When is the Right Time for hCG?

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The time between the hCG and retrieval
For an FSH injection cycle leading to insemination, it’s ok if the ovulation naturally occurs a little early (via a premature LH surge) because we can just do the insemination early. Rarely it’s too early, before the follicle is big enough, and we cancel the cycle. However, for an IVF cycle we have to cancel the cycle if there is an early natural LH surge, even if it’s only a little early, because the timing of the retrieval is very dependent on when the surge starts. The retrieval needs to be about 34-36 hours past the start of the surge (which would also be the time if the hCG shot).

Because we are not taking blood every hour, if the blood test shows a rise in the LH level, we don’t really know when the rise started so we don’t know the right time for retrieval. Lupron, Antagon and Cetrotide prevent the natural rise of the LH, so the premature surge usually cannot occur. However, these drugs do not interfere with the effects of an hCG injection. So there is no natural surge, but there is an artificial surge which starts the moment the hCG goes in.

Final Maturation
There is a second very important job of the LH Surge/hCG injection:
it causes the egg to mature. As the days of stimulation progress the eggs are slowly maturing, but more is needed for the final maturation. Necessary last minute changes occur inside the egg from the LH/ hCG.

Why is this important? An immature egg will not fertilize. If the retrieval is before about 33 hours after the hCG, the result will be immature eggs. Sometimes they are all immature, or just some.

If the retrieval is 38-39 hours after the hCG, the eggs will be mature but they will already have ovulated. We would retrieve none; they would be floating in the pelvis around the ovaries waiting to get picked up by the tubes. So we need to grab the eggs just after they mature but just before they ovulate, which is at about 34-37 hours after the hCG injection.

What day should you get your hCG?
hCG can only mature eggs that have been growing for enough time for the follicle to become large. The sizes of all of the follicles need to be taken into consideration before giving hCG in IVF cycle.

Not all of the follicles grow at the same rate. For example, if there are 10 follicles, and the biggest is 18mm, they will not all be 18 mm. Some will be mid-sized and some will be much smaller. Each follicle does not need to be 18 mm to produce an egg that is mature. As long as the biggest (the lead follicle) is 17-18mm, the mid-sized (13-16) should also have mature eggs. The small follicles (10-12) may or not be mature. But if the lead follicle is 14 mm, none of the eggs have yet reached maturity. Giving hCG would not be enough to achieve maturity.

How Important are Estrogen Levels?
Not very. When you are monitored for your IVF cycle, the follicle size is much more important that the estrogen (estradiol) levels. We need the estrogen to rise, but if midway through your cycle we see 10 follicles, with the biggest being 13 mm, we don’t really care if the estrogen level is 500 or 900. Estrogen is more important when we are monitoring someone who may be on track for hyperstimulation.

Therefore, we use mostly the size of the follicles, with not much emphasis on the estradiol levels, to determine when to give the hCG. At NYU we feel the best time to get the hCG is when the lead follicle reaches 18 mm. Now because there are many variations from cycle to cycle and from patient to patient, it’s not easy to say that 18 mm is the rule.

For example, let’s say there is one follicle 18 mm, three that are 15 mm and others that are smaller. Here we may worry that some of the small ones may be too immature, so we may wait another day before giving the hCG. Let’s say there are 20 follicles, with the biggest 17mm and an estrogen level of 2900. Here we are aware that the smaller follicles may be immature, but we also are concerned about the estradiol getting much higher because the woman would be increasing her risk of hyperstimulation. So we give the hCG at 17 mm, which may yield some immature eggs, but should give us enough mature eggs to work with.

And there are many more variations. Some women have gotten their hCG a little on the early side and have all mature eggs. Some women in their first cycle get the hCG at 18 mm with lots of good size follicles, and have ½ their eggs be immature. So next cycle we wait till the follicles are 20-22 mm before giving hCG. This sometimes gets more mature eggs but sometimes no matter what we do, that woman’s ovaries make more immature eggs than expected.

So why not wait and give hCG later? Because eggs can get over-mature. This over-maturity can lead to lower embryo quality and lower pregnancy rates.

When we see the records of women who have failed IVF elsewhere, many times we see that he hCG was given with large sized follicles. The first and easiest “fix” we can do is to give the hCG earlier in her next cycle, more inline with our standard procedures.

Why do some doctors wait longer to give the hCG?
Some may feel that the higher the estradiol level the better, so by waiting estrogen levels will go up. This is probably not important. Others may feel that it is necessary to wait so there will be no immature eggs. Well this sounds good, but it may not be worth sacrificing the quality of the eggs form larger follicles, which are probably the best eggs anyway.

And back to the original question.
What if instead of the average 11-12 days it takes to grow the follicles, they are of the right size after only 6 days or 8 days?
If the size is good, but it seems early, we usually go at least one more day that we normally would, maybe 2. If it’s day 9 and the follicles are 19-20 mm, it really sounds ok to give hCG. If it’s day 7 (so 5-6 days of FSH injections), and the follicles are 17-18 mm, more time would probably be a good idea.

Thanks for reading and don’t forget the disclaimer 5/17/06.

Dr. Licciardi

References:

  • Silverberg KM, Olive DL, Burns WN, Johnson JV, Groff TR, Schenken RS. Follicular size at the time of human chorionic gonadotropin administration predicts ovulation outcome in human menopausal gonadotropin-stimulated cycles. Fertil Steril. 1991 Aug;56(2):296-300.
  • Kyrou D, Kolibianakis EM, Fatemi HM, Tarlatzis BC, Tournaye H, Devroey P. Is earlier administration of human chorionic gonadotropin (hCG) associated with the probability of pregnancy in cycles stimulated with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone (GnRH) antagonists? A prospective randomized trial. Fertil Steril. 2011 Nov;96(5):1112-5.
  • Palatnik A, Strawn E, Szabo A, Robb P. What is the optimal follicular size before triggering ovulation in intrauterine insemination cycles with clomiphene citrate or letrozole? An analysis of 988 cycles. Fertil Steril. 2012;97(5):1089.
  • O’Herlihy C, Pepperell RJ, Robinson HP. Ultrasound timing of human chorionic gonadotropin administration in clomiphene-stimulated cycle. Obstet Gynecol 1982; 59:40.
  • Rahman SM, Karmakar D, Malhotra N, Kumar S. Timing of intrauterine insemination: an attempt to unravel the enigma. Arch Gynecol Obstet. 2011 Oct;284(4):1023-7.

10 responses to “When is the Right Time for hCG?”

  1. Dr,

    Thank you so very much for your blog. It has helped me over the years as I reach a place of acceptance as this is the route that we must take to have our first baby.

    This post has truly helped me to understand the process and what to expect when I cycle next Spring.

    Kind Regards,

    BFK

  2. dominant is antagonizing me says:

    Your blog is wonderful, thank you for taking the time for us IVF patients.

    I have a question in regards to dominant follicle. How would this play into the timing of hCG? My 2nd IVF cycle and again I’m developing a dominant. We changed protocols and still the same.

    1st IVF we pushed for the smaller ones to mature. We were only able to retrieve 5. 100% fertilization resulted in +, but ended in m/c at 9 weeks. 2 are still on ice.

    2nd IVF (current) yet again another dominant follicle. Have 11 going within the same range of 7-10 yet a big one at 17. Can’t believe this is happening again. Since we are only on cycle day 9 I”m considering canceling.

    My egg quality was not great and wonder if it was from pushing the dominant. My fsh is perfect for my age 37 w/ fsh 5-7 over the last couple years. I suppose it’s just AGE. My lining is always great, trip stripe current at 11 on cd 9.

    It’s this dominant follicle problem that I just can’t seem to find answers for. Age I guess? Poor responder?

    I’m thinking of heading to NY for the EPP. Would this be worth it for dominant follicle problem? Thank you.

  3. Anonymous says:

    Doctor – I just came to know of this blog today, and didn’t know where to post a question…so this question may be misplaced perhaps..Apologies for that. What do you think about effects of caffeine before and during cycling. Do you recommend stopping it? Do you recommend any other such lifestyle changes related to diet and exercise. Like I don’t exercise much at all, but am a fit person as such

  4. I have been researching the subject for years and I have learned a great deal from you blog. Thanks. http://www.infertilityconcerns.com

  5. Mandy Kimsey says:

    Hi … I am 25 years old and have been trying to get pregnant for a year and three months. We started seeing an RE at 11 months because I have insurance that covers fertility for now and will be loosing it soon. I have had every test under the sun taken. All come back fine. I have had tubes checked and even had lap/hysterscopy that showed very mild Stage 1 endometriosis which they lasered out.I had IVF done and transferred two perfect 10 cell embryos and no luck. Of the other embryos growing, none made it to freeze.Then the last two cycles I have had back to back IUI’s (one natural and one with clomid) and again negative. I also go a blood test for thrombophila after IVF to see if that is why maybe they didnt stick but that came back fine too. I asked my doctor if she could give me any reason why we cant get pregnant and she said wished she knew bc it would make her job easier. Just wondering if you can give me any reasons as to why it isnt happening for us? Thanks so much

  6. Mandy Kimsey says:

    I didnt mention that I made 21 eggs. 14 were mature. They froze 6 of those and ICSI the other 8. Of those, 7 fertilized and I had a 5 day transfer…

    Thanks again… I would love to get a true experts opinion.

  7. LBG says:

    Hello Dr. Licciardi,

    I’ve enjoyed your blog very much. It often answers questions that I wish I’d asked my own doctor.

    I’m a 39 yo who has gone through two IVF cycles. I have a question about co-culture.

    I made 11-12 nice eggs and had 3 grade 1/2 embryos in the first cycle and 4 grade 1/2 embryos the second cycle. All were transferred. First cycle ended in miscarriage at week 7 and second cycle was negative. My Dr is recommending co-culture for the next cycle. Can you explain co-culture and if it can actually improve odds of pregnancy?

    Thank you very much.

  8. I agrre with the information because it can help to many teen by do not be pregnant, so I think that we should make more blogs like this one.

  9. hCG is excreted in the urine of pregnant women. Detection of this hormone in urine or serum is an easy first method of diagnosis of pregnancy, or your post is about a different HCG?? I only know about this info!

  10. David bone says:

    Wow, nice post,there are many person searching about that now they will find enough resources by your post.Thank you for sharing to us.Please one more post about that..hcg

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