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Gender Selection IVF and PGD (Preimplantation Genetic Diagnosis)

PGD is a method applied in addition to in vitro fertilisation treatment and is based on the principle of genetic examination of babies in the cellular stage, namely embryos. In this way, sick babies are eliminated, and only healthy babies are allowed to be transferred, preventing the transmission of some genetic diseases to the baby. With PGD, research can be conducted on various subjects, from chromosome number anomalies to the baby's sex, from single-gene diseases to chromosome structure anomalies. For this research, the woman's egg must first be fertilised with the man's sperm outside the woman's body; in other words, the in vitro fertilisation method must be applied to perform PGD. According to current laws and regulations in the TRNC, optional gender selection with PGD is prohibited, but gender determination can be made for diseases transmitted with the sex chromosome. Therefore, all patients interested in PGD treatment should receive medical and, if necessary, genetic counselling before planning the treatment, which will help them take faster and more accurate steps on the path to pregnancy.

PGD and gender selection is a treatment method that involves collecting the eggs of the female patient after they have developed, fertilising them in a laboratory environment with a sperm sample taken from the male, monitoring the development of the embryos, taking cell samples from the embryos at a particular developmental stage and examining the genetically desired chromosomes or genes, and placing the embryo or embryos that are determined to be healthy for the determined chromosomes or genes into the mother's uterus, namely the endometrium, on the appropriate day according to the baby's development. Suppose the sperm is specifically selected and inserted into the egg during fertilisation. In that case, ICSI treatment is also added to this treatment, and since this is an element that increases the success of the treatment, it is routinely applied in some centres.

Preimplantation genetic diagnosis treatment minimises problems during pregnancy as it 100% guarantees that only healthy embryos are transferred to the mother for the selected chromosomes (e.g. 21, 18, 13 and sex chromosomes). In other words, since specific chromosomes or genes are genetically examined, there is no margin of error, and the result is guaranteed. In addition, in this way, there is no need for procedures such as amniocentesis to understand whether the baby has diseases such as Down Syndrome due to advanced age during pregnancy.

PGD treatment is not complex; it is a beautiful and exciting process that only requires the patient, doctor, embryologist and patient consultants to work harmoniously. The medical team's expertise, including the infertility specialist, doctor, and embryologist, ensures a secure and confident process for the parents-to-be. IVF treatment also has its difficulties; however, when it is considered that the family will be crowned with a healthy baby, these sweet difficulties will be memories of the effort spent for a beautiful result.

Tüm tüp bebek tedavileri, hem yumurta toplanması, hem embriyo gelişimi takibinin doğru yapılabilmesi gibi özellikli alanlar istediğinden hastanelerin tüp bebek ünitelerinde veya tüp bebek merkezlerinde uygulanmalıdır. Bir infertilite kliniğinde hastaların görüldüğü ve muayenelerin yapıldığı poliklinik kısmı haricinde özellikle tüp bebek işlemlerinin yapıldığı bir bölüm bulunur. Bir tüp bebek bölümü, içerisinde sadece tüp bebek işlemlerinin yapılacağı bir ameliyathane, yumurta ve embriyo yani hücresel safhadaki bebeğin geliştirileceği bir embriyoloji laboratuarı ve sperm inceleme ve hazırlığının yapılacağı bir androloji laboratuvarı içerir. Ayrıca preimplantasyon genetik tanı yani PGT işleminin de yapılabilmesi için tam donanımlı bir genetik laboratuvarının bulunması gerekir. İşlemlerin yapılacağı yer kadar işlemleri kimin yapacağı da önemlidir. Tüp bebek, sadece tüp bebek konusunda diploma ya da sertifika almış infertilite uzmanı yani kısırlık uzmanı tarafından yapılmalıdır. Kadın hastalıkları ve doğum uzmanlarından ancak bu ek eğitimi almış ve yetkili olanlar bu tedavileri uygulayabilecek bilgiye sahiptirler. Tüp bebek üst eğitimi almamış kadın hastalıkları ve doğum uzmanlarının bu tedavileri yapması hem hasta başarısı açısından sakıncalıdır, hem de yasal değildir. Bu nedenle, tüp bebek merkezinin seçiminden ziyade, tüp bebek doktorunun seçimi ön plana çıkmaktadır. Bu konuda, gerek hastanın doktorunun yönlendirmeleri, gerekse internet sitelerindeki danışmanların vermekte olduğu danışmanlık hizmetleri yol göstericidir ve bu şekilde hastaya, infertilite veya tekrarlayan gebelik kayıpları ile ilgili çözümde, onlar için en iyi tüp bebek tedavisi uzmanının bulunması sağlanabilir. Yrd.Doç.Dr. Burcu Özbakır, tüp bebek tedavileri üzerine İngiltere’de çalışmalar yapmış ve konu ile ilgili Kıbrıs ve Türkiye’de üst ihtisas denkliğinde diploma sahibi tek doktordur.

Since the selection of patient groups to be applied to the Preimplantation Genetic Screening treatment method is an essential element in success, first of all, an IVF treatment specialist evaluates the medical information of the couple, and then only the treatment is recommended to couples who will benefit from IVF treatment. The conditions for PGD treatment are summarised below:

  • Female patients aged 35 and over
  • Male patients aged 45 and over
  • Decreased ovarian reserve in female patients
  • Low sperm count, motility and structural features in male patients
  • Obtaining sperm surgically from male patients (TESE, TESA, etc.)
  • Couples who have had a chromosome number anomaly in their previous pregnancy
  • A family member of the couple to have a chromosome number anomaly
  • Those at increased risk of chromosome number anomalies due to balanced Robertsonian translocation in female or male patients
  • Carriers for a single gene disease in female or male patients or their family (such as Thalassemia, Cystic fibrosis, Haemophilia, Sickle cell anaemia)
  • A genetic disease in the personal or family history of female or male patients
  • Couples with unaccountable infertility issues
  • Couples with recurrent IVF failures
  • Couples with recurrent pregnancy loss
  • Couples who want to store healthy embryos
  • Patients with concerns about certain chromosomal anomalies in their children

The treatment process is determined by the research conducted before the treatment. Both the treatment program and the IVF drugs and doses are determined before the IVF process is started. The IVF and PGD treatment stages are explained to the patients in detail, and the preliminary preparations are completed. For example, screening for some infectious diseases before starting the treatment may be necessary in terms of both the treatment's timing and the treatment's management. In some cases, antibiotics may be required before IVF, while in some cases, additional washing of the sperm may be necessary.

Egg development period: The timing of the couple's treatment depends on the female patient's menstrual cycle, and the treatments start about the menstrual cycle. Therefore, IVF treatment cannot be started on any day in patients with regular menstrual cycles. A short or long treatment protocol can be selected according to the female patient's menstrual cycle. In the long protocol, the needle treatment that controls ovulation starts on the 21st day of the patient's menstrual period. With the next menstrual period, egg development needles are added to the treatment to ensure egg maturation. In the short protocol, egg development needles are started within the first 5 days of the menstrual period, and when the eggs begin to mature, the needle treatment that controls ovulation is added. Some egg development and ovulation control IVF needles are administered subcutaneously and intramuscularly. The needles administered subcutaneously are tiny and are usually preferred in the belly or arm area, and patients can administer their injections after a short training. Since the injections that need to be administered intramuscularly are usually administered from the hip, they should be administered by medical personnel. The medications used in IVF treatment for family balancing are not just injections; vitamins, antibiotics, drugs for the immune system and various treatments for the coagulation system can be added to the treatment depending on the patient's clinical condition.

During the treatment, the woman undergoes vaginal ultrasound several times to monitor the effects of the egg development drugs taken, to adjust the dose if necessary, and to add or remove medications if necessary. The reason for performing ultrasounds vaginally is that the measurements and images are much more accurate than ultrasounds viewed from the abdominal area. During the ultrasound, the follicles belonging to the developing eggs in the ovaries, namely the tiny egg cysts filled with fluid, are counted, each being measured individually. The growth rates of these measured follicles are monitored with serial ultrasounds, and the necessary medication adjustments are made. Another follow-up performed while monitoring egg development is the endometrium, or the thickness of the inner wall of the uterus, in in vitro fertilisation. The endometrium, where the baby will attach, also thickens under the effect of these stimulating drugs and its nutrition increases.

In both long and short-protocol treatment management, when the eggs are fully mature, an HCG-like drug called an IVF trigger injection is applied, and the eggs are collected between 34-36 hours after the injection. The timing of the egg collection process is critical because, in early collection processes, the number and quality of the eggs obtained will be worse. When it is too late, the eggs may not be collected because they will rupture. Since all the details can affect success, team harmony and success are higher when the IVF stages are shared with the patient.

Egg collection: Egg collection is performed while the female patient is under light anaesthesia (sedoanalgesia), meaning that the patient is asleep and does not perceive pain, but since there is no complete anaesthesia, she wakes up immediately after the procedure and does not take the risks of general anaesthesia. The duration of the egg collection procedure depends on the patient's egg count, the infertility specialist's experience and the general condition of the patient's ovaries. It is an average of 10-20 minutes. During this process, after the patient is asleep, the female genital area is cleaned, and the mature eggs are collected one by one by entering the abdomen through the vagina with a specific sterile needle. During this collection, the follicles containing the eggs are constantly monitored by vaginal ultrasound. As the eggs are collected, they are transferred to the embryology laboratory. The procedure is terminated after all the mature eggs are collected. Immediately after the procedure, before the patient wakes up, our doctor checks whether it is easy to enter the uterus with a trial catheter. In this way, it is decided which catheter or device will give better results in embryo transfer and the chance of success on the day of the transfer is increased.

Fertilisation of eggs: The answer to “How does IVF happen?” covers the baby’s formation process and begins after this stage. After the collected eggs are rested, the cells around each egg are cleaned, and the eggs (oocytes) can be observed. Four types of eggs are monitored at this stage. The egg type M2 refers to eggs ready to be fertilised, and the number of these eggs is essential. The egg type called M1 is an egg that is not yet suitable for fertilisation but is about to complete its maturation. These eggs can sometimes turn into M2 eggs when waited. For this reason, eggs that turn into M2 type after M1 eggs are kept for a while are also processed. The egg type called GV consists of eggs that are not suitable for fertilisation, are not fully matured, and are of no use. The egg type defined as postmature, or anomaly, describes eggs that are either old because they have been waited too long or have an abnormal appearance, and these eggs are not used because they are unhealthy.

Before or during the collection of eggs from a female patient, the male patient provides a sperm sample. A frequently asked question is, “Who is the sperm collected from?” Since the patient does not receive a sperm donation in standard IVF treatment, only the male partner’s sperm sample is used. The excess sperm sample used is discarded unless the patient has a special request for freezing. The best results are achieved if the sexual abstinence is between 2-4 days before sperm is provided in IVF treatment.

The embryologist washes and concentrates the given sperm sample. After the eggs are collected, the fertilisation process begins. In a traditional IVF treatment, a certain number of sperm are placed in the same area per egg, and the sperm is expected to perform fertilisation. ICSI, or intracytoplasmic sperm injection, can also be added to IVF treatment in some cases or all treatments. In the ICSI process, the best sperm in terms of movement and structure are selected from among the sperm and a sperm is injected into each egg. In other words, in the ICSI process, the sperm does not make an effort to penetrate the egg membrane and enter but is placed directly into the egg. Since this process is a method that increases the success of the treatment, it is added to routine IVF treatment by our centre.

Embryo growth (embryo culture): The first laboratory check is performed one day after fertilisation, and the number of fertilised eggs and the quality of fertilisation are recorded. While 2 PN indicates that fertilisation is healthy, 1 PN or 3 PN are signs of unhealthy fertilisation. In some eggs, no fertilisation may be observed. The fertilisation rate depends on the quality of the egg, the quality of the sperm, and the laboratory conditions of the IVF treatment. Embryos whose fertilisation has been observed are regularly monitored in particular nutrition and laboratory environments. While embryos not formed in good quality during development regress, the good ones continue to grow beautifully. Since the IVF formation process in a laboratory environment is a process that requires very sensitive monitoring and management, the order and monitoring of the laboratory environment are significant. The embryologist shares all the information they obtain when they check the embryos with the patients and the doctor daily.

While the embryos being monitored continue their development process, the female patient is given additional hormone support in the form of pills, gel, suppositories or injections to help the inner wall of the uterus mature.

PGD procedure: When the embryos are on their development 3rd to 5th day, a cell biopsy is performed on each embryo, and one or more cell samples are taken. These cells are examined in the genetic laboratory for the planned genetic screening. More than 90% of pregnancies compatible with life (continuing to grow in the first trimester) are anomalies of the 21st, 18th, 13th and sex chromosomes. For this reason, screening for abnormalities of the 21st, 18th, 13th and sex chromosomes is the most frequently used screening in the PGD procedure. In addition, if a familial genetic disease exists, these gene defects can also be investigated with previously prepared probes.

Embryo transfer: After the embryos are suitable for transfer, if healthy and transferable embryos are obtained due to PGD, the IVF treatment is completed with embryo transfer. The embryo transfer procedure is straightforward if there is no problem with the cervix or the shape of the uterus and does not require anaesthesia. The embryo transfer procedure is a very emotional moment, and female patients need to be involved in this procedure in terms of motivation. The embryo or embryos are transferred to the most suitable place in the uterus by our infertility specialist doctor through a thin catheter inserted through the cervix. Embryo transfer can be done between the 5th and 7th days, but the most commonly used embryo development days are the 5th and 6th days. The pregnancy success of an embryo that has survived to the 5th day is higher than that of an embryo on the 3rd day, and genetically screened embryos will also have a higher implantation success rate. The decision on which patient and on which day the embryo transfer will be made is made by the doctor, embryologist, and patient, depending on the embryo development rate. In our centre, all decisions regarding embryos are made together.

Another issue is how many embryos will be transferred. Medically, a maximum of three embryos are used as the transfer limit. However, this number is limited to 1 or 2 in many countries. As the number of embryos transferred increases, the chance of pregnancy in IVF increases. Therefore, patients can choose reliable countries where they can transfer up to 3 embryos. The laws in Cyprus legally allow the transfer of 1 to 3 embryos depending on the patient's condition. On the other hand, as the number of embryos transferred increases, the possibility of multiple pregnancies (especially twin pregnancies) increases. Since multiple pregnancy is a pregnancy that is more difficult to follow and riskier, the number and quality of embryo development, the clinical condition of the patient, and the patient's expectations are variables such as the patient's expectations. The doctor and the patient, who are aware of the embryo developments, meet, and the most appropriate management for the patient can be determined following this meeting.

On the day of embryo transfer, the embryos decided to be transferred are placed in embryo glue (i.e. embryo adhesive) liquid without any additional charge. In this way, the chances of their implantation after the transfer, so our patient's chance of pregnancy, is increased.

If our patients have good-quality embryos left, the remaining embryos can be stored on behalf of our couple with our patients' approval. In this way, if pregnancy is achieved, the same difficulties will not be experienced again for a second baby. If pregnancy is not achieved, a second treatment opportunity will be obtained much more easily.

The entire treatment process is determined according to the patient's treatment protocol. In patients who have applied a short protocol, the total treatment duration is 17-21 days. Since the treatment is started before menstruation in patients who have started a long protocol, the total duration, including drug treatment, is approximately 24-28 days. Since most of our patients do not live in Cyprus, to shorten this period, only the first part of our patients' drug treatments can be done where the patient is, and our doctor makes all arrangements regarding the drugs as a result of the examinations they have done in their home country. After our patients' eggs mature, they come to Cyprus, and the procedural parts of our treatment are completed there. In this way, the period our patients need to be in Cyprus will be approximately 7-9 days, depending on the day of the embryo transfer.

IVF treatment is a delicate process, and some precautions taken afterwards increase the success. Therefore, our support must continue after and during the treatment process.

Factors that primarily affect the success of IVF treatment with PGD are variables such as the female ovarian (egg) reserve, the male patient's sperm quality, the number and quality of embryos transferred, the female patient's uterine wall thickness and uterine structure, the couple's stress level, the couple's compliance with the treatment, the technical competence of the embryologist and doctor, and the quality of the laboratory. Since many variables in terms of IVF treatment success rate are clarified until embryo transfer, patients need to remain calm and not succumb to stress after embryo transfer. The recommended medications should be used regularly, and any additional problems should be reported to the coordinator.

Although it is recommended to be a little more careful only on the day of embryo transfer in IVF treatment with PGD, lying down for more than a few hours after embryo transfer does not increase success. For this reason, it is not recommended that patients lie down continuously after treatment. This situation increases stress and can even decrease success in some cases. What patients need to do is to be as active as they would be while pregnant.

Foods that should not be consumed after IVF treatment with PGD are beverages such as sage and green tea and drinks containing caffeine such as coffee and cola. It is also recommended that the patient avoid foods that will cause bloating in the abdomen. In other words, if the patient eats and drinks as if she is pregnant, she will not encounter any problems.

After PGD treatment, the pregnancy is understood with a B-Hcg test in the blood on the 10th to 12th day following embryo transfer. Suppose there is a pregnancy before the recommended day. In that case, positivity can be observed, but the reason for not testing much earlier is that the trigger needle can cause the test to be positive as if there was a pregnancy. Since the effect of the trigger needle will be zero on the 10th to 12th day, such a risk is not observed, and every positive result means pregnancy. The patient must share the result with their doctor or coordinator. The value in the test result is informative and will also be important in monitoring the speed of the increase in the test repetition 2 days later. While the increase in the test is usually in the form of doubling within 2 days, at least a 66% increase should be observed. Every patient with a positive test result should continue to use the medications they are using regularly. Our doctor also monitors and regulates what our patients must do during pregnancy and use medications afterwards.

As with all treatments, there is a possibility that pregnancy may not occur in IVF treatment. In such a case, a repeat test may be requested if necessary. It is recommended that patients with confirmed test results discontinue their current medications. In patients with treatment failure, detailed examination of the files and taking precautions before a new attempt may increase the chance of success in a subsequent attempt.

In Cyprus, IVF treatments are protected under the laws and relevant regulations, and all patient protective measures have been considered. For this reason, IVF treatment can be performed within a completely legal framework. PGD is performed on patients in the risk group under certain conditions, and only optional gender selection is not legal according to TRNC laws and regulations. One of the most frequently asked questions about the law is whether there is a marriage requirement for IVF treatment. Within the framework of the rules in Cyprus, there is no marriage requirement for procedures between patients. If the couple introduces each other as partners or the patients' eggs or sperm are used in the treatment, their names are recorded in the couple's file without the marriage requirement. Since the requirement of marriage is mandatory in many countries, we can perform the treatments of our patients who are not married for various reasons completely legally in our centre in Cyprus.

Due to the law, we cannot share information on egg-freezing prices on our website. You can contact us for detailed information.