Gonadotrophin Therapy
Most women who fail to ovulate regularly will have polycystic ovary syndrome (PCOS) and clomiphene citrate is usually chosen as first-line therapy. If, however, ovulation is not achieved with this or if the anovulation is due to low levels of natural follicle stimulating hormone (hypothalamic amenorrhoea) then gonadotrophins are used.
Gonadotrophins are pituitary hormones namely follicle stimulating hormone (FSH) and luteinising hormone (LH).These hormones are administered by a subcutaneous injection and stimulate the ovary to develop follicles containing the eggs. They are given during the first half of the cycle and are usually given daily although it can sometimes also be given on alternate days. You will be instructed on the dose and timing of this hormone.
There are large variations between patients 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 female partner's age, the cause of her sub-fertility, 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 your 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 (Puregon/ Gonal-F/ Menopur) will be started at the appropriate time of your cycle.
My choices?
The difference in the above mentioned 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 may choose them in combination or separately to suit. Sometimes it is necessary to use Menopur as it contains both FSH and LH whilst Puregon and Gonal-F contain only FSH.
How to inject?
Gonal-F, Puregon and Menopur 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, very pure and with an identical structure to pure FSH only. Menopur is extracted and purified from menopausal women's urine and is therefore a combination of naturally produced hormones. This can contain protein impurities at a very low level which can rarely give a skin reaction. There are no other reported complications.
Side effects
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.
Undesirable effects
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 ovarian hyperstimulation syndrome (see below for further details). We use 'step-up and/or step-down' methods to adjust and protect you from this risk during the stimulation phase.
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 own GP's nurse or come to the gynaecology ward.
When to take the injections?
The injection is taken once a day at approximately the same time. We will be able to estimate the day of your ovulation once the growth rate of follicles is established.
The hCG (Pregnyl) Injection
When your follicle(s) have reached an appropriate size, as assessed by scan, you are ready to be prepared for ovulation. Human chorionic gonadotrophin (hCG) mimics a surge of a natural hormone that normally causes ovulation (LH). It is given by subcutaneous or intramuscular injection, usually between the 9th and the 14th day of your menstrual cycle. You can administer the injection yourself but please remember that it needs to be stored at 5C (fridge temperature).
Timed intercourse
The hCG injection will be given during the day time and you can expect to ovulate 37 to 40 hours later, in other words during the night after you have had intercourse so that sperm are ready and waiting for the egg when it is picked up by the fallopian tube.
Intrauterine insemination (IUI)
If your ovulation induction is taking place in combination with IUI (see intrauterine insemination information leaflet) the hCG injection is usually given at about 11 pm with a view to performing the IUI 37 to 39 hours later i.e. between 12 noon and 2 pm.
At the end of the treatment cycle: If you are not pregnant a period will start within 14 days of ovulation. If you miss your period you need to have a pregnancy test and contact Mrs Moroney’s secretary on +44 1624 650330.
Risks of Gonadotrophin Induction of Ovulation
There are no treatments that are completely free of risk. In a treatment cycle there are the following risks:
Ovarian hyperstimulation syndrome (OHSS)
We judge the appropriate dose of hormonal stimulation for you after consideration of your age, body weight, cause of infertility and information that we may have from your previous treatments. The ovarian response to the same dose of the hormone varies between patients for many reasons. Hence these judgements can only be approximate and after your first cycle we can usually make adjustments for your specific needs. Occasionally you can respond by producing too many follicles to the dose that we give you. This can result in excessive number of eggs and also higher than optimum hormone levels.
If this occurs youmuststop the treatment cycle in order to avoid a high order multiple pregnancy and also to protect you from the risks associated with very high hormone levels. You will be advised not to have intercourse also in that cycle until a period occurs. The risk of this happening is greater in women with polycystic ovary syndrome.
General advice: You will be advised to drink normally and check that you are regularly passing normal amounts of urine. Although mild symptoms are common, severe ovarian hyperstimulation is rare and occurs in only 1 to 2 % cases.
If in doubt, please do not hesitate to contact Mrs Moroney through her secretary (telephone +44 1624 650330) or the on call gynaecology SHO at Noble's Hospital(telephone +44 1624 650000)
Recognised complications of OHSS: Fortunately with appropriate risk assessment, prophylactic monitoring, early detection and timely intervention most women will have no problems. Your co-operation is therefore essential in ensuring safety. It is a self limiting disorder and there are no problems after the cycle is complete. In women who become pregnant the risk period extends in to the first trimester of pregnancy and complications up to 12 weeks of gestation have been recorded.
Complications occur either as a result of thrombosis in large veins because of thickening of the blood and its sluggish flow or because of collection of fluid in body cavities such as the abdomen or the chest. Strokes, ascities, pleural effusions, pericardial effusion, cardiac tamponade and deaths have been reported in the literature. The risk of death is less than 0.01%.
Multiple pregnancy
This is a very important clinical matter for both us and you. We know that development of multiple follicles increases the likelihood of at least one continuing growth and implanting. However your risk of a multiple pregnancy is also increased with the ovulation of multiple follicles. Your chance of conceiving a multiple pregnancy depends most of all upon your own age, cause of sub-fertility and also the programmes overall success rate. Occasionally embryos split to form 2 identical babies and you can get identical twins from a single follicle. Overall the multiple pregnancy rates with ovulation induction runs in the region of 10% as opposed to 1% naturally.
The complications of multiple pregnancies include miscarriage, prematurity, fetal growth retardation, increased risk of pregnancy complications in the mother and the need for delivery by caesarean section. Additional complications of identical twinning include polyhydramnios and twin to twin transfusion syndrome. These complications have high risks for premature delivery.
Extremely premature birth has the risk of death in infancy or survival with long-term mental and physical handicap in the children.
Miscarriage
The risk of miscarriage after a positive pregnancy test alone is approximately 10 to 20%. This is no different to that after a normal conception. Once the pregnancy sac has been seen and the fetal heart action identified then the risk of miscarriage is substantially less. The risk of a congenital or genetic abnormality in babies born after ovulation induction is not any higher than that in spontaneously conceived pregnancies. Your personal risk is more likely to relate to your age, your family history and whether or not you have a multiple pregnancy.
Risk of an ectopic pregnancy
Sometimes even though the tubes have been checked and confirmed patent, they are not healthy within and embryos are not easily transported to the uterus. Thus they can remain in the tube where they implant when ready to do so. If left undiagnosed the tube may rupture and internal bleeding may take place. We endeavour to make an early diagnosis by performing an ultrasound scan at 6 to 8 weeks of pregnancy (2 to 4 weeks after your pregnancy test).
Failure to respond to medication
If your ovaries show little or no response and your chance of conceiving is consequently reduced treatment will be abandoned and recommenced the following month with the dose of medication adjusted.
Success rates of ovulation induction with gonadotrophins
These are generally measured per cycle and also over a batch of 3 or 6 cycles. We normally run a success rate of 20% per cycle and find that nearly 60 to 65% of our patients conceive within 3 cycles of treatment. A clinical pregnancy is defined as a pregnancy confirmed by ultrasound scans or by histology.
Please also ensure that you read this booklet carefully and seek clarification for all your queries. It is important for you to understand why and how things are done in order for the treatment to proceed uneventfully.
Monitoring the development of the follicle
It is important to assess the response to treatment when gonadotrophins are used to induce ovulation.
Its purpose is to ensure that you are producing a limited number of follicles and eggs and those they are growing in an appropriate fashion.
- We can do so by performing ultrasound scans at appropriate times and at regular intervals when required.
- We may also assess the function of follicles by measuring the oestrogen and progesterone levels at appropriate times in your cycle.
- We would abandon cycles or ask you to abstain when the number of mature follicles exceeds 2 in both ovaries.
How do we do it?
The ultrasound scans are performed vaginally and you need an empty bladder for the procedure. A probe is gently inserted into the vagina to visualise the ovaries and the uterus (womb). This procedure is not uncomfortable.
- A baseline scan is performed on day 2 or 3 of your cycle before starting your gonadotrophin injections.
- If your womb and ovaries appear normal you will start your daily injections and return for a further scan after a week. If there is no follicular development at that stage then the gonadotrophin dosage will be increased and a further scan will be arranged after a week.
- Once follicular development occurs you will have scans every 2 or 3 days until the largest follicle measures more than 17mm. At this stage the egg is mature and ready to be released.
- Depending on whether you are having timed intercourse or IUI you will be advised when to take the hCG injection
What happens at the end of the treatment cycle?
If you are not pregnant a period will start within 14 days of ovulation. If you miss your period, you need to have a pregnancy test.
What happens if I do not respond?
If your ovaries show little or no response and your chance of conceiving is consequently reduced. You will be advised to return to the clinic for further advice and discussion.
