Preventing Ovarian Hyperstimulation: The Lupron Trigger
Hello everyone, this is another important article on Ovarian Hyperstimulation. The response from readers on this subject has been very positive, thanks for your support.
Saving the best for last, an excellent way to prevent OHSS is to use Lurpon. This requires some explanation.
As many of you have experienced, Lupron is a drug that can be used during an IVF cycle. It is typically started about 1 week before the IVF cycle starts (day 21) or it can be started on day 2. The dose varies, but the usual options are regular lupron, low dose lupron or microdose lupron. None of these have anything to do with reducing OHSS, but I will get to that.
Lupron works by suppressing the pituitary’s ability to produce LH. This is good because in all of the Lupron protocols I just mentioned, one important job of Lupron is to prevent the premature surge of LH. The surge of LH causes ovulation, which is bad for an IVF cycle. If LH surges before the hCG injection, we cancel the cycle for premature ovulation.
We can’t get the eggs when we want them if they have ovulated prior to the retrieval. Lupron prevents this. Before Lupron was invented, we needed to cancel about 15% of IVF cycle for early ovulation.
Some of you are wondering why we trigger ovulation if we want to get eggs from the ovary. LH, hCG and Lupron cause the eggs to mature and then ovulate. For an IVF cycle, we need those medications to get the eggs to mature while still in the ovary, but we grab them before they are released.
Over the past decade we have been using other drugs, like Cetrotide and Ganarelix, to prevent the premature LH surge. These are easier to use than the Lupron because they are only given 2-4 days prior to the hCG. Some doctors still prefer to use Lupron.
Now on to OHSS and Lupron. In a natural ovulation cycle using no drugs, the follicle develops over about 2 weeks, and then a strong surge in LH causes ovulation. While Lupron causes the pituitary to cease LH secretion, in the first 1-2 days of Lupron use, there is a strong release of LH. That’s why we normally give it early in the cycle, before follicles have developed. Premature ovulation does not occur when we give it early because there are no follicles to ovulate.
It is this strong release of LH that makes Lupron great as a hCG substitute for the trigger shot. The quick surge results in a very short blast of LH, which could take place over 1-2 hours. This is very similar to the body’s LH surge that takes place in a natural cycle. After that, the LH has left the system, ovulation occurs 36 hours later, and ovarian stimulation stops. hCG, on the other hand, stays in the body for days, even up to 2 weeks. All of this time, hCG stimulates and stimulates the ovaries, which is too much for ovaries that have released many eggs.
Why give an hCG instead of a LH injection? For iui and IVF we use hCG as opposed to LH because hCG is easier to make and cheaper than LH, and hCG works just as well. The molecules of hcg and LH are very similar and act in similar ways. Plus, the drug companies have not yet figured out how to get the necessary large amounts of LH cheaply into one little vial.
The bottom line is that Lupron, because it causes just a short burst of LH, works very well in preventing OHSS. We are using it more and more and are very pleased with the results. We commonly use it for our egg donors.
One down side to lupron is that, in very small percentage of cases, it may not cause ovulation. This is a rare occurrence and is more likely to happen in women who are hypothalamic, i.e. they do not get regular ovulation due to exercise, dieting or some other factor. In these cases, there is no LH in the pituitary for Lupron to trigger.
In cases where the threat of OHSS is evident, it’s worth taking a chance with the Lupron. We measure LH levels the day after the Lupron injection. If they are very low, the lupron did not work, and there is no LH surge. Therefore we can give hCG the next day, unless the fear of OHSS causes us to cancel the cycle.
Another detail of Lupron use is that for luteal support, we add estrogen. The ovaries just shut down after Lupron use, and therefore estrogen and progesterone are produced in very low quantities. Typically we prescribe progesterone post IVF, but with Lupron we also give estrogen. Not much of a big deal, as estrogen can be given in the form of a pill three times per day. Estrogen patches can also be used.
Lupron cannot be used for triggering if Lupron has been used in the same cycle. So you are taking Lupron starting on day 21, day 2 or using microflare lupron, a Lupron trigger will not work at all. Here hCG would be the only option.
Many other physicians have been increasing their use of Lupron for ovulation triggering. You should ask your doctor if Lupron is used in his practice to prevent ovarian hyperstimulation.
That’s it for today, thanks for reading, and please read disclaimer 5/17/06.
Dr. Licciardi
Saving the best for last, an excellent way to prevent OHSS is to use Lurpon. This requires some explanation.
As many of you have experienced, Lupron is a drug that can be used during an IVF cycle. It is typically started about 1 week before the IVF cycle starts (day 21) or it can be started on day 2. The dose varies, but the usual options are regular lupron, low dose lupron or microdose lupron. None of these have anything to do with reducing OHSS, but I will get to that.
Lupron works by suppressing the pituitary’s ability to produce LH. This is good because in all of the Lupron protocols I just mentioned, one important job of Lupron is to prevent the premature surge of LH. The surge of LH causes ovulation, which is bad for an IVF cycle. If LH surges before the hCG injection, we cancel the cycle for premature ovulation.
We can’t get the eggs when we want them if they have ovulated prior to the retrieval. Lupron prevents this. Before Lupron was invented, we needed to cancel about 15% of IVF cycle for early ovulation.
Some of you are wondering why we trigger ovulation if we want to get eggs from the ovary. LH, hCG and Lupron cause the eggs to mature and then ovulate. For an IVF cycle, we need those medications to get the eggs to mature while still in the ovary, but we grab them before they are released.
Over the past decade we have been using other drugs, like Cetrotide and Ganarelix, to prevent the premature LH surge. These are easier to use than the Lupron because they are only given 2-4 days prior to the hCG. Some doctors still prefer to use Lupron.
Now on to OHSS and Lupron. In a natural ovulation cycle using no drugs, the follicle develops over about 2 weeks, and then a strong surge in LH causes ovulation. While Lupron causes the pituitary to cease LH secretion, in the first 1-2 days of Lupron use, there is a strong release of LH. That’s why we normally give it early in the cycle, before follicles have developed. Premature ovulation does not occur when we give it early because there are no follicles to ovulate.
It is this strong release of LH that makes Lupron great as a hCG substitute for the trigger shot. The quick surge results in a very short blast of LH, which could take place over 1-2 hours. This is very similar to the body’s LH surge that takes place in a natural cycle. After that, the LH has left the system, ovulation occurs 36 hours later, and ovarian stimulation stops. hCG, on the other hand, stays in the body for days, even up to 2 weeks. All of this time, hCG stimulates and stimulates the ovaries, which is too much for ovaries that have released many eggs.
Why give an hCG instead of a LH injection? For iui and IVF we use hCG as opposed to LH because hCG is easier to make and cheaper than LH, and hCG works just as well. The molecules of hcg and LH are very similar and act in similar ways. Plus, the drug companies have not yet figured out how to get the necessary large amounts of LH cheaply into one little vial.
The bottom line is that Lupron, because it causes just a short burst of LH, works very well in preventing OHSS. We are using it more and more and are very pleased with the results. We commonly use it for our egg donors.
One down side to lupron is that, in very small percentage of cases, it may not cause ovulation. This is a rare occurrence and is more likely to happen in women who are hypothalamic, i.e. they do not get regular ovulation due to exercise, dieting or some other factor. In these cases, there is no LH in the pituitary for Lupron to trigger.
In cases where the threat of OHSS is evident, it’s worth taking a chance with the Lupron. We measure LH levels the day after the Lupron injection. If they are very low, the lupron did not work, and there is no LH surge. Therefore we can give hCG the next day, unless the fear of OHSS causes us to cancel the cycle.
Another detail of Lupron use is that for luteal support, we add estrogen. The ovaries just shut down after Lupron use, and therefore estrogen and progesterone are produced in very low quantities. Typically we prescribe progesterone post IVF, but with Lupron we also give estrogen. Not much of a big deal, as estrogen can be given in the form of a pill three times per day. Estrogen patches can also be used.
Lupron cannot be used for triggering if Lupron has been used in the same cycle. So you are taking Lupron starting on day 21, day 2 or using microflare lupron, a Lupron trigger will not work at all. Here hCG would be the only option.
Many other physicians have been increasing their use of Lupron for ovulation triggering. You should ask your doctor if Lupron is used in his practice to prevent ovarian hyperstimulation.
That’s it for today, thanks for reading, and please read disclaimer 5/17/06.
Dr. Licciardi
posted by Dr. Licciardi at 3:37 PM
10 Comments:
My first IVF I used Microdose Lupron. No follicles, nothing and IVF canceled. My new doctor used Cetrotide and this was given about 4 days before egg retrieval. When I went in for egg retrieval I had already ovulated. What's next? I am planning on a #3 try but don't want to go through this whole process if I am going to ovulate too early again. How do you stop this? My doctor said that ovulating too soon is not normal.
I am 34 years old & have been ttc #1 for 3 1/2 years. Had all the basic tests (blood work, HSG, semen analyis, ultrasounds) and was diagnosed with unexplained infertility. I became pregnant in November from my first IUI with Menopur but miscarried at 9w2d. The last few months I've noticed I've been bleeding rectally during my period only. Had a rectal exam and have no polyps or hemorroids. Do you think I should have a lap to check for endo even though I had a clear HSG and ultrasound? I have cramping during my period and start about a week after O and also have clotting. This month I had rectal pain during my period as well but it's a new symptom. Thank you for your help.
Thank you for your blog. I have PCOS and overstimulated with injectibles. Had to cancel my IUI cycle because of the overstimulation.
Question: History of PCOS, after my last successful pregnancy, got pregnant spontanously 20 months later but miscarried at 6w3d. POC tested 46xx. Periods after my last pregnancy were every 40 days or so, could it have been LPD that caused the miscarriage. I started taking Progesterone 50mg IM when I found out but still miscarried. How soon should I wait before trying again? 38y so time is not on my side.
Thank you.
This group CHR, that is also in New York, seems to have a lot of experience with infertility and PCOS. Do you know anything about them?
I am 31 years old, and in the beginning stages of our fertility journey. Husband just got semen analysis results back. Count is 86 million, motility is 61%, morphology is 1%. Will this be an issue with trying to conceive naturally?
Also, the RE I am seeing wants me to come in for day 3 bloodwork. I normally spot for about 5-7 days prior to my actual "flow". My RE considers day 3 to be the third day of spotting, which doesn't really conicide with my BBT temps (temps don't normally go down below coverline until the "flow" starts) Is RE correct with this?? What would you consider day 3??
Thanks much!!
How must is enough to have and IVF, I don't know but It can really take all your savings without results. I feel sorry for those.
My RE used this protocol for me.. A Lupron trigger..I'm a high responder, so I was on a low dose of meds...I ended up producing a lot of eggs and still developed OHSS. It was late onset..due to pregnancy, but still had to have the fluid aspirated..I'd be interested to know what percentage of decreased OHSS cases there are from the Lupron trigger..
This is a new information that could be used in order to know the relationship of OHSS and Lupron. Through this information we will be able to learn how Lupron works and all its possible things that it could make and produce. In case you have fertility concerns, I found this site that maybe helpful. http://www.natural-fertility-prescription.com
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