DOWN REGULATION CYCLES
- Key days:
- day 21 midluteal check
- day 3 stimulation start
- monitoring visits
- day of hcg
- maternal serum
- retrieval
- transfer
The down regulation cycle spans two menstrual cycles. Very little happens during the first cycle. The early portion of the cycle usually involves only a visit to the office for day three blood tests. This updates your FSH ( follicle-stimulating hormone) level and tells us whether a major adjustment needs to be made to the planned stimulation
The ivf cycle and its stages
protocol. If there are any other checklist items that have not been completed, typically these are done during the first portion of this menstrual cycle. If all else is done, the next visit takes place for what we call the “mid-luteal check.” This is a blood test where we check the estradiol and progesterone levels in order to determine whether or not you have ovulated. The key to the Lupron down regulation type stimulation is to start Lupron in the luteal phase, in other words after ovulation has occurred. If ovulation has occurred, the progesterone level will rise-and a progesterone level in our lab above three, indicates that we can safely start the Lupron. Why is this so important? We have found that if we start Lupron in the follicular or pre-ovulatory portion of the menstrual cycle, the Lupron will stimulate the early or recruited follicle and delay the onset of the next menstrual cycle. It will also not have its desired suppressive effects on the body’s own stimulation of the ovaries.
Starting Lupron does not have to be on an exact day. We usually use the 21st day of the menstrual cycle for reasons of standardization. We could have easily used a 22, 23 or 24. If you have very short or very long menstrual cycles, we may adjust the day when you come in for your mid-luteal check. Occasionally the mid-luteal check shows that you have not yet ovulated. Sometimes we only need to wait a few more days. Sometimes we actually need to give you some outside progesterone in order to allow us to start Lupron. Again, the blood tests will tell us and direct us as to what we need to do.
The mid-luteal check is also the time when we ensure that you are cleared by the Financial Department. This is a safeguard that St. Barnabas put into place in order to ensure that no payment problems exist before the start of the cycle. If the couple is not cleared financially at the time of the mid-luteal check, we have a several day leeway in which to take care of any necessary paperwork. It’s important to know that in no way will this have any bad effect on the outcome of the cycle.
If the mid-luteal check blood tests look fine, Lupron is started that day. Usually we use a dose of .5 mg. This corresponds to 10 units on the insulin syringe. The Lupron is given nightly through the onset of the next period. While the period usually comes at about the time it normally would, it’s not unusual for the period to be delayed by a few days while on Lupron. This is not harmful in any way. If your menstrual cycle has not arrived a week after you expected it, it’s a good idea to give us a call.
Rarely, patients will conceive and then start the Lupron prior to knowing that they’re actually pregnant. Research so far has failed to show any increase in the risk of problems with these pregnancies and the Lupron appears not to effect the pregnancies in any adverse way.
Usually the period comes 7-10 days after starting Lupron. At this point, we ask that you call and leave a voice mail message that you have gotten your period and we ask that you come in for a monitoring visit on the third day of the cycle. We define day one of the cycle as the first day of full menstrual flow. It’s important to realize that the menstrual cycle is essentially “on hold” while you are on the Lupron. This means that the body is essentially waiting for us to tell the body what to do in terms of stimulation of the ovaries. For that reason, any of the early days in the cycle are appropriate times to start a stimulation. Trying to precisely pinpoint the start of the menstrual cycle is not necessary and could be the cause of unnecessary anxiety on a couple’s part.
When you report for monitoring on day three, we perform a transvaginal ultrasound, check an estradiol level and a progesterone level. We look for several things. We want the uterine lining to be thinned out, as the lining has been sloughed off since the last period. Usually the lining is 3-5mm. in thickness. We like the ovaries to be “quiet.” This means that we usually will see either no or a small number of small follicles in each ovary. We may also see what we call hemorrhagic cysts which may be the result of endometriosis, old bloody follicles, or an old ovulated follicle. These usually can be ignored and the stimulation performed around them. Rarely we will see a large, clear cyst. Depending on the blood test levels and the appearance of the cyst, we may recommend that the cyst be aspirated (sort of a mini egg retrieval process) prior to starting the stimulation.
Usually we find a thin lining, quiet ovaries, low estradiol and progesterone levels, and at that point the stimulation is ready to be started. We usually decrease the Lupron dose to .25mg. or 5 units on the insulin syringe. Stimulation with whichever gonadotropin form we are using (Gonal-F, Follistim, Fertinex, Pergonal, Metrodin, Humegon or Repronex) will usually start that evening. Not uncommonly, however, we may delay the start of the stimulation by one or more days. There are many possible reasons for this. One might be that the uterine lining needs to shrink a bit. Another might be that the estrogen level needs to come down a little further. Another might be just that there are too many patients presenting for cycle starts at the same time. We try to limit the number of cases that are started each day in order to keep a consistent flow of cases through the laboratory. We find that this contributes to an efficient running of the laboratory and high pregnancy rates. Please note that in no way is the cycle compromised by your waiting a few days to start the stimulation. The Lupron effectively keeps the cycle “on hold.”
After each monitoring visit you will have the results of your ultrasound entered into our computer database. By 12:00 noon, the results of your blood tests are available and these too are entered into the database. We usually meet from 1:00 to 2:00 and review that day’s results. We determine the next steps for each patient and the patients are then called later in the afternoon. If need be, we will adjust medication dosages up or down and we will give you instructions as to when we want to see you for your next monitoring visit.
Patients often understandably want to know how their cycle is proceeding. Our philosophy is to tell you what we’re thinking as well. It’s important to realize, however, that each cycle will unfold in its own way and there are many days during which the information we receive from the monitoring merely tells us to keep going. It may give us very little indication as to the outcome of the cycle.
This is a recurring theme and this bears repeating many times. We generate many pieces of information during the IVF cycle. Though much of this information tells us whether things are going relatively well or relatively poorly, in no way is it absolutely predictive. Except for the unusual circumstance where we have too few ovarian follicles to give the IVF cycle a chance to work, there are no cases where we can rule out the possibility of a pregnancy from the cycle. The reverse is true as well. We may tell you at each step of the way that everything is going fine, but we will not know until the pregnancy test a few weeks later whether or not these signs along the way truly predicted the outcome.
We therefore ask you to do the impossible: to try to keep your expectations somewhat on hold as you go through the early part of the cycle. Feelings of stress and a bit of loss of control are inevitable in anything as complex as an IVF cycle; however, it’s important not to try to read too much into the bits of information that we share with you as we move along. These bits of information are merely signs and tools that we use to steer you through the stimulation phase and to maximize the chance of having good eggs at retrieval.
In the afternoons while phone calls are being made to patients, the orders for the next day’s monitoring are placed into the computer. Once in a while an order will not be entered. And when this occurs a patient may come in and the order is not on the list that the receptionist has for that morning. In these cases, the receptionist checks with the nurse, who in turn checks with the computer stimulation sheet and knows what you are there for. We have several of these check-and-balance systems in place so that no one ever “falls through the cracks” during their cycle. If the receptionist does not have you on an immediate list or does not quickly know why you have come in at a given morning, that information is readily available and the proper tests and procedures will certainly be done.
In a down regulation cycle we will often decrease your daily medication towards the end of the stimulation. This may take several forms. We may drop each of the morning and evening doses. We may also just stop the morning dose, and effectively have the total dose in so doing. We usually continue the Lupron until the day of the HCG injection, the final injection of the stimulation. As we get close to the HCG injection, we may ask you to increase the frequency of your monitoring visits. It is not unusual to be seen two, three or even four mornings in a row as we approach the completion of the stimulation. This allows us to pinpoint the day that best serves your stimulation. During one of these mornings, the doctor performing the ultrasound will suggest that you speak to the nurse who is doing morning duty, to review the pre-retrieval protocols. The nurse will review with you the method for mixing and injecting the HCG shot, the timetable and schedule for arriving for retrieval, and the procedure by which we draw the maternal serum sample that we will use as part of the fluid for incubation of your embryos. You will be notified as to which day and time you will take your HCG during one of the afternoon telephone calls. The HCG is given approximately 35 hours prior to the time of retrieval. It is important that you try to administer the injection as close to the assigned time as possible. If you find that this was impossible to do, and that you have to give the injection either much earlier or much later, or if you had great difficulty with the injection and fear that it may not have been absorbed, please let us know the next day. We may need to adjust the time of your retrieval. Please make sure you feel comfortable about the administration of the HCG injection when you are meeting with the nurse to go over the pre-retrieval procedures.
When you’ve been given instructions to administer HCG, you will no longer use Lupron and you will no longer use the stimulation medications. The day after the HCG administration you will have a last monitoring visit, during which the maternal serum sample will be drawn. You will use no medication that day.
Because intravenous sedation is used for retrieval, we ask that you not eat or drink anything after midnight the night before your egg retrieval. After the retrieval, you will start your next medications, the injectable progesterone which will be administered nightly, and the antibiotic (usually Tetracycline), and the steroid (usually Medrol) which you will use until the transfer. The injectable progesterone which you start on the day of retrieval will be continued through the pregnancy test and, if you are pregnant, for the first weeks of the pregnancy.
We hope this overview of the medication regimens for the Lupron down regulation has been helpful.
FLARE OR MICROFLARE STIMULATIONS
- Key days:
- day 3 FSH test to start birth control pill
- pill stop
- 3 days after pill stop
- lupron start
- stimulation start
- hcg
- retrieval
- transfer
Many patients will use the so-called flare or microflare stimulations. We usually use these for women who may benefit from a bit of extra stimulation and extra recruitment.
Like the down regulation, the flare stimulation bridges two cycles. Patients will present on day three of the cycle and have an FSH level checked. If this level is normal, they are placed on the birth control pill.
Birth control pill? Why would someone take the birth control pill when they are trying to get pregnant? The answer lies in the stimulation phase of the flare protocol. The specific recipe that we use, which we will detail in the next paragraph, often results in a reactivation of one of the recently ovulated follicles from a past cycle. This in turn causes an early and unwanted rise in progesterone. Remember that we do not want progesterone in the bloodstream until after egg retrieval or after ovulation. Putting you on the birth control pill for two weeks effectively takes away this possibility.
It’s not necessary to take the birth control pill for an entire cycle. Two weeks will usually suffice. At the end of the two weeks we have you stop the pill. Three days later you present for another monitoring visit. We perform a vaginal ultrasound, FSH, estradiol and progesterone levels. If the ultrasound shows that the uterine lining is thin, the ovaries are quiet, and the estradiol/progesterone levels are low, and the FSH level has remained in the normal range, we can initiate the stimulation.
In flare cycles we use very low doses of Lupron. We will dilute your Lupron (add extra water to make very low dosing possible) and you will use 50 micrograms twice a day. In the flare stimulation the Lupron is given by itself for only one day, followed by the initiation of stimulation. The low dose of Lupron is administered twice a day as is the stimulation, usually in a dosage of three ampoules of powder twice a day. After each monitoring visit, you will receive a phone call that afternoon with instructions as to how to proceed from there. In this way the flare cycles are very similar to the down regulation cycles. Pre-retrieval preparation, use of progesterone, Tetracycline, and Medrol are all the same in both protocols.
Of note we usually recommend that the husband take antibiotics (usually Doxycycline or Vibramycin) from the start of the stimulation phase until the day of egg retrieval.
It bears repeating that there are many twists and turns that occur during the stimulation phase. The results of one day of monitoring may be concerning for that time, but then the results of the ensuing days are very reassuring. We feel it is important that you know what we are thinking as the cycle proceeds, but please recognize that we would not keep any cycle going if we thought things were going so poorly that all hope was lost. It is human nature, during an IVF cycle, to overemphasize anything that seems negative and to dismiss any positive information we may give you. Ultimately most patients find a good middle ground between recognizing this level of uncertainty and the very normal and expected concern they will have with the day-by-day and step-by-step details of the stimulation. There are many situations that will arise during your stimulation where we simply have to see what happens next. If something unexpected happens, if a response to stimulation is more or less than expected, if only one or two follicles starts to stimulate too quickly leaving everything else behind, or if a particular hormone level doesn’t look the way we would expect it to on a given day, the cycle will often right itself by itself, or we may have very straight forward ways of compensating.