What is superovulation?
Superovulation involves the use of fertility drugs to stimulate the ovaries. The aim is to grow several mature eggs rather than a single egg that normally develops each month. With the introduction of cryopreservation, excess embryos can now be stored so that the woman does not have to go through ovarian stimulation and egg collection each cycle.
Some IVF clinics carry out natural cycle IVF treatments; this does not employ fertility drugs. However, with only one egg is usually obtained; the pregnancy rate per treatment cycle initiated is much lower than when superovulation is used. Obviously there will be no additional cost for medication. Natural cycle IVF is not recommended, except in special circumstances such as when gonadotropins are contraindicated. Women who have had breast cancer which is estrogen receptor positive may be offered natural cycle IVF. Natural IVF cycles may also be offered to older patients who have failed to become pregnant after stimulated IVF cycles and women who have regular ovulatory cycles.
Pre-treatment in IVF
Many patients are prescribed the contraceptive pill or a progestogen before they start their fertility drugs. The contraceptive pills is usually prescribed the month before treatment is planned. The rationale for taking the pills is to enable the ovaries to rest and can be used to bring on a bleed in woman who are prone to irregular cycles. Furthermore, by manipulating the number of pills taken, the dates of treatment can be scheduled which can help patients and their partners plan treatment.pre-treatment does not affect the chances of having a live birth.
A number of different drugs and protocols are used in IVF treatment. Because the treatment is individualized, a couple may find out that their drugs and protocols differ from other couples. This is quite normal.
The duration of treatment also varies with the drug regimen and ranges from 2-4 weeks. During the treatment, the patients usually attend the clinic for about 2-4 visits for monitoring.
Some of the commonly used drugs include:
- Clomiphene tablets and hCG
- FSH and/or hMG and hCG
- GnRh analogues (agonist or antagonist) and FSH or hMG and hCG
The first two drug regimens are not often used nowadays in IVF stimulation. But are usually used for standard ovulation induction with or without intrauterine insemination.
The most commonly used protocol for IVF involves giving a drug called gonadotropin releasing hormone analogue either by daily subcutaneous injection e.g. busereline, lupron or a long-acting injection such as zoladex or as a nasal spray. The logic behind giving the agonist is to temporarily suppress the woman's natural hormones (down-regulation) and allows for greater control over the treatment cycle. There are different protocols for administering these drugs; each has its pros and cons.
Currently, the long protocol is preferred because it is more convenient and has shown superior efficacy. Marcus et al (1993).
In the long protocol the agonist is usually started around day 21 of the cycle preceding IVF cycle or the second day of the treatment cycle. Symptoms such as hot flushes, headaches, mood changes, night sweats, breast tenderness or pain, constipation, dizziness, fatigue, irritation at the injection site, and vaginal dryness may be noticed. These symptoms usually last for a relatively short period of time and will usually disappear once the hormonal injections have started.
Approximately two weeks after the start of GnRh agonist a vaginal ultrasound scan will be performed to ensure that the ovaries are inactive and that the lining of the womb is thin. A blood test may also be required to estimate the hormone levels in order to ensure down regulation.
After achieving "down regulation" it is common to be advised to continue to take GnRh agonist but to reduce the dose to maintenance and to begin to take gonadotropin injections such as FSH and or hMG injections to stimulate the ovaries . The initial dosage of the injections will be chosen to suit each individual. The injections are usually given once a day for about 10-12 days. The dose of the gonadotropin is adjusted later depending on the response.It is recommended that the dosage of follicle-stimulating hormone should not exceed 450 IU/day (NICE guidelines 2013). Furthermore, it recommended offering gonadotrophin-releasing hormone agonists only to women who have a low risk of ovarian hyperstimulation syndrome. The use of gonadotropin releasing hormone antagonists may allow for shorter treatment cycles and lower doses of gonadotropin injections but are associated with lower pregnancy rates. Urine derived purified gonadotropins and recombinant FSH are equally effective when used with down-regulation.
The short protocol involves administering the GnRh agonist from day 2 of the treatment cycle, this is continued till the day of HCG. The gonadotropins start the same day or the day after GNRH agonist commenced. The regimen is generally recommended for women who had previously responded poorly to the long protocol, older patients and women with a raised FSH levels at the beginning of their periods.
One of the biggest advantages of giving purified or recombinant gonadotropins is that it is more convenient to the patient because they are administered simply by subcutaneous injection (with a very short needle into the fat just under the skin) using an auto injector. Most women learn to give their own injections, this is advantageous as it reduces the number of clinic visits.
Although CJD has never been reported in a recipient of urine-derived fertility hormones, The committee on the saftey of medicine in the United Kingdom has advised that no medical products using urine sourced in a country which has reported case(s) of the variant form of human Creutzfeldt Jakob Disease be used for treatment. This includes Metrodin high purity (February 2004).
If fewer than three mature follicles develop, the outcome of the treatment is likely to be poor and in most cases the doctor will advise canceling the treatment cycle. Conversely, some women over respond producing many follicles and are at risk of developing ovarian hyperstimulation syndrome. Superovulation does not lead to an early menopause or more severe menopausal symptoms (Reproductive Bio Medicine, 2008).