The Natural LH Surge vs. the HCG Injection
We are still working towards the timing of the hCG shot, but we first need a little more background. We need to go over difference between the natural LH surge and the hCG injection.
After LH leaves the pituitary during the surge, it causes the ovulation by landing on specialized spots on the ovarian cells, the LH receptors. All hormones act by landing on (binding to) their specific receptor, and usually one hormone does nothing if it lands on the receptor of a different hormone. There has to be a match.
This is usually dictated by shape. It’s like a lock that recognizes the shape of the key. FSH and LH are similar hormones, but their shapes are a little different. So if LH comes across a FSH receptor, it would not bind.
There is a notable exception. Because hCG and LH are chemically very similar, with very similar shapes, hCG can bind to the LH receptor, and can do it well. Since hCG can land on the LH receptor, hCG can do the same job as LH.
This is actually very important to pregnancy. Pregnancy needs progesterone, which comes from ovarian cells with LH receptors. So LH causes the ovary to make progesterone after ovulation. Good: the progesterone allows the embryo to implant. Then the embryo makes hCG. Better: this causes the ovary to make even more and more progesterone which keeps the implantation going strong. Both occur via the LH receptor.
That hCG can behave like LH is good for treating fertility patients because we can cause ovulation with an injection of hCG instead of an injection of LH. This is good because hCG is easier to get than LH.
So why not just give LH? Up until very recently, LH was not available. Years ago the only way to get FSH for our fertility drugs was to extract it from the urine of menopausal women.
(This is a whole story by itself. Initially, starting in the 1970’s, the urine was obtained from menopausal Italian nuns who would leave jugs of pee for the drug company Serono to pick up in the mornings. Menopausal women have really high amounts of FSH in their blood, and most of it comes out in the urine. The pee would be taken to a factory with a swimming pool-sized pee vat, and they would somehow get the FSH from the pee. Serono went on to be the most profitable company in the world. The Catholic Church was rewarded for its cooperation. Even today, pee swimming pools exist for companies who make fertility drugs from urine.)
Because FSH and LH are similar molecules, the methods used to pull out the FSH grabbed LH too. Once we got the FSH/LH mix, we didn’t have the science to separate the two. So we could not get enough pure LH to cause ovulation. Today we can get pure LH made in a lab, but still in small amounts, not enough to get a good ovulation going.
How do we get the hCG? That is piece of cake, we get it from placentas. There are tons hCG in placentas and it’s easy to extract. Today hCG is also made in a lab, that’s the Ovidrel. It’s pure stuff, and that’s why it can be given in the skin. The placental hCG is given IM because it’s contaminated. hCG is also a protein, and the system for extracting the hCG protein from placentas is pretty crude, so tons of other placental proteins get caught in the net too. These extra proteins can cause a local allergic reaction when given in the skin, but not when given in the muscle.
When we used to get fertility drugs from urine, same thing, they had protein contaminants and needed to be given into the muscle. Recent exceptions are Menopur and Bravelle. These are from urine but using new systems that are better at cleaning out most of the unwanted contaminating proteins. Gonal-F and Follistim are both made in the lab and do not have the contaminants. They are given into the skin.
Today there are 2 products, placental hCG given in the muscle, and the lab-made hCG given in the skin. The placental is still cheaper and words great.
In a cycle stimulated with injected FSH (for IUI or IVF), most of the time the natural LH surge does not occur at all, so we need to give the hCG. In some cases the LH surge does occur, but it happens too soon, before the eggs are mature. This is probably due to the fact that estrogen levels are higher earlier in a medicated cycle, so the LH rises earlier. We don’t know why a premature LH surge only happens in about 20% of cases.
The bottom line is that we cannot count on the natural surge to occur at all, or at the right time, when we are using FSH injections. We need to use the hCG injection for proper timing of ovulation and proper timing of the egg retrieval.
That’s it for now. Next time we finish up by talking about the right time to give the hCG shot.
Thanks for reading,
Dr. Licciardi
After LH leaves the pituitary during the surge, it causes the ovulation by landing on specialized spots on the ovarian cells, the LH receptors. All hormones act by landing on (binding to) their specific receptor, and usually one hormone does nothing if it lands on the receptor of a different hormone. There has to be a match.
This is usually dictated by shape. It’s like a lock that recognizes the shape of the key. FSH and LH are similar hormones, but their shapes are a little different. So if LH comes across a FSH receptor, it would not bind.
There is a notable exception. Because hCG and LH are chemically very similar, with very similar shapes, hCG can bind to the LH receptor, and can do it well. Since hCG can land on the LH receptor, hCG can do the same job as LH.
This is actually very important to pregnancy. Pregnancy needs progesterone, which comes from ovarian cells with LH receptors. So LH causes the ovary to make progesterone after ovulation. Good: the progesterone allows the embryo to implant. Then the embryo makes hCG. Better: this causes the ovary to make even more and more progesterone which keeps the implantation going strong. Both occur via the LH receptor.
That hCG can behave like LH is good for treating fertility patients because we can cause ovulation with an injection of hCG instead of an injection of LH. This is good because hCG is easier to get than LH.
So why not just give LH? Up until very recently, LH was not available. Years ago the only way to get FSH for our fertility drugs was to extract it from the urine of menopausal women.
(This is a whole story by itself. Initially, starting in the 1970’s, the urine was obtained from menopausal Italian nuns who would leave jugs of pee for the drug company Serono to pick up in the mornings. Menopausal women have really high amounts of FSH in their blood, and most of it comes out in the urine. The pee would be taken to a factory with a swimming pool-sized pee vat, and they would somehow get the FSH from the pee. Serono went on to be the most profitable company in the world. The Catholic Church was rewarded for its cooperation. Even today, pee swimming pools exist for companies who make fertility drugs from urine.)
Because FSH and LH are similar molecules, the methods used to pull out the FSH grabbed LH too. Once we got the FSH/LH mix, we didn’t have the science to separate the two. So we could not get enough pure LH to cause ovulation. Today we can get pure LH made in a lab, but still in small amounts, not enough to get a good ovulation going.
How do we get the hCG? That is piece of cake, we get it from placentas. There are tons hCG in placentas and it’s easy to extract. Today hCG is also made in a lab, that’s the Ovidrel. It’s pure stuff, and that’s why it can be given in the skin. The placental hCG is given IM because it’s contaminated. hCG is also a protein, and the system for extracting the hCG protein from placentas is pretty crude, so tons of other placental proteins get caught in the net too. These extra proteins can cause a local allergic reaction when given in the skin, but not when given in the muscle.
When we used to get fertility drugs from urine, same thing, they had protein contaminants and needed to be given into the muscle. Recent exceptions are Menopur and Bravelle. These are from urine but using new systems that are better at cleaning out most of the unwanted contaminating proteins. Gonal-F and Follistim are both made in the lab and do not have the contaminants. They are given into the skin.
Today there are 2 products, placental hCG given in the muscle, and the lab-made hCG given in the skin. The placental is still cheaper and words great.
In a cycle stimulated with injected FSH (for IUI or IVF), most of the time the natural LH surge does not occur at all, so we need to give the hCG. In some cases the LH surge does occur, but it happens too soon, before the eggs are mature. This is probably due to the fact that estrogen levels are higher earlier in a medicated cycle, so the LH rises earlier. We don’t know why a premature LH surge only happens in about 20% of cases.
The bottom line is that we cannot count on the natural surge to occur at all, or at the right time, when we are using FSH injections. We need to use the hCG injection for proper timing of ovulation and proper timing of the egg retrieval.
That’s it for now. Next time we finish up by talking about the right time to give the hCG shot.
Thanks for reading,
Dr. Licciardi
posted by Dr. Licciardi at 10:10 AM
19 Comments:
Great blog. You are wonderful and generous to share your wealth of knowledge here. And, I love the vision of giant steaming pools of pee. Truly inspiring.
Why would 20% of patients still experience premature LH surge if it's largely preventable with timely use of ovulation surpression drugs?
Thanks, and Keep bloggin
Oops. Did you mean that 20% of patients who are NOT taking ovulation surpression drugs would experience premature ovulation?
Amazing blog! I've read through the bulk of every post from day 1. Husband and I have been trying 15 months now and I just happened to fall on your blog last week. We are slowly working through our testing and treatment and will hopefully get some answers as we are young (23 & 24) but have not yet conceived naturally. I'm sure as our results come through I will find great comfort in reading your blog. You seem to truely care about your patients and your work. Hard to did that in a doc these days! Now it's too bad you're all the way out in NY. I'm from a little country north of you, canada :)
Keep up the blog, you've mentioned a few times it's time consuming but the time you put into it really does show and it's very appreciated.
Wow, loved the explanations of how the injectable meds are made. Now I know why the Gonal-f was so expensive--makes me want to run right out and buy Merck stock!
Success story: I am 41 and my son was born last April, the result of our second IVF cycle. I love that doctors like you can help make our dreams come true.
Your timing is excellent for me (I hope). Any chance you can give a sneak preview and tell us how you time one IUI after a trigger shot? The nurse mentioned 12 to 24 hours, but that surprised me because everything I've read is 24-36.
I'm going in Friday for my second monitoring ultrasound in advance of my first trigger shot.
I am amy...great blog!i wish i have found earlier...I am just done with first ivf with ICSI cycle..no luck..my age is 27 & husbands 33..ended up spontaneous abortion after 4 weeks..embryo's looked great... had 5 day transfer done..had 4 embryos 1 grade A and 1 B and 2 c...just transfered one grade a embryo.....sperm count issue...wonder what might be the reason....planning for FET...what could be my chances of success this time??? any help is appreciated...
Hi Dr Licciardi,
I am 37 and my husband is 39. We have been TTC since Feb08. I have an AMH level of 6 (no other issues) and he has 92% abnormal forms (no other issues). We have done IVF twice this year.
IVF#1 was a long down reg which produced 3 follicles and only 2 eggs. Both fertilised (ICSI) and were transferred resulting in a chemical pregnancy.
IVF#2 was a flare cycle which produced 5 follicles and only 2 eggs again. I had the OPU today and we'll see if there's anything to transfer on Sunday.
If not, my doctor has recommended a Clomid + Gonal-F + orgalutran cycle for the next try. I have not found much information about this type of cycle and wondered if you could provide some for me.
Thanks for writing such a useful blog, it is much appreciated.
Me again. Hope you don't mind me asking something, of course I know you can't answer everything. It's just more of a curiosity thing then anything else.
I had my hsg done 2 days ago now. Quite the experience I have to say. My specialist conducted it. Anyway, in went dye and showed left tube very clear but right tube blocked. I'm glad I read your posts as I didn't panick right away knowing where the blockage was made a big difference (thanks!!!). Anyway, doc attempted to clear it with another round of dye and was successful!! She says my odds have now increased tremendously.
Questions: based on ovulation pains I am almost certain I generally ovulae more on the right, is that possible that it doesn't alternate evenly between both ovaries?
Would this have caused such a long time of no luck? (16 months now)?
What are the odds it will become blocked again and if it will be prone to block is there increased risk of ectopic?
All my blood work came back normal so could this truely have been such a big bearin on my inability to conceive? We know my husbands numbers and they aren't incredible but they are still good enough and above the who recommendation (he will be undergoig embolization for varicoceles which doc says based on his situation will have a positive effect on his count... And pain).
I am so thankful to both my doc and you. Your blog has given me lots to look forward to when I started to lose hope. My doc is also referring y husband to an infertility urologist at a clinic with great reviews. The urologist also has great reviews so I am regaining confidence in our ability to conceive before the end ofthe year (hoping!!).
Hi Dr. Licciardi,
I can’t thank you enough for writing this blog. I hope you’ll be able to help me with some answers I’m desperately looking for.
I’m 31, my spouse is 36 and we’ve been through 3 Clomid IUI, 1 FSH IUI, 3 IVF(icsi) cycles with my own eggs, all unsuccessful. I’ve been diagnosed with ovarian dysfunction (normal fsh but high E2 levels) while my husband’s semen was deemed quite normal. Earlier this year we decided to move on to Donor Eggs, but shockingly enough, we now have added 2 failed donor egg ivf cycles to our painful infertility diary so far.
The 1st DE cycle, out of 12 eggs retrieved, 9 fertilized, 6 embryos remained by day 3 and we transferred 2 day 6 blasts (3bb and 1bb-), none to freeze and I ended up with a chemical pregnancy. Our RE said we cannot conclude it’s a sperm issue.
Even so, we decided do our next DE cycle with Donor Sperm split 50-50 between hubby and known donor. Out of 20 eggs retrieved, 15 mature, 10 day 3 embryos and 2 day 6 blasts (1bc from the donor sperm and 1bb- from hubby) and none to freeze. Negative result on hcg blood test. This time our RE said he was out of any explanations.
Both the Egg Donors were proven (had previous successful live births). My uterine lining is 8mm - 10.4mm.
What are we doing wrong? Is there a next step for us? Could you please do a post on the causes of Donor Egg ivf failure?
Best regards,
J
Great work Doc!!
Thanks for taking the time and making this effort.
Regarding early LH surge: can you explain the reason and is there a way to overcome this hurdle so to speak??
I am 37 and had 5 failed iui ( clomid x 2 and follistim high dose x 3).
With follistim everytime I had a single good size follicle ( 18-20) with good E2 ( 300+) numbers and LH surge ( 30+)
by cd 7-9.
Would decreasing dose follistim prevent the rapid surge??
And allow for more follicles?
My RE has given me an option of iui with lower dose if I want ( he states statistics don't support the theory but willing to give me a chance) or move to MDL IVF.
Your blog was timely but it's like an unfinished tv episode when you need to know what is to come next week, now.
I know you can't answer all questions, thanks anyways!
Ishika
Doctor,
Is there a weight limit for doing in-vitro? My current doctor said he won't do it until I lose weight (a large amount) because he isn't at a hospital. Although I am currently dieting, we are on a time crunch and I'm afraid it will take too long- if I moved to a doctor at a hospital, would the same restrictions apply (anesthesiologist restrictions?)Or can anyone undergo in-vitro fertilization?
Thank you,
J.P. in CT
Dr. Licciardi, can you explain the role of steroids during ovulation? I cycled with you on 2008, and had an e/p. You told me you thought I should keep trying (although I've done 7 fresh cycles including donor eggs). I'm thinking about cycling again, but now I live in s.america. The question is if you think dexamethasone can help produce more eggs, better quality. I think I might have congenital adrenal hyperplasia, but haven't been tested for it. The thing is by day 5 (during a non medicated cycle) I already have a dominant follicle of 20 mm. But that follicle does not produce estrogen, so I end up "ovulating" by day 21, after estrogen raises. During IVF cycles i'm ready by day 7. I produce around 5 eggs, but during that cycle with you I produced 12 eggs. Of those only 5 fertilized.... So my only option i guess is to use something that helps me produce more eggs. I'm 35 now and have a son from cycle #2. Thanks you so much for your help. I love reading your blog.
A 61-year-old woman gave birth to her own grandchild using an egg donated by her daughter, a clinic in Japan has said.
The surrogate mother is believed to be oldest woman to have given birth in Japan. http://infertilityuk.wordpress.com/2009/09/23/egg-donation/
Frozen embryos ‘make healthier babies than fresh ones’
http://infertilityuk.wordpress.com/2009/09/24/frozen-embryos-make-healthier-babies-than-fresh-ones/
I'm 27. My husband is 37. He has a child from a previous marriage. Prior to my starting birth control pills 10 years ago, I had one or two periods a year (which my dr said were not ovulatory cycles but merely "the bottom falling out").
We've been married for 3 years and decided it was time to start our family. I tossed the pills in April. And then nothing. Start Clomid in July - didn't work the first cycle, did the next two. Still not pregnant.
My doctor does not do much follow up with the Clomid. Could I be ovulating but have immature eggs? I take Prometrium from the time of a positive OPK until my period occurs. Could my progesterone level still be too low?
Do you recommend an RE? My regular obgyn wants me to give her a few more cycles of Clomid and even consider letting her do up to three rounds of IUIs, but... should I really already be at an RE?
I am so glad that I stubmled uppon your blog, I have a question on a Septate uterus, I am having such a hard time finding any information on repeat Hysteroscopy Resections.
I had a placenta abruption at 26 weeks, we lost our baby and since then I have been seeing a RE, we discovered that through MRI and Sono that I had a uterine Septum. I had a resection in July.
I had a sonohystogram yesterday and found out that the septum has grown back down on one side.
Is this something you see much?
My RE wants to resect it again in 2 weeks but I am not sure how many times I am going to have to have surgery and if I want to continue all of this. Mostly I would love a 2nd opinion
that's exellent topic. I also have further question; I received HCG injection and the next morning I had positive OPK. As a curiosity I took another OPK test following morning (day of iui, about 35 hour folloving HCG injection) and this time OPK was also positive. I was so exciting that finally the timing is so perfect. My excitment didn't last too long. 24 hours following iui, I continue to check OPK, which this time showed positive result also but with the LH line much darker then two previus tests. What does that mean? Was it too early for iui? Are those mini follicle continue to grow? Could it be just my natural LH but the body doesn't produce LH after egg was released ( no increase of estrogen). Please help.
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When a woman experiences her LH surge, it is prime time for conception. This is because the sperm can live for several days once it is inside the woman’s body, and so it will be ready once she ovulates...Cialis Online
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