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Case Study: Poor Quality Eggs/Embryos in Young Women With Normal Ovarian Reserve: Case #1 – Polycystic Ovarian Syndrome
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After contemplating how to make my blog posts more helpful to patients with unexplained IVF failures, I have decided to profile the case histories of a number of patients who sought my input after having failed at IVF (often repeatedly). I will try to identify the various potentially remediable reasons for failure, and then make specific recommendations as to how I personally would address (or have addressed) these issues. In some cases, the patients underwent subsequent treatment with me, in which case I have indicated the details and outcome of their treatment.
To make this exercise useful, I have decided to discuss these cases in specific categories that will highlight often overlooked factors that can lead to (unnecessary) IVF failure.
Cases will be presented in three categories:
- Women who ended up with poor quality eggs/embryos.
a. Younger women with normal or exaggerated ovarian reserve
b. Older women (over age 39) with normal and/or diminished ovarian reserve (DOR) - Women who failed to conceive because of embryo implantation dysfunction
- IVF failures following third party IVF (Egg Donation and Gestational Surrogacy)
Please note that the case reports and commentaries will include links to other articles on this site that will hopefully expand on the explanations given.
The first three posts in this series will address Category 1.a – younger women who ended up with poor quality eggs/embryos.
Today’s post profiles a patient with Polycystic Ovarian Syndrome (PCOS) and the various effects of this condition (along with the prescribed IVF protocols) on egg/embryo quality. Friday’s post will discuss a case in which poor egg/embryo quality was due to an occult male factor infertility issue. Next Tuesday I will post case #3, which will detail a patient with poor egg/embryo quality due to advanced endometriosis.
In coming weeks, I will address more cases under the current heading and will then go on to cases involving the other categories listed above.
—————————————–
Case History #1
“Ann” aged 34 years had been trying to conceive for 3 years. She had never conceived previously (Primary Infertility) in spite of having a fertile male partner, undergoing four attempts at intrauterine insemination using clomiphene citrate (Serophene) for induction of ovulation, and 2 prior IVF procedures. Her menstrual periods were grossly irregular with cycles ranging from 20–35 days apart. Her day-3 blood hormone levels were as follows: Follicle Stimulating Hormone (FSH): 4.5 MIU/ml; Luteinizing Hormone (LH): 9.1 MIU/ml; Estradiol (E2): 62pg/ml; Antimullerian Hormone (AMH): 5.6
Ann had been diagnosed with Polycystic Ovarian Syndrome (PCOS). Both of her IVF treatment cycles (prior to consulting with me) involved ovarian stimulation with Menopur and Ganirelix (beginning on day 6 of stimulation). By the time of the hCG trigger (7-8 days after stimulation started) most of her 40+ follicles were still somewhat under-developed measuring 15-17mm in mean diameter, having not yet attained optimal size (18-22mm), and her peak blood [E2] exceeded 6,000 pg/ml. She was told that she needed to be triggered with hCG at that time to stop the process of follicle growth, which would prevent her blood [E2] from spiraling out of control and potentially causing her to develop the life-endangering condition of Severe Ovarian Hyperstimulation Syndrome (OHSS). In both of these prior cycles, only about 40% of the follicles yielded eggs at the time of egg retrieval. Many of her eggs were immature (MI’s), and those that were mature (MII’s), yielded poor quality embryos after fertilization by ICSI.
She had developed moderately severe ovarian hyperstimulation (abdominal fluid collection, backache and some difficulty in breathing) prior to the embryo transfer (ET), which in both cycles involved the transfer of three (3) day-3, poor quality embryos to her uterus. She did not conceive, but her ovarian hyperstimulation got worse in the ensuing days. She experienced a reduction in urine output, diarrhea, worsening abdominal pain, and progressively more difficult breathing. These symptoms and signs, along with abnormal blood tests pointed to OHSS, which is a life-threatening condition, which fortunately, in the absence of pregnancy is self-limiting and disappears 10-14 days after the hCG shot. Thus, since she did not conceive, she recovered about 10 days later.
Commentary
In my opinion, the reason for the poor egg/embryo quality in these two IVF cycles preceding her final attempt with us, was likely due to the IVF stimulation protocol that was used, as well as premature timing of the hCG trigger. In my experience, women with elevated basal blood [LH] do poorly on protocols that do not down-regulate the LH before and during the stimulation cycle (women with PCOS commonly have elevated blood [LH]). Since the “antagonist” (Ganirelix) was only commenced six days after the stimulation was initiated with Menopur, by the time it suppressed her high pituitary LH production, her eggs had already been exposed to excessive LH-induced ovarian male hormones or androgens (mainly testosterone). It was probably this that had a deleterious effect on her developing eggs and subsequently on her embryo quality.
In addition, because her eggs developed poorly, many of them remained firmly attached to the inner walls of her follicles and could not be retrieved. This would serve to explain why she had so many “empty follicles”. It also probably explains the low percentage of mature (MII) eggs produced in prior cycles and her subsequent poor quality embryos that ultimately led to failed IVF. In addition, Menopur (which aside from FSH also contains 50% LH/hCG) was not the ideal gonadotropin to use in this case, because the additional LH would simply add more “fuel to the fire”.
Another factor here is that the hCG trigger was administered relatively early in her cycle, such that her follicles did not have sufficient time to develop optimally before the process of development was abruptly arrested by the trigger. This was clearly done deliberately in an attempt to reduce the risk of OHSS developing…unsuccessfully in this case.
Follow up
The patient subsequently went through a cycle of COS with me. We prepared Ann for an IVF cycle by starting her on a birth control pill and thereupon, given that she was a “high responder,” we put her on a low-dosage, long pituitary down-regulation protocol with Follistim and Luveris to properly maintain a low LH. She produced 47 follicles which by day 8 of stimulation were (14m-16mm) and her [E2] was 2700pg/ml. At this point I commenced the “prolonged coasting” process by discontinuing the gonadotropins while maintaining the daily “agonist” (Lupron) injections. This would give her follicles and eggs an opportunity to develop optimally (18-22mm) before administering the hCG trigger. Her blood [E2] rose and peaked at 7700pg/ml by day 9 and then began to fall, reaching below 2,500pg threshold by day 12. At this point the follicles were mostly 18-22mm in mean diameter and I administered 10,000U of hCG (Profasi) to trigger ovulation. We retrieved 42 eggs, 34 of which were mature (MII’s) and were fertilized using ICSI. Thirty-one (31) MII’s fertilized and by day-3 post-ICSI, most were 6-9 cells. By day-6, we counted 11 expanded blastocysts and transferred two of these into her uterus. She conceived with a singleton and at this time is nearing the end of the 1st trimester and is doing well. This treatment approach likely prevented OHSS and helped optimize embryo quality.
Addendum:It is important to understand that IVF is an ART-Science blend and not all practitioners agree on the same strategies.Thus, in the final analysis, it is important, after discussion with your personal doctor, to follow his/her advice to the letter.Feel free to present your case history in the comments and I will do my best to offer my opinion.
30 Responses to “Case Study: Poor Quality Eggs/Embryos in Young Women With Normal Ovarian Reserve: Case #1 – Polycystic Ovarian Syndrome”
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Ask Our DoctorsA Question
Hello Dr Sher this is my case;
history
Pregnant once 4 ½ yrs ago.. MC at 8 weeks
6 months on clomid in 2011 all BFN’s
2012 3 failed iui’s on 50mg puregon, (created 2-3 follicles each cycle) all BFN’s
1 cancelled iui due to overstimulation on 75mg puregon (had 4 follicles)they cancel cycle
First IVF
125units puregon/75 units menopur every night starting on day 3 of cycle (Thursday) DAY ONE OF STIMS… had 4 days on stims then in on
Day 5 OF STIMS (Monday)blood work and U/S blood shows elevated LH not sure exact # LH reached (estradiol 5000 ish) was called in a panic to take ogalutran asap was able to take it by 1pm that day
Was told to stay on same puregon/menopur and orgalutran then return in two days
Was back in 2 days later “day 7 of stims” ( Wednesday) blood/US (LH dropped to 3.4 but estradiol was at 12000ish) multiple egg count on ultrasound (taken off puregon for remainder of cycle)
Took orgalutran and menopur only for two days
Back in Friday “day 9 of stims” blood/US (estradiol 21000 LH ??)
Back in Saturday “day 10” blood/US again couldn’t measure follies very well due to u
many irregular shape follies especially in right ovary (LH 1.71 estrodiol 32000) triggered me that night with Lupron at 10:30pm instead of HCG due to risk of OHSS and egg retrieval don Monday at noon 12pm
After egg retrieval, they gave me injection of HCG as they said Lupron affects integrity of lining
35 eggs retrieved of them 18 mature.. 9 fertilized with icsi and 4 with ivf 13 total fertilized .
No fertilized Eggs survived to day 1
They deemed it due to egg quality.. advised me to try taking DHEA and try again in 3 months with different meds ie gonal F and luverif and/ or consider egg donor.
Cabergaline 10 days following egg retrieval to tx OHSS ended up with moderate OHSS
I do not want to consider egg donor just yet, your opinion would be very appreciated.
Yours sounds very much like a ovarian stimulation problem. Consider attending a webinar that I will be hosting on Thursday ecvening, 11/8 where this will be addressed. Also, M go to the home page on this site, find a “search bar” in the upper right hand column and 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)
“IVF success: Factors that influence outcome”
I invite you 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). While an audiovisual (Skype) interaction is much more personable and preferable than a discussion by telephone, either will suffice.
Geoff Sher
should also mention i am 34 year old caucasian very healthy athletic build, no acne, facial hair and completely unexplained infertility.. had a LAP done in sept 2012 all clear not one problem found. Partner semen analysis was amazing they called him superman at the clinic he is also healthy 37 yr old male. thanks for your time and consideration.
Copy!
Sorry .. also left out my day 3 blood work for this ivf cycle that just ended last week with heart breaking news. my day 3 blood work was FSH(8.4), LH(7.98), TSH(1.74), prolactin(16), E2(?)
Interesting! Have you ever been diagnosed with polycystic ovarian syndrome (PCOS).
Go to the home page of this blog and type in “PCOS” into the search bar and read up on PCOS.
Geoff Sher
no, RE says i dont have the characteristics of pcos, however, she believes i could have very mild form of it. I never understood just what that meant. I have a skype interview with you next tuesday. I was wondering just with the meds, if you are able to write and mail prescriptions to canada so that my insurance will pay. They pay 100% of my drugs. But they dont cover ivf. My clinic charged $6000 for icsi. Who can i talk to about the process of financials at your clinic.
also, what time is your webinar begin tonight
Webinar begins at 5:30 Pacific/8:30 Eastern: http://new.livestream.com/haveababy/failed-ivf
Lets wait until we communicate via Skype next week.
Geoff Sher
Dr. Sher – I am hoping to get your opinion my case. I have not been diagnosed with PCOS nor do i have any of the characteristics. my day 3 stats: amh = 2.8ng/mL, FSH = 4.9 mIU/mL and estradiol is 29 pg/mL. I am 33 yrs and we have male factors.
my first IVF: day 1 and 2 – 225units of follostim with 20 units of mini HCG, Estradiol after 2 days of stimming is 480pg/mL; LH=1.22mIU/mL
day 3 and 4 – 200 unit of follostim with 20 units of miniHCG. estradiol after 4 days of stimming is 1350 pg/mL; LH=2.45mIU/mL
day 5 – 200unit of follostim with 20 units mini HCG and 0.25mg Ganirelix
day6 – drop follostim to 175 units; estradiol after 6 days is 2877 pg/mL
day 7 – 175 units of follostim; 5200 pg/mL estradiol
I triggered at day 8; retrieved 35 hours later with 27 eggs. 15 of 27 are mature. 12 of 15 fertilized with ICSI; 10 of 12 survived day 3; but only 4 got to day 5; 2 of 4 are PGS normal.
I am planning on another IVF but just wondering if this protocol is appropriate since i got so many immature eggs and so few normal blasts. should I add ganirelix earlier to keep LH low or should i tried to stimm one more day? at day 8 checkup (7 days of stimming), I had 4 follicles between 18-21mm and about 16 total above 15mm.
really looking forward to your suggestions. Thanks!
This is not a good yield of normal blastocysts in a person who like yourself with a peak E2 of> 5000pg/ml, must have had in excess of 30 follicles….and thus should have produced a comparable # of eggs, 2/5 of which should have been chromosomally normal. 70-80% of such normal eggs and upon fertilization should have produced chromosomally normal embryos/blastocysts. This I respectfully submit has to a large degree have to do with the protocol of ovarian stimulation. I do not agree to the addition of hCG (which has LH like activity) during stimulation. Nor would I recommend mid-follicular antagonist (e.g., Ganirelix) . In my opinion you would best benefit from a long pituitary down regulation protocol using low-dosage recombinant FSH (e.g. Follistim) + a small amount of Menopur. Please see the article below on an “individualized approach to ovarian stimulation for IVF”.
You might not have true PCOS, but given the way you hyper-responded you could have a a PCOS-like picture. I would be interested in knowing what yourv day 3, LH level was and what your blood Testosterone, androstenedione, DHEAS and 17-OH progesterone levels were.
Please go to the home page on this blog (www.IVFauthority.com) and when you get there find the “search bar” in the right hand column. 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”
“Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.
“Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)
“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)
“IVF success: Factors that influence outcome”
“PCOS”
“Embryo Banking”
“Egg Donation”
“Gestational Surrogacy”
You might consider calling 800-780-7437 or 702-699-7437 to arrange a telephone or Skype consultation with me (free of charge to those who reside in the United States or Canada). While an audiovisual (Skype) interaction is much more personable and preferable than a discussion by telephone, either will suffice.
Geoff Sher
Hi Dr. Sher,
this is our (long) case history:
TTC for 3.5 years.
my wife is 31 with PCOS (lean, no hirsutism). history of anorexia. When we started she did not ovulate at all.
I am 36 (sperm seems ok).
we tried IUI for about 5-6 times, then moved to IVF.
1st cycle: 75 IU FSH (puregon) and later antagonist (cetrotide) and HCG as trigger. leading follicle was ~18mm. 13 eggs were harvested, all immature.
2nd cycle: following dr’s recommendation tried IVM (in a different lab). 9 eggs were harvested, none succeeded to mature in vitro.
we then took a break and she changed to a more balanced diet + added natural medicine and acupuncture. amazingly she began to regularly, spontaneously ovulate within 1 month. moreover, with almost no intervention (only HCG shot when follicle naturally reached 23mm and E2 was around 2000 pmol/L) she got pregnant but unfortunately miscarried in week 7 (chemical preg). we tried naturally a few more months and got back to IVF with a different Dr and lab. she also started taking metformin and dexamethasone on a daily basis.
3rd cycle: using Menopur and cetrotide, went out of control and she reached E2 ~10000 IU. fearing OHSS dr gave her agonist (0.2mg decapeptyl) instead of HCG to get ovulation with flare-up. 35 eggs harvested, and although some of the follicles were 18 and 19mm, all eggs were immature (GV stage). 2 days later 7 reached M2, rescued using ICSI we got 2 embryos that were transferred but no pregnancy.
4th cycle: we tried natural cycle IVF. 1 egg harvested, mature but abnormal (huge PVS), ICSI used but no fertilization.
5th cycle: we tried down regulation using the pill for 2 weeks, then 110IU Menopur and later cetrotyde. gave HCG when leading follicle was 21mm and E2 around 3000. 6 eggs harvested, 4 were mature. 2 ICSI- no fertilization. 2 co-culture produced a single 4-cell embryo with good morphology, but no pregnancy.
we are now starting a new cycle, down-regulating using slow-release agonist (decapeptyl 3.75mg), then he plans using 150 IU Menopur, aiming at around 10 follicles so we can wait with HCG without risking OHSS.
I should add that her LH and male hormones are not high. 3rd day bloodwork following down regulation: E2 206pmol/L, P4<1.7, 17OHprog 0.94nmol/L, LH 2.3, FSH 5.7, testosterone<0.9, androstenedione 3.25nmol/L, DHEA 1.76umol/L, SHBG 159nmol/L.
your opinion would be very appreciated.
Thank you for taking the time to provide all that information.
With PCOS:
1. there is always the risk of severe hyperstimulation. Prevention requires a very individualized and modest stimulation protocol and readiness to institute “prolonged coasting” proactively.
2. With PCOS there tends to be a greater percentage of poorly developed eggs. This requires a very strategic long pituitary down regulation protocol…similar to the one you are on and triggering should be done with 10,000U of hCG or 500mcg of Ovidrel…not less!
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”
“Polycystic Ovarian Syndrome (PCOS) and IVF”
“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)
“IVF success: Factors that influence outcome”
“Staggered IVF”
Consider calling 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
Me 40 – one endometrioma removed, normal cycles, ovulate, tubes open, unexplained. 2 small fibroids removed, borderline insulin resistance, PCO bit not syndrome, some facial hair – lost 5 kilos, try to lose another 2 to get normal bmi.
husband 45 – no issues
5 x clomid and timed intercourse
2x iui – 1 with clomid, second with gonal f
4 Ivf icsi
1st cycle – gonalpeptyl 0.2 on day 2 and 3, 6×300 iu gonal f day 5-11, 10,000 chromion 10000. 5 eggs retrieved, 5 fertilised, transfered
3 blasts day 5. Not pregnant.
2nd cycle – day 3-9 300 gonal f and 150 menopur.day 10 centrotide rising lh, chorimon 1000. 6 retrieved none matured, none fertilised.no transfer.
3 cycle -, birth control, dhea l’ argine? Coq10. gonalpeptyl 0.2 on day 2 and 3, 7x 300 iu gonal f day 6-12, chromion 5000. 17 eggs retrieved, 13 fertilised, transfered
3 day 3 embryos. 3 compacted and grade 2. 5 – 8 to 10 cell grade 2, 2 – 8 cells grade 1. Pregnant miscarried 8 weeks. transfered
3 day 3 embryos. 8 frozen. Lining 7.2 at day 11.
Fet – all 8 defrosted, 2 transfered not pregnant.
Change re
Cycle 4 – Pgs test chromosomes. birth control, l’ argine, Coq10. Synarel,12x 375 iu gonal f day 3 – 14 , ovidrelle 250mcg. 15 follicles,8 eggs, 5 fertilised. All 5 biopsied day 3. All grew to blastocyst. All genetically abnormal therefore no transfer.
Estrogen patches every other day for lining, as was 6mm on day 13. from day
Can I do anything to improve egg quality, embryo to try having some genetically normal. Should I stay on the same protocol as recent cycle. Disappointed not as many eggs retrieved and all abnormal. Is this a reflection that next go will yield same amount of abnormals? Always had good graded embryos.
Would appreciate your expertise.
Many thanks
I really think I can help here, but we need to talk. As i see it, the issues are:
1.endometriosis with an endometrioma and the effect this could have on ovarian reserve, egg quality and immunologic implantation dysfunction
2. PCOS and the manner in which this affects egg quality and ovarian response and the need to individualize protocols of ovarian reserve to address such challenges.
3. Embryo selection through CGH, Staggered IVF and Embryo banking.
4. Endometrial thickness and IVF”
Please go to http://www.IVFauthority.com . When you get to home page, 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.“Embryo Banking”
11. “Endometriosis”
12. “Endometrioma and IVF”
13. “Endometrial thickness and Viagra therapy”
Next Tuesday I will have a blog here that addresses a similar clinical situation to yours. Please look out for it.
Consider calling 702-699-7437 to arrange a Skype or telephone consultation with me 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
Hi Dr. Sher,
First, I would like to thank you for your availability and all the information you provide. We are in Europe, but otherwise we would love to be treated in one of your fertility clinics, if we lived in the USA.
I have recently turned 35 and we are using donor sperm. We did our first IVF recently after several IUIs with no success (medicated and unmedicated). The IVF cycle protocol was gonal-f 150 (cycle day 3 to 10), with orgulatran from cycle day 8 and double pregnyl shot on cycle day 10. It was apparently going very well, my cycle day 8 results were 529,6 estradiol and 0,5 progesterone and on cycle day 10 the follicles were looking very good and my endometrium was 9mm. Egg collection happened on cycle day 12, with 14 mature eggs collected, 13 fertilized and 12 developed into embryos. However when we went back for egg transfer none were good enough for freezing (too much fragmentation, they said) and they transfered only one day-2, 2-cell Grade 2 with 10-20% fragmentation embryo (the original reasoning was to avoid twin pregnancy – but now we have realised we should really have requested for the transfer of two embryos). My lab results have always been very good, my ovarian reserve is good (my FSH is usually 6,63 on cycle day 3), except for the DHEA-S which was 286 (just slightly higher), but I was told that it is not necessarily bad for fertility and that it probably means I have a mild form of micropolycistic ovaries. I was also told it was not normal that my embryo quality was not good, because I was still young.
I would like to ask you what we should in terms of protocol, egg/embryo improvement, as we do not understand why I am apparently healthy but it has been impossible to get pregnant. Thank you.
Thank you very much for your kind sentiments.
First, no doubt the protocol of ovarian stimulation should be adjusted. Second, I am concerned about the elevated DHEAS for 2 reasons: 1) It points to an adrenal component (hyperplasia of the zona reticularis) and 2) The increased DHEA from the adrenal gland will result in increased androgens and in my opinion this is harmful to egg development and thus embryo quality (competency). The adrenal component requires down-regulation for several weeks on corticosteroid (I would suggest dexamethasone) and then a repeat DHEA measurement to confirm successful treatment. Only then should you be re-stimulated for another cycle of IVF (in my opinion…using a long agonist down regulation protocol coming off a BCP (see 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. “PCOS”
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”
Consider calling 702-699-7437 to arrange a Skype consultation with me so we can discuss your case in detail.
Good luck!
Geoff Sher
Dear Dr. Sher,
Thank you so much for your reply.
I have now received my latest blood results and the DHEA-S has gone down by itself to 233. My thyroid results are fine as well. However, we have found out that my ANA is positive: 160. Our fertility doctor has dismissed it as not being important, but I am not convinced. I have made an appointment with a rheumatologist who is also specialized in immunology and pregnancy and I am hoping she will take it seriously. I have read that taking a low dose of aspirin can help. Should I try that? Thank you for your offer of a Skype consultation. I will consider it seriously especially after the rheumatologist consultation.
Kind Regards.
WE should talk. Unfortunately, a Rheumatologist will not likely have enough background in Reproductive medicine.
Give us a call and let’s interact.
Geoff Sher
\
P.S. Aspirin will not help here!
Hi Dr. Sher,
Thank you for all your helpful information. We have been reading it intently after our first failed IVF attempt and would appreciate your input.
I am 30 years old, relatively healthy with no known issues. I do have long cycles, but ovulate. My AMH was 9.4, FSH 9.33, and E2 25 on a Day 3 test.
We tried to conceive naturally and with Clomid for 2 years and then found we have MFI. His morphology is at 0%. He is also found to have low testosterone and is taking Clomid and depotestosterone.
We did IVF with ICSI on the long Lupron protocol. I was on BCP for about 30 days and then began 10u of Lupron for 13 days. I then did the following:
3 days of 5u Lupron, 150u Follistim, 75u Menopur
E2 was 137 on day 4
2 days of 5u Lupron, 150u Follistim, 150u Menopur
E2 was 395 on day 6, 9 follicles
3 days of 5 u Lupton, 300u Follistim, 150u Menopur
E2 was 1922 on day 9, 12 follicles
3 days of 5u Lupron, 250u Follistim, 150u Menopur
E2 was 2937 on Day 11, 11 follicles with 4 being larger than 16 mm
Trigger shot was 10,000 of hCg on Day 12- E2 was 3721
When we went to egg retrieval, we had 10 eggs retrieved and 7 fertilized with ICSI. By day 1, only 2 eggs fertilized normally. By day 2, they were abnormal and graded a 3 and 4. By day 3, they had stopped growing.
When we met with the Dr, she mentioned my eggs were bad quality. I have started taking DHEA and Co-Q10 to help with quality. We are looking at doing an antagonist protocol next.
We have wondered about high testosterone levels in me, because I do have cystic acne (only BCP help it to go away) and started to get darker facial hair and coloring on my face. We read that high levels could effect egg quality.
Do you have any suggestions on how to move forward? We aren’t sure whether we are good candidates to move forward and want to make the best decisions possible.
Thank you for your time!
Hi Jessica,
Respectfully, there is in my opinion no basis for giving depot testosterone alone or in combination with clomiphene to men with sperm dysfunction. he testosterone will likely suppress response to clomiphene. This is in my opinion a counter-intuitive strategy. Also, I need to need to know much more about your husband’s pre-treatment blood FSH, testosterone and his exact sperm parameters at that time.
I think you know from this blog that DOR requires a very individualized approach to ovarian stimulation and that in my opinion, flare protocols are less than ideal in such settings. Also, I do not believe in DHEA to try and improve response and/or egg quality. It metabolizes to testosterone in the ovary and too much testosterone can be harmful.
I think first the issue of sperm quality needs to be addressed you need to consider a more aggressive protocol of stimulation such as am agonist-antagonist conversion protocol . Then ICSI—— followed by staggered IVF with embryo banking of chromosomally normal embryos for subsequent transfer to a receptive uterine environment.
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.“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
Hi Dr. Sher,
I am from India and this is my case background:
Me: 30 yrs old, thalassemia minor, severe PCOS (i have all the PCOS symptoms except for acne). I also dont ovulate on my own. Husband has no known issues.
Started trying 2.5 years back.
Did not respond to clomid 50g, 100g or 150g. Did not respond even to follistim.
Went through Ovarian Drilling (left tube was found to be blocked and I was told that it was unblocked successfully; uterine septoplasty was also performed during the drilling) in March 2012 after which I responded to Clomid 100g in one cycle(produced 1 follicle) and did an IUI which was a BFN. After that, did not respond to Clomid in any other cycle.
Was given injectibles (Menogon 75) and again did not respond.
In the next cycle, was given Gonal F 75IU, produced 1 follicle and did a 2nd IUI which was again a BFN.
I was then advised in Dec 2012 to go for an IVF. I was put on birth control for 28 days and was given Lupron 0.5.
From day 5, I was put on menopur 150 (E2 was 45 on day 9). Increased menopur dosage to 225 and then to 375.
E2 on Day 14 was 950 after which it was not tested again.
Scan on Day 17 showed 20 follicles between 18-23mm and 21 follicles between 13-17mm; ET lining was 8.1mm. HcG (10000iu) was given the same night and 18 eggs were retrieved out of which 9 were fertilised using ICSI. 7 embryos were formed which were all given A rating.(I had also developed mild to moderate OHSS before embryo transfer). 2 were transferred (it was a 2-day transfer) but the cycle was a failure as neither implanted.
I then went for a Frozen cycle in March 2013. I was again put on birth control for a month and on lupron. ET was 8.3 with triple lining. The 5 remaining embryos from the 1st cycle had been frozen, out of which 4 survived the thaw and all 4 were transferred. However, again none implanted and the cycle failed.
Now I am advised to undergo a fresh cycle again. Before I do that, I have a few questions which I hope you could answer:
1. Was it advisable in my case to go for a 2-day transfer instead of waiting for the embryos to reach the blastocyst stage?
2. My LH:FSH ratio is 3:1 (LH: 19; FSH:6). Given such elevated LH levels, is it advisable to go for menopur instead of stimulating entirely by Gonal-F?
My RE insists that only FSH injections are not enough to stimulate the ovaries; however, after reading your above case, I feel certain that menopur further increased my already super high LH levels, thus destroying the quality of the eggs.
3. What else do you think went wrong in both my cycles?
I do not understand how all 6 “perfect” embryos failed to implant. RE says it happens but I’d really be grateful if you could shed some light on my above questions and give me some clarity.
Thank you so much for your time. I really look forward to hearing from you at your earliest convenience.
Yours is a complex case which we would need to consult on.The issues are related primarily to the protocol used for ovarian stimulation and the effects on egg/embryo development and “competency”..
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. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
5.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
6. “IVF success: Factors that influence outcome”
9. “PCOS”
Consider calling 702-699-7437 to arrange a Skype consultation with me so we can discuss your case in detail
Geoff Sher
Dear Dr. Sher
I have been following your articles for a while; I would really appreciate your input in my case.
Here is my history:
conceived my first baby in 2009 (@33 years) after 3 IVF cycles.
the optimal protocol for me was BCP’s followed by Lupron microdose + Gonal F.
upon my insistence during my last (and successful cycle), my RE agreed to coast for a day till my lead follicle reached at least 20 mm. E2 = 2700 on the day of trigger.
triggered with Ovidrel. ER 39 hours later.
that was a successful cycle.
Fast foward to 2012. Started trying for baby#2. different city, different RE. he decided to replicate the successful protocol with some tweaks.
Dec 2012 Protocol:
BCPs for three weeks.
Follistim (not Gonal-F) + Lupron microdose + Growth Hormone + low dose HCG.
dismal response; the follicles quit growing after day 10 of stimulation. ER canceled.
April 2013 Protocol (EPP):
estrace for 2 weeks followed by Follistim (not Gonal-F) + Lupron microdose + Growth Hormone + low dose HCG.
lead follicle ONE day before trigger: 16 mm. about five in 14.7-16 mm range. E2=1700.
no measurements done on day of trigger.triggered with 10,000 units Pregnyl. ER 35 hours later.
retrieved 5 eggs, only 2 mature and fertilized.
Transferred 1 4 cell, 1 6 cell embryo on day 3. Not very hopeful about the outcome – yet to find the result.
MY RE suggested DHEA for a couple of months before stimming but I believed it can androgenize me and lead to worse results. especially because I have DOR (highest measured FSH 15 although in recent months it has been closer to 10).
My questions/ concerns are:
I am devastated by the low number of mature eggs in my latest cycle. In my 2009 cycles, I always retrieved a large proportion of mature eggs on IVF#2, IVF#3 (6 out of 7, 7 out of 8) even with moderate hyperstimulation (E.
do you think low dose HCG during the stimulation phase has benefits or will it mimick the action of LH and can lead to worse results due to ovarian androgen production?
In my 2009 cycles, my first IVF was a disaster – no mature eggs. my RE was of the view that I need more time to mature my eggs – hence he went 39 hours between trigger and ER; and it worked. In my current cycle, this time was reduced to 35 hours. I have a gut feeling this was a big culprit. What are your thoughts?
I also feel that the trigger could have waited at least a day so that the lead follicle size was close to 20 mm at trigger. Do you think this would make a difference? Unfortunately, my current RE strongly believes that anything over 14 mm can have a viable egg; I dont know why when most clinics believe in 18-20 mm. I have observed that at my current RE practice, everyone is rushing to trigger instead of waiting out a day or so; even if there are no signs of over stimulation.
Do you think growth hormone during stimulation can have adverse effects on egg maturity?
Does it matter whether one uses Pregnyl or Ovidrel for trigger? is one better than the other?
Overall, I would love to hear your thoughts on how things can be improved during my next cycle.
The issues clearly are that you have progressively experienced diminishing ovarian reserve.Your baseline FSH, your reduced responsiveness bear this out. In my opinion you were wise to reject taking DHEA, but I also want you to know that you should not come off a birth control pill and go directly on to stimulation (see article referenced below titled “use of the birth control pill in IVF”. Also, I do not agree with the use of Ovidrel 250mcg to trigger. In my opinion it lacks biological potency. If you use Ovidrel the dosage in my opinion should be doubled (500mcg) to be equivalent in effect to 10,0000U of hCG (Pregnyl/Novarel/Profasi). Also, the use of HGH has been around since the early 90′s and there is no tangible evidence of a benefit.
Clearly time is of the essence and your biological clock is on the move. I think, if you let me, I can help you. My approach would be aggressive stimulation using the “agonist/antagonist conversion protocol (A/ACP)”, “Staggered IVF” with “metaphase CGH embryo selection” and “Embryo Banking”….. before you run out of both time and opportunity leaving egg donation as the only alternative.
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. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
5.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
8. “IVF success: Factors that influence outcome
6. “Staggered IVF”
7.“Embryo Banking”
8. “Egg Donation”
12. Use of thew birth control pill in IVF”
I suggest you call 800-780-7437 or 702-699-7437 on Monday and 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
Thank you so much, Dr. Sher, for your prompt reply.
Yes, I agree with the bcp part. I did bring it up after my failed IVF in Dec 2012 but it did not get across I guess and EPP was used this cycle.
I will be very happy to discuss my case with you – talk to you at the earliest opportunity.
I suggest you call on Monday to 702-699-7437 and set up a Skype consultation with me.
Geoff Sher
Definitely!
Thanks!
Geoff Sher