This section has been written in the expected order of various steps in treatment. You may find helpful to refer to this section regularly during treatment.
First clinic appointment where diagnosis is known. A full discussion of the relevant aspects of your treatment takes place in the clinic. We aim to minimise your visits and do not repeat investigations unless deemed essential for the conduct of your treatment.
Screening tests. These tests are arranged as explained above at your first appointment in the clinic.
New Patient’s Seminar. We very strongly recommend that you attend this open seminar by the team. Dates are available on request from the unit.
Follow up clinic visit. You will attend the clinic for discussion of screening tests and you have this opportunity to clarify any outstanding issues that have arisen in your mind with respect to your treatment. At this visit, you will receive a prescription and also be advised to see the nurse co-ordinator on your way out so that the NHS funded patients can be given a start date for your treatment within the government target of 18 weeks. The NHS self funded patients will be added to the waiting list and the nurse co-ordinator will provide an estimate of the month in which you may receive treatment.
Appointment with the Finance officer. The Unit’s finance officer will provide the invoice for the NHS fee paying patients, receipt payment and book a nurse consultation appointment in the weeks prior to your treatment start date.
Consultation with the Nurse Specialist. Both Partners must attend this appointment (see details) because you both will be required to sign consents, receive instruction for self administration of injections and a cycle plan.
Suppression of your natural hormones. When the ‘long protocol’ is used, your naturally produced hormones are suppressed from the 1st or the 21st day of the menstrual cycle using a nasal spray, a daily injection or a single depot preparation. This is maintained until you are ready to receive hCG and can in total last for approximately 5 to 7 weeks. When the ‘short protocol’ is used, we prescribe a second injection in parallel with the stimulation drugs from an appropriate stage. A baseline scan is performed, usually prior to starting this phase, unless you have had another recent scan within the preceding 3 months.
Ovarian Stimulation. Hormones are administered in this period to help your ovaries produce multiple eggs. This treatment can lasts for approximately 9-14 days. In women receiving the ‘long protocol’ a pre-stimulation / down regulation scan will be performed before to confirm that natural hormones have been suppressed. You will receive further scans to monitor growth of the follicles.
HCG injection. This injection prepares the eggs for ovulation and is given late in the night (usually between 10 p.m. and 2.00 a.m.).
Egg Collection. The eggs are collected approximately 35 to 38 hours after the hCG injection.
Insemination or ICSI. Male partner gives a sperm sample for preparation and insemination of the eggs by the direct method or by the ICSI procedure.
Checking Fertilisation. You will receive a telephone call with necessary information on the day after egg collection.
Embryo Transfer and Hormonal Support. The embryos are replaced in the womb and you will receive further medication afterwards to provide hormonal support in this phase of the cycle.
Luteal phase monitoring. This is provided to all those women who we feel could be at risk of developing ovarian hyperstimulation syndrome.
Pregnancy test. You are given a date for the pregnancy test at the time of embryo transfer.
Pregnancy scan or Follow-up consultation. This is arranged after the pregnancy test and the outcome of treatment is known.
As explained above, during your IVF cycle the response from other glands (the pituitary) may interfere and affect the maturation of eggs. As this can lead to a lessening of your success rate, when using the Long Protocol we choose to inactivate this gland before stimulating your ovaries.
A vaginal scan is performed before starting any medication unless the scan performed as part of Pre-assessments was done within the last 3 months. This is to ensure that there are no new developments that we should be aware of before starting the drugs.
Pre-stimulation or Down regulation scan
The scan is repeated at the appropriate time after starting the suppression phase. This should show inactive ovaries and a thin lining of the womb. The usual time taken for this phase is 10 days to 2 weeks.
A number of methods can be employed for the same ultimate effect. These, in our programme include the following:
Nafarelin Nasal Spray: This is taken as one sniff in one nostril three times per 24 hours at 8 hourly intervals for first 2 weeks and then twice daily thereafter until the day of HCG. This medication is not suitable for those suffering from hay fever, chronic nasal discharge or who may not remember to use the spray regularly.
The Buserelin Injection: This injection is taken once a day sub-cutaneously with a very fine needle-injection just under the skin. It is given daily at approximately the same time but an absolute and accurate precision is not essential (give or take 30 minutes).
Prostap Depot Injection: This is a once only injection and works for 4-5 weeks in total. This is very convenient for many patients except those with reduced ovarian reserve. If the suppression phase is prolonged because of the agonistic/stimulatory response from the ovary, a ‘top-up’ with Buserelin/Nafarelin in the later stages of the cycle may be needed.
Hot flushes, night sweats, headaches, vaginal bleeding, temperamental behaviour. These are due to a fall in your oestrogen level, usually last for a short time and will disappear once we start stimulating your ovaries.
Agonistic/ stimulatory response: In the initial stages all of the 3 preparations above can stimulate the ovary. This means that a follicle or cyst develops that has to resolve before we can proceed with treatment. It can naturally take up extra 2-3 weeks. If the cyst is aspirated the resolution may be slightly earlier and this requires an extra scan to see it disappear and for the endometrium to become thin. If you are prone to develop agonistic response seen in the form of cysts after starting this medication, we can use the oral contraceptive pill for a few days before starting the downregulation and this usually avoids such problems recurring.
Time to start
This treatment can be started on the first or the second day of your cycle especially when your cycle length is variable. It can also be started on the 21st day of the preceding cycle if your cycle is very regular.
We can prescribe any one of the above preparations and methods dependent on your preference and knowledge of past response. They are equally effective and are self administered. There is a relatively small difference in their costs with Buserelin being the cheapest.
The Nafarelin nasal spray and/or the Buserelin treatment is continued in the stimulation phase. We will specifically advise in writing when to discontinue which is the day you are advised to take hCG. Those with Prostap normally do not have to take additional medication during the stimulation phase.
There are large variations between donors in the number of eggs recruited and developed in response to the same dose of the stimulating hormones (see below). This response is mainly dependent on the donor’s age, her body weight and past treatments or ovarian surgery. There are other genetic determinants also. Having preformed the pre-treatment assessments, we judge the starting dose bearing in mind all clinical circumstances. When uncertain we may perform additional early scans to use the option of ‘stepping-up’ or ‘stepping down’ during the stimulation phase for a better response.
What does it involve?
The hormones (Merional / Fostimon / Menopur/Gonal-F/ Puregon) will be started when your ovaries have been adequately suppressed as judged by your pre-stimulation or the downregulation scan (see previous section).
The difference in drugs is mainly in the way they are prepared, their purity, in the way they are administered and their costs. They are equal in terms of their success rate. We often choose them in combination or separately to suit.
How to inject?
Merional, Fostimon, Menopur, Gonal-F and Puregon are usually given by a subcutaneous injection (very fine needle-injection in the fat layer under the skin).
How are they prepared?
Gonal-F and Puregon are synthetic compounds and produced in a laboratory, are very pure and with an identical structure to one form of PURE FSH only. Menopur and Merional are extracted and purified from menopausal women’s urine and are a combination of two naturally produced hormones. Fostimon is also extracted and purified from menopausal women’s urine and contains all forms of naturally produced FSH.
As stated above, to date the only additional side effect with urinary preparations has been that of an occasional rash on the injection site and rarely a more generalised allergy has been reported. Other risks with protein impurities are purely theoretical and there have been no cases reported to cause concern.
This can happen with any of the preparations available. Sometimes the ovaries will recruit a large number of eggs especially in young women and those with polycystic ovaries. This can put you at risk of developing an illness called The Ovarian Hyper-stimulation Syndrome (see later for further details). We use ‘step-up and/or step-down’ method to adjust and protect you from this risk during the stimulation phase.
How effective are they?
We have used the Pure and Urinary preparations quite extensively and are happy with them all.
Who should give the injections?
The injections can be administered yourself or by your partner. We strongly advise you to consider learning self-administration. Independence will save you time, effort and stress of professionals not being available when needed. However, if you are extremely anxious then you may seek the help of your doctor’s nurse.
When to take the injections?
The injection is taken once a day at approximately the same time but an absolute and accurate precision is not essential. We will be able to estimate the day of your egg collection once the growth rate of follicles is established. It will also help in deciding the time of abstinence in preparation for the semen sample to be given on the day of egg collection.
The hCG (Gonasi or Pregnyl or Ovitrelle) Injection
When your follicles have reached an appropriate size, as assessed by scan, you are ready to be prepared for the egg collection. The hCG injection is essential to bring the eggs to the correct stage of maturation for this stage.
This injection is usually given late in the night normally between 10.00 p.m. and 2.30 a.m. It is specifically timed to be between 35-37 hours before the time of your egg collection.
Important notice: We will give you precise instructions as regards the time and day this injection has to be administered. It is essential that the hCG injection is given as close to the prescribed time as is possible. Please read the instructions before you leave the unit so that you can ask a member of The Centre if you do not understand any of the instructions.
The progesterone support
When your donor’s follicles have reached an appropriate size, as assessed by scan, she is ready to be prepared for the Egg Collection. The hCG injection is essential to bring the eggs to the correct stage of maturation for this stage.
This injection is usually given late in the night normally between 10.00 p.m. and 2.30 a.m. It is specifically timed to be between 35-37 hours before the time of your egg collection and to start the rise in progesterone levels which is the 2nd hormone much needed during the implantation phase and afterwards for support of the pregnancy.
Your ovaries cannot produce progesterone. So on the same day as the donor’s day of HCG, you will start progesterone support.
What does it involve?
The hormone progesterone after the initial growth of the lining of the womb brings in the second phase of development. It is given in the form of progesterone pessaries or injections. The pessaries can also be used in your back passage as a rectal suppository.
The pessaries once inserted in the vagina or the rectum, will dissolve and from there the skin of the vagina or the bowel will absorb it and transfer it to the uterus through local and systemic blood supply.
The progesterone injections involve inserting the hormone into the muscle from where it is absorbed into the blood stream and transferred to the womb for necessary action. Blood levels of this hormone are much higher after injections than after inserting the pessary but it is thought that some progesterone gets to the womb from local transfer/ exchange mechanism.
There is no difference in the drug that is eventually delivered to the womb. However there is a difference in the preparation and how it reaches there. Some absorb the drug better from the vagina or the bowel than others. There are individual variations also in how the womb reacts to the same dose of medication.
How to take medication?
Pessaries can be inserted in prescribed doses digitally in the vagina or the back passage 4 times per 24 hours with reasonable but not accurate amount of equal spacing.
Injections are given once a day into the gluteus muscle (buttock) or in the Quadriceps muscle (thigh). We ask you to rotate the injection site as repetitive injection at one site can cause pain and local reaction.
The oral tablets or the oestrogen skin patches or both continue during this second phase also as prescribed. They could continue as previously in the following regimens:
Fixed and continuously given moderately high dose to ensure timely and adequate endometrial development.
Step wise escalation to try and mimic the natural rise in oestrogen
Step wise rise to promote endometrial growth when the response is suboptimal.
The progesterone as in the second half of the natural menstrual cycle can cause abdominal bloating, breast tenderness, feeling of lethargy, tiredness and even a change in temperament or mood. These problems do not necessarily occur and stress of treatment is also an important factor to remember.
Early bleeding with pessaries and local pain at the site of injections are undesirable effects.
How effective are they?
There is evidence that injections achieve better results than the pessaries in fresh IVF-ICSI cycles. Whether this is also true for egg donation and frozen embryo transfer cycles is not known. We are involved in research projects that aim to assess these very issues at present and therefore cannot give conclusive answers.
We have used both the pessaries and the injections for many years and all preparations are used freely to suit individual circumstances and clinical preferences.