I have questions about treatment.
1 I am concerned about the size of my follicles, and the timing of my HCG shot.
- 4.1.1 How big should my lead follicle be before I take my HCG shot?
A lead follicle should be at least 16 mm on an hMG like Pergonal, it should be at least 18 mm on a recombinant FSH like Gonal-F, and should be about 22 mm on Clomid. Occasionally Gonal-F can produce mature eggs in smaller follicles, in which case other measurements such as E2 and progesterone should be used to indicate maturity. (The difference in ideal size is due to the difference in mechanisms by which the medications work. For example, the mechanism by which Clomid works often takes a bit longer because it is indirect. Therefore, the follicle has more time to grow before the egg is actually mature).
- 4.1.2 How much do follicles grow each day?
Follicles grow 1 to 2 mm a day both while taking ovulatory stimulants and after the HCG shot.
- 4.1.3 Will smaller follicles "catch up" in time to release eggs?
Follicles generally need to be at least 15-16 mm to contain fertilizable eggs (although it is possible in rare cases for follicles to be as small as 14 mm and still contain fertilizable eggs). If the smaller follicles are close in size to the lead, they may "catch up" and release. HCG will usually result in most mature follicles releasing eggs. Otherwise, most likely only the lead follicle will ovulate.
- 4.1.4 Do I usually have more than one follicle on an unstimulated cycle?
Yes, it is normal to have numerous small follicles develop, but usually only one will continue to maturity without stimulation.
4.2 I have leftover cysts on my ovaries. My doctor wants me to sit out this cycle.
- 4.2.1 What causes these cysts?
A corpus luteum, or functional cyst, is simply a leftover follicle that has outstayed its welcome. Some continue to produce progesterone and estrogen, which may delay the arrival of the next period.
Functional cysts almost always go away with time. Birth Control Pills are sometimes prescribed to hasten their resolution.
- 4.2.3 How big do they need to be to reduce chances of pregnancy? Research has shown that any cyst 10 mm or larger is associated with a lower chance of getting pregnant. In a study on women doing IVF, those that had a 10 mm cyst at the beginning of a cycle had half the pregnancy rate of those who had no cysts (and the groups were equal on all other relevant characteristics). So it does not eliminate your chances of pregnancy, but it does sharply decrease them.
- 4.2.4 Why do they reduce my chances of pregnancy?
Cysts do not eliminate the possibility of pregnancy in a cycle, but they do reduce it. They do this through two mechanisms. First, physically, they can crowd out the development of new follicles. Also, if the cyst is secreting hormones at the wrong time of the cycle, (for example, progesterone during the follicular phase), it interferes with the chemical balance required for good quality ovulation and drastically reduces the chances of pregnancy.
- 4.2.5 If I have cysts of any size, should I be concerned?
It is normal to have small cysts, which may be very small leftover follicles or follicles that are preparing for the next cycle. Anything under 10 mm shouldn't be cause for concern as long as your baseline hormone levels are in range.
4.3 What exactly is an endometrial biopsy?
In an endometrial biopsy (EMB), a small catheter is threaded into the uterus and a sample is taken of the lining, or endometrium, during the last week of your cycle. (It causes brief cramping for which Ibuprofen, taken ahead of the procedure, is helpful). Once the sample is obtained, it is rated according to the day of a 28-day cycle for which it would be typical. For example, a lining at the beginning of the luteal phase is different from a lining at mid luteal phase or during the follicular phase. An out-of-phase endometrium means that the endometrial appearance is typical of a time in the cycle other than the time it was taken. This biopsy does have the potential to disrupt a pregnancy in progress. Many doctors will test for pregnancy before doing the biopsy, to be on the safe side. An EMB may also be done to check for abnormal cells in the endometrium (hyperplasia). This is a concern when a woman has very infrequent periods (bleeding less than once per three months) or when ultrasound reveals a thick lining. For this purpose, the EMB can be done on any cycle day.
4.4 How long should I use Clomid before I move to Injectables/IUI?
The vast majority of Clomid pregnancies occur during the first 4-5 ovulatory cycles. Some physicians also indicate that of those pregnancies, the majority occur during the first 3 attempts. (Also, if you do not stimulate well on Clomid at a reasonably high dosage, you might consider moving on to Injectables earlier. The maximum dosage is 150 mg., according to the manufacturer, and it may be wise to move on if unsuccessful after two cycles at that dosage). The average number of cycles on Clomid before moving on is three to six.
4.5 How many times should I try IUI before moving on to IVF?
Once a patient has had 3-6 IUI cycles with injectables, they might consider moving to IVF as the chance of a successful IUI cycle is reduced.
4.6 What is the maximum recommended dosage for Clomid?
As mentioned about, the maximum dosage is 150 according to manufactures. It may be wise to move on if there is no response to 150 mg, as the risk of antiestrogenic side effects of Clomid increase sharply as the dosage goes up.
4.7 Should I be taking Clomid on days 3-7 or on days 5-9?
In theory, days 3-7 of Clomid lead to more follicles and fewer side effects on the lining and the mucus. Days 5-9 lead to better development of just a few follicles. It seems to make a difference for some women and does not make any difference in others. Little conclusive research on the issue exists.
4.8 Why would my physician mix my Clomid treatment with injectables?
Mixing injectables and Clomid is an attempt to get some of the stimulant, cervical mucous, and lining benefits of injectables without spending as much money as would be required by doing only injectables.
4.9 I have heard that Clomid is not recommended for women over 40. Why?
As women pass 35, many doctors do begin to be more cautious about using it for a couple of reasons. One, women approaching 40 tend to have more lining problems and Clomid can have deleterious effects on the lining. Secondly, if a woman is perimenopausal, the mechanism by which Clomid works is not always effective, because the body is somewhat inured to low Estradiol levels.
4.10 I am on a cycle of injectables or Clomid/injectables. Should I use an Ovulation Predictor Kit? If I don't, how will they time the HCG shot?
Some women don't get a positive OPK when they are on injectables or even a mix of Clomid and injectables. You have to base the timing of the HCG shot on the Estradiol levels and follicle sizes. The use of progesterone also helps determine when to give HCG. It is best, for an IUI, to administer HCG when the progesterone level rises over 1.5.
4.11 How long should my partner abstain before the IUI? His semen analysis is normal.
For most men, a 2-3 day break is ideal. That gives the "sample" an opportunity to regenerate. Too "old" of a sample raises the risk of poor motility, white cells, and other problems. (An "old" sample would be that which is taken after more than 7 days of abstinence).
4.12 What is a sample protocol for IUI?
The simplest protocol is Clomid 50-mg days 3-7 (or 5-9) of the cycle. Use a urine LH or ovulation detector kit daily starting day 11 of the cycle. Perform the IUI the day following the LH surge. With the addition of vaginal ultrasound monitoring on the day of the LH surge or by day 14 if no LH surge, you may be given an HCG injection and IUI performed 36 hours later. Adjustments in the ovulation induction protocol can be made in subsequent cycles depending upon your response (as measured by LH kit and ultrasound).
4.13 What tests should I have after my IUI?
You should at least have a 7-dpo-progesterone test. Your RE may also check the pattern and thickness of the uterine lining via ultrasound at the same time.
4.14 Why am I taking Lupron with my cycle?
Most commonly, Lupron is given to IUI patients because they have a history of surging prematurely, before it was time to administer the hCG shot. Lupron greatly reduces the chance that this will happen. It is also sometimes used for patients who have a tendency to develop only one dominant follicle, even on ovulatory stimulants. Normally Lupron is only used in conjunction with injectables.
4.15 How should my IUIs be timed?
In most cases, doctors who do two IUI's do the first about 24 hours after the HCG shot and the second about 48 hours after the shot. Some studies have shown that doing one IUI about 36 hours after the HCG is equally effective. However, some recent research suggests that higher pregnancy rates may be achieved by doing two IUI's, one at 12 hours past the hCG shot and one at 34 hours.
4.16 What are the logistics of injectables? How many days will I take them? How big are the needles? Who administers the injection? Are they painful?
Typically, they are taken daily for 7-12 days (although it is possible to take them as long as 14 days). If you are taking subcutaneous injections, they are administered in the stomach, upper arm or thigh, with a 1/2- or 5/8 inch needle. If they are intramuscular, they are given in the hip/buttocks area using a 1.5-inch needle. The partner usually administers the IM shots. You can also give the IM injection to yourself in the thigh. They feel like a flu shot or vaccine.
4.17 What is the standard IVF protocol?
There are several variations on the IVF protocol. Described below is a sample "down regulation" protocol. This is an example of one which doctors commonly start with when the patient is under 35 and has a history of good response to stimulation. In the down regulation protocol, you start the cycle before your stimulation and retrieval cycle. On CD3 of that cycle, your FSH level is measured. On CD21, you do a progesterone test to see if you have ovulated. (If you are annovulatory, they will often put you on a BCP regimen to give you a predictable cycle). If you have ovulated, then you start Lupron shots once a day. The dosage varies from doctor to doctor to some extent. You may start out on 20 units and then drop down to 10 units after five days. Your period should arrive close to its due date. On CD1 or 2, you are tested to ensure that Lupron has shut down your own hormone system, so that they can use drugs for stimulation and have a more predictable cycle. Suppression is determined primarily by your estrogen level, but your doctor may also check progesterone and LH. If you are adequately suppressed and an ovarian scan shows no cysts, you will usually start injectables on CD3 or so. Your Lupron dose may be lowered to 5 units at this time. Your medication dosage depends on your diagnosis, age, and response history if you have taken injectables before. You might take two amps in the morning and two in the evening. After three days of ovulatory stimulants, your follicles and Estradiol levels will be checked. It is good to see the E2 levels above 100 after three days of stimulation. There will not be a great deal of follicle development yet. If needed, your medications will be adjusted. You will go in a few days later for a second round of blood work and a follicle check. After that, you might report to your clinic daily for blood work and ultrasounds. Once your follicles have reached an appropriate size and your E2 levels are good, you stop the stims and Lupron, and are given the hCG shot. This is about 34 hours before the retrieval is scheduled. The cut-off for the hCG shot, again, varies. Some clinics check for good blood flow to the uterus and a triple layer pattern in the uterus before retrieval as well. They might use this as a determining factor on whether to order baby aspirin. Retrieval is generally an out patient procedure. It can be done with a local anesthetic or an IV anesthetic. The IV anesthetic is much like the IV sedation used in dental procedures, and is very comfortable. The eggs are retrieved using an ultrasound probe that has a needle at the end of it. They put the needle through the vaginal wall and aspirate the follicles. You will generally start progesterone immediately following the retrieval. The post-retrieval events vary according to whether you are doing a day 3 or day 5 transfer, but you will generally receive updates about the number of eggs retrieved, the number fertilized, and the progress of the embryos. The transfer itself is much like an IUI, although most doctors use u/s to guide the catheter in, because placement is so critical. Pregnancy tests are generally done somewhere between 12 and 14 days after transfer.
Two other variants on the down regulation protocol are used in women over 35 or women with a history of poor response. The "flare" protocol has you start Lupron around the same time you start your stims, rather than during the luteal phase of the previous cycle. A "stop" protocol means that you take Lupron for several days but then stop it at some point while you are still taking your stims. Each protocol has its plusses and minuses. Women on the down regulation protocol require a greater amount of stimulation, often over a longer period of time. However, women on stop and flare protocols are more likely to have a premature LH surge and are more likely to develop a single dominant follicle (not a good thing in IVF).
4.18 I hear so much about taking baby aspirin. Should I be taking it too?
More and more RE's are using this as part of their protocol, especially for patients with histories of miscarriage and lining problems. See the Baby Aspirin fact sheet for the pros and cons of taking baby aspirin. Consult your RE before taking a regular regimen of any over-the-counter-drugs during your fertility treatment.
4.19 Should I take progesterone supplementation during treatment?
Some RE's put patients on progesterone during the luteal phase automatically. The underlying concept is that if you wait and find out if the progesterone is low, even at seven days past ovulation (7 dpo), it can be too late because the lining may not be receptive to implantation. Low progesterone can cause implantation failure, because its role is to vascularize and maintain the uterine lining, which is where implantation takes place. Sometimes women require more progesterone support in the luteal phase on injectables, even if they have a good progesterone level. This may have to do with the high levels of estrogen that occur during injectable cycles. There are four different common methods of progesterone supplementation: progesterone in oil shots (PIO), progesterone suppositories or vaginal capsules, Crinone (progesterone) vaginal gel, and oral progesterone. Also, hCG "boosters" given five days or so after the first dose, are commonly used to cause the Corpus Luteum to produce more progesterone. Progesterone, even in the form of over-the-counter creams, should not be taken before ovulation because it can block ovulation and make the cervical mucus hard for the sperm to penetrate. Crinone and suppositories deliver progesterone in a more effective manner than oral supplementation. Oral progesterone is not used by some RE's due to ineffective absorption. Crinone is quite expensive and progesterone suppositories can be messy. Vaginal capsules (identical in appearance to a capsule used for oral medication, but inserted into the vagina) may be a little hard to place, but are quite inexpensive and available in a variety of doses in the same manner as suppositories. PIO shots can be uncomfortable, but they are effective. Discuss the best medication method and dosage with your doctor.
4.20 Should we try a hamster test to determine if we have male factory infertility?
Most clinical studies have failed to show a significant correlation between hamster egg penetration and human fertility. A Mannose Receptor Binding Assay of sperm is more useful.
4.21 Should I use a BBT chart?
A Basal Body Temperature chart is not a very reliable way to predict ovulation. Although the temperature shift associated with ovulation can be detected on a basal thermometer, it can sometimes take as long as two days before this shift shows up on a BBT. This generally means that by the time a temperature shift is detected, it is too late to time intercourse effectively. Further, there are many things that can negatively affect the reliability of BBT monitoring: A change in sleep patterns, getting up to go to the bathroom in the night, a cold or flu, etc., can all skew the results. Often, couples devote a great deal of unwarranted energy and concern over these tests, which are of very questionable value. The one value in a BBT is to provide a piece of retrospective evidence of ovulation during the past cycle. The presumptive evidence of ovulation is a rise in body temperature for eight days. BBT charts can give your practitioner an idea of your ovulatory history, but remain a dubious tool for timing intercourse. The most reliable method to effectively time intercourse is to test for the LH surge with an ovulation predictor kit. This is a chemical test for the presence of luteinizing hormone (LH), which is released about 24 to 36 hours before ovulation and triggers the final maturation process. Because women generally have the most fertile cervical mucus on or about the day of LH surge, and because sperm can survive for up to 72 hours in the woman's reproductive tract, it is often advised to time intercourse for the day of LH surge.
4.22 My RE wants to me to "coast" for a while on this cycle. Why is he slowing me down?
The idea of coasting is either to get a too-high level of Estradiol to drop a bit or to slow down development -- generally eggs are of better quality if the patient has at least 7-8 days of stims. In addition, they may possibly want to slow down some of the lead follicles and get some of the smaller follicles to catch up a little. Several studies have shown that coasting does not reduce success rates for a cycle, and it can also reduce the risk of ovarian hyperstimulation syndrome (OHSS).
4.23 I heard that multiple cycles with fertility drugs increase the chance of getting ovarian cancer. Is this true?
No. There is no evidence that shows a statistically significant increase in the ovarian cancer risk.
4.24 My doctor has recommended a hysteroscopy, laparoscopy, or folloposcopy. Where can I get more information?
INCIID has an excellent fact sheet on Reproductive Surgeries.
4.25 Do your chances increase with each consecutive cycle?
No, each cycle is independent. Your per-cycle chances do not increase.
