A. Treatment Overview
After the infertility evaluation your consultant will have come to an understanding of the factors that may be preventing you from achieving pregnancy. Your treatment options will depend on the diagnosis made and the chances you have of conceiving with the different options available. Your consultant may suggest trying other methods for several months before turning to IVF. If the chances of pregnancy are very low or non-existent using these methods, then Assisted Reproductive Technology may be the best option. With older women IVF may be suggested as the optimal treatment, as their chance of success with other alternatives needs to be balanced with the impact of age on their fertility.
During the woman's natural menstrual cycle, a vaginal ultrasound is done to check for the presence of the developing follicle. Blood tests or urine tests are used to find when the surge of luteinizing hormone (LH) commences, which signals the beginning of ovulation. Occasionally an HCG injection is used to trigger maturation and ovulation of the egg instead of waiting for the natural hormone surge. The consultant will then advise you on when to have sexual intercourse. A post-coital test may also be scheduled for this cycle as part of the fertility evaluation.
Artificial insemination (AI)
This procedure can be performed during a natural cycle or with artificial hormonal stimulation. Usually an injection of HCG is given when follicle development has reached a certain stage. An appointment is made for the man to visit the laboratory and provide a sperm sample by masturbation. The sperm may be used un-prepared, or separated from the semen, washed and suspended in a salt solution. This preparation is then injected into the cervical mucus or directly into the uterine cavity (intra-uterine insemination - IUI). Artificial insemination may be used in cases of unexplained infertility, hostile cervical mucus, minor sperm abnormalities and male sexual disorders.
Artificial insemination can also be done using donor sperm, either from an anonymous or a known sperm donor. Insemination with donor sperm is used when the husband does not produce sperm, when the sperm is of very poor quality or if there is a high risk of passing on genetic diseases. This is often abbreviated to DI - donor insemination. In this case, it is important to have explored all the issues involved with a counsellor beforehand, especially as the laws in relation to disclosure have recently changed.
Clomiphene citrate and artificial hormone preparations of follicle stimulating hormone (FSH) may be used to encourage the development of one or more follicles and thus more than one egg, during the woman's cycle. This process is known as ovulation induction if the woman is anovulatory, or super-ovulation she is already ovulating without treatment. Clomiphene may be used in conjunction with timed intercourse, or artificial insemination, to ensure that the sperm are introduced at exactly the right time. The cycle is monitored more closely than a natural cycle with vaginal ultrasounds and/or blood tests to check follicle development and observe hormone levels. HCG is used to trigger the process of ovulation.
There are side effects and risks associated with the use of fertility drugs. Clomiphene can have a negative effect on cervical mucus and the uterine lining. With these drugs there is also the risk of multiple pregnancy. About 10% with clomiphene citrate (most of which are twins) and up to 25-30% with FSH (this risk can be reduced to approximately 12% by using the home monitoring system for daily urine testing), or with frequent ultrasounds. Your consultant will monitor the number of follicles developing and discuss the options if there is a high risk of this.
Occasionally a couple may be converted to an IVF cycle if there are many follicles present. One or two embryos are then transferred and any surplus embryos that result can be frozen for later use.
Fertility drugs are generally used for women who have ovulation disorders due to hormonal imbalances or sometimes for couples when no cause of infertility can be found.
The diagnosis of tubal damage will usually have been made at laparoscopy.
In some cases, surgery to remove scar tissue (adhesiolysis) or to correct tubal damage (eg tubal anastomosis) will be recommended. Some types of tubal surgery may be performed through the laparoscope (adhesiolysis, salpingolysis), while other procedures (such as tubal anastomosis) may require an "open" operation using the operating microscope, known as microsurgery.
Where surgery has not resulted in successful pregnancy, or where damage to the tubes and other pelvic organs has been so severe as to make surgery unlikely to be successful, IVF becomes the treatment option with the best chance of success.
Endometriosis is a condition in which endometrial cells (those lining the uterus) grow in places outside the uterus. It may cause symptoms such as painful periods, pain with intercourse or infertility. Treatment depends, in part, on the extent of the disease, and may involve surgical removal of the endometriosis and associated scar tissue, or hormone treatment to suppress the menstrual cycle and inhibit the growth of endometriosis.
Where treatment for endometriosis has not resulted in successful pregnancy, IVF may be an appropriate treatment option.
B. Assisted Reproductive Technology
For many couples Assisted Reproductive Technology (ART) is the treatment option that offers the best opportunity of achieving a pregnancy. With in vitro fertilisation (IVF) the eggs are fertilised by the sperm in the laboratory as opposed to fertilisation happening inside the woman's fallopian tubes. The process was initially developed to help overcome blocked or damaged tubes, where fertilisation could not occur due to the obstruction between the egg and sperm. Over the years the technology has been found to be appropriate for couples with other factors affecting their fertility, including sperm problems, endometriosis, unexplained infertility and anti-sperm antibodies.
The introduction of the intra cytoplasmic sperm injection technique (ICSI) has addressed some problems of male factor infertility that IVF was unable to overcome. Where previously there were not enough normal sperm for fertilisation, or where the sperm were unable to penetrate the egg, with ICSI the sperm is injected directly into the egg and only one sperm, per egg, is needed.
IVF using donor gametes is appropriate where DI (donor insemination) in natural cycles has not been successful or where egg factors (premature menopause, absent ovaries, poor response to ovarian stimulation) exist.
IVF used with ovarian hyperstimulation (the use of FSH injections to encourage multiple follicle development) optimises the chances of pregnancy from a stimulated cycle, as more than one egg is obtained in the cycle. Usually 8-12 eggs (range of 0-60) are obtained with 60% of these expected to fertilise and develop into embryos. With the transfer of 2 embryos comes a 15-20% chance of a baby, and if more than 2 embryos develop, the remaining embryos can be saved by freezing for transfer in subsequent cycles.
Treatment at Sure Fertility
It is our policy to offer a service which optimises the outcome of treatment but minimises the disruption to our patients' lives. To achieve these ends certain guidelines have been incorporated into our policy.
Sure fertility strictly limits the number of embryos transferred at each embryo transfer procedure. While increasing the number of embryos transferred obviously increases the chance of a successful pregnancy it also greatly increases the chance of multiple pregnancies. As our success rates at MIVF continue to get better and better, so too does the chance of creating a multiple pregnancy. With very few exceptions, your MIVF consultant will only allow you to have a maximum of two embryos transferred at a time. In most cases, especially with young women, your consultant will strongly encourage you to think about having a single embryo transferred each time. Multiple pregnancies may seem very appealing to a couple who have tried for years to achieve a pregnancy but there are significantly increased risks with multiple pregnancy. Your doctor will talk to you about this in detail.
We have adopted a minimal monitoring approach to treatment that is less invasive to the woman and leads to less disruption in a couple's life during a stressful time. Careful research and practice have proved this is a safe and effective form of treatment.
We offer the option of home treatment (in regard to medications) which reduces clinic visits and encourages participation by the partner in the treatment cycle, making it more of a shared experience. Treatment at home allows for more flexibility, with the time of injection chosen to suit the woman or couple.
The egg pick-up operation is done through the vagina and in most women a light anaesthetic only (with the woman awake although sedated) is necessary. The woman's partner may remain with her during the procedure.This is the only day in the entire process where you will be actually admitted to hospital, albeit only for a few hours. Most women would be quite well enough to go to work the following day.
During a cycle your consultant plans your treatment and undertakes the ovum pick-up and embryo transfer, ensuring safe and personal care. If your own consultant will be absent during your treatment cycle, you will be informed of this and your care provided by one of the other MIVF doctors.
C. 9 stages of Treatment
The first step
The first step is usually the hardest - making that initial call. But remember, you are not alone, simply phone us in the strictest confidence and one of our friendly team will help guide you through the options open to you.
Whether you have recently become concerned about your fertility or have had treatment elsewhere and want another opinion, we will do our best to help you achieve a successful outcome.We can generally offer an initial consultation within a few days, and for your convenience we offer appointments Monday to Saturday from 8am to 8pm and on Sundays from 8am to 2pm.
Your first visit
At the first consultation one of our medical consultants will complete a detailed review of your medical history and may also conduct an examination. More importantly, the medical consultant will be able to answer any questions you have.
You and your partner will undergo various straightforward screening tests prior to commencing treatment to establish your reproductive health.
These may include blood tests, swabs and a semen assessment for the male partner where appropriate.
Many factors are considered during assessment, including who will be legally responsible for and who will bring up any child born as a result of treatment. To address this it is our usual practice to ask the couple/individual seeking treatment to complete a questionnaire.
Following the initial consultation you will meet a specialist fertility nurse who will talk you though your plan of treatment, including any necessary drugs and further tests that you may need, and answer any further questions you may have.
We consider counselling to be a key element in the provision of fertility services for all patients. We are sensitive to the emotions experienced by people having difficulties conceiving and the stress of the treatment itself. Counselling is available to you at any time whilst you are a patient attending our Clinic.
Prior to treatment
On day two or three of your period, following successful completion of the medical review, you will have a blood test to determine that the required hormone levels are present and correct. A number of screening tests will follow. It is advisable, if you haven’t done so already, to start a course of folic acid and to continue until you are a minimum of three months pregnant.
The treatment begins on or around day 21 of the menstrual cycle. You will take medication to suppress your existing levels of hormones for around two weeks or until satisfactory levels are achieved. Some courses of treatment do not include this period of down regulation. You can decide which is most appropriate with your doctor/consultant?.
Stimulation of the ovaries
The next stage is a process called ‘super-ovulation’ involving injections to stimulate the ovaries. The purpose is to grow numerous mature follicles rather than the single follicle that is usually produced each month.
The treatment cycle is then monitored to test the development of the follicles, using ultrasound scans and by adjusting the dose of the drugs if necessary. When the follicles are large enough, usually after 10 - 12 days, you will have an injection that ensures the eggs in your follicles mature. It is carefully timed to allow egg collection to be performed at a mutually convenient time, about 36 hours later.
This procedure is usually performed under intravenous sedation (rarely a general anaesthetic). This simple procedure takes approximately 30 minutes. You will be awake during the procedure. A scan probe is passed through the vagina and into the ovary under ultrasound guidance; the fluid from each follicle, which contains the egg, is extracted. It is usual to obtain an egg from about 80% of follicles. You may feel a few twinges but should not be in pain. You will need to rest at the Clinic for a short time before going home.
If your partner's sperm is being used to fertilise the eggs, a sample will be required on the day of the egg collection. Three days’ sexual abstinence is advised prior to the sperm sample. The sperm is washed and prepared in order to separate the sperm from the seminal fluid. The eggs are collected into a receptacle and each egg is graded by its development. The eggs are placed in an incubator for between three - eight hours before they are mixed with the selected sperm. 100,000 sperm are combined with each egg in a special culture medium.
Usually about 60 - 70% of the eggs collected will be fertilised. Regrettably, some five to ten per cent of couples will not achieve fertilisation of any eggs. It takes approximately 18 hours for the egg to be fertilised and about 12 hours later the fertilised egg will start to divide. After about 48 - 72 hours from egg collection, the embryos will usually consist of four to eight cells each, and are now ready for placement into the woman’s uterus. At each stage of this important process, our team will keep you informed of how the embryos are developing and when you need to return for embryo transfer.
We will contact you the day after egg collection to let you know if fertilisation has taken place and to arrange a time for embryo transfer.
In the meantime, ‘cleavage’ or division of cells is occurring within the fertilised embryos. Although the mass of the embryo remains constant, the cells get smaller and smaller, increasing in number. The quantity of cells is not critical to quality, as each embryo develops at its own rate. Embryos may have up to six cells by the second day. Based on their regularity and appearance, the embryos are graded for quality. Good quality embryos that are surplus to immediate transfer needs can be frozen and stored for future use.
The embryo transfer procedure is similar to a smear test. It may cause some minimal discomfort.
Using a vaginal speculum, the medical consultant exposes the cervix, which is then cleaned. The culture medium containing the embryos is loaded in a thin plastic tube called a catheter with a syringe on one end. The doctor carefully guides the catheter through the vagina and cervix, and deposits the embryos into the uterus. Implantation begins three - four days later.
High quality embryos remaining after the transfer can be frozen for use at a later date if the usual consents are completed.
In accordance with the Human Fertilisation and Embryology Act, a maximum of two embryos can be transferred in any cycle, other than in exceptional circumstances.
If you have not had a period fourteen days after embryo transfer, you should test yourself with the test kit provided by us.
If you are pregnant, we may recommend hCG injections or further progesterone suppositories. An ultrasound scan will be performed at six or seven weeks’ gestation to confirm a visible heartbeat and ongoing pregnancy.
If, unfortunately, you do have a normal period, a follow-up consultation can be arranged to discuss options. Support counselling is always available.
Sure Fertility offers a 3-cycle Package that can greatly increase the cost effectiveness of IVF. If after three treatments you are not pregnant, we will arrange a consultation free of charge to discuss future management/your options.
D. Preparing for Treatment
As with all couples attempting to achieve a pregnancy, you should focus on your own general health and lifestyle. It makes sense to be aiming for a healthy approach to life, but often advice in this area can be confusing and is not always supported by hard evidence. It is worth discussing any health concerns and medications you or your partner are taking with your doctor. Some medications have an effect on the production of sperm for the man, and for the woman there may need to be a change of medication before or during pregnancy.
As there is strong evidence that female smokers have reduced fertility and a higher miscarriage rate, this is the time to stop. Smoking during pregnancy has adverse effects on the growing baby and can contribute to many childhood illnesses. It is important to avoid smoking on the day of egg collection, as smoking can lead to anaesthetic difficulties. Husbands/partners should also stop smoking as there is increasingly clear evidence about the harmful effects of passive smoking.
While it is not possible to set "safe" limits of alcohol consumption, higher intakes are known to be harmful to the developing baby. The National Health and Medical Research Council (NH&MRC) recommends no more than two drinks per day for women and four for men, with at least two alcohol-free days per week, and considers abstinence to be desirable during pregnancy. We lack specific information about alcohol and infertility, except that a heavy intake in men can affect sperm production. It is important to be moderate in the second half of the menstrual cycle if pregnancy is possible, and in the weeks following a positive pregnancy test, as this is when the baby is developing. But there is no need to feel tortured with guilt if an occasional drink is taken.
A normal well-balanced diet, with plenty of leafy green vegetables for folic acid, is encouraged. The NH&MRC recommends that women take folic acid supplements of 0.5mg daily for the month before pregnancy and until the pregnancy is over 12 weeks, in the hope of reducing the risk of neural tube defects (most commonly spina bifida) in their babies. Although the effectiveness of this is not totally proven, there is good evidence linking folic acid with a reduced incidence of such abnormalities in high risk women. Women who take anti-epileptic medication and those with a family history of neural tube defects should take 5mg of folic acid daily.
If you are significantly overweight or underweight this can adversely affect fertility, it is worth considering your diet and perhaps discussing this with your doctor with the aim of getting dietary assistance.
High caffeine intake has been linked with female infertility in some research studies, but the reason for this is not obvious. Therefore it is worth considering a moderate coffee intake if you are trying to get pregnant.
Regular moderate exercise is totally acceptable. There is some evidence that strenuous exercise performed more than four times a week during pregnancy can have adverse effects. Frequent strenuous exercise, such as some athletic training programs, can also affect the body's hormone balance and thus the woman's fertility.
Direct relationships between stress and fertility have not been established; certainly some people conceive at times of high stress in their lives, while others will respond with ovulation disorders or a decreased libido. It makes sense to reduce stress in your life while undergoing IVF and trying to achieve a pregnancy. There are times before or during treatment that you may feel quite emotional or stressed; remember our counsellors are always available and are experienced in helping individuals and couples deal with difficult emotions and situations.
Prior to commencing the IVF program your consultant will order several routine tests. Each woman will have her rubella (German Measles) immunity checked (even if vaccinated in the past as immunity can fall). If the level is too low, a vaccination will be performed before attempting pregnancy, and a wait of 6 weeks is usually recommended before conceiving. Rubella can have devastating effects on the developing baby during pregnancy, and the disease is still prevalent in the community. You will also be screened for varicella (Chicken Pox). This virus can also harm the pregnancy and it is now possible to vaccinate if you have no natural immunity. We will ask both partners to be screened for syphilis. This is an uncommon but very serious disease which has profound effects on the pregnancy if not treated. It is easily treated with antibiotics.
Both partners will be checked for Hepatitis B and C, and for HIV. A small particle of the hepatitis virus may remain in the blood and/or other body fluids for many years after the initial (often unsuspected) hepatitis infection. The presence of hepatitis B or C, or HIV, may have significance for your future health, as well as for your partner, and for those who process your blood and semen samples.
If the woman has not had a Pap smear in the last couple of years, it is worth having one during this time and it should be repeated every two years - more often if abnormalities are found. Each month the woman should check her breasts for lumps or irregularities, and have her doctor check her breasts annually. It is worth considering that infertile women have a slightly increased incidence of cancer of some reproductive organs, and so these checks are important to your health.
E. Stimulation Cycle
The aim of using follicle stimulating hormone preparations in a "stimulated cycle" is to encourage the development of several oocytes (eggs) in the woman's ovaries leading to the potential for several embryos, which optimises a couples' chances of pregnancy from a single stimulated cycle. AtSure Fertility we use a minimal monitoring approach to a stimulated cycle which, through literature searches and our own research, has proven to be a safe and effective treatment method. In this approach we reduce disruption and anxiety in our patients' lives during a busy and stressful time by reducing, or even dispensing with, blood tests and decreasing the number of vaginal ultrasounds.
Patients undergoing their first IVF cycle at Sure fertility have an appointment during which their treatment is explained in detail, their partner can be taught injection techniques and they have an opportunity to meet some of the staff who will be caring for them. It is often easier and more convenient to arrange this appointment with the nurses prior to the planned cycle as a greater choice of dates and times will be available.
There are several stimulation protocols used and your Infertility Specialist will select the drugs, dosages and the protocol that is best for you.
The most common combinations are:
• Synarel nasal spray or Lucrin injections (gonadotrophin releasing hormone) with Gonal F or Puregon injections (follicle stimulating hormone)
• Clomid tablets with or without Gonal F or Puregon injections
A typical stimulated cycle can be visualised by this time line, though your consultant may choose a different protocol which would be explained to you.
S 1 - 1st day of period
S 2 - Start Synarel (S)
S/G 3 - 3 Start Gonadotophin (G)
S/G 11 - Scan
S/G 12 - HCG
14 - OPU
16 ET - Start preg. pessaries (P)
P 29 - Preg. Test
Most women will have daily injections starting during their period and continuing for 6-10 days, when the vaginal ultrasound is done.
The Ultrasonographer conducting the ultrasound will record the number and size of the follicles, the endometrial thickness and if any irregularities, such as ovarian cysts, are present. Based on the ultrasound information, one of our Infertility Specialists will make a decision on the optimum time to administer the HCG injection and therefore when Ovum Pick-up (OPU) will occur.
Occasionally a poor result or an over stimulation may be found on the scan, in which case the Infertility Specialist will discuss the best option for that situation.
10 to 15% of cycles commenced will be cancelled usually due to a poor ovarian response, detected on the day 10 ultrasound scan.