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.
Dear Dr Sher!
I am wondering how important grading of embryos if they were PGT tested? For example, what are the chances of BC embryos if they were PGT and came back euploid?
In my opinion, PGS/PGT testing overrides the morphological grade.
In the past, embryos were graded microscopically (morphologically). The higher the grade, the greater the likelihood that the embryo was “competent” (able to propagate a viable conceptus). The higher the grade of a day 3 (cleaved) embryo, the greater was the likelihood of it developing into a blastocyst by day 5-6 post fertilization and of that blastocyst being “competent”. But such morphologic/microscopic grading systems, while helpful, were flawed. For example, regardless of its grade, a cleaved, day 3 embryo that failed to progress to blastocyst by day 6 post-fertilization almost invariably was “incompetent”. Moreover, cleaved (day 3) embryos that developed into blastocysts while representing the ones that were the more likely to be “competent”, often times also turned out to “incompetent”.
It was not until 2005 that SFS physicians became the first to report reliably on the fact that it is the numerical chromosomal integrity (karyotype/ploidy) of an embryo that is the most important (but not the only) factor that determines its “competency”. Using a method called preimplantation genetic screening known as PGS /PGT-A (preimplantation genetic screening/testing for aneuploidy) , where advanced embryos are biopsied to remove one or more of their cells (blastomeres) for chromosomal karyotyping (using Comparative Genomic Hybridization-CGH or Next generation gene sequencing- NGS) to identify euploid embryos for selective transfer , our SFS team was able to show and report on the observation that by selectively identifying and freezing storing (vitribank) these for dispensation to the uterus in a subsequent frozen embryo transfer (FET) cycle, we could dramatically improve IVF outcome. This was especially the case in older women and women with DOR who tend to propagate a greater percentage of “incompetent” eggs/embryo and in women with RPL and those who experience recurrent IVF failures.
Furthermore, by using PGS/PGT-A, we were able to limit the number of embryos/blastocysts transferred to one, or at most two at a time, thereby dramatically improving the “baby rate” per embryo transferred, reducing the incidence of high order multiple pregnancies (triplets or greater), aneuploidy-related miscarriages and birth defects such as Down syndrome. Finally we corroborated the pre-PGS/PGT-A assertion that those embryos that failed to reach the advanced (pre-implantation) phase of development (blastocyst) by the 6th day post-fertilization were almost invariably aneuploid and “incompetent” and that transferring them earlier would NOT have improved their ability to propagate viable pregnancies.
. Could it actually go either way?
A: Yes it could. However, I respectfully differ with your RE in the importance of removing sizeable (>1cm) endometriomas as in my opinion, the affected ovary’s egg quality can be adversely affected. If sclerotherapy is not available hane surgical ablation is a good idea.
Advanced endometriosis is often associated with ovarian endometriotic cysts, known as endometriomas. In my opinion, such cysts, if numerous or sizable (>1cm) can and often do activate the surrounding ovarian connective tissue to locally produce excessive amounts of male hormones such as testosterone. This effect can often not be detected in the blood but nevertheless occurs in the affected ovary where, upon entering the follicles, it can i(n my opinion) compromise egg development which in turn often can result in abnormal egg development during ovarian stimulation. This can in my opinion, lead to increased numerical chromosomal abnormalities (aneuploidy), reducing egg/embryo competency”. Thus it is my opinion that any ovarian endometriomas larger than 1cm in diameter, should be removed eliminated before embarking on IVF.
Aside from compromising egg quality in the involved ovary, endometriomas can also cause severe and intractable pelvic pain, heavy menstruation (menometrorrhagia) and painful intercourse. They can also rupture leading to dissemination throughout the abdominal-pelvic cavity. Accordingly, they are best addressed sooner rather than later.
SurgicalTreatment: Conventional treatment of endometriomas involves complete surgical removal, usually conducted laparoscopically. Unfortunately, with surgery normal ovarian tissue can inadvertently be removed/damaged and result in scarring that that can compromise subsequent egg development in the affected ovary. Since many women who have endometriomas have already undergone previous surgery (ies) for endometriosis. Both the surgery (ies) and the advanced endometriosis will often have resulted in significant scarring and adhesion formation that can compromise subsequent visualization of, and access to anatomic structures during surgery, thereby increasing the risk of surgical complications. As such, many women with recurrent ovarian endometriomas are uncomfortable with the prospect of repeat surgery and its avoidance is often a factor in their decision to proceed with IVF.
Sclerotherapy: About 15 years ago I reported on a new, safe and highly effective outpatient approach to treating endometriomas in women planning to undergo IVF. This treatment, referred to as sclerotherapy involves ultrasound needle guided aspiration of the “chocolate colored liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline hydrochloride into the cyst cavity. In more than 75% of cases, this will result in disappearance of the lesion within 6-8 weeks. In some cases the injection of tetracycline into the endometrioma causes a reaction that results in clear or blood stained fluid collecting in the original cyst cavity where the endometrioma had been. Upon re-aspirating the fluid in the seroma, the lesion will usually disappears permanently. In a small number of cases, the endometrioma comes back and sclerotherapy must be repeated or surgical removal undertaken.
Ovarian sclerotherapy can be performed under local anesthesia or under conscious sedation. It has the advantage of being an ambulatory in-office procedure, low cost, and has a low incidence of significant post-procedural pain or complications as well as the avoidance of the need for invasive surgery. As such, sclerotherapy is in my opinion, the preferred treatment of endometriomas in women contemplating IVF and thus wish to preserve as much ovarian function as possible. It is a safe, effective and relatively inexpensive alternative to surgery. Since the procedure is associated with a small, but yet realistic possibility of pelvic adhesion formation its use should in my opinion be confined to cases where IVF is the only treatment available to the patient or for women who intend to try and conceive through fertilization in their fallopian tubes (e.g. following natural conception or intrauterine insemination), who in my opinion would be better off undergoing laparotomy or laparoscopy for the treatment of their endometriomas.
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2. Statistically because IVF dates are accurate, aren’t there medical journals that link chromosomal abnormalities with small foetus size? Isn’t it obvious that something is quite wrong as it is measuring behind? Could IVF babies actually catch up in your experience?
A: There is a link in some cases. AND yewsst the baby can “catch up”
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3. Different tables show different size measurements for gestational age. According to 1 of them, I am 6w1d and according to another, I am 6w3d. Which chart is accurate and is there a standard chart IVF doctors rely on?
A: Being only a few days behind is not in my opinion, relevant. US measurement is not that specific.
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4. I never have had implantation issues, always seems to be egg quality and my RE insists nothing can be done about that so she continues as normal with a short antagonist protocol (Elonva and Purguveris) and I barely get one fertilised embryo from 6-10 eggs collected. I am not sure what to do if an experienced and successful RE does not believe that much more can be done in improving my chances. I don’t want to put myself through endless cycles on the off chance one egg will make it at some point. And I am desperately running out of time.
A:When women with infertility due to endometriosis seek treatment, they are all too often advised to first try ovarian stimulation (ovulation Induction) with intrauterine insemination (IUI) ………as if to say that this would be just as likely to result in a baby as would in vitro fertilization (IVF). Nothing could be further from reality It is time to set the record straight. And hence this communication!
Bear in mind that the cost of treatment comprises both financial and emotional components and that it is the cost of having a baby rather than cost of a procedure. Then consider the fact that regardless of her age or the severity of the condition, women with infertility due to endometriosis are several fold more likely to have a baby per treatment cycle of IVF than with IUI. It follows that there is a distinct advantage in doing IVF first, rather than as a last resort.
So then, why is it that ovulation induction with or without IUI is routinely offered proposed preferentially to women with mild to moderately severe endometriosis? Could it in part be due to the fact that most practicing doctors do not provide IVF services but are indeed remunerated for ovarian stimulation and IUI services and are thus economically incentivized to offer IUI as a first line approach? Or is because of the often erroneous belief that the use of fertility drugs will in all cases induce the release (ovulation) of multiple eggs at a time and thereby increase the chance of a pregnancy. The truth however is that while normally ovulating women (the majority of women who have mild to moderately severe endometriosis) respond to ovarian stimulation with fertility drugs by forming multiple follicles, they rarely ovulate > 1 (or at most 2) egg at a time. This is because such women usually only develop a single dominant follicle which upon ovulating leaves the others intact. This is the reason why normally ovulating women who undergo ovulation induction usually will not experience improved pregnancy potential, nor will they have a marked increase in multiple pregnancies. Conversely, non-ovulating women (as well as those with dysfunctional ovulation) who undergo ovulation induction, almost always develop multiple large follicles that tend to ovulate in unison. This increases the potential to conceive along with an increased risk multiple pregnancies.
So let me take a stab at explaining why IVF is more successful than IUI or surgical correction in the treatment of endometriosis-related infertility:
1.The toxic pelvic factor: Endometriosis is a condition where the lining of the uterus (the endometrium) grows outside the uterus. While this process begins early in the reproductive life of a woman, with notable exceptions, it only becomes manifest in the 2ndhalf of her reproductive life. After some time, these deposits bleed and when the blood absorbs it leaves a visible pigment that can be identified upon surgical exposure of the pelvis. Such endometriotic deposits invariably produce and release toxins” into the pelvic secretions that coat the surface of the membrane (the peritoneum) that envelops all abdominal and pelvic organs, including the uterus, tubes and ovaries. These toxins are referred to as “the peritoneal factor”. Following ovulation, the egg(s) must pass from the ovary (ies), through these toxic secretions to reach the sperm lying in wait in the outer part the fallopian tube (s) tube(s) where, the sperm lie in waiting. In the process of going from the ovary(ies) to the Fallopian tube(s) these eggs become exposed to the “peritoneal toxins” which alter s the envelopment of the egg (i.e. zona pellucida) making it much less receptive to being fertilized by sperm. As a consequence, if they are chromosomally normal such eggs are rendered much less likely to be successfully fertilized. Since almost all women with endometriosis have this problem, it is not difficult to understand why they are far less likely to conceive following ovulation (whether natural or induced through ovulation induction). This “toxic peritoneal factor impacts on eggs that are ovulated whether spontaneously (as in natural cycles) or following the use of fertility drugs and serves to explain why the chance of pregnancy is so significantly reduced in normally ovulating women with endometriosis.
2.The Immunologic Factor: About one third of women who have endometriosis will also have an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells (NKa). This will require selective immunotherapy with Intralipid infusions, and/or heparinoids (e.g. Clexane/Lovenox) that is much more effectively implemented in combination with IVF.
3.Surgical treatment of mild to moderate endometriosis does not usually improve pregnancy potential:. The reason is that endometriosis can be considered to be a “work in progress”. New lesions are constantly developing. So it is that for every endometriotic seen there are usually many non-pigmented deposits that are in the process of evolving but are not yet visible to the naked eye and such evolving (non-visible) lesions can also release the same “toxins that compromise fertilization. Accordingly, even after surgical removal of all visible lesions the invisible ones continue to release “toxins” and retain the ability to compromise natural fertilization. It also explains why surgery to remove endometriotic deposits in women with mild to moderate endometriosis usually will fail to significantly improve pregnancy generating potential. In contrast, IVF, by removing eggs from the ovaries prior to ovulation, fertilizing these outside of the body and then transferring the resulting embryo(s) to the uterus, bypasses the toxic pelvic environment and is therefore is the treatment of choice in cases of endometriosis-related infertility.
4.Ovarian Endometriomas: Women, who have advanced endometriosis, often have endometriotic ovarian cysts, known as endometriomas. These cysts contain decomposed menstrual blood that looks like melted chocolate…hence the name “chocolate cysts”. These space occupying lesions can activate ovarian connective tissue (stroma or theca) resulting in an overproduction of male hormones (especially testosterone). An excess of ovarian testosterone can severely compromise follicle and egg development in the affected ovary. Thus there are two reasons for treating endometriomas. The first is to alleviate symptoms and the second is to optimize egg and embryo quality. Conventional treatment of endometriomas involves surgical drainage of the cyst contents with subsequent removal of the cyst wall (usually by laparoscopy), increasing the risk of surgical complications. We recently reported on a new, effective and safe outpatient approach to treating endometriomas in women planning to undergo IVF. We termed the treatment ovarian Sclerotherapy. The process involves needle aspiration of the “chocolate colored liquid content of the endometriotic cyst, followed by the injection of 5% tetracycline hydrochloride into the cyst cavity. Such treatment will, more than 75% of the time result in disappearance of the lesion within 6-8 weeks. Ovarian sclerotherapy can be performed under local anesthesia or under conscious sedation. It is a safe and effective alternative to surgery for definitive treatment of recurrent ovarian endometriomas in a select group of patients planning to undergo IVF
I am not suggesting that all women with infertility-related endometriosis should automatically resort to IVF. Quite to the contrary…. In spite of having reduced fertility potential, many women with mild to moderate endometriosis can and do go on to conceive on their own (without treatment). It is just that the chance of this happening is so is much lower than normal.
IN SUMMARY: For young ovulating women (< 35 years of age ) with endometriosis, who have normal reproductive anatomy and have fertile male partners, expectant treatment is often preferable to IUI or IVF. However, for older women, women who (regardless of their age) have any additional factor (e.g. pelvic adhesions, ovarian endometriomas, male infertility, IID or diminished ovarian reserve-DOR) IVF should be the primary treatment of choice. ______________________________________________________________________________________________________ 4. In the future, if I pursue another cycle and only get a grade 2 blastocyst (even if it looks wonderful under the microscope), should I discard it if it can't be tested instead of going through yet another potential miscarriage and D&C. Isn't the fact that it is an early blastocyst quite telling in itself? A: I would not discard it. I would transfer it. Chromosomal testing will not alter embryo competency. Iti is just a selection method. Good luck! Geoff Sher
Iam 44 years old . My AMH is 5.8 and FSH is 7. I have done two ivf cycles. First resulted in 6 embroyas with 5 abnormal and one no DNA detected. Second cycle only one embroyo made it to day 5 and currently waiting for PGT testing result. Iam taking levothyroxine 50 mcg and cabergoline 0.5 mg half a tablet twice a week. I concieved naturally but miscarried at 8 weeks in 2019. I have been visiting doctors since 2019 and no baby yet. Can you please advice and help me being a mother.
Both the Thyroid condition and age could be playing a role here.
WE should talk. Please contact my assistant Patti Converse (&02-533-2691 and set up an online consultation with me.
Please see the 2 articles below:
1. Age, Diminished Ovarian Reserve and IVF:
When it comes to reproductive performance, humans are the least efficient of all mammals. Even in young women under 35y, at best only 1 out of 2 eggs are chromosomally numerically normal (euploid). The remained have an irregular number of chromosomes (aneuploid) and are thus “incompetent”. The incidence of egg aneuploidy increases with age such by age 39 years, 3 in 4 are competent, and by the mid-forties, less 8 to 9 out of 10 are aneuploid. The fertilization of an aneuploid egg will inevitably lead to embryo aneuploid and an aneuploid embryo cannot propagate a normal pregnancy
Within hours of the spontaneous pre-ovulatory luteinizing hormone (LH) surge, and also following administration of the human chorionic gonadotropin (hCG) “trigger” shot (given to induce ovulation after ovarian stimulation with fertility drugs), the egg embarks on a rapid maturational process that involves halving of its 46 chromosomes to 23. During this process, (known as meiosis) 23 chromosomes are retained within the nucleus of the egg while the remaining (now redundant) 23are expelled, enveloped by a thin membrane. This small structure comes to lie immediately below the “shell” of the egg (the zona pellucida) and is known as the 1st polar body or PB-1. The spermatozoon, in the process of its maturation also undergoes meiosis at which time it too reduces its chromosomes by half. Thus in the process of fertilization the sperm divides into two separate functional gametes, each containing 23 chromosomes such that with subsequent fertilization, the 23 chromosomes in the egg, fuse with the 23 chromosomes of the mature sperm resulting in the development of an embryo that has 46 chromosomes (the normal human genome) comprising a combination of the genetic material from both partners.
For the embryo to have exactly 46 chromosomes (the euploid number), both the mature egg and mature spermatozoon must contain exactly 23 chromosomes. Only euploid embryos are “competent” (capable of developing into healthy babies). Those with an irregular number of chromosomes (aneuploid embryos) are “incompetent” and are incapable of developing into healthy babies. While embryo “incompetence” can result from either egg or sperm aneuploidy, it usually stems from egg aneuploidy. However, in cases of moderate or severe male factor infertility, the sperm’s contribution to aneuploidy of the embryo increases significantly.
While embryo ploidy (numerical chromosomal integrity) is not the only determinant of its “competency, it is by far the most important and in fact is rate-limiting factor in human reproduction. It is causal in most cases of “failed implantation” which in turn is responsible for most cases of failed IVF. It causes early miscarriages and is responsible for many chromosomal birth defects such as X-monosomy and Down’s syndrome. . In most cases, embryos that develop too slowly as well as those that grow too fast (i.e. ones that by day 3 post-fertilization comprise fewer than 6 cells or more than 9 cells) and/or embryos that contain a large amount of cell debris or “fragments” are usually aneuploid and are thus “incompetent”. Additionally, embryos that fail to survive in culture to the blastocyst stage are also almost always aneuploid/”incompetent”. At a certain point in the later stage of a woman’s reproductive career, the number of remaining eggs in her ovaries falls below a certain threshold, upon which she is unable to respond optimally to fertility drugs. Often times this is signaled by a rising day 3 blood follicle stimulating hormone (FSH) level. Such women with diminishing ovarian reserve produce fewer eggs in response to ovarian stimulation. While diminished ovarian reserve is most commonly encountered in women over 40 years of age it can and indeed sometimes does occur in much younger women. A few important (but often overlooked concepts should be considered in this regard: 1. Age: It is advancing chronologic age and NOT declining ovarian reserve (as evidenced by abnormal blood AMH or FSH that results in an increased incidence of egg/embryo “incompetence” due to aneuploidy 2. DOR: The ovaries and developing eggs of women with diminished ovarian reserve (regardless of age) are highly susceptible to the adverse effect of excessive Luteinizing Hormone (LH)-induced overproduction of male hormones (mainly testosterone). A little testosterone produced by the ovary promotes normal follicle growth and orderly egg development but too much testosterone has the opposite effect. That is why (especially in women with diminished ovarian reserve who often have high LH and increased ovarian testosterone production , the use of ovarian stimulation protocols that fail to down-regulate LH production prior to initiating stimulation with gonadotropins, often prejudices egg/embryo quality and IVF outcome. Simply stated, while age is certainly the most important factor in determining the incidence of egg/embryo aneuploidy, women with diminished ovarian reserve (regardless of their age), unless they receive customized/individualized protocols of ovarian stimulation are less likely to propagate euploid (competent) eggs/embryos.
Selection of the ideal protocol for controlled ovarian stimulation: While NOTHING can be done to lower the incidence of age-related aneuploidy, it is indeed possible to avoid a further increase in egg/embryo aneuploidy by individualizing the protocols of ovarian stimulation used.
My Preferred Protocols .
a) The conventional long pituitary down regulation protocol: BCP are commenced early in the cycle and continued for at least 10 days. Starting 3 days before the BCP is to be discontinued, it is overlapped with an agonist such as Lupron 10U daily for three (3) days and continued until menstruation begins (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst. Simultaneously, the Lupron dosage is reduced to 5U daily and an FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is commenced for 2 days. On the 3rd day the gonadotropin dosage is reduced and a small amount of daily menotropin (Menopur 75U daily) is added. Daily ultrasound and blood estradiol measurements are done starting on the 7th or 8th day of gonadotropin administration and continued until daily ultrasound follicle assessments indicate that most follicles have fully developed. At this point egg maturation is “triggered” using an intramuscular injection of 10,000U hCG. And an egg retrieval is scheduled for 36h later.
b) The agonist/antagonist conversion protocol (A/ACP): This is essentially the same as the conventional long down regulation protocol (as above), except that with the onset of post-BCP menstruation, the agonist is supplanted by daily administration of a GnRH antagonist (e.g. Ganirelix, Cetrotide or Orgalutron) at a dosage of 125mcg daily until the day of the hCG trigger
When it comes to women who have DOR I favor the use of the A/ACP, adding supplementary human growth hormone (HGH). In some cases where the DOR is regarded as severe, I also augment the process with estrogen priming, preferring twice weekly intramuscular administration of estradiol valerate (Delestrogen), starting with the commencement of antagonist injection and continuing for 1 week before commencing gonadotropins and continued until the hCG “trigger. I further recommend that such women be offered access to preimplantation genetic screening (PGS) for4 embryo selection and in some cases, for embryo banking (stockpiling). This is followed in a later hormone replacement cycle with the selective transfer of up to two (2) PGS-normal, euploid blastocysts. In this way we are able to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” , significantly enhancing the opportunity to achieve a viable pregnancy
The following Ovarian Stimulation Protocols which in my Opinion best Avoided:
a) Microdose agonist (e.g. Lupron) “flare” protocols
b) High doses of LH/hCG-containing fertility drugs (E.G. Menopur).
c) Protocols that incorporate supplementation with male hormones (e.g. testosterone)
d) Supplementation with DHEA
e) Clomiphene citrate or Letrozole which cause an elevation in LH and thus increase ovarian male hormone (testosterone and androstenedione output.
f) “Triggering” egg maturation using too low a dosage of hCG (e.g. 5,000U rather than 10,000U) or Ovidrel e.g. 250mcg of Ovidrel rather than 500mcg)
g) “Triggering” women who have large numbers of follicles using an agonist such as Lupron, Superfact or Buserelin.
Preimplantation Genetic Screening (PGS):
The introduction of preimplantation genetic screening (PGS) for the first time permits identification of all the chromosomes in the egg and embryo such that we can now far better identify “competent” (euploid) embryos for selective transfer to the uterus. This vastly improves the efficiency and success of the IVF process. This additional tool has better equipped us to manage cases with DOR. In my opinion, next generation gene sequencing (NGS), currently represents the most reliable method for performing PGS
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2. Thyroid Autoimmune Disease and IVF:
Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.
Hi, I will be using donor embryos due to infertility. The egg donor was 35 when she went through IVF, which resulted in a dozen embryos. The sperm donor was 40. I am planning on getting them PGT tested due to the age of the egg donor. My doctor said the frozen embryos were right on the cusp of PGT testing being recommended since the donor was 35. What are your thoughts? Any other tests or donor results needed in order to make an educated decision on if it I should proceed with testing?
While pregnancies do occur when frozen embryos are thawed, biopsied and then re-frozen to await the results of testing, it is my opinion that this is too traumatic on the embryo and reduces the success potential. Therefore my advice is to transfer without doing PGS.
Good luck!
I developed Asherman after a D&C. The scaring got cleared after three hysteroscopies. A saline sonogram was done, and it showed restricted distension, but my doctor says the cavity is open and wide enough to accept and grow a baby.
After a year of trying to get pregnant naturally, we decided to try IVF, but it failed (I got a positive test, but beta-HCG stopped growing). My lining is thin and doesn’t respond much to medication…grows from 4mm to 6mm.
My doctor has said my endometrium is not the problem, as it gets secretory, and we got a positive pregnancy test after IVF.
I am worried. I don’t want to keep spending on several rounds of IVF if I have no chance of success. What do you think about my condition and chances of getting pregnant?
Very respectfully, I strongly disagree with your RE’s take on your situation. We should talk! Please call my assistant Patti Converse at 702-533-2691 and set up an online consultation with me to discuss in detail.
Asherman syndrome is a condition characterized by the presence of severe intrauterine adhesions (synechiae) that destroy most of the basal layer of the endometrium from which, under the influence of the hormones, estrogen and progesterone, the uterine lining (endometrium), develops. When most of the basal endometrium is incapacitated so that virtually no regeneration of the endometrium can take place, amenorrhea (cessation of menstruation) and infertility follows.
Asherman syndrome most commonly results from post-partum or post-abortal inflammation involving the uterine lining (endometritis), but it can also occur following uterine surgery such as removal of fibroid tumors (myomectomy) that encroach upon or penetrate the uterine cavity.
Treatment involves a procedure called hysteroscopic resection, whereby a telescope-like instrument is introduced via the vagina and cervix into the uterine cavity, to allow direct surgical resection of as much scar tissue as possible. The objective is to remove as much scar tissue as possible and to free adhesions that fuse the walls of the uterine cavity together to uncover and enable viable basal endometrium to resume growth and progressively cover as much of the surface of the uterine cavity as possible. Post operatively, a small balloon is often placed in the uterine cavity for a day or two, to keep the opposing surfaces separated in the hope of preventing recurrence of adhesion formation. The woman usually receives supplemental estrogen, corticosteroid (prednisone), and antibiotic to encourage endometrial growth.
Endometritis of a severity sufficient to produce Asherman Syndrome usually scars and blocks the uterine entrance to the fallopian tubes. However, sometimes one or both tubes remain open (although there is usually always some degree of damage to the inner lining). While in such cases, the uterus is often incapable of allowing proper embryo implantation, a pregnancy could implant in a fallopian tube leading to an ectopic pregnancy, which unless it is diagnosed early (by ultrasound examination) and treated medically or surgically, will rupture with severe intra-abdominal bleeding.
Unfortunately, with Asherman syndrome, even after surgical removal of as much scar tissue as possible, the uterine lining often remains quite thin and insufficient to allow implantation. In these cases, there is such widespread destruction of the basal endometrium (from which fresh endometrial cells must be generated), that improving blood flow with Viagra is usually unsuccessful in improving estrogen-mediated endometrial development sufficient to achieve “adequate” improvement in endometrial growth. In such cases, women should consider adoption or resort to gestational surrogacy.
I got preg quick miscarried after heard heartbeat. No abnormalities found. Year later after first transfer that failed learned have hashimotos. My current clinic doesn’t test me for natural killer cells or any other immune issues for some reason. My high risk OB has a plan but I want a second opinion and really want to do a full work up of me. I only have two normal embryos from six retrievals. First retrieval I did transfer like I said before. I’m 40 now. Can your place test for that or I need an actual immunologist?
Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
•The Fundamental Requirements for Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
•Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
•Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
•Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID) Why did my IVF Fail
•Recurrent Pregnancy Loss (RPL): Why do I keep losing my Pregnancies
•Genetically Testing Embryos for IVF
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
•Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
•IVF: Selecting the Best Quality Embryos to Transfer
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
•Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
•Intralipid (IL) Administration in IVF: It’s Composition how it Works Administration Side-effects Reactions and Precautions
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
•Should IVF Treatment Cycles be provided uninterrupted or be Conducted in several Pre-scheduled “Batches” per Year
•A personalized, stepwise approach to IVF
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ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher