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 Dr. Sher,
My husband and I are both 38. We started trying for children 1.5 years ago immediately after we got married. After not getting my period for 7 months after stopping birth control (which I had been on consistently for 20 years) I was finally diagnosed with PCOS (polycystic ovaries on ultrasound and anovluation, but normal hormonal function). My periods before getting on birth control at 18 were also normal from what I remember. We have been under the care of a Reproductive Endocrinologist for over a year, but unfortunately the clinic was shut down for 3 months during early covid. In that time (March-May 2020), I ovulated twice and my husband and I were able to actually conceive naturally in May 2020, but we had a chemical pregnancy (1 week of positive tests). When the clinic reopened in June 2020, we then proceeded to have an IUI, but it failed. We then had a genetic carrier screening test done and decided to go directly to IVF when my test came back as a carrier for an x-linked disorder (OTC). We had an egg retrieval in September 2020 with very good results despite a very slow rise in estrogen (44 eggs retrieved, 35 mature eggs to attempt fertilization, 22 fertilized embryos, 9 embryos survived to blastocyst stage). After genetic testing on the embryos we had 4 euploid embryos and 1 female embryo who is a carrier for OTC (only 1 embryo was aneuploidy with a sex chromosome, 2 were male embryos with OTC, and 1 came back inconclusive but did not expand when we thawed it out to rebiopsy). We next did an ERA biopsy which came back as prereceptive, so my doctor adjusted my FET protocol accordingly. After four straight months of weekly acupuncture sessions with a fertility specialist and daily Chinese herbs three times a day, we finally attempted our first FET transfer in January 2021, but it, too, was another chemical pregnancy (very low HCG that initially doubled but then declined). Before attempting another FET transfer, I convinced my doctor to do some basic immunologic testing, which came back as follows:
(1) ANA positive (as I knew it would be since I had two previous ANA positive tests in 2018 and 2016 when testing for autoimmune disorders) but with a low titer of 1:40 (the two previous ANAs in 2018 and 2016 had a higher titer of 1:80 but those tests were done at a different lab). I had a Speckled pattern for AC-2, 4, 5, 29; and Homogenous pattern for AC-1;
(2) Beta-2 Glycoprotein Antibodies (IGG, IGA, IGM) were negative;
(3) Cardiolipin Antibodies (IGG, IGA, IGM) were negative;
(4) Lupus Anticoagulant was not detected, although PTT-LA screen was 39 seconds and DRVVT screen was 43 seconds;
(5) Thyroid Antibodies were normal;
(6) Thyroid Peroxidase Antibodies were normal.
All other fertility testing that I’ve had done over the last year has been normal, including estrogen and progesterone levels: TSH (1.48), Free T4 (1.2), Vit. D (58), Testosterone (54, very slightly high), Free Testosterone (4), Hemoglobin A1C (5.1), Prolactin (6.5), LH (4.9), FSH (6), AMH (14.64), Ferritin (20.2).
My linings are always good (but not great) and get at least above 8mm before each procedure, although I have very short and light periods that last only about 2 days (which I’ve been working on with the acupuncture and Chinese herbs). I have always asked my doctor whether that is significant and he will never really answer the question. Finally, I only have one small polyp that is on the outside of my uterus.
My doctor now has me on two weeks worth of antibiotics (Doxycycline 100mg twice/day) under the assumption that I might have chronic endometritis and I will go in for a biopsy two weeks after finishing the antibiotics to make sure there is no infection. If clear then we will proceed with a second FET transfer. My doctor also has also referred me to hematology due to the positive ANA test.
My doctor is not easy to communicate with, nor is he personal as he frequently forgets who I am and all that we have done, and he is not open to listening to my suggestions. I pushed for each and every un-traditional test that I’ve had done (genetic carrier screening, ERA, immunologic testing, etc.) each of which has returned results that have changed our course of treatment and planning. Our plan is to attempt one more transfer at our clinic before transferring our remaining embryos elsewhere. We have a hysteroscopy scheduled for June but decided to go forward with another transfer before then given that June is just too far off. I want to do everything in my power to cross every t and dot every i before the next transfer just so I can know that I did everything I could in case it also fails.
My questions for you are:
(1) Whether you would recommend any further testing (immunologic or otherwise) before our next transfer?
(2) Also, what do you think is the cause for the multiple chemical pregnancies? Of the year-and-a-half we have been on this nightmare journey, we have only had 4 opportunities to get pregnant (2 natural ovulations, 1 IUI, 1 FET transfer) which has resulted in two chemical pregnancies. I know there is no way to know the quality of the first embryo from the natural conception, but the embryo from the FET was euploidy. I am worried that the chemical pregnancies will be a recurrent theme and just want to know that there are no more unanswered questions or paths to pursue before we burn through the rest of our embryos. Because our insurance doesn’t cover any fertility costs, we could only afford one egg retrieval and after these embryos are gone we will be out of options.
(3) Is a hematologist the best person to see given the positive ANA tests? I kind of feel that I should see an immunologist but my doctor referred me to a hematologist.
(4) What would you recommend in terms of the next FET protocol given the positive ANA test. The first protocol was basic (baby aspirin, estrace pills, progesterone in oil shots for 6 days given prereceptive status on ERA)? Should I push for prednisone/prednisolone and/or heparin to be included, or anything else?
(5) My acupuncturist suggested I ask for a D&C to clean out everything and start again. Is this necessary or a bit too drastic? I was on birth control for almost 20 years before stopping it 1.5 years ago, and I did not have a period for at least the last 8 of those years given that I only took the active pills. Would that have caused issues with my lining just sitting there and not shedding all those years? Would it be the reason that I have super light and short periods despite having normal thickness of lining before procedures? I know a D&C would also delay everything even longer and every week that goes by before our next attempt already feels like an eternity.
Any advice would be greatly appreciated.
Hi Dr. Sher,
I just had my first IVF retrieval with disappointing (to me) results and wanted to check in.
I am 33 years old, AMH of 1.96, FSH of 6.5. I am super healthy but petite (5’2″, 102 lbs). Regular but short cycles. I “primed” with all the typical supplements, ubiquinol, and omnitrope. My husband’s sperm are picture perfect. We’re trying to bank multiple healthy embryos for 2-3 kids and I’m getting old (33).
I was on 300 gonal and 150 menopur. Stimulation went well despite an annoying, giant follicle that popped up on day 3 of stims – it was already 18mm on day 3. Luckily, things still went well and my scans over the course of the week showed 15-22 follicles. I stimmed 8 days.
Retrieval was this past Monday. Disappointingly, I somehow only had 11 eggs. No idea what happened to my other follicles between trigger day scan and retrieval day. Only 8 were mature. Luckily all 8 fertilized. Now we wait.
Based on my final scans, it seems so strange that 1) I had so few eggs and 2) that any were immature. I was originally only going to trigger with double lupron because the staff thought I was at high risk for OHSS given my nice follicles and small body size. After reading your website, I was able to convince them to also let me do 5,000 HCG in addition to double lupron. I had no bloating or difficulty after the retrieval. This makes me wonder if I would have done better with a 10,000 HCG trigger.
I’m going to wait another cycle to get a plan in place with my doctor, we are going to follow-up once my PGS results are in. After a quick check-in, he is thinking I should do lower stimulation and some estrogen priming. My questions for you:
1.) Would you keep me at 300 gonal/150 meno? We are trying to bank as many healthy embryos as possible before I’m really old (we are PGS testing and doing frozen transfer). I did feel good on this, and it seemed to be working until retrieval.
2.) Anything I can do to avoid that annoying giant lead follicle this time around? I’ve heard the words “estrogen prime” on your website and from my MD, but have no clue what it means. I assume this means I would use estrace or prometrium?
3.) Should I do 10,000 HCG trigger next time? Would I do that in addition to or instead of lupron? I would have rather have been miserable for a few days if it meant having more mature eggs.
Thank you!
I really think your experience was possibly linked to the protocol used for ovarian stimulation and/or its implementation. We need to talk. I suggest that you contact my assistant, Patti Converse at 702-533-2691 and set up an online consultation with me.
The most important application of the IVF art-science blend concept is best appreciated when applied to the selection and implementation of protocols for controlled ovarian stimulation (COS):
The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by t IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome. While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.
Gonadotropins (LH and FSH), whether produced by the pituitary gland or administered by way of fertility drugs, have different “targeted” sites of action in the ovary. FSH targets cells that line the inner wall of the follicle (granulosa cells) and also form the cumulus cells that bind the egg to the inner surface of the follicle. Granulosa cells are responsible for estrogen production.
LH, on the other hand, targets the ovarian connective tissue (stroma/theca) that surrounds ovarian follicles resulting in the production of male hormones such as testosterone (predominantly), androstenedione and DHEA. These androgens are then transported to the granulosa cells of the adjacent follicles in a “bucket brigade fashion”. There FSH converts testosterone to estradiol, causing granulosa cells to multiply (proliferate) and produce estradiol, follicles to grows and eggs to develop (ovogenesis) It follows that ovarian androgens (mainly testosterone) is absolutely indispensable to follicle/ egg growth and development.
However, the emphasis is on a “normal” amount of testosterone. Over-exposure of the follicle to testosterone can in my opinion, compromise egg development and lead to an increased likelihood of chromosomal irregularities (aneuploid) following LH/hCG-induced egg maturational division (meiosis) and compromise embryo “competency/quality.
Ovarian androgens can also reach the uterine lining where they sometimes will compromise estrogen receptor -induced endometrial growth and development.
A significant percentage of older women and those who have diminished ovarian reserve (DOR) have increased LH activity is increased. Such women either over-produce LH and/or the LH produced is far more biologically active. Chronically increased LH activity leads to overgrowth of ovarian connective tissue (stroma/theca). This condition, which is often referred to as Stromal Hyperplasia or hyperthecosis can result in excessive ovarian androgen/testosterone production and poorer egg-embryo quality/competency, Similarly, women with polycystic ovarian syndrome (PCOS), also characteristically have Stromal hyperplasia/hyperthecosis due to chronically increased LH activity. Thus they too often manifest with increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often also a feature of PCOS.
In my opinion, the over-administration of LH-containing menotropins such as Menopur, [which is comprised of roughly equal amount of FSH and hCG ,which acts similar to LH)], to older women, women with DOR and those who have PCOS can also lead to reduced egg/embryo competency . Similarly, drugs such as clomiphene or Letrozole that cause the pituitary gland to release excessive amounts of LH, are also potentially harmful to egg development and in my opinion, are best omitted from IVF COS protocols. This is especially the case when it comes to older women and those with DOR, who in my opinion should preferably be stimulated using FSH-dominant products such as Follistim, Puregon, Fostimon and Gonal-F.
Gonadotropin releasing hormone agonists (GnRHa): GnRHa such as Lupron, Buserelin, Superfact, Gonopeptyl etc. are often used to launch ovarian stimulation cycles. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in LH levels falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. When GnRHa are administered for about 7 days prior to initiating gonadotropin stimulation (“long” pituitary down-regulation”), the LH depletion that will exist when COS is initiated, will usually be protective of subsequent egg development. In contrast, when the GnRHa administration commences along with the initiation of gonadotropin therapy, there will be a resultant immediate surge in the release of pituitary LH with the potential to increase ovarian testosterone to egg-compromising levels , from the outset of COS. This, in my opinion could be particularly harmful when undertaken in older women and those who have DOR.
GnRH-antagonists such as Ganirelix, Cetrotide and Orgalutron, on the other hand, act very rapidly (within hours) to block pituitary LH release. The purpose in using GnRH antagonists is to prevent the release of LH during COS. In contrast, the LH-lowering effect of GnRH agonists develops over a number of days.
GnRH antagonists are traditionally given, starting after 5th -7th day of gonadotropin stimulation. However, when this is done in older women and those (regardless of age) who have DOR, LH-suppression might be reached too late to prevent the deleterious effect of excessive ovarian androgen production on egg development in the early stage of ovarian stimulation. This is why, it is my preference to administer GnRH-antagonists, starting at the initiation of gonadotropin administration.
My preferred Protocols for Controlled Ovarian Stimulation (COS):
1.“Long” GnRHa (Lupron/Buserelin/Superfact/Gonopeptyl) Pituitary Down-regulation Protocol: The most commonly prescribed protocol for GnRHa/gonadotropin administration is the so-called “long protocol”. Here, GnRHa is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH , which is rapidly followed by a precipitous fall to near zero. It is followed by a withdrawal bleed (menstruation), whereupon gonadotropin treatment should commence, while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the “long protocol” which I prefer prescribing for older women and in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a GnRHa-induced bleed, the agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I often supplement with human growth hormone (HGH) in such cases in an attempt to enhance egg mitochondrial activity and so enhance egg development. This approach is often augmented with preimplantation genetic screening (PGS) of all embryos that reach the expanded blastocyst stage of development by day 5-6 post-fertilization. I also commonly recommend blastocyst banking to many such patients.
2.Short (“Flare”) GnRHa Protocol: Another GnRHa usage for COS is the so called “(micro) flare protocol”. This involves initiating gonadotropin therapy commensurate with initiation of gonadotropin administration. The supposed objective is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” constitutes “a double-edged sword”. While it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal/thecal androgen production which could potentially compromise egg quality, especially when it comes to older women and women with DOR. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially when it comes to COS in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe such protocols to my IVF patients.
3.Estrogen Priming – This is the approach I sometimes prescribe for my patients who have virtually depleted ovarian reserve , as determined by very low blood anti-Mullerian hormone AMH levels (<0.2ng/ml or 2 pmol/L) and are thus likely to be very “poor responders”. It involves a modified A/ACP. We start with estrogen skin patches applied every 2nd day (or with the BCP) for 10 days or longer, overlap it for 3 days with a GnRHa whereupon the estrogen priming is stopped. Th GnRHa is continued until the onset of menstruation (usually 5-7 days later) to cause pituitary LH, down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, The patient is given twice-weekly injections of estradiol valerate (Delestrogen) for a period of 7-8 days whereupon COS is initiated using a relatively high dosage FSH-(Follistim, Fostimon, Puregon or Gonal F), which is continued along with daily administration of GnRH antagonist until the “hCG “trigger.” This approach is often augmented with HGH administration throughout the process of COS and by preimplantation genetic screening (PGS) of all embryos that reach the expanded blastocyst stage of development by day 5-6 post-fertilization. I also commonly recommend blastocyst banking to many such patients.
Estrogen Priming has succeeded in significantly enhancing ovarian response to gonadotropins in many of otherwise very poor responders.
Triggering egg Maturation prior to egg Retrieval: hCG versus GnRHa
With ovulation induction using fertility drugs, the administration of 10,000U hCGu (Pregnyl; Profasi, Novarel) or 500mcg hCGr (Ovidrel/Ovitrel) “trigger”) sends the eggs (into maturational division (meiosis). This process is designed to halve the chromosome number, resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes they had prior to the “trigger”. Such a chromosomally numerically normal (euploid), mature (MII) eggs, upon being fertilized will (hopefully) propagate euploid embryos that have 46 chromosomes and will be “: competent” to propagate viable pregnancies. In my opinion, the key is to always “trigger” with no less than 10,000U of hCGu or 500mcg hCGr (Ovidrel/Ovitrel). Any lesser dosage often will reduce the efficiency of meiosis and increase the risk of the eggs being aneuploid. I personally do not use the agonist (Lupron) “trigger”, unless it is combined with (low dosage) hCG. The supposed reason for using the agonist, (Lupron) “trigger” is that by inducing meiosis through compelling a surge in the release of LH by the pituitary gland, the risk it reduces the risk of OHSS. This may be true, but it comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the likelihood of aneuploid and immature (MI) eggs. And there are other better approaches to preventing OHSS (e.g. “prolonged coasting”), in my opinion.
Use of the Birth Control Pill (BCP) to launch IVF-COS.
In natural (unstimulated) as well as in cycles stimulated with fertility drugs, the ability of follicles to properly respond to FSH stimulation is dependent on their having developed FSH-responsive receptors. Pre-antral follicles (PAF) do not have such primed FSH receptors and thus cannot respond properly to FSH stimulation with gonadotropins. The acquisition of FSH receptor responsivity requires that the pre-antral follicles be exposed to FSH, for a number of days (5-7) during which time they attain “FSH-responsivity” and are now known as antral follicles (AF). These AF’s are now able to respond properly to stimulation with administered FSH-gonadotropins. In regular menstrual cycles, the rising FSH output from the pituitary gland insures that PAFs convert tor AF’s. The BCP (as well as prolonged administration of estrogen/progesterone) suppresses FSH. This suppression needs to be countered by artificially causing blood FSH levels to rise in order to cause PAF to AF conversion prior to COS commencing, otherwise pre-antral-to –antral follicle conversion will not take place in an orderly fashion, the duration of ovarian stimulation will be prolonged and both follicle and egg development may be compromised. GnRH agonists cause an immediate surge in release of FSH by the pituitary gland thus causing conversion from PAF to SAF. This is why women who take a BCP to launch a cycle of COS need to have an overlap of the BCP with an agonist. By overlapping the BCP with an agonist for a few days prior to menstruation the early recruited follicles are able to complete their developmental drive to the AF stage and as such, be ready to respond appropriately to optimal ovarian stimulation. Using this approach, the timing of the initiation of the IVF treatment cycle can readily and safely be regulated and controlled by varying the length of time that the woman is on the BCP.
Since optimizing follicular response to COS requires that prior to stimulation with gonadotropins, FSH-induced conversion from PAF to AF’s first be completed and the BCP suppresses FSH, it follows when it comes to women launching COS coming off a BCP something needs to be done to cause a rise in FSH for 5-7 days prior to menstruation heralding the cycle of CO S. This is where overlapping the BCP with a GnRHa comes in. The agonist causes FSH to be released by the pituitary gland and if overlapped with the BCP for several days and this will (within 2-5 days) facilitate PAF to AF conversion…. in time to start COS with the onset of menstruation. Initiating ovarian stimulation in women taking a BCP, without doing this is suboptimal.
I strongly recommend that you visit www.SherIVF.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
•The Fundamental Requirements For Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•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.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
•Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
•Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
•Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
•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?
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
•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?
•PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
•IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.
______________________________________________________
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
Hi,
I’ve had 2 rounds of IVF, first resulted in a miscarriage at 6 weeks, I’m on the second round now and at my 7 week scan there was no fetal pole or heartbeat, at my 8 week scan the gestational sac looks to have grown but still no fetal pole or heartbeat, I’ve had no other symptoms of miscarriage and I’m left facing a decision on whether to have a D&C or wait it out as I’m still clinging on to a bit of hope. If it is a miscarriage I’ve continually asked for blood tests for clotting issues as there is a history of DVT in my family, what tests would you advise to give me confidence that a next round of IVF would work? I feel that there is an issue around the embryo getting past the 6-7 week mark and have concerns about a blood issue, low progesterone or an issue with my womb. I am 41 years old, I had low fertilisation rates and only ended up with 1 blastocyst on each round, the second being high quality. Thank you, Louise
I suggest a D&C to clear out all products and prevent retained products of conception that could become infected and damage your uterus. Also, it will provide an opportunity to test for a chromosomal cause (the most likely explanation).
Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1.Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2.Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about 15y ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3.The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
4.Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
a.A“ thin uterine lining”
b.A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c.Immunologic implantation dysfunction (IID)
d.Endocrine/molecular endometrial receptivity issues
e.Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
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.
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•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?
•Blastocyst Embryo Transfers should be the Standard of Care in IVF
•IVF: How Many Attempts should be considered before Stopping?
•“Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
•IVF Failure and Implantation Dysfunction:
•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)
•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!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF?
______________________________________________________
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
Hi I am currently 5 days post frozen embryo transfer and am on vagina progesterone as well as 2ml of intramuscular progesterone in oil. Last night I forgot to take the vaginal progesterone but not the injection. Will missing one night of the vaginal progesterone cause a sudden drop that could ruin this FET?
It doubt there will be an adverse effect on outcome!
Geoff Sher
Dr. Sher,
Reposting again, as I don’t think my previous reply went through.
What is Your email address will not be published. Required fields are marked *
your recommendation on ideal time to initiate the BCP? Assuming it is started after bleed, for 10 days, are you still saying another bleed will come within a week? That would just be 17 days from prior period.
Thanks
Kathy,
WE should talk.
I invite you to call my assistant, Patti Converse (702-533-2691) and to set up an online consultation with me to discuss!
Geoff Sher