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|The following simple approximation of events that follow the course of your ICSI treatment with us can be used to determine the number of days you may wish to take leave from work for and the number of days you may wish to book accommodation for in Turkey.
To manage the starting date of your treatment cycle you will be asked to take the contraceptive pill (OCP – active only) starting preferably on the 1st day of your full menstrual bleed in the cycle prior to your treatment cycle and continuing for 21 days (or up to 30 on your clinicians advice). After stopping the pill you will have 5 days in which to travel to Turkey. We will need you to be at the clinic on the 26th day of your cycle to start your follicle stimulating drugs. You will need to stay in Turkey for at least 18 days on average from the day of starting your drugs by which time your embryo transfer should have taken place.
The majority of patients at the IVF clinic will undergo controlled ovarian stimulation using what is known as the ‘short protocol’. In the ‘short protocol’ drug treatment starts on day 2 or 3 of your menstrual cycle, egg collection occurs on day 11-14 of your cycle and the transfer of your embryos to your uterus will occur 4 or 6 days after egg collection. In the ‘short protocol’ 3 drug types are commonly used, stimulating drugs, regulatory drugs and triggering drugs.
The main drug in your treatment regimen is the drug needed to initiate and promote follicular growth commonly known as FSH. Many different product brands exist, which differ mainly as a result of their production methods. All the FSH containing drugs are administered by subcutaneous injection. For complete ovarian stimulation FSH will need to be administered daily for 9-10 days, but may depending on individual response be shorter or longer.
1. FSH only: Gonal F, Puregon, Fostimon
2. FSH+LH (HMG): Menogon, Menopur, Merional
*Drug names may vary depending on the conditions of the day.
During ovarian stimulation a regulatory drug is required to prevent premature ovulation (the release of eggs from their follicles). The drug is started once the largest follicular reaches 14mm in size, also administered subcutaneously, and continued to the day of ovulation induction, usually 4-5 days.
1. GnRH antagonists: Cetrotide and Orgalutran.
*Drug names may vary depending on the conditions of the day.
During controlled ovarian stimulation, using stimulatory and regulatory drugs, follicular growth is checked regularly using ultrasound (and if needed blood tests). Once the largest 3 follicles reach 17mm in size ovulation can be induced using a trigger injection. The trigger injection must be administered at the correct time, to time the egg collection procedure correctly 36 hours after taking the trigger.
1. hCG trigger; Ovitrelle
2. GnRH agonist trigger; Decapeptyl
*Drug names may vary depending on the conditions of the day.
These drugs are used to improve endometrial lining of the uterus, to which the transplanted embryo adheres to, and promotes the hormonal environment required for pregnancy. These drugs are started on the day of egg collection and continued until your pregnancy test 14 days later, if pregnant you may have to continue with the drugs until the 10th week of pregnancy.
1. Progesterone; Crinone
2. Estrogen; Estrofem
*Drug names may vary depending on the conditions of the day.
Comparative Genome Hybridization
|A number of studies have now confirmed that a high proportion of oocytes and embryos derived from IVF procedures have genetic abonormalities. A oocyte or embryo with no abnormality is termed euploid, and oocytes or embryos with abnormalities are termed aneuploid. Aneuploidy in oocytes and embryos leads to poor IVF reproductive outcomes, such as, a lower implantation chance (pregnancy chance) and a higher chance for pregnancy loss. In IVF the selection of embryos or blastocysts for cryopreservation or the transfer to a patient uterus is still mostly based on morphological characteristics. However, morphology alone has been shown not to be able to exclude aneuploid embryos or blastocysts totally. Screening embryos or blastocysts before use has been shown to improve the chances of implantation and reduce the chances of pregnancy loss. In the past the only technology available was fluorescence in situ hybridization (FISH), which had limited success because it was only able to screen a limited number (5-12) of chromosomes. The new technology available such as comparative genomic hybridization (CGH) have the advantages of being able to screen all 24 chromosomes , thereby producing a more reliable and accurate result. Although abnormalities persist to the blastocyst stage there is evidence to suggest that a larger proportion of blastocysts are euploid (genetically normal) than cleavage stage embryos. The use of blastocysts therefore have an advantage over the use of cleavage stage embryos, because of the lower incidence of abnormalities and more than one cell can usually be screened (increasing overall accuracy). The pregnancies achieved at our IVF clinics using aneuploid screened blastocysts show the pregnancy chance when replacing one screened blastocyst may be as much as 20% higher than when replacing 2 fresh unscreened blastocysts.|
In vitro fertilization (IVF)
|IVF stands for in vitro fertilisation. IVF was originally devised to overcome infertility caused by blocked or absent fallopian tubes, but today IVF is used to treat many more reproductive problems, including irregular ovulation, low sperm count or motility, and unexplained infertility. In IVF fertilisation of eggs and embryo development occur outside the body of the woman, in a culture dish held in the controlled environment of an incubator.
First the woman’s ovaries are stımulated with the use of drugs to recruit and promote the growth of a suitable number of follicles each containing an egg. Follicular growth is monitored regularly by ultrasound during stimulation stage to decide on the right time to trigger the maturation of the eggs. Approximately 36 hours after taking the trigger injection the oocytes are collected in surgery by aspirating the follicles using an ultrasound guided aspiration needle. The aspirated follicular fluid from each follicle is checked in the laboratory and all collected eggs are placed in a culture dish and placed in an incubator until the time for insemination.
Sperm injection types
ICSI stands for intracytoplasmic sperm injection. All mature eggs are inseminated by this procedure 3-4 hours after they were collected, by injecting a sperm into each egg.
IMSI stands for intracytoplasmic morphologically selected sperm injection. IMSI is a process that uses high magnification optics (up to 6000X magnification) to select the best sperm for injection – the most morphologically normal sperm. IMSI is indicated for couples where the male partner has significant known sperm morphology problems and possibly for couples who have experienced recurrent unexplained implantation failure or miscarriage.
Embryo culture and replacement
|Fertilized eggs are cultured for 1-4 days. During this time the developing embryos are checked regularly to decide on the best day to replace the embryos and which embryos to replace. One or two embryos with the best chance of a pregnancy from the treatment cycle are selected for replacement. The selected embryo(s) are placed in the woman’s uterus under ultrasound guidance using an embryo transfer catheter.|
Assisted hatching is when the zona (the soft shell of the egg) is breached using a laser beam before the embryo is replaced to promote embryo implantation.
Embryos can be transferred to the uterus any time after fertilization has occurred. Embryos have mostly been replaced day 2 or day 3 into the uterus in the past, but with improving culture conditions, more embryos are developing into blastocysts by day 5. The blastocyst is the first stage of embryo differentiation, its cells having separated into two distinct cell-lines, the inner cell mass and the trophectoderm. The blastocyst stage is the final stage of development before the embryo can hatch and implant in the uterus. In theory, blastocyst culture offers the possibility of a higher pregnancy rate mainly due to better embryo selection. Many embryos may have chromosome abnormalities. These abnormalities stop the embryo developing much beyond the 8-cell stage, or day 3 of development after egg collection. Blastocyst formation may therefore be a good indication of a high pregnancy potential embryo. Blastocyst culture may not be appropriate in all patients to ensure an optimal chance for pregnancy. Your specialist will discuss the advantages and disadvantages of blastocyst culture before the start of your treatment.
|Embryo cryopreservation stands for the freezing of an embryo suspended in cryoprotectant and the storage of the frozen embryo in a cryotank. Often more suitable embryos than the one or two selected for replacement are cultured in an IVF cycle. Good quality embryos not replaced can be frozen, and thawed in a subsequent cycle to give more chances for a pregnancy. In the past most embryos were frozen using a programmable apparatus to freeze the embryos, in what is called the slow freezing method. Today most embryos and blastocysts are frozen by vitrification a rapid freezing method that results in lower cell damage, therefore embryos with greater pregnancy potential.|
Thawed embryo replacement
|When there have been embryos frozen following an IVF cycle, they can be thawed and transferred into the uterus in subsequent cycles. İn most cases a transfer cycle will be manufactured, using drugs, to ensure the uterus lining is sufficient and to time the embryo thaw with the appropriate uterus stage. Improvement in assisted conception technologies have seen pregnancy outcomes from frozen embryo replacement cycles improve to such an extent, that they now have an equal to or better pregnancy outcome than fresh embryo replacements.|
Preimplantation genetic diagnosis(PGD)
|Our IVF partners works in association with an internationally recognized genetics laboratory to offer a comprehensive chromosomal and or genetic screening service.
PGD stands for preimplantation genetic diagnosis a highly sophisticated scientific method to identify embryos from IVF that are free of genetically inherited conditions, including birth defects and genetic disorders. PGD involves the removal of one or more cells from an embryo or blastocyst and the subsequent genetic testing of these cells for specific genetic conditions or chromosomal disorders. Only those embryos diagnosed as being of normal genetic order or free of a specific disorder are selected for replacement in PGD-IVF cycle, thereby maximizing the chance of a healthy baby.
Pre-implantation Genetic Diagnosis may be considered if there is any concern about any of the following issues;
|Sperm cryopreservation stands for the freezing of a mixture of sperm solution and cryoprotectant and the storage of the frozen sample in a cryotank.
There are a number of reasons why you may wish to have a sperm sample frozen;
Before a medical or surgical procedure that may affect your sperm production (such as chemotherapy, radiotherapy).
If you, the male partner, is concerned that you may not be able to produce a semen sample on the day of IVF treatment.
If you, the male partner, will not be available on the day of the IVF treatment to produce a semen sample.
If your, the male partner’s, ejaculate contains very low numbers of sperm and there is a risk that on the day of the IVF treatment, your ejaculate may contain no sperm.
Sperm from semen ejaculates and sperm from testicular extractions can be frozen and stored. In cases of extremely low numbers of sperm a device called the ‘cell sleeper’ can be used to freeze small numbers of sperm collected using a microneedle.
Surgical sperm retrieval (TESA and TESE)
|TESA stands for testicular sperm aspiration and TESE for testicular sperm extraction. These are techniques to obtain sperm from the testis of men who have no sperm in their ejaculate (azoospermia) or who are unable to produce an ejaculate. Both procedures are performed under surgical conditions. Sperm obtained from the testicular tissue can be used fresh, if the procedure is performed on the same as the egg collection procedure, or can be frozen and stored until required.|
Your Fertility, Life Style, Age Factors
A typical fertile couple in their mid-to-late 20s having regular sex has about a 20-25% chance of conceiving each month. After 6 months at least three-quarters of such couples will be pregnant, and after a year at least 90%. Infertility is therefore defined as not being able to become pregnant after one year of trying. Approximately half of infertility is male based and about half female based. Whatever the cause of the infertility it is a couple's problem and requires the couple to work together towards a solution.
A woman’s age is the single most important factor affecting a couple’s chances of conceiving. That’s why it is strongly recommended you seek assistance after 6 months of trying if you are over the age of 35, and after 12 months of trying if you are under 35.
At our partner IVF clinics we consider the examinations and analyses before starting IVF treatment fundamental to successful conception and delivery of a healthy baby. The examinations and analyses must therefore lead to an accurate diagnosis of your infertility and indicate any factors that must receive possible treatment.
Causes of infertility are many and varied and involve male, female or a combination of factors. In 10-20% of couples no cause will be found, this is called Unexplained Infertility, which can be particularly frustrating for you and your partner.
In female infertility the most common diagnoses include one or more of the following factors; tubal infertility, endometriosis, ovulation disorders, polycystic ovaries, recurrent miscarriage, hormonal disorders, and auto-immune disorders. The most commonly used tests and procedures done to diagnose female infertility are; simply a blood test or tests done around the time of ovulation to determine the occurrence of ovulation, an ultrasound scan to examine the uterus, the uterus lining and the ovaries, a quantitative ultrasound scan of the ovaries to determine the number of antral folllicles in each ovary to determine the patients ovarian reserve, more critical examination of the fallopian tubes, uterus and ovaries by procedures such as, sonohysterography (a relatively non-invasive examination of the uterus and the fallopian tubes), hysterosalpingography (using X-rays to confirm the fallopian tubes are open, this does not provide any information about the ovaries and provides only limited information about the uterus), laparoscopy and hysteroscopy (surgical procedures for the evaluation of the uterus, fallopian tubes and ovaries). Laparoscopy and hysteroscopy procedures are also used for therapeutic purposes in female infertility management. In approximately half of the time the reason for a couple’s infertility maybe because male infertility issues. Often a man could be completely healthy, but produce poor quality sperm. Sperm have a life cycle of 72 days, so if you are ill or stressed it can temporarily affect your sperm production quality. In male infertility the most common causes of a male infertility factor are; retrograde ejaculation, blocked ducts, absence of vas deferens, undescended testes in childhood, autoimmune (antibody) disorders, hormonal disorders and or genetic abnormalities. A basic semen analysis would more than often indicate if any of these factors are present. Semen analyses at our partner IVF clinics are performed according to the World Health Organization (WHO 2010) guidelines on semen analysis. A semen analysis is done to accurately measure the number of sperm, their motility (ability to move), their morphology (size and shape), and the volume and consistency of the ejaculated sample. The male partner will need to produce a semen sample by masturbation, following 3-5 days of abstinence from ejaculation. Two private rooms are available at the clinic that can be used by you to produce a semen ejaculate for examination. It is important to ensure that your hands are clean before masturbation. The whole ejaculate must be collected in the sterile specimen container provided, if not, this must be reported the laboratory scientist as this may affect the outcome of the semen analysis.
For both women and men it is important getting your body and mind in a conception-fit state to improve your chances of conceiving and having a normal healthy baby. The following lifestyle challenges should be discussed with your general practitioner or your specialist prior to starting your fertility treatment.
Age, female age and to a lesser extent male age, is one of the most important factors when it comes to conception. Fertility levels diminish with increasing age particularly with women, but recent research indicates that age maybe an important fertility factor in men also.
The chance of pregnancy for a woman reduces with age, especially after the age of 35 years, so that by the age of 45 the chances of pregnancy will have fallen to extremely low levels. The reason for this fall in pregnancy is only partly understood, but what we do know is that egg quality plays an important part. The term egg quality mostly refers to the extent of damage to the female genome (DNA) in the egg. With an increase in age there is a decrease in the number of eggs available in the ovaries, as well as, an increase in the proportion of eggs that are genetic abnormal. Advancing age also increases the chances of miscarriage, abortion and the chances of genetic abnormalities in babies born.
There is good evidence that folic acid reduces the chances of having a baby with spina bifida (when the spine does not develop normally). The recommended dose is 0.8mg of folic acid daily for two months before conceiving and until 12 weeks of pregnancy.
Cigarettes have a huge impact on both male and female fertility. Women who smoke are only 60% as likely to conceive as non-smokers and smoking is also associated with miscarriage, small babies and earlier menopause. Men who smoke have lower sperm counts and more malformed sperm than non-smokers and are more likely to have children who develop childhood cancer.
High alcohol intake is known to have severe effects on fetal development during pregnancy. Research has, however, not been able to identify a safe level of alcohol intake for fertility and pregnancy, so it’s probably better not to drink alcohol while trying to conceive and during pregnancy. In men alcohol also affects fertility through impaired testicular function, so they too should reduce their alcohol intake or stop in support of promoting the chances of conception in their relationship.
Caffeine intake can affect fertility in women, as it is associated with a longer time to conceive and also reduced chances of becoming pregnant on an IVF program. Caffeine is not only contained in coffee but also in a variety of other products such as tea, cola, energy drinks, some frozen desserts and chocolate; so be aware of your overall caffeine intake. Male fertility does not appear to be affected by caffeine.
Healthy body weight
An unhealthy weight – in either partner – can also have a significant impact on the ability to conceive, so it is important to keep your body weight within the normal healthy range. Body Mass Index (BMI) is an indication of your body weight and can be calculated by dividing weight by height (kg/m2 [height x height]). You should aim for a BMI above 19.5 and below 30 as this will optimize your chances of conception. A BMI below 19, may affect ovulation and increase the chances of miscarriage. A BMI of >30 can reduce fertility by 50% and if pregnancy does occur the pregnancy is often associated complications, such as, maternal diabetes, increased risk of miscarriage, high blood pressure, birth defects and still birth. In men, being overweight may also reduce sperm count and affect the DNA of sperm.
Couples experiencing infertility definitely experience considerable stress, so stress management strategies should be discussed with a counselor or psychologist before starting treatment.
The current dietary advice is to eat a healthy balanced diet with lots of fresh fruit and vegetables. There are no wonder diets for improved fertility, however, there are some foods you could eat more of. Studies suggest that antioxidant rich foods can substantially benefit both men and women in promoting conception, foods such as;
all types of berries and fruits such as grapes, oranges, plums, pineapple, dates, kiwifruit, mandarins, dried fruit such as apricots and prunes, vegetables such as red cabbage, peppers, parsley, artichokes, Brussels sprouts, tomatoes, spinach; brightly coloured vegetables are particularly rich in antioxidants, legumes such as broad beans, groundnuts, soybeans, cereals such as barley, millet, oats and corn, nuts and seeds such as walnuts, brazil nuts, sunflower seeds, garlic, ginger and dark chocolate
There is a surprising lack of data on the effect of exercise on fertility. However, moderate exercise is always a healthy option and should be encouraged as it may improve the physiological processes of the body and the mind.