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AMH (Anti-Mullerian Hormone)

Hello to all. In this blog I will review the usefulness of Anti-Mullerian Hormone, otherwise referred to as AMH.  AMH is one of the hormones, along with estrogen and a few others, produced by the ovary.

Like estrogen, AMH is produced by the granulosa cells. The granulosa cells are the small cells that surround each egg.  These small cells are tightly attached to egg surface whereby they help to vitalize and, when the time is right, mature the egg.   This egg-granulosa cell unit is called the follicle.

No one yet knows what the function of ovarian AMH in females.  AMH is present in males, and we know that it has a very important role in the development of normal male sexual anatomy.  What we do know about AMH in females is that the more healthy follicles one has, the higher the AMH levels.

Measurement of AMH levels can help us predict a woman’s fertility, in a very general way.  We already said that estrogen is also produced by the granulosa cells, so why wouldn’t we just need to measure estrogen levels to find out about ovarian health?  Because estrogen only comes from follicle at a time; the one that is in the process of ovulation. A woman may have 100,000 follicles, but on most cases only one per month gets involved in ovulation and becomes an estrogen producer.   Follicles may make different amount of estrogen each month, so judging fertility based on an estrogen test is not helpful.

Many follicles at one time, however, are producing AMH. Now it’s not every follicle, but it is a large number.  It works like this. The ovary contains different follicles in different stages of maturity.  Here is a microscopic view of the ovary.


Some follicles are very immature and have few granulosa cells; just one layer surrounding the egg.   Some follicles are more mature and their granulosa cells have multiplied into more cells in multiple layers.  These are the ones producing the most AMH.  In general, if you have a lot of eggs, you have plenty of follicles in all of the stages of development, giving you higher AMH levels.  Lower AMH levels mean fewer follicles of all types.

Follicles are always making AMH therefore levels can be measured any day in the cycle. In fact, it does not matter if a woman is on oral contraceptives, AMH is still produced and can be measured.

AMH may turn out to be and excellent way to measure a woman’s fertility potential, but we are not quite there yet. We do know that a high AMH is good and a low AMH is bad. What’s a good high level? We are still not sure. We know a little.  Any level over 2 is really not bad at all. Certainly, higher than 2 is better still. We know that undetectable levels, less than 0.16, are bad.  But, we have had women with these low levels become pregnant.  The odds of pregnancy are much worse for women with low levels, but people frequently get pregnant with low odds.  Some women have asked me if the level can be too high.  High levels may indicate the presence of polycystic ovaries (ovaries with an above average number of follicles).  While it is true that some women with polycystic ovaries have trouble conceiving, a high AMH level is not the issue.

Recent studies (one was in the headlines a few weeks ago) have used AMH levels to predict IVF outcome.  But again, really high levels were shown to be good and really low levels bad, but overall, not predictive enough to tell someone they can or can not get pregnant.

What we typically do is to put all of the information we have together to estimate ovarian health.  If we use age, FSH levels, AMH, antral follicle counts, the prognosis becomes a bit more clear, but the system is still not perfect.

AMH testing will become more useful sometime soon. More and more women need to have the test done do we can compare levels to outcomes on a large scale. In addition the laboratories need to get better at the testing.  But once we get better with AMH levels, we may be able to do some very important things.

For instance, some studies have been done comparing AMH levels to the time of menopause. Again, not ready for prime time, but the concept may be very important.  What if we could measure AMH in a young woman and determine at what age she will start losing her fertility? Or at what age will she lose half her fertility? What if we could measure AMH levels in a woman destined for chemotherapy and determine if she should freeze her eggs first?

These would all be wonderful uses of this test and it may be that in the future we could reach these goals.

It’s more likely that newer tests will be developed to improve ability to predict.  As alluded to before, combination tests may be more accurate. For example labs are starting to market “fertility profiles” based on AMH, FSH, inhibin and other hormones.

But in the end, like in all of medicine, the genetic tests will dominate.  Scientists are looking for a gene or groups of genes that control the fertile lifespan of women.  As genetic testing becomes less expensive and as we increase our ability to look at more and more genes at one time, the goal of accurately determining a woman’s ovarian age and potential will be reached.


Thanks for reading and please don’t forget to read the disclaimer from 5.17.06


Dr. Licciardi


Important Final Words on Pre-Implantation Genetic Diagnosis

These past few blogs covering PGD raise a few important issues. There are some well-know fertility centers that are really pushing TE biopsy. The feeling is that the technology has finally become accurate and safe enough.  It may be that doing IVF with PGD leads to a higher pregnancy rate and a lower miscarriage rate.  Plus, if you know you are getting a normal embryo, we can transfer fewer embryos, lowering the rates of twins and triplets.

This all sounds good, however, I think we need just a little more time, but maybe not much more.  In a good center, the pregnancy rate for a woman under 37 years of age is 40-50% without PGD.  PGD adds an invasive procedure. The shell of then embryo has to be opened, usually by a laser beam, then some of the embryo, even if it’s a small piece, has to be chopped away.  We make it sound simple, and so far it seems safe, but no one should promise you all of the safety data is in.  Not to mention the additional costs, which could vary from program to program, but $6,000 is a safe estimate.

In theory, ideally, PGD will be the way to go and everyone doing IVF will have their embryos tested, the pregnancy rates will go up, miscarriage rates will go down and we will say goodbye to IVF twins.   And if the system works really well, in the end this will save money because people will need fewer IVF cycles for success (not to mention the drug cost savings if fewer cycles are needed).

Encouraging news concerning PGD is coming out of the data on miscarriage. Good PGD does decrease the rate of miscarriage. A very high percentage of miscarriages are caused by aneuploidy, which means an abnormality in the number of chromosomes present in the embryo. Just one example of aneuploidy is Down’s syndrome, which is the result of an extra chromosome 21 (also called trisomy 21).  The bulk of PGD is performed looking for aneuploidy.

The reduction of miscarriage rates after PGD has 2 important implications. One is that preventing a woman from having a miscarriage is obviously a welcome idea, as the emotional toll of pregnancy loss is significant. The second is that miscarriage takes time.  While many miscarriages occur early, many women do not suffer their loss until 7-10 weeks, later if the fetus survives to the CVS (10 weeks) or amnio (17 weeks).  When you add in the recovery time of 1-2 months before a woman can try again post-miscarriage, the total time lost could be 2-4 months. This is especially difficult in an older woman whose reproductive time is already limited.

One shortcoming of this technology is that this new method of testing requires a blastocyst. Many IVF programs are still not comfortable growing their embryos to blastocyst; they prefer transferring their embryos on day 3.  These programs will not be able to provide these new services until they become very good a growing embryos out to day 5, which for some clinics could take a very long time.

Lastly, not everyone who wants PGD is a candidate for PGD.  The group that may benefit the best from a PGD cycle is those who are above the average age for reproduction. However in this group, egg production is lower, as is the rate of good (biopsyable) blastocyst formation. So there may be the intention for PGD at cycle start, but if the egg number or embryos quality is low, the option for PGD in that cycle may be lost. Straight IVF may or may not still be a viable option, but at times even those are not possible.  I try to be positive to the end, but it is always necessary to cover all eventualities.


Well, that’s quite a bit about PGD. Thanks very much for reading.

Don’t forget to read the disclaimer from 5.17.06.

Dr. Licciardi


  • Braude P. Preimplantation diagnosis for genetic susceptibility. N Engl J Med 2006; 355(6):541-3.
  • Gutiérrez-Mateo C., Colls P., Sánchez-García J., Escudero T., Prates R., Wells D., Munné S. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011; 95: 953-958.
  • Twisk M, Mastenbroek S, van Wely M, Heineman MJ, Van der Veen F, Repping S. Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilization or intracytoplasmic sperm injection. Cochrane Database Syst Rev 2006; 25(1):CD005291.
  • Munne S, Fischer J, Warner A, Chen S, Zouves C, Cohen J, Referring Centers PGD Group. Preimplantation genetic diagnosis significantly reduces pregnancy loss in infertile couples: a multicenter study. Fertil Steril. 2006; 85(2):326-32.



Trends in Pre-implantation Genetic Diagnosis

So what are the new developments increasing interest in PGD?


The first is that there is more laboratory expertise on growing the embryos to blastocysts (see blog on blastocyst). These are embryos that have grown not 3, but 5 days in the lab.  As the embryo grows with time, the total number of cells increases from 6-8 to 30-60. Because the cell number is much higher, we can more safely remove more than on cell, maybe 3-5 cells. All of that extra DNA helps us reach much more accurate results.


The second has to do with the way we test the DNA.  The DNA amplification techniques have improved, as have the techniques for identifying important areas in the DNA.


An advantage of blastocyst biopsy is that in a good blastocyst, we can tell by looking which cells will be the embryo (the inner cell mass) and which will be the placenta (the trophectoderm- thus the term trophectoderm biopsy, also called TE biopsy for short).  Naturally, at the time of the biopsy, it is the placental cells we take as not to interfere with the fetal cells. Taking a few extra cells from the placenta is much less harmful than taking cells needed for the fetus.


Another advantage of performing the biopsy on day 5 is that mosaicism is much less of a problem in a blastocyst. (The last blog explains mosacism), The cells we get on day 5 more accurately reflect the DNA status of the embryo as a whole.   We are not sure why mosacisism is less of a problem on day 5, it may be that it’s common for an embryo to start off with some abnormal cells, but with time the normal cells outgrow the bad ones.


One downside to TE biopsy is that in most cases, the results of the biopsy take 1-3 days to process. We do not want a day 5 embryo growing extra days in the lab waiting for the results. Therefore, we usually freeze the blastocysts just after the biopsy, get the results a few days later, and then have the patient come back the next month for a thaw cycle.  This gives the patient a one month delay, which may or not be an important factor, depending on the expectations of the patient.  There are some programs that offer same cycle PGD biopsy and transfer, but usually those women with only the fastest growing and best looking are candidates for the same cycle process.


Patients are naturally concerned about embryo freezing, as is it is mostly true that embryos in a frozen cycle have lower pregnancy rates than when the embryos are transferred when fresh.  However, there may be some very explainable reasons why freezing normal blastocysts may not be problematic.  In a standard fresh cycle, the best embryos are transferred. While the extra embryos may look very good, the best ones go back originally, leaving the left overs for the frozen cycle, and this could explain the lower rates.  In a PGD cycle, even the best embryos are frozen, upping the odds for a successful cycle after the thaw.  Also, at least from what I have seen, normal embryos seem to thaw and freeze very well. So if you know you have a good one in the freezer odds are good that it will survive the freeze and thaw and have good potential for success.


In addition, freezing techniques have really blossomed in the past few years.  Most programs have moved to vitrification (the fast freezing method), and embryos do have better outcomes when preserved this way.


On top of all of this, there are some doctors who believe that all embryos, even without biopsy, should be frozen. There is the revival of an old theory that the endometrium of an IVF cycle is not ideal for implantation, possibly due to excessive estrogen levels caused by the fertility drugs. Others feel that the relationship between the timing of ovulation and embryo transfer is altered with IVF, lowering the ability of the embryo to implant.  I’m not so sure about theses theories, but I am raising the point here to say that a frozen embryo cycle is not necessarily a bad thing.


There are still a few more points about PGD that I will go over next time.


Thanks for reading, and don’t forget the disclaimer 5.17.06


Dr. Licciardi



  • Braude P. Preimplantation diagnosis for genetic susceptibility. N Engl J Med 2006; 355(6):541-3.
  • Gutiérrez-Mateo C., Colls P., Sánchez-García J., Escudero T., Prates R., Wells D., Munné S. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011; 95: 953-958.
  • Twisk M, Mastenbroek S, van Wely M, Heineman MJ, Van der Veen F, Repping S. Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilization or intracytoplasmic sperm injection. Cochrane Database Syst Rev 2006; 25(1):CD005291.
  • Munne S, Fischer J, Warner A, Chen S, Zouves C, Cohen J, Referring Centers PGD Group. Preimplantation genetic diagnosis significantly reduces pregnancy loss in infertile couples: a multicenter study. Fertil Steril. 2006; 85(2):326-32.


Cancelling IVF, Converting to IUI, and a Few Other Things.

What if you are on drugs for an IVF cycle and there is a low number of follicles? Should you do cancel and have an iui (provided there is sperm and at least one tube is open) or should you have the retrieval?

The number of eggs is less important the younger you are. So at age 31, 4 eggs still results in an excellent pregnancy rate. At age 41, 3 eggs is much worse than having 10. So is there a “cutoff” number? Not really, and if there is it will vary from program to program. There are no strict guidelines for who should be retrieved and who should not. In most cases, when there are 1-4 eggs developing, the doctor will say that the odds with IVF become so low that it’s not worth the cost and effort of the IVF, so the better thing to do is the iui.

There was a very interesting paper presented at the last meeting of the American Society of Reproductive Medicine. One IVF center compared the pregnancy rates for women who decided to cancel to iui vs. those who decided to have the retrieval, when 1-2 eggs were present. Those women who continued on and had their retrieval had a higher pregnancy rate than those who had the iui. Now the rates for IVF were still in the single digits, but the rates were better than the iui numbers. So IVF is better than cancelling to IVF, but the odds of getting pregnant from that retrieval is quite low. Would you have a retrieval if your odds were 2% with iui but 5% with IVF? Some patients would, some would not.

I have mentioned before that we all know or suspect that there are IVF programs who cancel the 3 eggers because they are worried about lowering their statistics. I think there is less of that going on. I see patients being informed of their odds and then be allowed to make the decision. And the threshold may be different depending on your perceived potential. If it’s your first try and the doctor really thinks that a different protocol will do you better, cancelling makes more sense. If you have been cancelled for 3 follicles, and after protocol changes you make 3 again, well you make 3 and that’s it, so retrieve away.

What about multiple egg issues at the same time?
For example there are some women who make a large percentage if immature eggs, have low fertilization rates and have low embryo quality. Others have different mixes such as high rates of polyspermy, low rates of normal fertilization and poor embryo development. Others have mature eggs that do not fertilize without ICSI despite normal sperm, and then poor embryo quality. Is there one basic problem with the eggs that is leading to a completely bad scenario? This may be, but we don’t know what it is. The reality is that most women with a large percentage of immature eggs do pretty well with the ones that are mature. And women who have polyspermy, do pretty well with the eggs that fertilized normally. But for some of you, everything seems to be wrong despite protocol changes and changes with icsi, in hcg timing and day of transfer. Yes there may be a missing link resulting in multiple problems at once. It’s a matter of trying a few times and keeping all of your options open.

Persistently elevated prolactin levels need a full workup, which usually means an MRI of the pituitary.

What if your FSH is a little high and your AMH is a little low, but you have a good number of resting follicles and make a good number of eggs for IVF?
Those hormone tests are more about predicting egg number than quality. I believe the numbers have less of an effect on egg quality. Others may disagree, ask your doctor.

What if you suffer from autoimmune disorders and are having trouble conceiving? Is there a relationship?
Overall women with autoimmune disorders seem to be as fertile as anyone else. High risk OB practices are busy dealing with pregnancy complications of Lupus, RA and others. However, there are so many unknown factors related to fertility and the immune system, it does make one think that there may be a relationship when pregnancy is not occurring. I have seen a few cases of relatively young women with autoimmune disease who are very poor responders. I think there is a relationship between their disease and antibodies to their ovaries. Unfortunately there is still no good test to measure ovarian antibodies. There are good tests for thyroid antibodies, adrenal gland antibodies, but not yet for the ovary.

Here are a couple sperm questions.
Sperm counts that go from 100 million to zero then up again? He needs to be evaluated for intermittent obstruction: a blockage somewhere that occurs some of the time. Also could be intermittent retrograde ejaculation. Send him to a reproductive endocrinologist.

What if the urologist finds low counts and motility and does a thorough workup and tells you the numbers are what they are, can’t be increased and recommends IVF. You are always welcome to get another opinion, but it sounds like this guy is honest and he is telling you what most men are told. I believe in seeing a urologist because sometimes surprises are identified, but in most cases of very low counts and or motility, nothing is found and the only answer is IVF.

Yes ovarian hyperstimulation and ovarian torsion are related.
Torsion becomes more likely as the ovaries enlarge and become heavier. This increases the chances of the ovary rolling over and twisting on its stalk. Torsion with clomid can happen, but it’s much rarer because the ovaries have fewer follies and are smaller and stay lighter.

Thanks again for reading and please read disclaimer 5/17/06.
Dr. Licciardi

If You Live in the State of New York, the Government May Help Pay for Your IVF.

I am sorry that this blog only applies to a small percentage of you: residents of the State of New York, but the message is so important I feel I need to spread the word.

New York State gives money to those who need it for IVF. The program is called the New York State Infertility Grant Program, or “The Grant” for short. To be eligible you must be 21-44 years of age, a New York State resident and have a combined household income of less than 200,000. You must show your most recent federal and NYS tax returns. If your income is 100,000, the state will pay for approximately ½ your cycle. If you make less they pay for more; if you make more they pay for less. This is approximately how it works. Our billing managers can tell you more about the details and any other costs.

Also, you must have commercial health insurance. Any one will do except Medicare, Medicaid, and HealthPlus; these are not commercial carriers.

You need to have had 4 cycles of ovulation induction (OI), unless you are not a candidate for OI due to tubal disease or severe male factor infertility.

There are a few other rules. Start by going to and click under financial information. On the left you will see NYS Infertility Project. On that page you will find everything you need to get started. You can also click a link to the New York Department of Health.

It’s easy to fill out the application and it does not take very long for the application to get reviewed.

Some patients have come to our office knowing about the grant; in fact the grant is what brought them to see us. In other cases, patients are very happily surprised when I tell them such a grant exists. I am even more surprised that they had not heard of this great opportunity.

Only certain IVF centers are approved by NYS to be grant sites, and those centers are listed on the New York State Department of Health website. You can hit the link from the NYU site. I want to also say that I am not the only doctor in our office that can work with you as a patient on the grant. Drs Noyes and Berkeley would be happy to see you too.

So if you need IVF, live in New York, and have commercial health insurance, IVF may have just become less expensive for you.

I’ll try to get another blog out within the week.

Dr. Licciardi

Minimal Stimulation

Does taking a lower dose of fertility drugs improve your chances of becoming pregnant with IVF? I think not, but I can tell you of some exceptions. Mostly I have had some very good experiences with patients confirming that lower is not better.

How do I know?

Well, as it turns out over the past few years I have been seeing more patients from Europe. There are a few things that have contributed to this. One is the blog. It’s been fun getting e-mails and seeing patients from around the world. The second is the exchange rate: for some, New York is now a “reproductive tourism” destination. The third has to do with laws in Italy, Germany and other countries that restrict IVF and donor egg.

Anyway, the European doctors give their patients a much lower dose of drug that we do in the US. Part of this is due to the fact that they may not be allowed to fertilize more than a few eggs, so they don’t bother trying to get more. Another reason may just be due to a general philosophy that less drug is better.

So the typical European woman that sees me has done IVF many times, usually making just a few eggs on a lower dose of drug. Unless she has had a fantastic response, I increase the dose for her IVF cycle with me. In most cases, the egg yield is much higher (still in a safe range) and the pregnancy rate in these women is very high. So the point is that in these women, a higher dose is better because it increases the number of eggs, and therefore there are more embryos available for selection.

Do some women make more eggs with a lower dose? I have seen a few cases of this. This is typically the woman who was given a lower dose for IUI and develops more follicles than she did with her higher dose IVF cycle. Should we go back to the lower dose for the next IVF cycle? It’s a gamble and it takes a little courage. It is really hard emotionally to go into an “experimental” IVF cycle.

Many patients considering this have had many attempts and may not be ready to give up a couple months for a “let’s see” cycle. If you and your doctor can stomach it, you can give it a try. I can tell you I have one woman, who had been through many cycles, who wanted to give it a go, and she did better with less. Was that her month to make more, regardless of drug dose? Who knows, but let’s give her the credit.

But I do think starting on a minimal dose, just because your doctor thinks it’s more homeopathic and will result in better quality embryos, is not correct. To return to our common theme, if one of the self proclaimed experts in minimal stimulation wants to take 100 women and give them minimal stimulation, and take another 100 and give them regular stimulation, and then show us that minimal is better, great. But until this happens we have to say that it’s not better, and may be worse for most people. I know some of you can tell me that you did minimal and got pregnant. I just feel that my experience has shown that overall, regular may be better.

Please read disclaimer 5/17/06, and thanks again, Dr. Licciardi


  • Zarek SM, Muasher SJ. Mild/minimal stimulation for in vitro fertilization: an old idea that needs to be revisited. Fertil Steril. 2011 Jun 30; 95(8):2449-55.
  • Fauser BC, Nargund G, Andersen AN, Norman R, Tarlatzis B, Boivin J, Ledger W. Mild ovarian stimulation for IVF: 10 years later. Hum Reprod. 2010 Nov; 25(11):2678-84.

Why is Progesterone Used for IVF?

Why is Progesterone Used for IVF?

Thank you Kami for the question.

In a natural cycle, progesterone is made by the corpus luteum(CL)(see blog from August 17, 2007). In most cases it’s just one, and for many millions of women around the world, this one little CL puts out enough progesterone get the job done. During IVF, there are usually many more than one CL, and therefore one might expect that there should be plenty of extra progesterone produced and available for the pregnancy. So why give more? There are 2 reasons.

The first is that the natural CL and the extra CLs that are produced during ovulation induction with insemination are different than the CL of IVF. The CLs of IVF were all disturbed by the IVF needle. The CLs from IVF all started as follicles containing eggs. At the retrieval, the needle is placed into the follicle, the egg is removed, and other cells can also be removed. The follicle is mostly fluid, but it also contains tons of cells that make up the follicle and surround the egg. These are called the granuslosa cells, and these are the cells that convert to progesterone CL cells after ovulation. So if the needle removes some of these cells, as is usually the case, the CL may not work as well and less progesterone would be produced.

The second has to do with the IVF medications. The CL makes the hormone progesterone, but the CL needs a hormone to help it perform this function. Leutinizing Hormone(LH) is the one. Yes the famous LH, of the LH surge. LH comes from the pituitary gland, and it is produce in high amounts just before ovulation to get ovulation to occur. (for IVF we use the LH substitute hCG, just to help with the timing). After ovulation, LH comes from the pituitary gland, in smaller amounts, to “leutinize” the follicle, or to get it to make the progesterone. LH is secreted throughout the luteal phase to keep the CL making progesterone. If a pregnancy occurs, the hCG from the pregnancy takes over to stimulate the CL progesterone system. If there is a problem with LH production in the luteal phase, there will be a problem with progesterone production and there will be a problem with the pregnancy.

Almost all women who undergo IVF are given a medication that causes a problem for LH production. Whether it’s Lupron or Antagon, LH production stops. Sounds bad? No it’s good, at least initially. Stopping LH means preventing a premature LH surge, which can ruin 10% of IVF cycles. In a natural pregnancy, or when doing iui, surges are fine, they cause ovulation. In IVF, we need to time the retrieval to the hour, so that a surge at the wrong time ruins everything. Therefore, we give medications to stop LH, but what they do is stop LH for a while, and this compromises the ability of the to make progesterone.

So there you have it. Progesterone may be lower than normal during IVF for 2 reasons. The second is probably more important than the first. That is, if we didn’t use the Lupron or Antagon, progesterone production would be fine for most women doing IVF. There are so many CL during IVF, a little needle disruption may not be a big deal.
Dr. Licciardi


  • van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev. 2011 Oct 5 ;(10):CD009154.
  • Licciardi FL, Kwiatkowski A, Noyes NL, Berkeley AS, Krey LL, Grifo JA. Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study. Fertil Steril. 1999 Apr; 71(4):614-8.
  • Feinberg EC, Beltsos AN, Nicolaou E, Marut EL, Uhler ML. Endometrin as luteal phase support in assisted reproduction. Fertil Steril. 2012 Nov 5. pii: S0015-0282(12)02238-8. doi: 10.1016/j.fertnstert.2012.09.019. [Epub ahead of print]
  • Engmann L, DiLuigi A, Schmidt D, Benadiva C, Maier D, Nulsen J. The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study. Fertil Steril. 2008 Mar; 89(3):554-61.