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During superovulation, drugs are used to induce the patient's ovaries to grow several mature eggs rather than the single egg that normally develops each month. This is done because the chances for pregnancy are better if more than one egg is fertilized and transferred to the uterus in a treatment cycle. Depending on the program and the patient, drug type and dosage vary. Most often, the drugs are given over a period of nine to twelve days. Drugs currently in use include: Human Menopausal Gonadotropin (HMG), Follicle stimulating Hormone (FSH), Human Chorionic Gonadotropin (HCG) and gonodotropin releasing hormone (GnRH) analogue.
Today, most IVF programs use GnRH analogues in combination with gonadotropins during ovulation enhancement. Treatment with the analogues prevents the release of FSH and LH from the pituitary gland during treatment ("down regulation") and thereby prevents premature ovulation. This, therefore, gives the doctor much more control over the superovulation phase. GnRH analogues can be used either in the form of a long protocol (when they are started from Day 21 of the previous cycle); or as a short protocol (when they are started from Day 1 of the cycle). Another option is to use the newer GnRH antagonists, which can selectively suppress the LH surge, and it is hoped that these may provide better control.
An ultrasound scan is done on Day 3 to confirm that there are no cysts in the ovary. A blood test for estradiol can also be done to ensure that the ovaries are quiescent and down regulated, and the result should be less than 50 pg/ml. The HMG injections for superovulation are then started from Day 3. The dose of HMG used needs to be individualized for each patient. Our standard dose is 225 IU for patients less than 35; 300 IU for patients more than 35; and 150 IU for patients with PCOD.
Timing is crucial in an IVF treatment cycle in order that the doctor recovers mature eggs. To monitor egg production, the ovaries are scanned frequently with vaginal ultrasound, usually on a daily or alternate day basis from Day 10 onwards. Blood samples are also drawn in some clinics to measure the serum levels of estrogen, and sometimes luteinizing hormone (LH). While some clinics do this on a daily basis, we feel this is very unkind to the patient, who often ends up feeling like a pincushion! For most patients, the ultrasound scan provides enough information, and it is very rarely that we need to do blood tests for our patients - we try to be kind! The dose of the HMG is adjusted, depending upon the ovarian response.
By interpreting the results of the ultrasound, we can determine the best time to harvest or remove the eggs. Follicles usually grow at a rate of 1-2 mm/day, and a mature follicle has a diameter of about 16-20 mm in size. Thus, if a patient has about 10 follicles on ultrasound, of which the largest is more than 18 mm, we know that the follicles are mature and the eggs are ready for retrieval. The endometrium should also be examined carefully on the vaginal scan, and this should be thick (more than 7 mm, and have a triple texture). Some clinics also measure the blood estradiol level to provide additional information, and each mature follicle produces about 200-300 pg/ml of estrogen. When the follicles are mature, we prescribe an injection of human chorionic gonadotropin (HCG) to trigger off ovulation. The use of HCG allows us to control when ovulation will take place - and this is 36 - 39 hours after the HCG injection. This precise control allows the IVF team to be prepared to harvest eggs just before that time. The HCG simulates the woman's natural LH surge, which normally triggers ovulation.
With older forms of superovulation regimes using clomiphene and HMG, the treatment cycle was cancelled in roughly one quarter of the IVF cycles. One of the reasons for this was that some of these women had a premature, spontaneously occurring LH surge with resulting premature spontaneous ovulation. When this happened, the follicles ruptured prior to egg collection, and the eggs were lost in the pelvic cavity, as a result of which they could not be retrieved. While spontaneous LH surges are very rare with the use of GnRH analogues, we still need to cancel cycles in about 10 % of patients.
The commonest reason for canceling a cycle today is a poor ovarian response. If patients grow less than three follicles, and if the estradiol level is low, the chances of a pregnancy are poor, and patients may decide to abandon the cycle. The problem of a poor ovarian response is commoner in older women and in women with elevated FSH levels, and these can be difficult patients to treat! Patients who have a poor ovarian response during IVF treatment are often very upset, because this is not something they (especially if they are young) are mentally prepared for. Most young women expect to grow a lot of eggs, and are shattered when they don't do so. However, remember that this is not the end of the road - it simply means that the superovulation regime will need to be modified for the next treatment cycle. The doctor may need to increase the dose of HMG in order to grow more follicles, and this is often helpful for young women.
The other reason to cancel a cycle is when patients grow too many follicles! These are usually patients with PCOD; and if there are more than 25 follicles, or if the level of the estradiol is more than 6000 pg/ml, many clinics will cancel the cycle, because the risk of ovarian hyper stimulation syndrome (OHSS) is very high. An alternative option is to go ahead with egg collection, and freeze all the embryos. This allows the doctor to salvage the cycle; and if the embryos are not transferred, the risk of OHSS is reduced. The frozen embryos can then be transferred later, giving the patient a good chance of achieving a pregnancy.
© Dr. Aniruddha Malpani and Dr. Anjali Malpani www.drmalpani.com
Credits: How to Have a Baby: Overcoming Infertility
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