embryos suitable for freezing after the transfer of those assessed in the laboratory and selected for transfer, these can be frozen and stored for transfer at a later date.

In Türkiye, the number of embryos that can be transferred is determined by regulations; for women under 35, it is limited to 1 embryo for the first 2 attempts, and for women over 35, it is limited to a maximum of 2 embryos. Under no circumstances is the transfer of more than two embryos permitted.

During the IVF treatment, ultrasound scans and blood tests are carried out during the egg stimulation phase to monitor egg development and adjust the dosage. On average, you will need to visit the hospital four or five times during the treatment process for these check-ups. As the time spent at the hospital during these check-ups is brief, they can be carried out without disrupting daily life or work routines.

Success Rates

The most up-to-date measure of success is the live birth rate of a single healthy baby per IVF cycle initiated. Multiple pregnancies are now considered high-risk, and transferring embryos one at a time wherever possible has become a global trend.

There are many variables that determine the chances of success in IVF, but the most important of these are the woman's age and ovarian reserve. In younger women with high ovarian reserve, the pregnancy rate (defined as the proportion of pregnancies resulting in live birth following the sequential transfer of all embryos obtained from a single egg retrieval) is higher. However, in women over the age of 40, this rate decreases, and by the age of 45, it drops to very low levels. Unfortunately, these results are not altered by supplements or 'rejuvenating' agents administered to the ovaries. AMH is one of the most reliable markers of ovarian reserve. Although a low AMH level does not necessarily mean pregnancy will or will not occur, it indicates that the number of oocytes picked up during the oocyte pick-up procedure will be low. Sperm quality is also a factor that directly affects embryo quality and the chances of pregnancy. In cases where there are very few sperm in the semen or where sperm must be retrieved from the testicles, embryo development is adversely affected.

Ovarian reserve is determined by an experienced physician performing a transvaginal ultrasound scan to assess the number of antral follicles present in the ovaries and their distribution. With advancing age, there will be a loss in the ovarian reserve; concurrently, there will be a reduction in ovarian volume and a decrease in the number of antral follicles. In addition to ultrasound, anti-Müllerian hormone (AMH) is the marker that best reflects ovarian reserve. Low AMH levels allow us to predict that the response from the ovaries during treatment will be poor, enabling us to tailor the treatment protocol accordingly.

In patients who have previously undergone unsuccessful IVF attempts, the most important factor determining the chances of success in the next treatment is the information regarding the ovarian response and embryo quality from the first treatment. When planning a new treatment, data from the previous treatment cycle is taken into account to plan how to obtain the healthiest and highest number of eggs from the ovaries. A history of low oocyte pick-up or poor-quality embryo development may be due to factors related to the patient, or it may be linked to the treatment protocol and medication doses used, as well as laboratory conditions. Other reasons for failure to achieve success include fibroids, polyps, blocked fallopian tubes, uterine malformations and intrauterine adhesions. Correcting these issues, where applicable, will increase the chances of pregnancy. Additional tests and assessments, such as investigations into coagulation disorders (congenital or acquired) and immune function, are not routinely recommended. The cause-and-effect relationship for both is unclear.

Various supportive medications, primarily the hormone progesterone, are used to support the embryo's implantation in the uterus following embryo transfer. The use of medications without scientific evidence (such as aspirin, blood thinners, agents that inhibit uterine contractions, immunosuppressive drugs, etc.) or strict bed rest will not increase the embryo's chances of implantation and will only cause unnecessary anxiety and expense.

Cost and SGK Support

In IVF treatment, state funding can be obtained by producing an IVF report (signed by three people). To obtain this report, you must apply to centers authorised to issue such reports. Your physician must determine that IVF is necessary for the report to be issued. To obtain the report, one of the spouses must have at least 5 years of service with the Social Security Institution and a minimum of 900 days of contribution days, and the female partner must undergo a medical examination confirming she has no medical conditions preventing pregnancy. If deemed appropriate, an SGK report may then be issued.

Here, the couple's medical history and current condition regarding IVF treatment are significant. Following the physician's assessment, different methods to increase the chances of pregnancy or mandatory procedures to achieve pregnancy may be required. Services can be categorised as those related to laboratory and embryology, genetic and advanced diagnostic services, freezing and storage services, and services related to uterine preparation. These procedures include Embryo Glue, the microchip technique, IMSI, genetic embryo biopsy, and hysteroscopy/hysteroscopic polyp removal.

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