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.
I just did a FET. My beta HCG 9dp5dt was 75, but then only 98 at 11dp5dt. At 14dp5dt it went down to 85. I was told to stop all medications, which were 1ml of PIO and 3 endometrin suppositories daily, along with .25 of Delestrogen twice a week.
I stopped everything but the endometrin, which I continued. I missed two doses of PIO and one of Delestrogen. My beta today at 16dp5dt went up to 123. My RE said I could start the medications again, but that I only had a 1% chance of a viable pregnancy.
I felt foolish, but started them again. I know it’s looking bleak. My question is, could those missed doses of medications ruined any chance I had at all? The nurse could not really give me an answer.
Thank you!
Sadly, this does not look like a viable pregnancy to me. Your doctor needs to track the hCG level and do an US in a week or so to rule out an ectopic (tubal) pregnancy.
Good luck!
Geoff Sher
What are you thoughts on transferring a mosaic monosomy embryo? I am a young healthy female with no known fertility issues, my husband had PESA done to extract sperm and then we did IVF with ISCI, PGS indicated that all 9 embryos are genetically abnormal and prior to PGS all my embryos were graded chromosomoly high 5 AA, 5 AB etc. Apparently the clinicians that I have been working with do not have answers for me as to why, as originally they never would of thought this would of been the outcome. I feel like there is a process issue and quite possibly the mosaic monosomy embryos may develop upon transfer and create a healthy child. What are your thoughts?
Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or pre-implantation embryo development, and represents a major cause of early pregnancy loss. About a decade ago, I and an associate, Levent Keskintepe Ph.D were the first to introduce full embryo karyotyping (identification of all 46 chromosomes) through preimplantation genetic sampling (PGS) as a method by which to selectively transfer only euploid embryos (i.e. those that have a full component of chromosomes) to the uterus. We subsequently reported on a 2-3 fold improvement in implantation and birth rates as well as a significant reduction in early pregnancy loss, following IVF. Since then PGS has grown dramatically in popularity such that it is now widely used throughout the world.
Most IVF programs that offer PGS services, require that all participating patients consent to all their aneuploid embryos (i.e. those with an irregular quota of chromosomes) be disposed of. However, there is now growing evidence to suggest that following embryo transfer, some aneuploid embryos will in the process of ongoing development, convert to the euploid state (i.e. “autocorrection”) and then go on to develop into chromosomally normal offspring. In fact, I am personally aware of several such cases occurring within our IVF network. So clearly , summarily discarding all aneuploid embryos as a matter of routine we are sometimes destroying some embryos that might otherwise have “autocorrected” and gone on to develop into normal offspring.
Thus by discarding all aneuploid embryos we and in so doing, the possibility exists that we could be denying some women the opportunity of having a baby. This creates a major ethical and moral dilemma for those of us that provide the option of PGS to our patients. On the one hand, we strive “to avoid knowingly doing harm” (the Hippocratic Oath) and as such would prefer to avoid or minimize the risk of miscarriage and/or chromosomal birth defects and on the other hand we would not wish to deny patients with aneuploid embryos, the opportunity to have a baby.
The basis for such embryo “autocorrection” lies in the fact that some embryos found through PGS-karyotyping to harbor one or more aneuploid cells (blastomeres) will often also harbor chromosomally normal (euploid) cells (blastomeres). The coexistence of both aneuploid and euploid cells coexisting in the same embryo is referred to as “mosaicism.” Many such mosaic embryos will In the process of subsequent cell replication convert to the normal euploid state (i.e. autocorrect)
It is against this background, that an ever increasing number of IVF practitioners, rather than summarily discard PGS-identified aneuploid embryos are now choosing to cryobanking (freeze-store) certain of them, to leave open the possibility of ultimately transferring them to the uterus. In order to best understand the complexity of the factors involved in such decision making, it is essential to understand the causes of embryo aneuploidy of which there are two varieties:
1.Meiotic aneuploidy” results from aberrations in chromosomal numerical configuration that originate in either the egg (most commonly) and/or in sperm, during preconceptual maturational division (meiosis). Since meiosis occurs in the pre-fertilized egg or in and sperm, it follows that when aneuploidy occurs due to defective meiosis, all subsequent cells in the developing embryo/blastocyst/conceptus inevitably will be aneuploid, precluding subsequent “autocorrection”. Meiotic aneuploidy will thus invariably be perpetuated in all the cells of the embryo as they replicate. It is a permanent phenomenon and is irreversible. All embryos so affected are thus fatally damaged. Most will fail to implant and those that do implant will either be lost in early pregnancy or develop into chromosomally defective offspring (e.g. Down syndrome, Edward syndrome, Turner syndrome).
2.“Mitotic aneuploidy” occurs when following fertilization and subsequent cell replication (cleavage), some cells (blastomeres) of a meiotically euploid early embryo mutate and become aneuploid. This is referred to as mosaicism. Thereupon, with continued subsequent cell replication (mitosis) the chromosomal make-up (karyotype) of the embryo might either comprise of predominantly aneuploid cells or euploid cells. The subsequent viability or competency of the conceptus will thereupon depend on whether euploid or aneuploid cells predominate. If in such mosaic embryos aneuploid cells predominate, the embryo will be “incompetent”). If (as is frequently the case) euploid cells prevail, the mosaic embryo will be “competent” and capable of propagating a normal conceptus.
Since some mitotically aneuploid (“mosaic”) embryos can and indeed do “autocorrect’ while meiotically aneuploid embryos cannot, it follows that an ability to differentiate between these two varieties of aneuploidy would be of enormous clinical value. Since some mosaic embryos can “autocorrect” and even go on to propagate a viable baby, the ability to confirm that aneuploidy is mitotic (potentially reversible) would provide a strong argument in favor of preserving certain aneuploid embryos for future dispensation. Unfortunately however, there is presently no microscopic or genetic test that can reliable differentiate between meiotic and mitotic aneuploidy.
Aneuploidy, whether meiotic or mitotic in origin involves the addition of one or more chromosomes to a given pair in human embryos. Certain aneuploidies involve only a single, chromosome pair (simple aneuploidy) while others involve more than a single pair (i.e. complex aneuploidy). Evidence suggests that complex aneuploidy, whether meiotic or mitotic in origin is almost always lethal while all forms of meiotic aneuploidy are permanent. Some aneuploidies, especially those that involve addition of a chromosome to any pair (trisomy) will at times progress to clinical pregnancies (e.g. trisomy 15, 18, 21 or when the sex chromosomes are involve). And as stated previously, most aneuploid embryos, should they attach, will miscarry or result in a chromosomally defective offspring.
On the other hand, some aneuploid embryos have one chromosome (in a given pair) missing (i.e. monosomy). Aside from monosomy involving absence of the y-sex chromosome (i.e. XO) which can resulting in a live birth (Turner syndrome) all other monosomies involving autosomes (non-sex chromosomes) are lethal and will not result in viable offspring.
Since it is presently not possible, without removing more than 1 cell from an embryo (a very traumatic event) to differentiate between meiotic and mitotic aneuploidy, it follows that making a diagnosis of embryo aneuploidy does not allow for identification of mosaic embryos for transfer. This is especially true when it comes to trisomic embryos that can and sometimes do, propagate chromosomal birth defects such as Down syndrome. It is important to bear in mind that the transfer of trisomic embryos (whether due to meiotic or mitotic aneuploidy) can result in miscarriage or a birth defect. This makes any attempt to transfer such embryos to the uterus such a transfer, fraught with risk and in my opinion, ill advised. Conversely, since true meiotic autosomal monosomic embryos cannot propagate viable pregnancies, performing embryo transfer in such cases in the hope that the aneuploidy is mitotic (mosaic) in origin and will spontaneously “autocorrect”, is a rational consideration. Needless to say, such action would require full disclosure, the completion of a detailed informed consent agreement which would include an expressed commitment to undergo prenatal genetic testing aimed at excluding a chromosomal defect in the developing baby and/or a willingness to terminate the pregnancy should a serious birth defect be diagnosed.
Since it is meiotic rather than mitotic aneuploidy that is invariably lethal and given that meiotic aneuploidy originates in the egg, it is my belief that the closer to fertilization that embryo biopsy is done for PGS, the more likely it is that any aneuploidy detected, will be meiotic in origin. The longer you wait thereafter, the greater the likelihood that with repeated mitotic division, mutational changes will result in mitotic aneuploidy (mosaicism). This is why I strongly believe embryo biopsies should be performed on day 2-3 post fertilization rather on day 5-6 days (the blastocyst stage).”.
I hope this helps!
Geoff Sher
PH: 702-699-7437
Dear Dr, Sher,
My bloods showed I was ovulating but 16 days later there is still no period.
1)Is it possible to ovulate and not get a period?
2)How long is too long for a luteal phase?
3)why does luteal phase get longer than usual?
Sincerely
Claire
Either you are pregnant or you possibly have a corpus luteum cyst. Check your beta hCG (urine pregnancy test) and if it is -ve, see your GYN for an ultrasound.
Good luck!
Geoff Sher
Dear Dr. Sher,
I’m 36 yrs old with infertility and PCOS. I did a hysterosalpingography last June which showed nothing abnormal except a narrow fallopian tube end on the right side.
After two recent unsuccessful IUIs, our gyno put me on to a fertility specialist/surgeon who suggested ovarian drilling. After viewing my previous tests he felt quite positive about my ability to get pregnant without IVF. He explained that other issues which may have been undetectable on ultrasound (endometrial growth etc.) could be corrected because they would be able to “see” any possible obstacles and deal with them during the surgery.
I noted that you have a somewhat unfavourable view of ovarian drilling and ovarian wedge resection. I’d like to know more about these options as I’m quite fearful of the risks of reduced ovarian reserve/early menopause, scar tissue and adhesions etc. The surgeon didn’t actually mention the wedge resection bit so I will ask him if he intends to do that in addition to the drilling.
I also wanted to know if the drilling could reduce my risk of OHSS if I end up having to resort to IVF.
For my two IUI cycles, I was on a 37,5 dose of Gonal, then the same dose of Menopur, and got one dominant follicle in the right ovary both times. I know it’s not a great turnout, but my gyno has been very cautious when it comes to the hormone treatments and I do appreciate her carefulness.
Any guidance you could offer would be greatly appreciated!
Lindsey
In my opinion, ovarian drilling is counter-productive. First, it does not help significantly. Any benefit is short lived (maby a few months) because thew underlying problem has not been addressed. Besides, it does cause adhesions too and will not prevent OHSS with subsequent ovarian stimulation. Wedge resection is not done any longer and belongs in the history books.
Polycystic ovary syndrome (PCOS) is a common hormonal system disorder among women affecting between 5% and 10% of women of reproductive age worldwide. Women with PCOS may have enlarged ovaries that contain small collections of fluid — called follicles — located in each ovary as seen during an ultrasound. The condition is characterized by abnormal ovarian function (irregular or absent periods, abnormal or absent ovulation and infertility), androgenicity (increased body hair or hirsutism, acne) and increased body weight –body mass index or BMI. The ovaries of women with PCOS characteristically contain multiple micro-cysts often arranged like a “string of pearls” immediately below the ovarian surface (capsule).interspersed by an overgrowth of ovarian connective tissue (stroma).
PCOS is one of the most common causes of menstrual irregularities, infertility, and hirsutism, Despite an enormous effort to define its cause, the etiology of PCOS remains unclear, and there is no definite cure at this time. PCOS is clearly a heterogeneous disorder which often has a familial (genetic) basis. Infertility associated with PCOS has been attributed to numerous factors, including dysfunctional gonadotropin pituitary secretion, peripheral insulin resistance, elevated adrenal and/or ovarian androgen (male hormone) levels, and dysfunction of several growth factors. Women with this condition are often obese and insulin resistant. The compensatory hyperinsulinemia further stimulates ovarian androgen production which may be detrimental to egg maturation and there is a clear link between the degree of insulin resistance and anovulation. PCOS is also a significant long-term health risk for women, thus necessitating vigilance through regular annual examinations (non-insulin dependent diabetes mellitus, hypertension, hypercholesterolemia, cardiovascular disease and endometrial cancer). Whereas PCOS-related infertility is usually manageable through the use of fertility drugs, lifestyle changes (diet and exercise) remain a mainstay of long-term therapy. More recently, ovulation rates, circulating androgens, pregnancy rates and perhaps even first-trimester miscarriage rates have been shown to improve when insulin sensitizers like metformin are used to correct the underlying insulin resistance.
Most patients with PCOS are young and have excellent pregnancy rates with oral clomiphene. Those that require more aggressive treatments with injectable medications probably represent a subgroup of PCOS patients with severe ovarian dysfunction. These women often have explosive response to gonadotropins which can result in serious complications like Severe Ovarian Hyperstimulation Syndrome (OHSS…see below) and high order multiple births. In those women, the ability to perform “prolonged coasting” (see below) and selectively transfer fewer embryos during IVF offers a clear advantage over standard gonadotropin injections.
Egg quality in PCOS
The potential for a woman’s eggs to undergo orderly maturation, successful fertilization and subsequent progression to “good quality embryos” is in large part genetically determined. However, the expression of such potential is profoundly susceptible to numerous influences, especially intra-ovarian hormonal changes during the pre-ovulatory phase of the cycle. Proper follicular stimulation as well as precise timing of egg maturation with LH (Luteinizing Hormone) or hCG (human chorionic gonadotropin) is crucial to optimal egg maturation, fertilization and ultimately embryo quality. Both pituitary gonadotropins, LH and FSH (follicle stimulating hormone) play a pivotal but different role in follicular development. The action of FSH is mainly directed toward granulosa cell (cells lining the inside of the follicle) proliferation and estrogen production (E2). LH, on the other hand, acts primarily on the ovarian stroma (the connective tissue that surrounds the follicle) to produce androgens. While small amounts of ovarian androgens, such as testosterone, enhance egg and follicle development, over-exposure to them can have a deleterious effect. Furthermore, excessive ovarian androgens can also compromise estrogen-induced endometrial growth and development.
Suppressing pituitary secretion of LH with gonadotropin releasing hormone (GnRH) agonists such as Lupron®, is particularly useful in PCOS. In that condition, serum LH levels are elevated, leading to stromal overgrowth, follicular arrests (so-called cysts) and high levels of androgens synthesis. It is therefore not surprising that these follicles often yield poorly developed (“immature”) eggs” at the time of egg retrieval (ET) and that “poor egg/embryo quality”, inadequate endometrial development and high miscarriage rates are common features of this condition. However, contrary to popular belief, this is not due to an intrinsic deficit in “egg quality”. Stimulation protocols geared toward optimizing follicle and egg development and avoiding over exposure to androgens correct these problems ad result in pregnancy rates similar to those of non-PCOS women. Whereas the overuse of LH-containing preparations such as Menopur® and Luveris® further aggravates this effect. In conclusion, to maximize ultimate oocyte maturation, we strongly recommend against the exclusive use of such products in PCOS patients, preferring FSH-dominant products such as Folistim®, Gonal F® or Bravelle® over a period of at least 9 days following pituitary suppression with Lupron®.
PCOS women often have a family history of diabetes and demonstrable insulin resistance (evidenced by high blood insulin levels and an abnormal 2-hour glucose tolerance test).This underlying Diabetes mellitus tendency could play a role in the development of PCOS and contribute to the development of obesity, an abnormal blood lipid profile, and a predisposition to coronary vascular disease. Women with PCOS are slightly more at risk of developing uterine, ovarian and possibly also breast cancer in later life and accordingly should be evaluated for these conditions on a more frequent basis than would ordinarily be recommended to non-PCOS women.
Most women with PCOS either do not ovulate at all or they ovulate irregularly. As a consequence thereof they in addition usually experience delayed, absent or irregular menstruation. In addition, an inordinate percentage of the eggs produced by PCOS women following ovulation induction, tend to be chromosomally abnormal (aneuploid). Rather than being due to an intrinsic egg defect being inherent in PCOS women, the poor egg quality more than likely the result of over-exposure to male hormones (predominantly, testosterone) produced by the ovarian stroma. These two factors (ovulation dysfunction and poor egg quality) are the main reasons for the poor reproductive performance (infertility and an increased miscarriage rate) in PCOS women.
PCOS patients are at an inordinate risk of severely over-responding fertility drugs, both oral varieties (e.g. Clomiphene, Serophene & Femara) and especially the injectables (e.g. Follistim, Puregon, Gonal F, Menopur and Bravelle) by forming large numbers ovarian follicles. This can lead to life endangering complications associated with sever ovarian hyperstimulation (OHSS). In addition PCOS women receiving fertility drugs often experience multiple ovulations putting them at severe risk (40%+) of high order multiple pregnancy (i.e. triplets or greater) with often devastating consequences.
VARIETIES OF POLYCYSTIC OVARIAN SYNDROME:
1) Hypothalamic-pituitary-PCOS: This is the commonest form of PCOS and is often genetically transmitted and is characteristically associated with a blood concentration of Luteinizing Hormone (LH) that is uncharacteristically much higher than the Follicle Stimulating Hormone (FSH) level (FSH is normally higher than the LH concentration) as well as high-normal or blood androgen ( male) hormone concentrations (e.g. androstenedione, testosterone and dehydroepiandrosterone -DHEA).Hypothalamic-pituitary-ovarian PCOS is also often associated with insulin resistance and in about 40%-50% of the cases.
2) Adrenal PCOS: Here the excess of male hormones are derived from overactive adrenal glands rather than from the ovaries. Blood levels of testosterone and/or androstenedione raised but here, but here, the blood level of dehydroepiandrosterone (DHEAS) is also raised, clinching the diagnosis.
3) Severe pelvic adhesive disease secondary to severe endometriosis, chronic pelvic inflammatory disease and/or extensive pelvic surgery: Women who have this type of PCOS tend to less likely to hyperstimulate in response to ovulation induction . Their. DHEAS is also is not raised.
TREATMENT OF INFERTILITY DUE TO ASSOCIATED OVULATION DYSFUNCTION:
Hypothalamic-pituitary-/ovarian PCOS: Ovulation induction with fertility drugs such as clomiphene citrate, Letrozole (Femara) or gonadotropins, with or without intrauterine insemination (IUI) is often highly successful in establishing pregnancies in PCOS women. However, IVF is fast becoming a treatment of choice (see below).
In about 40% of cases, 3-6 months of oral Metformin (Glucophage) treatment results in a significant reduction of insulin resistance, lowering of blood androgen levels, an improvement in ovulatory function, and/or some amelioration of androgenous symptoms and signs.
Surgical treatment by “ovarian drilling” of the many small ovarian cysts lying immediately below the envelopment (capsule) of the ovaries, is often used, but is less successful than alternative non-surgical treatment and is only temporarily effective. The older form of surgical treatment, using ovarian wedge resection is rarely used any longer as it can produce severe pelvic adhesion formation.
Adrenal PCOS is treated with steroids such as prednisone or dexamethasone which over a period of several weeks will suppress adrenal androgen production, allowing regular ovulation to take place spontaneously. This is often combined with clomiphene, Letrozole and/or gonadotropin therapy to initiate ovulation.
PCOS attributable to Pelvic Adhesive Disease is one variety which often is associated with compromised ovarian reserve, a raised FSH blood level and ovarian resistance to fertility drugs. In many such cases, high dosage of gonadotropins (FSH-dominant) with “estrogen priming” will often elicit an ovarian response necessary for successful ovulation induction and/or IVF. Neither steroids nor Metformin are helpful in the vast majority of such cases.
PCOS women undergoing ovulation induction usually release multiple eggs following the hCG trigger and are thus at inordinate risk of twin or higher order multiple pregnancies. They are also at risk of developing OHSS. Many now believe that IVF should be regarded as a primary and preferential treatment for PCOS. The reason is that it is only through this approach that the number of embryos reaching the uterus can be controlled and in this manner the risk of high-order multiples can be minimized and it is only in the course of IVF treatment that a novel treatment method known as “prolonged coasting” ( see below) which prevents OHSS, can be implemented
SEVERE OVARIAN HYPERSTIMULATION SYNDROME (OHSS):
As indicated above, there is an inordinate propensity for women with PCOS to hyper-respond to gonadotropin fertility drugs and in the process produce large numbers of ovarian follicles. If left unchecked this can lead to OHSS, a potentially life endangering condition. The onset of OHSS is signaled by the development of a large number of ovarian follicles (usually more than 25 in number). This is accompanied by rapidly rising plasma estradiol (E2) levels, often exceeding 3000pg/ml within 7 or 9 days of stimulation, often rapidly peaking above 6,000 pg/ml prior to hCG administration. When this happens, the risk of OHSS developing is above 80%.
Symptoms and signs of OHSS include: abdominal distention due to fluid collection (ascites), fluid in the chest cavity (hydrothorax), rapid weight gain (of a pound or more per day) due to tissue fluid retention, abdominal pain, lower back ache, nausea, diarrhea, vomiting, visual disturbances such as blurred vision and spots in front of the eyes (scotomata), a rapidly declining urine output, cardiovascular collapse and failure of blood to clot which sometimes results in severe bruising (echymosis) and frank bleeding. These symptoms and signs may appear before pregnancy can be diagnosed. If pregnancy occurs, the condition is likely to worsen progressively over a period of 3-5 weeks whereupon it rapidly resolves spontaneously over a few days. If no pregnancy occurs, the symptoms and signs all disappear spontaneously within 10-12 days of the hCG injection.
When increasing fluid collection in the abdominal cavity (ascites) starts to compromise breathing raising the head of the bed rose slightly by placing a 4-6 inch block at the base of each head post and using a few additional pillows, will sometimes help ameliorate the problem. In cases where this does not help or symptoms become severe, all or most of the fluid can readily and safely be drained through t transvaginal sterile needle aspiration (vaginal paracentesis-performed once or sometimes twice a week) can be performed once or twice weekly . The problem will usually self corrects within 10-12 days of the hCG shot if pregnancy does not occur or, by the 8th week of pregnancy.
Urine output should be monitored daily to see if it drops below about 500ml a day (about two cups and a half). A chest X-ray, to evaluate for fluid collection in the chest and around the heart should be done weekly along with blood tests for hematocrit, BUN, electrolytes, creatinine, platelet count and fibrin split products (FSP). If indicated on the basis of a deteriorating clinical situation, hospitalization might be needed for close observation and if necessary, to provide intensive care.
In all case of OHSS, the ovaries will invariably be considerably enlarged. This is irrelevant to the final outcome, unless ovarian torsion (twisting of the ovary on its axis), an extremely rare complication occurs. The latter would usually require surgical emergency surgical intervention.
It is important to know that symptoms and signs of OHSS are severely aggravated by rising hCG levels. Thus such patients should not receive additional hCG injections.
Does PCOS cause poor egg/embryo quality? It is an undeniable fact that women with PCOS undergoing IVF are commonly found to have poorly developed (“dysmorphic”) eggs, with reduced fertilization potential and yielding “poor quality embryos”. However, in the author’s opinion (which admittedly runs contrary to popular opinion), this is unlikely to be due to an intrinsic deficit in egg quality. Rather, it more likely relates to intra-ovarian hormonal changes brought about by hyperstimulation and which compromise egg development. This effect, in the author’s opinion, can often be significantly reduced through implementation of an individualized or customized ovarian stimulation protocols that minimize exposure of the developing follicles and eggs to excessive LH-induced ovarian androgens. This can be best achieved by limiting the use of LH-containing gonadotropins such as Menopur through selective institution of “prolonged coasting” (see below).
In the past, the onset of OHSS, heralded by the presence of large numbers of developing ovarian follicles and rapidly rising plasma estradiol levels often led the treating physician to prematurely administer hCG in an attempt to abruptly arrest the process and prevent escalation of risk to the patient. However the premature administration of hCG, while abruptly arresting further proliferation of estrogen producing granulosa cells in the follicles, unfortunately also prematurely arrests egg development. Since the ability of an egg to achieve optimal maturation upon hCG triggering is largely predicated upon it having achieved prior optimal development, the untimely administration of hCG which triggers meiosis, probably increases the risk of numerical chromosomal abnormalities (aneuploidy) of the egg. This in turn would lead to reduced fertilization potential, poor egg/embryo quality and low embryo implantation potential.
In women with PCOS the connective tissue that surrounding the follicles (ovarian stroma) is often characteristically overgrown (stromal hyperplasia). It is the stroma that produces androgens (mainly testosterone) in response to LH. It is this, coupled with the fact that PCOS women also often have elevated blood LH concentrations (see above) results in the excessive production of androgen hormones, which is so characteristic in PCOS. While excessive exposure of developing eggs to ovarian androgens compromises follicle and egg growth it also impairs endometrial response to estrogen, which could explain the common finding of poor endometrial thickening in many PCOS women undergoing IVF.
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The obvious remedy for these adverse effects on egg and endometrial development is to employ stimulation protocols that limit ovarian over-exposure to LH and allowing the time necessary for the follicles/eggs to develop optimally, prior to administering hCG through the judicious implementation of “Prolonged coasting” (PC).
“PROLONGED COASTING”:
In the early 90’s we were the first to report on “prolonged coasting” (PC), a novel approach that protects egg quality while preventing the development of OHSS. PC has since, gained widespread acceptance as a method of choice for preventing OHSS and has established itself as the “standard of care”. It involves withholding gonadotropin therapy while continuing the administration of the GnRHa and waiting until the plasma estradiol concentration drops below 2,500 pg/ml. Thereupon hCG is administered. In such cases, regardless of the number of developed follicles or the number of eggs retrieved, these women rarely, if ever develop OHSS. It has been reported that while PC virtually eliminates the risk of life-endangering complications associated with OHSS, there are reports in the literature that “the price to pay with PC” is often a poorer fertilization rate and reduced embryo implantation potential, compromising the pregnancy”. It is the author’s opinion an experience in the development of PC that egg/embryo quality deficit likely has little to do with the process of PC, itself and can be explained as follows: When PC is initiated too early, follicle growth and development may cease (as evidenced by the estradiol level plateauing or falling immediately, rather than showing an initial continued increase), and when PC is started too late, the follicles will often become cystic, measuring >21mm by the time the estradiol level falls below the safe threshold of 250000pg/ml, and so harbor dysmorphic eggs. Thus precise timing of the initiation of PC is critical. It should in pact be initiated preemptively in all cases when there are more than 25 follicles and the plasma estradiol reaches or exceeds 2,500pg/ml in association, provided that at least 50% of the follicles measuring 14-16mm in mean diameter. Not a day sooner or a day later. If PC is initiated with precise timing, it will usually be followed by a further progressive rise in the estradiol concentration. After a few days, the estradiol level will plateau and then it will start to fall (often rapidly). The temptation to trigger with hCG before the estradiol level falls below 3000picogtrams per milliliter must be resisted …even if the level falls below 1,000pg/ml by the time hCG is given.
Since when using agonist ( Cetrotide/Ganirelix/Orgalutron) pituitary suppression throughout the stimulation phase with gonadotropins, the plasma estradiol level often under expressed follicle growth, this method of pituitary blockade should not be used in cases ( such as with PCOS) where PC might be required.,
Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and 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.
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•How Many Embryos Should be Transferred: A Critical Decision in IVF.
•The Role of Nutritional Supplements in Preparing for IVF
•Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”.
•Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & Con’s!
I invite you to call 702-699-7437 or 800-780-7437 or go online on this site and set up a one hour Skype consultation with me to discuss your case in detail.
I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoff Sher
Dear Dr Sher, I’m now 23dp5dt , I did beta on 18dp5dt was 6554 progesterone 55
Than on 21dp5dt in the evening I saw in the restroom brown dark spotting on my ped , so next day on 22dp5dt I did again blood test and beta 16,183 and progesterone is 71
Is it still normal ? By the way today I don’t have anymore brown spotting , but I have like period pain is it normal ?
Thank you so much for your answer , God bless you .
I think all is well…but have an US examination done to put your mind at ease.
Geoff Sher