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An Individualized Approach to Ovarian Stimulation for IVF is Crucial!

Dr. Geoffrey Sher Recommends

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Understanding the Basis for Individualizing Protocols for Ovarian Stimulation:
In order for any organism to attain an optimal state of maturation (ripening) it must first undergo full growth and development. A fruit plucked from a tree before having developed fully or a poorly developed fruit might still ripen (mature) on the shelf and might even appear as enticing as one that had previously undergone proper development, but it will lack the same quality. The same principles apply to the development and maturation of human eggs. Proper development as well as precise timing in the initiation of egg maturation with LH or hCG is no less crucial to optimal egg maturation, fertilization and ultimately to embryo quality. In fact, in cases where egg maturation is improperly timed (LH or hCG is released/given too early, i.e. prematurely or too late, i.e. post-maturely) there is an increased risk of aneuploidy (structural and numerical chromosomal abnormalities) leading to compromised reproductive performance.

The potential for a woman’s eggs to undergo orderly maturation, successful fertilization, and subsequent progression to “good quality embryos” that are capable of producing healthy offspring, is in large part, genetically determined. However, the expression of such potential is profoundly susceptible to numerous extrinsic influences, especially to intra-ovarian hormonal changes during the pre-ovulatory phase of the cycle.

During the normal ovulation cycle, ovarian hormonal changes are orchestrated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, while small amounts of ovarian male hormones (predominantly testosterone) are essential to enhance egg and follicle development, over-exposure to excessive amounts of the same hormones can seriously compromise egg (and subsequently, also embryo) quality. It follows that protocols for ovarian stimulation should be geared towards optimizing follicle and egg development while avoiding overexposure to ovarian male hormones. The fulfillment of these objectives requires a very strategic and individualized approach to ovarian stimulation and precise timing of the human chorionic gonadotropin (hCG) “trigger.”

It is important to recognize that the pituitary gonadotropins, LH and FSH, while both playing a pivotal role in follicle development, have different primary sites of action in the ovary. The action of FSH is mainly directed at the cells that line the inside of the follicles (i.e. granulosa cells). LH, on the other hand, acts primarily on the connective tissue that surrounds the follicles (i.e. the ovarian stroma or theca) to compel the production of male hormones. Only a small amount of these hormones (predominantly testosterone) is necessary for optimal estrogen production. Overproduction has a deleterious effect on granulosa cell activity, follicle growth/development, egg maturation, fertilization potential and subsequent embryo quality. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.
In conditions such as polycystic ovarian syndrome (PCOS), which is characterized by increased blood LH levels, there is also an increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” and inadequate endometrial development are often features of this condition. The use of LH-containing preparations such as Repronex might further aggravate this effect. Thus we strongly recommend against the exclusive use of such products, in PCOS patients, preferring FSH-dominant products such as Folistim and Gonal F. While it would seem prudent to limit LH exposure in all cases of ovarian stimulation, this appears to be more relevant in older women, who tend to be more sensitive to LH

Preparing for Ovarian Stimulation:
Before embarking on ovarian stimulation it is essential to try and define the woman’s ovarian reserve (i.e., the number of eggs still available in her ovaries). Determination of the ovarian reserve will assist in defining the protocol of ovarian stimulation that would most safely yield the optimum number and quality of follicles/eggs in a given case. The ovarian reserve can best be assessed by determining the woman’s blood FSH and estradiol (E2) measurement on the 3rd day of a spontaneous menstrual cycle and by evaluating the manner in which she responded to a most recent cycle of treatment. Other blood tests that can also be selectively used to assist in assessing ovarian reserve are measurement of blood antimullerian hormone and inhibin B levels.
Once the ideal stimulation protocol is selected, the next step is to choose a suitable time for IVF treatment. For women who require a repeated cycle it is advisable that at least one-month be allowed to elapse (“resting cycle”) between IVF treatments, in order to allow the ovaries to fully recover from the preceding stimulation.

It is both clinically beneficial as well as convenient to launch IVF cycles with the woman having been on at least 10 days of combined birth control pill (BCP) such as Desogen or Orthonovum 135. A word of warning: one often hears the expressed opinion that the BCP suppresses response to ovarian stimulation. This is NOT the case, provided that the BCP is overlapped with administration of a GnRH agonist (e.g. Lupron, Buserelin) for several days leading up to the start of menstruation and the initiation of ovarian stimulation cycle with fertility drugs. If the latter precaution is not taken, and the cycle of stimulation is initiated coming directly off the BCP the response will often be blunted and subsequent egg quality could be adversely affected. The explanation for this is that in natural (unstimulated) as well as in cycles stimulated with fertility drugs, the ability to properly respond to FSH stimulation is dependent on the recruited follicles having reached the antral phase of development by the time the cycle begins (or similarly, stimulation with fertility dugs is initiated).

The transition of early primary follicles to develop into antral follicles (AF) takes a 3-6 day period of a sustained rise in blood FSH prior to the onset of menstruation.. The BCP (as well as prolonged administration of estrogen/progesterone) suppresses FSH. This suppression needs to be countered by artificially causing blood FSH levels to rise otherwise development will not take place. GnRH agonists (e.g. Lupron, Buserelin, Nafarelin and Synarel) do this by triggering a rapid increase in FSH production. Thus, by overlapping the BCP with an agonist for a few days prior to menstruation the early recruited follicles are able to complete their developmental drive to the AF stage and as such, be ready to respond appropriately to optimal ovarian stimulation. Using this approach, the timing of the initiation of the IVF treatment cycle can readily and safely be regulated and controlled by varying the length of time that the woman is on the BCP.

It is also important that there be no functional ovarian cysts at the time ovarian stimulation commences. To insure this, the patients can undergo an ultrasound examination while on the BCP or at the onset of menses immediately prior to initiating ovarian stimulation. At the onset of bleeding a measurement of blood estradiol (E2) is done to insure that it is low enough (under 70 pg/ml) to start administering the fertility drugs. The commonest cause of an elevated blood E2 level around this time is the existence of one or more ovarian follicular cysts. These should be allowed to absorb, or be aspirated as soon as possible (I personally prefer to aspirate cysts under local anesthesia, on the spot COH.

Unlike GnRH agonists that exert their LH (and FSH) lowering effect by exhausting the pituitary gland of its over 4-7 days GnRH antagonists (such as Ganirelix, Orgalutron, Cetrotide ) do so directly and immediately (within a few hours of administration).Thus both agonists and antagonists of GnRH both serve to establish a “low LH environment” in which follicular and egg development can proceed optimally.

The Choice of Gonadotropin Products to be Prescribed:
The recent availability of DNA-recombinant FSH and LH gonadotropins has made this an easy choice. In my opinion, it is no longer necessary to prescribe urinary-derived menotropins where there could be significant variations in batch to batch biological potency and thus in response to stimulation. There is also (in my opinion) little advantage in using combined FSH/LH urinary-derived products where the additional LH contained in the preparation might in some cases compromise rather than enhance follicle and egg development. Accordingly, with few exceptions I personally only advocate the use of pure DNA-recombinant FSH (Folistim, Puregon and Gonal-F) and LH (Luveris) products for my IVF patients. The exception to this rule is when it comes to prescribing an hCG product. Here I advocate the use of urinary-derived hCG (Profasi, Pregnyl and Novarel) over the DNA recombinant hCG (Ovidrel). In my opinion, at the suggested dosage of administration, Ovidrel lacks the required biological potency. In order to optimize its effect the dosage would have to be doubled and this increases the cost. Besides, the urinary derived hCG products are very effective.

The Protocols:
1. Long GnRH Agonist Protocols: The most commonly prescribed protocol for agonist/gonadotropin administration is the so-called “long protocol”. An agonist (usually, Lupron) is given either in a natural cycle, starting a 5-7 days prior to menstruation or is overlapped with the BCP for two days whereupon the latter is stopped and the Lupron, continued until menstruation ensues. The agonist precipitates a rapid rise in FSH and LH level, which is rapidly followed by a precipitous decline in the blood level of both, to near zero. This is followed by uterine withdrawal bleeding (menstruation) within 5-7 days of starting the agonist treatment, whereupon gonadotropin treatment is initiated (preferably within 7-10 days of the onset of menses) while daily Lupron injections continue, to ensure a relatively “low LH- environment”. Gonadotropin administration continues until the hCG trigger.

2. GnRH-agonist(“micro-flare”) protocols: Another approach to COH is by way of so-called “microflare protocols”. This involves initiating gonadotropin therapy simultaneously with the administration of GnRH agonist. The intent is to deliberately allow Lupron to affect an initial surge (“flare”) in pituitary FSH release so as to augment ovarian response to the gonadotropin medication. Unfortunately, this approach represents “a double edged sword” as the resulting increased release of FSH is likely to be accompanied by a concomitant (excessive) rise in LH levels that could evoke excessive production of male hormone by the ovarian stroma. The latter in turn could potentially compromise egg quality, especially in women over 39 years of age, women with diminished ovarian reserve, and in women with polycystic ovarian syndrome (PCOS) – all of whose ovaries have increased sensitivity to LH. In this way, “microflare protocols” can potentially hinder egg/embryo development and reduce IVF success rates. While microflare protocols usually are not harmful in younger women and those with normal ovarian reserve, I personally avoid this approach altogether for safety sake.

3. GnRH antagonist protocols: The use of GnRH antagonists as currently prescribed in ovarian stimulation cycles (i.e. the administration of 250mcg daily starting on the 6th or 7th day of stimulation with gonadotropins) may be problematic, especially in women over 39 yrs., women with diminished ovarian reserve (i.e. “poor responders” to gonadotropins), and women with PCOS. Such women tend to have higher levels of LH to start with and as such the initiation of LH suppression with GnRH antagonists so late in the cycle (usually on day 6-7) of stimulation fails to suppress LH early enough to avoid compromising egg development. This can adversely influence egg/embryo quality and endometrial development. As is the case with the “microflare”approach (see above) the use of GnRH antagonist protocols in younger women who have normal ovarian reserve, is acceptable. Again, for reasons of caution, and because I see no benefit in doing so, I personally never prescribe this approach for my patients.

Presumably, the reason for the suggested mid-follicular initiation of high dose GnRH antagonist is to prevent the occurrence of the so called “premature LH surge”, which is known to be associated with “follicular exhaustion” and poor egg/embryo quality. However the term “premature LH surge” is a misnomer and the concept of this being a “terminal event” or an isolated insult is erroneous. In fact, the event is the culmination (end point) of the progressive escalation in LH (“a staircase effect”) which results in increasing ovarian stromal activation with commensurate growing androgen production. Trying to improve ovarian response and protect against follicular exhaustion by administering GnRH antagonists during the final few days of ovarian stimulation is like trying to prevent a shipwreck by by removing the tip of an iceberg.

4. The agonist/antagonist conversion protocol (A/ACP): With a few (notable) exceptions I preferentially advocate this protocol for many of my patients. With the A/ACP, as with the long protocol (see above) the woman again prepares to launch her stimulation cycle by taking a BCP for at least ten days before overlapping with an agonist such as Lupron. However, when about 5-7 days later her menstruation starts, she supplants the agonist with a half dosage (125mg) of an antagonist (e.g. Ganirelix, Orgalutron or Cetrotide).Within a few days of this switch-over, gonadotropin stimulation is commenced. Both the antagonist and the gonadotropins are then continued until the hCG trigger. The purpose in switching from agonist to antagonist is to intentionally allow only a very small amount of the woman’s own pituitary LH to enter her blood and reach her ovaries, while at the same time preventing a large amount of LH from reaching her ovaries. This is because while a small amount of LH is essential to promote and optimize FSH-induced follicular growth and egg maturation, a large concentration of LH can trigger over-production of ovarian stromal testosterone, with an adverse effect of follicle/egg/embryo quality. Moreover, since testosterone also down-regulates estrogen receptors in the endometrium, an excess of testosterone can also have an adverse effect on endometrial growth. Also, since agonists might suppress some ovarian response to the gonadotropin stimulation, antagonists do not do so. It is for this reason that the A/ACP is so well suited to older women and those with some degree of diminished ovarian reserve.

The follicles/eggs of women on GnRH-agonist “micro-flare protocols” can be exposed to exaggerated agonist-induced LH release, (the “flare effect”) while the follicles/eggs of women, who receive GnRH antagonists starting 6-8 days following the initiation of stimulation with gonadotropins can likewise be exposed to pituitary LH-induced ovarian male hormones (especially testosterone). While this is not necessarily problematic in younger women and those with adequate ovarian reserve (“normal responders”) it could be decidedly prejudicial in “poor responders” and older women where there is increased follicle and egg vulnerability to high local male hormone levels.

5. Long protocol (or A/ACP) with estrogen priming: Women who have a significant degree of diminished ovarian reserve are first given GnRH agonist for a number of days to effect pituitary down-regulation. Upon post-BCP/agonist-induced menstruation, the dosage of GnRH agonist is drastically lowered (or commonly is supplanted by 125mg daily of an antagonist) and the woman is given twice-weekly injections of 2-4mg of estradiol valerate (E2V) for a period of 7-10 days. Ovarian stimulation is then initiated using a relatively high dosage of an FSH-dominant gonadotropins such as Folistim, Puregon or Gonal F for a few days, whereupon the dosage is reduced and a small amount of DNA-recombinant LH (Luveris) is added daily. Both the FSH and the LH are then continued along with daily administration of GnRH agonist (or antagonist) until the “hCG trigger”. The reason for the “estrogen priming” is because it enhances follicle response to FSH and also helps optimize the uterine lining.

We recently reported in a prestigious medical Journal on results using the A/ACP with estrogen priming in older women and women with diminished ovarian reserve where the approach has proven to be most advantageous.

There is one potential drawback to the use of the A/ACP. We have learned that prolonged use of a GnRH antagonist throughout the ovarian stimulation process can compromise the predictive value of serial plasma E2 measurements to evaluate follicle growth and development. It appears that when the antagonist is given throughout stimulation, the blood E2 levels tend to be significantly lower than when the agonist alone is used or where antagonist treatment is only commenced 5-7 days into the ovarian stimulation process. The reason for this is presently unclear. Accordingly, when the A/ACP is employed, we rely more on follicle size monitoring than on serial blood E2 trends to assess progress. Also, younger women (under 30 years) and women with absent, irregular or dysfunctional ovulation, and those with polycystic ovarian syndrome are at risk of developing life-threatening severe ovarian hyperstimulation. The prediction of this condition requires daily access to accurate blood E2 levels. Accordingly we currently tend to refrain from prescribing the A/ACP in such cases, preferring instead use the “standard long-protocol” approach.

Tags: Controlled Ovarian Hyperstimulation, FSH, IVF Authority, LH, Polycystic ovary syndrome (PCOS)

34 Responses to “An Individualized Approach to Ovarian Stimulation for IVF is Crucial!”

kim says:

November 22, 2010 at 9:04 pm

Great information here, thank you! Sheds some light on why my first two IVF cycles (with PCOS) were such a mess.

Reply
Geoffrey Sher, MD says:

November 23, 2010 at 11:20 am

Thanks,

Feel free to call 800-780-7437 if you wish to discuss your case with me.

Geoff Sher

Reply
Kathleen says:

November 23, 2010 at 3:35 pm

Oh my gosh! This is fantastic. I've been wondering why my last cycle sucked so bad by my first one was great. The difference in protocol likely explains a lot of it! Thank you sharing this well written explanation!

Reply
Geoffrey Sher, MD says:

November 23, 2010 at 5:36 pm

Thanks so much Kathleen!

Geoff Sher

Reply
Richa says:

April 7, 2011 at 5:02 am

Hello Dr Sher….thnks so much for this info on PCOS !!! I wanted to discuss my case.
I am 30 yr old female. I have recently been diagnosed with PCOS though I have been suffering with irregular periods, acne and facial hair since many yrs. My free androgen level was 7.5. I did conceive naturally but had a missed miscarriage at 9 weeks as the baby didnt develop a heartbeat. This is my second mc in a row due to the same cause. Could these mc be related to PCOS? Could I take any medication to help me have a baby? What shud be normal androgen level ?

Thanks a ton !!!
Richa

Reply
Geoffrey Sher, MD says:

April 8, 2011 at 6:23 pm

Dear Richa,

So sorry for your miscarriages.

You need to consider whether the losses were due to egg issues (PCOS women tend to produce more chromosomally abnormal eggs, especially when the wrong protocol of ovarian stimulation is used). Also, don't automatically exclude an immunologic implantation dysfunction. You need to be fully and thoroughly evaluated at tghis time.

Feel free to call and set up a free telep[hone conference with me to discuss.

Geoff Sher

Reply
Kishore says:

April 8, 2011 at 10:39 pm

Hi Dr Sher,
My wife and I are going through our second cycle of ivf. I dint know if it was the long or short protocol. She was given gonalF starting from the second day and then certitude starting from the 5-6 th day. She was given the gnrh on day 15 and egg retrieval on day 17. The doc has asked us to come on the 5th day after the retrieval. I am starting the count one day after retrieval. Is this the normal procedure. Is it sure that he would be transferring blastocysts only. So the chance are better this time?

The last time my wife had a little bit of OHSS and because of high e2 levels they had to coast for 2 days.

Thanks Kishore

Reply
Miranda says:

April 18, 2011 at 1:05 am

Hello,
I just had an IVF treatment which my doctor described as co-flare 3+3 protocol. This is what happened:
Day 2 Results:
FSH 6.6
E2 86 pg
From Day 3 to 14 I had 3 Fostimon (75ml) and 3 Merional (75ml) every day, plus suprefact.

Even though it seemed that I was starting with 7-8 follicles only 4 developed. The doctor was only able to get 2 eggs. They told me they were not good for fertilization. I am 38 years old.

It seems that I am not reacting well to this therapy. Plus, whenever I had taken Fostimon before my FSH level in the next cycle shot to over 20 and then it was back to normal.

Please help me! Your posts make so much sense but I am lost and hopeless!!!

I just signed up for a consultation with you Dr Sher.

thank you,
Miranda

Reply
Geoffrey Sher, MD says:

April 18, 2011 at 10:53 am

It is the "Flare protocol that you were on. I suggest you read the information on this very blog relating to this protocol.Since (in spitre of a normal FSH) you responded so poorly, I suspect that in actual fact you might have diminished ovarian reserve and if so this, in my opinion is not the ideal protocol for you.

You need to repeat the day 3 FSH and E2 and at the same time do an AMH test as well as an Inhibin B.

Geoff Sher

Reply
Miranda says:

April 21, 2011 at 12:57 am

Thank you so much Dr Sher.

This really kills me but I will do the tests. So, I understand that depending on whether I have 'some' or 'severe' form of diminished ovarian reserve I would choose either 4 or 5.

This is the most useful information I have read in the past 2 years of trying to understand what is happening to me!

thank you,
Miranda

Reply
Geoffrey Sher, MD says:

April 25, 2011 at 10:47 am

Good luck!

Geoff Sher

Reply
Wendy says:

April 27, 2011 at 6:39 pm

This information is extremely helpful. I posted my situation under the name "fortyplus" on the SIRM West blog. I would love your opinion on whether or not you think I may have a chance of conceiving with my own eggs. I detailed my cycle results, I was on Gonal F, Menopur, and Cetrotide for cycles 1 and 3, and a Lupron protocol for the second. Thank you

Reply
Geoffrey Sher, MD says:

April 28, 2011 at 5:55 pm

I think we should talk. Consider callling 800-780-7437 and setting up a free telephone consultation…at your convenience.

Geoff Sher

Reply
Kamya says:

June 24, 2011 at 12:44 am

hello Dr Sher,
Thanks so much for your information regarding embryo quality depending on stimulation protocals. I am staying in johannesburg , South Africa. I am 29 years old and my husband is 31.I have mild PCOS. My DH's sperm count is very low and thats why our RE asked us to start for ICSI. In Dec 2010 we started our first ICSI. Since that time we have 2 failed ICSI cycles both ended up with cancelled embryo transfer as no embryo made uptp balstocyst stage. After both the cycles my RE said it was due to the poor egg quality. He said the same as you that viability of an embryo depends on how good eggs are.Now he is saying to start Co-Q, stamingro , Royal jelly , Vit-c , vit D etc to improve my egg quality and to go for 3 sittings of acupuncture one month prior to next ICSI. I am very much confused what to do now as I am not that old to have poor egg quality. In my both failed ICSI cyles no. of eggs retreived were 27 and 20 respectively.

First failed ICSI stimulation protocol:
1.Down regulation with lucrin from 21st day of my cycle.

2. Started 2 -GonalF and 1 Luveris from the first day of my menstruation.

3. First scan after5 days , then 7 days .

4. E2 levels were checked, Ovidrel shot on 8th day.

5. 27 Eggs were collected on 10th day

6. Out of which 14 fertilized and finally noone could make up to blast stage for transfer.

Second failed ICSI stimulation protocol:

1. Scan on 3rd of my menstruation cycle to make sure there is no cyst.

2. started 2 Gonalfs and 1 luveris from day 3.

3.From 6th day 1 cetriotide also started with Gonal f and Luveris.

4. U/s on 7th day ..

5. On 8th day E2 checked and then again 2 ovidral inj given for ER after 36hrs.

6. 20 eggs were collected out of which only 13 were mature and 8 were fertilized finally. But once again onone could make upto blast stage again.

I am really upset Doctor Sher. Dont know what to do now. Your advice is welcome whole heartedly.

Thanks
Kamya

Reply
LifeOfE says:

May 25, 2012 at 12:20 pm

Dr. Sher, on the a/acp w/estrogen priming protocol, what days are best to start the BCP? In other words is there a period or day in cycle where the follicles have had too much time and too much exposure to FSH? Thank you!

Reply
- admin says:
  
  May 26, 2012 at 5:35 am
  
  The BCP should start before day 6 of the period, ideally.
  
  Good luck!
  
  Geoff Sher
  
  Reply
andrea brown says:

July 31, 2012 at 3:44 pm

HI Dr Sher, I live in Australia but if i lived in the US i would definately be coming to see you for IVF. I have used your blog as a basis for all my understanding on what I am going through while TTC.
I have my first IVF appointment and just got my blood tests back and was shocked to see that my AMH level is 114.5pmol/L… that is very very high right?? I dont have any other indicators of PCOS except that I do nto ovulate regularly at all but BMI is 20 and i have no facial hair/acne problems.
What ovarian stimulation protocol would you recomend for someone with such a high AMH?

Reply
- Geoffrey Sher says:
  
  August 1, 2012 at 3:27 pm
  
  The fact that you have no physical characteristics does not rule out PCOS. You obviously need a very low stimulation. Go to the articles on this blog entitled “An individualized approach to ovarian stimulation for IVF”; “PCOS”; “Ovarian Hyperstimulation syndrome”; and “Prolonged coasting”.
  
  Good luck!
  
  Geoff Sher
  
  Reply
Kate says:

December 15, 2012 at 1:02 am

Dear Dr Sher
I just went through my first IVF cycle and did not response well – only 5 follicles and one egg retrieved. My doctor did not initially sense a DOR problem (I’m 33, AMH 16, and normal FSH levels), and the focus was on my husband who has azoospemia, so that was considered our biggest hurdle (now we are hoping to do IVF with donor sperm). It wasn’t until my scans during the follicle development stage that he mentioned he was surprised I wasn’t responding to the drugs and that DOR might be an issue. In the end I went through the ER hoping there would be 5 eggs, which could be frozen. There was only 1 retrieved.
Based on your article above, I think I was on a protocol similar to the Long GnRH Agonist (which I guess might have been appropriate anyway given the DOR). My protocol was down regulation on BC for 19 days, overlapping with Synarel (continued thru until trigger), followed by Gonal F (250 iu first 3 days, increased to 450 iu for another 8 days), then the ovidrel (250) hcg trigger. Based on your article this sounds like the better protocol for patients with DOR and if I didn’t respond to that, now what should be my next steps?
Kind regards
Kate

Reply
- Geoffrey Sher says:
  
  December 15, 2012 at 8:41 pm
  
  Sounds that way…however, in my opinion, it is best to start at a higher dosage of FSH and then drop…not the other way round. That gives far better response. I also do not favor the use of nasal GnRHa (*Synarel). The parenteral equivalent (Lupron or Buserelin) is more evenly absorbed in my opinion. Also, in my opinion, you need 500mcg of Ovidrel to obtain the ideal biological effect….250mcg might not be enough….. Frankly, 10,00U of Pregnyl, Novarel or Profasi does just as well and at a much lower cost.
  
  I would love to review your case with you. Feel free to call 702-699-7437 if you wish to discuss your case with me via Skype or telephone (preferably the former).
  
  Geoff Sher
  
  Reply
- Geoffrey Sher says:
  
  December 15, 2012 at 9:36 pm
  
  Hi kate,
  
  I agree with the long protocol in your case but:
  
  1. I am not a fan of nasal GnRHa (Nafarelin or Synarel) because it is poorly absorbed. I favour the use of I.M. GnRHa such as Lupron and Buserelin.
  
  2. I personally feel that it is better to start stimulating with a high dosage of FSH and then reduce the dosage after a few days…Not the other way round.
  
  3. In my opinion, 250mcg of hCGr (Ovidrel) is too low a dose to have optimal biological effect. 500mcg is perhaps better. However, I still prescribe urinary hCH 10,00U (e.g. Novarel, Pregnyl and profasi).
  
  Please go to the home page of this blog (www.IVFauthority.com ). When you get to the look for a “search bar” in the upper right hand corner. Type in the following subjects into the bar and it will take you to all the relevant articles I posted there.
  
   “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)
   “Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”
   “Agonist/Antagonist Conversion Protocol”
   “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
   “A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
  Feel free to call 800-780-7437 or 702-699-7437 to arrange a telephone or Skype consultation (free of charge to those who reside in the United States or Canada) so we can discuss your case in detail.. While an audiovisual (Skype) interaction is much more personable and preferable than a discussion by telephone, either will suffice.
  
  Geoff Sher
  
  Reply
Fiona says:

January 19, 2013 at 2:05 pm

Thanks for writing this article Dr Sher. It is really helpfull and detailed, it has definitely educated me a lot more on the process.

Iam 34 years old, In my last IVF cycle my protocol was starting on BCP for about 14 days, then started on 0.5ml of Lupron and stoping BCP after 4 days. Then stimulating with 150iu of Fostimon for the first 3 days, on day 4 started on 75iu of Merionel (LH), and reduced fostimon to 75iu until trigger with pregnyl. I had 8 eggs retrived all fertilized 5 went to blast, 2 were put back and 2 frozen. I have regular period, normal FSH and AMH and have a tendency to over respond(my first IVF i had 18 eggs retrieved). I did get pregnant in this cycle.

I am about to go through another cycle now, with identical protocol as my last cycle. I am concerned that the amount of LH in my protocol may be reducing the quality of my Embryos. Do you think this amount of LH 75iu launched at 4th days of stimulation is too much?

Your advice would be greatly.

Thanks for your advice.

Regards
Fiona

Reply
- Geoffrey Sher says:
  
  January 19, 2013 at 7:13 pm
  
  Thank you Fiona. However, I doubt that at your age with what sounds like normal ovarian reserve, that the menotropins you are on will harm your eggs through excessive exposure to LH. However, there could be other explanations for your failed cycle. Might I suggest you call 702-699-7437b and set up a nfree consultation by phone or Skype with me so we can discuss in detail.
  
  Good luck!
  
  Geoff Sher
  
  Reply
Angela says:

April 9, 2013 at 10:26 am

Very interesting article! Thank you Dr Sher!
On the A/ACP protocol do we take the last dose of 125mg antagonist in the morning of HCG trigger day ( as it is the case with the antagonist protocol ) or the half dose is last taken the day before HCG trigger?

Thank you and kind regards,
Angela

Reply
- Geoffrey Sher says:
  
  April 9, 2013 at 11:25 am
  
  On the morning of!
  
  Good luck!
  
  Geoff Sher
  
  Reply
Michaela says:

April 28, 2013 at 10:14 am

Dear Dr Sher,
I am 37 years old, POF since 32. high FSH (16-20). AMH 0,9. regular menses. 4 IUI, 1 IVF in 2011 (4 eggs, 3 A-quality embryos transfered) all negative. I always started on Day 1 with Decapeptyl (triptoreline) 0.05 mg every Day and Starting Day 3 with FoStimon 300 UI. Day 13 Ovitrelle 250 and IUI Day 15.
would you do a different Protocol?
Do you at Sher Clinic already do treatments creating new egg cells from stem cells?
Kind regards.

Reply
- Geoffrey Sher says:
  
  April 28, 2013 at 5:59 pm
  
  I would use an agonist/antagonist conversion protocol (LA-8) coming off a birth control pill and I would prefer using recombinant DNA-FSH (e.g., Puregon, Gonal-F )Please read the articles below.
  
  Please go to the home page of this blog, http://www.IVFauthority.com . When you get there, look for a “search bar” in the upper right hand corner. Type the following subjects into the bar, click on it and it will take you to all the relevant articles posted there.
  
  1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)
  
  2. “Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”
  
  3. “Agonist/Antagonist Conversion Protocol”
  
  4.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
  
  5. “Staggered IVF”
  
  6.“Embryo Banking”
  
  Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype consultation (free of charge to those who reside in the United States or Canada) with me so we can discuss your case in detail
  
  Geoff Sher
  
  Reply
- Geoffrey Sher says:
  
  April 28, 2013 at 6:06 pm
  
  No it is presently not feasible to create eggs from stem cells.
  
  Geoff Sher
  
  Reply
Michaela says:

April 30, 2013 at 2:13 am

Thank you Dr Sher.

Reply
- Geoffrey Sher says:
  
  April 30, 2013 at 6:37 am
  
  You are most welcome Michaela!
  
  Geoff Sher
  
  Reply
Jd says:

May 19, 2013 at 3:20 am

Dr Sher
I was wondering if you could shed some light on our situation. We have had two failed attempts at IVF both protocols were exactly the same: Buserelin 0.3ml once a day and gonal f 300iu a day followed by cephradine three times a day and doxyclcline twice a day for two days.I have had extensive endometriosis for years (I’m 41 now and husband is 34) and had 2 major operations to clean up the damage endometriosis having both my fallopian tubes removed due to endometriosis damage. The first IVF resulted in embryo transfer but no pregnancy the second attempt there was no embryo. On both occasions there was only one egg. Any ideas? I’m concerned that both attempts were a trial run and we are running out of money. I asked the Doctor about changing the regime and he said there was no point as I was on the top dose. I wonder if test should have been done to see if there was any underlying problem with me? Any ideas gratefully received.
Many thanks in advance.
JD

Reply
- Geoffrey Sher says:
  
  May 19, 2013 at 11:22 am
  
  A lot depends on your age , your ovarian reserve (as determined by basal FSH/E2/AMH), the status of your husband’s fertility. I also need to know thew precise details about the protocol of stimulation because that is the most important factor that will influence your egg/embryo quality. Finally you need to know that 1/3 of women who have endometriosis, regardless of its severity will also have activated uterine natural killer cells (NKa) that would thwart implantation regardless of whether your eggs or donor eggs are used.
  
  Please go to the home page of this blog, http://www.IVFauthority.com. When you get there, look for a “search bar” in the upper right hand corner. Type the following subjects into the bar, click on it and it will take you to all the relevant articles posted there.
  
  1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)
  
  2. “Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”
  
  3. “Agonist/Antagonist Conversion Protocol”
  
  4. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.
  
  5. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)
  
  6. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
  
  7.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
  
  8. “IVF success: Factors that influence outcome”
  
  9. “Staggered IVF”
  
  10.“Endometriosis”
  
  11. “Use of the Birth Control Pill in IVF”
  
  12. “Egg donation”
  
  Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype consultation (free of charge to those who reside in the United States or Canada) with me so we can discuss your case in detail
  
  Geoff Sher
  
  Reply
STK73 says:

May 20, 2013 at 9:52 pm

Dr Sher,
I’m 39yrs old. Hubby is 32yrs old. I’m about to do my last fresh cycle and need someone’s opinion as to the correct protocol to use.
I’ve just completed my 8th cycle (4 of which were Agonist cycles). I have low AMH level of 3.5 but this was tested 2 years ago. I’m sure it has reduced again.

My husband has low morphology but count/volume is fine.

I have always been able to achieve a 5 day blastocyst and my embryo numbers range from 10-2 (fertilised) – which I don’t think is that bad.

Last August we did a frozen transfer of one embryo and fell pregnant with what should have been twin boys. At 8 weeks I was told it was a blighted ovum and it wouldn’t progress any further. A D&C was performed and we found aneuploidy issues.

Our next few IVF cycles we decided to do CGH testing. The first CGH cycle we were able to test 2 embryos but both were incompetent for various different chromosomal reasons. The next cycle I used Saizen and the whole cycle was a disaster. Only 2 embryos fertilised. CGH Testing was not able to be done. This last cycle I had 6 eggs, 4 fertilised. On day 5 I had 1 hatching blastocyst, 1 A grade blastocyst and two morulas (1 compacted and 1 about to become a blastocyst).

I opted to CGH test the hatching blast, freeze the A grade blast and transfer the two morulas.

The hatching blast on day 6 was unable to be tested or frozen as it went backwards. The two morulas didn’t result in a pregnancy either.

I fear that as I’ve done back to back Agonist cycles, that perhaps my ovaries aren’t producing enough follicles and mature eggs.

I intend to take the next 3 months off, speak with a fertility nutritionist, continue with acupuncture, take DHEA, Royal Jelly, Bee Pollen and Vitamin D3 and hope that this will improve my egg quality.

What would be your suggestion with regards to my next and last protocol? Should I do an A/AP protocol?

I would very much appreciate any feedback you have.

Thank you!
Simmone

Reply
- Geoffrey Sher says:
  
  May 21, 2013 at 7:39 am
  
  I really cannot say with the information provided. It is possible that you need a different approach to stimulation (see below). However an implantation issue cannot be ruled out. We should talk…
  
  Please go to http://www.IVFauthority.com . When you get there, go to the home page and look for the “search bar” in the upper right hand corner. Type the following subjects into the bar, click on it and it will take you to all the relevant articles posted there.
  
  1. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.
  
  2. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)
  
  3. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
  
  4.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
  
  5. “IVF success: Factors that influence outcome”
  
  6. “An Individualized approach to Ovarian Stimulation for IVF”
  
  7. “Agonist/Antagonist Conversion Protocol (A/ACP)”
  
  Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype consultation (free of charge to those who reside in the United States or Canada) with me so we can discuss your case in detail
  
  Geoff Sher
  
  Reply

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