Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Hi. I have a frozen blastocyst from a natural cycle 3bb. I decided after this to switch to a clomid & merinol cycle but have found my fsh and lh significantly increasing suddenly. Can this be due to the stimm – I am of advanced maternal age – can things diminish that quickly – fsh now 14 and last month lh was 10.9 day 3 but dropped to 1.9 day 8. 3 mature eggs retrieved – 1 empty zona, 1 3PN, 1no fertilisation
Sorry to add my fsh was 9.5 in June and since taking the clomid and Stimson it has been elevated. I also switched from dhea to micronised dhea in august – could this contribute to rising lh.
Clomiphene increases LH/FSH. None the less it sounds as if you might have diminished ovarian reserve. It is important to have an AMH done. This is much more reliable than FSH/LH and is not chronically affected by clomiphene. Finally, I advoise against the use of DHEA (see below).
Dehydroepiandrosterone (DHEA), is steroid hormone produced by the adrenal glands and ovary. It is involved in producing the male hormones, androstenedione testosterone and also estrogen. DHEA blood levels tend to decline naturally with age.
Under the effect if luteinizing hormone (LH), DHEA is metabolized to testosterone in ovarian connective tissue (theca/stroma). Thereupon the testosterone is transported to the granulosa cells that form the innermost layer of the ovarian follicles where, under the influence of follicle stimulating hormone (FSH)-induced desmolase and aromatase enzymatic activity the testosterone is converted to estradiol. As this happens, granulosa cells multiply, follicle fluid volume increases along with estrogen output and egg development is promoted.
It is recognition of the essential/indispensable role that male hormones (mainly testosterone) play in follicle and egg development that prompted the belief that by giving DHEA and boosting ovarian testosterone production might benefit follicle/egg development. This belief was given some credence by an Israeli study that in 2010 reported on improved fertility when a group of infertile women were given the administration of 75mg of oral DHEA for 5 months. However, this study was seriously flawed by the fact that it did not separate out women who had diminished ovarian reserve, older women and those with PCOS, all of whom have increased LH-induced production of testosterone. In fact, we recently completed a study (currently being processed for publication) where we conclusively showed that when follicular fluid testosterone levels exceeded a certain threshold, egg quality was seriously prejudiced as evidenced by a marked increase in the incidence of egg chromosomal defects (aneuploidy).
Consider the following: Ovarian testosterone is needed for follicular development. However, the amount required is small. Too much ovarian testosterone spills over into the follicular fluid and has a deleterious effect on egg/follicle development. Some women (women with diminished ovarian reserve –DOR, older women and those with polycystic ovarian syndrome-PCOS) who tend to have increased LH biological activity, already over-produce testosterone. To such women, the administration of DHEA to such women, by “adding fuel to the fire” can be decidedly prejudicial, in my opinion. Young women with normal ovarian reserve do not over produce LH-induced ovarian testosterone, and are thus probably not at significant risk from DHEA supplementation. It is noteworthy that to date, none of the studies that suggest a benefit from DHEA therapy have differentiated between young healthy normal women with normal ovarian reserve on the one hand and older women, those with DOR and women with PCOS on the other hand.
In Some countries DHEA treatment requires a medical prescription and medical supervision. Not so in the U.S.A where it can be bought over the counter. Since DHEA is involved in sex hormone production, including testosterone and estrogen, individuals with malignant conditions that may be hormone dependent (certain types of breast cancer or testicular cancer) should not receive DHEA supplementation. Also, if overdosed with DHEA some “sensitive women” might so increase their blood concentrations of testosterone that they develop increased aggressive tendencies or male characteristics such as hirsuites (increased hair growth) and a deepening voice. DHEA can also interact other medications, such as barbiturates, corticosteroids, insulin and with other oral diabetic medications.
BUT the strongest argument against the use of routine DHEA supplementation is the potential risk of compromising egg quality in certain categories of women and since there is presently no convincing evidence of any benefit, why take the risk in using it on anyone.
Finally, for those who in spite of the above, still feel compelled to take DHEA, the best advice I can give is to consult their health care providers before starting the process.
Addendum: One potential advantage of DHEA therapy if used appropriately came from a study conducted by Washington University School of Medicine in St. Louis, MI and reported in the November 2004 issue of the “Journal of the American Medical Association” which showed that judicious (selective) administration of 50mg DHEA daily for 6 months resulted in a significant reduction of abdominal fat and blood insulin in elderly women.
Geoff Sher
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Hello Dr. Sher,
I had FET yesterday. The clinic is abroad and after transfer I received instructions but I cannot count on their further support. I am supposed to continue with my local obgyn but I am not sure if he is familiar how to handle artificial cycle. This is why I would love to hear your opinion on dosage of estradiol and progesterone.
ESTRADIOL: From cd 1 I was taking vaginally estradiol 2mg-2mg -2mg and orally 2mg-0mg -2mg; around cd 10 because the lining was not growing much I increased it to 4mg-4mg-4mg vaginally. I panicked because my dr. abroad was out of reach and this is what my previous clinic would do. So now at the transfer I am told to decrease it from 3x4mg vaginally to 3x2mg vaginally + 2x2mg orally and continue like that until 10th week if pregnancy is confirmed.
Q1. Is in your opinion OK to decrease estradiol so dramatically just after transfer?
Q2. Should estradiol be taken until 10th week in the same dosage?
PROGESTERONE:
I am taking Utrogestan vaginally 300 mg -200mg -300mg. I am told to continue until wk 10 with the same dosage if pregnant.
Q3. Shouldn’t dosage be adjusted based on blood levels of Progesterone? I know if taken vaginally, blood levels are not adequate but shouldn’t give some idea?
And my last concern but most important to me because I am loosing my mind from thinking about it! So I took acupuncture before and after FET. Around half an hour after transfer I had the second session during which the acupuncturists did few very painful points on my legs and hands but because I was not expecting this pain, I involuntarily, sudenly and strongly contracted my tummy muscles during those painful points (I think it happened 4 times) So I am very worried that uterus contracted at the same time as it is all conected I think… and I know uterus contractions should be avoided.
Q4. Do you think I did any harm? I cannot sleep because of it! I am afraid I compromised entire process. Is it possible that during those short contractions of tummy muscles I could “push” the embryo out of my uterus?
Thank you so much for creating this forum and all the precious information!
Aga
Since you are not my patient and you are currently receiving treatment by another RE, I cannot for ethical and medico legal reasons, inject myself here and intervene.
Sorry!
Geoff Sher
Dear Dr Sher, My wife had undergone pick up cycle recently. 9 eggs were retrieved, out of which 8 eggs were mature, 5 were fertilized and three embryos reach day 3 stage with 2 embryos grade A (8 cells) and one embryo grade B (6 cells). Our doctor told us that the egg quality was not good and there is very little chances of implantation with these embryos and asked us to go for donor egg. doctor is planning to transfer our embryos as well as donor egg embryo in single cycle to enhance the success rate. I would be grateful if you could answer my below queries:
1. Can poor egg quality produce grade A embryos
2. If yes, does chances of these grade A embryos getting implanted are minimal?
3. What would be your recommendation in our case? should we go for IVF with our own embryos or donor egg?
Thank you.
1. Can poor egg quality produce grade A embryos
A: Yes they can but not all day 3, grade A embryos are “competent”the real test would be to allow them to go to blastocyst and whether they test normal by PGS.
2. If yes, does chances of these grade A embryos getting implanted are minimal?
A: See #1 above
3. What would be your recommendation in our case? should we go for IVF with our own embryos or donor egg?
A: No, I would have your doctor take the Grade A embryo(s) to blastocyst and biopsy them for PGS.
Geoff Sher
Hello Dr. Sher!
I am 17dpiui and currently pregnant 🙂 However, I have been having some spotting and what seems like a “light period” starting from 12piui. It began as brown spotting, increased to a light flow of red bleeding on days 14 and 15piui, and now back to just red spotting. Mainly on the toilet paper when using the bathroom. My first HCG at 14dpiui was 46, and my second on 16dpiui was 108. So doubling as it should which is reassuring. Im just concerned about the spotting/red blood I am seeing. Not having any cramping or clots. My third HCG is tomorrow. Very anxious, as I miscarried 3 months ago but had low HCG without doubling from the start. Is this a cause for concern? Your advice it GREATLY appreciated!!!
Amy
I suspect that all will be well. It is not uncommon at all to experience benign spotting at this stage of early pregnancy.
I wish you well!
G-d bless!
Geoff sher
Oh I forgot one more question. Have had an issue with empty follicles at egg retrieval when my doctor gave me 250 ovidrel. Other cycle doctor gave CHORAGON 10,000 with more success. He now wants me to use ovidrel again but 2 so 2x 250 ovidrel. I’m nervous bevause everytime we use ovidrel they are empty. Would it be better to use 500 ovidrel or 10,000 iu Choragon? Once again thank you as always
25o mcg of Ovidrel is insufficient in my opinion. 500mcg should be much better.
Frequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to “Empty Follicle Syndrome.” This is a gross misnomer, because all follicles contain eggs. So why were no eggs retrieved from the follicles? Most likely it was because they would/could not yield the eggs they harbored.
This situation is most commonly seen in older women, women who have severely diminished ovarian reserve, and in women with polycystic ovarian syndrome (PCOS). In my opinion it is often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger shot.”
Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).
Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid, its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).
Older women, women with diminished ovarian reserve, and those with polycystic ovarian syndrome, tend to have more biologically active LH in circulation. LH causes production of male hormone (androgens, predominantly testosterone), by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced ovogenesis (egg development). Too much LH activity compromises the latter, and eggs so affected are far more likely to be aneuploid following meiosis.
Women with the above conditions have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the hCG trigger, leading to fruitless attempts at retrieval and the so called “empty follicle syndrome.”
The developing eggs of women who have increased LH activity (older women, women with diminished ovarian reserve, and those with PCOS) are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Because of this, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole), drugs that contain LH or hCG (e.g., Menopur), or protocols of ovarian stimulation that provoke increased exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols”) and the use of “late pituitary blockade” (antagonist) protocols can be prejudicial.
The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used, and the timing of its administration in such cases cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG (hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.
There is in my opinion no such condition as “Empty Follicle Syndrome.” All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation.
Good luck!
Geoff Sher