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 & I have been ttc for 4 yrs & I wanted to get your opinion of our infertility journey and what to do next. I went off BCP (was on them for approx. 10 yrs) & we didn’t think anything about infertility for the 1st 2 yrs. My cycles were always 28 days while on BCP & went to 32-33 days when I went off. For the past 6 mo, some of my cycles have been 35-40 days.. Blood work done by my OBGYN prior to any infertility trmts indicated that I did not ovulate. I did clomid for 6 mo, all BFN. Blood work on 1st mo on clomid indicated I ovulated. My OBGYN said my cycles should go back to 28 days while on clomid but they never did. I advised him of this & he just said my body was “weird”. HSG was clear & sperm was normal. Began trmt w/ RE: 1st IUI (letrozole; sperm- 65 million, 67% motility, morph not tested; CD 12- 1 folli (right) 21.6 mm); 2nd IUI (natural, I ovulated on my own!; sperm- 36 mil, 55% motility, morph not tested; CD 12- 1 folli (right) 23.6 mm); 3rd IUI- 75 IU gonal F (1st attempt was canceled, growth stopped around CD 12; sperm- 53 mil, 77% motility, 5.5 morph); (2nd attempt, increased gonal F to 200 IU; sperm- 58 million, 66% motility, morph not tested; CD 8- E2 1037 ; CD 9- E2 1,699 [6 follis (left) & 3 follis (right). I had a very painful follicle aspiration & developed mild OHSS (my RE said they’ve never seen anyone get mild OHSS during an IUI cycle, lucky me!) My lining was always normal during all IUI’s. All IUI’s were BFN’s & I have never been pregnant before. My diagnosis is ovulatory dysfunction, anovulatory cycles. Antral follicle: 27; AMH: 3.3; 17-OH Prog: 112; TSH: 1.94; high cholesterol, BMI: 33. My RE said I do not have PCOS, ovaries not polycystic& not insulin resistant & metformin would not help me. We have an appt in a week to start the IVF process. Any suggestions as to what protocol we should consider? Do you think we are good candidates for IVF? Do you think we could be facing a larger infertility problem that we haven’t been tested/diagnosed with? Any tests we should do before IVF? Thank you so much for all that you do & for providing this valuable resource!! 🙂
It sounds lke PCOS to me (normal AFC and AMH of 3.3ng/ml). The time has come for IVF and I think you would probably be a high responder and at risk of hyperstimulation (OHSS) unless precautions are taken with regard to the stimulation protocol used. Alkso bear in mind that PCOS women have a propensity for producing a higher than normal incidence of chromosomally abnormal, “incompetent” eggs and that the protocol used for ovarian stimulation is pivotal here.
My approach is consistently to use a long pituitary DR protocol with an agonist, coming off 1-2 months on the BCP. The latter is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling ovarian androgen release. I then stimulate with low dosage FSHr to which I add a smidgeon of LH/hCG (Luveris/Menopur) from the 3rd day and watch for the # of follicles and [E2] starting on the 7th day of COS. If there are > 25 follicles, I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. Then, provided the [E2] is >2500pg/ml, I stop the agonist and the gonadotropin stimulation and follow the E2 (only) daily, without doing further US examinations. The [E2] will almost invariably climb and I watch it go up (regardless of how high the concentration of E2reaches) and track it coming down again. As soon as the [E2] drops below 2500pg/ml (and not before then ever), I administer 10,000U hCGu or hCGf (Ovidrel/Ovitrel-500mcg) as the “trigger” and perform an egg retrieval 36h later. ICSI is a MUST because “coasted” eggs usually have no cumulus oophoris and eggs without a cumulus will not readily fertilize on their own. All fertilized eggs are cultured to blastocyst (up to 6 days). And up to two (2) are transferred transvaginally under US guidance.
The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If you start too early, follicle growth will stop and the cycle will be lost. If you start too late, you will encounter too many post-mature/cystic follicles (>22mm) that usually harbor abnormally developed eggs.
Use of the above approach avoids unnecessary cycle cancellation, severe OHSS, and optimizes egg/embryo quality. The worst you will encounter is mild to moderate OHSS and this too is uncommon.
I do not use antagonists in high responders (e.g., PCOS) because it interferes with the assay of E2 (often causing the value to be understated), a valuable index in assessing risk for the development of severe/critical OHSS. I also do not believe in the agonist trigger to prevent OHSS. The reason is that the magnitude of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the oocyte aneuploidy index.
Please visit my new Blog at http://goo.gl/4hvjoP , 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
•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.
•Launching Ovarian Stimulation with a BCP: How Does it Affect Response?
•Frozen Embryo Transfer (FET): What Does it Involve?
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•The Role of Nutritional Supplements in Preparing for IVF
•Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
•Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & Con’s!
•Micro-IVF: Often Preferable to Ovarian Stimulation with or Without IUI
•Confronting the Financial and Emotional Costs Associated with Doing IVF
•Molar Pregnancy: What is it and How Should it be Treated?
•Fragile X Syndrome: Which IVF Candidates Should be Tested and How Should Results be Interpreted?
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
Hi Dr. Sher,
My husband and I are a DQ Alpha match. We had 4 miscarriages while using immune meds and Ivf before deciding to use donor sperm and were successful and had a son. My question is for our next child, can we still use the same donor, or will we run into the same problem of miscarrying?
Thank you for your time!
The likelihood is that the same donor would work for you again.
Good luck!
Geoff Sher
Hi there,
I have done 5 IVF cycles, my last one I cancelled due to a dominant follicle and poor response. My first 3 were pre- Lap for endometriosis removal and I started on 225IU FSH antagonist and went up to 350IU on some cycles. There was no endo on my ovaries and no endometriomas, it was all behind my uterus. They graded it stage 3. I am just turned 37, but have had a very poor response overall. I noticed my egg quality on my 4th cycle (the only one post Lap) seemed better – much less fragmented, but again they were very slow to divide and behind what they should be in cell number. My 4 mature eggs all fertilised with ICSI but none made it to blast – one nearly did but degraded at day 6.
I have tried your antagonist/agonist conversion protocol for one cycle, I have also tried going on the pill prior for 14 days and then antagonist cycles and found I was oversupressed. I seem to always have a dominant follicle. What can you suggest for me? What are your thoughts on why my embryos are slow to divide? Could it be mitochondrial issue? My husband has very good sperm parameters except his morphology is quite low – varied between 6-16% when tested.
My last cycle I did oestrogen priming for about 8 days in luteal phase and continued into the stims till trigger and I added HGH 3IU per day from day 2 to trigger. I was on Elonva day 2 then topped up at day 8 225IU FSH and 150Menopur, I had a dominant follicle again and really only ended up with 2 follicles that were in contention (there were quite a few other smaller ones) – a 22mm and a 14mm day before trigger. I converted it to an IUI.
Any help or advice on why this is happening to me would be much appreciated! My husband and I are both homo MTHFR C677T, but no other findings except high NK cells/cytokines.
Unfortunately, as far as the protocol needed for ovarian stimulation, the information you provide is not sufficient for me to provide an authoritative opinion. I need to know much, much more about your ovarian reserve, the exact stimulation used, its implementation, timing and the exact response. It would be best if we talke. I can however tell you that aside from this issue, you need also to consider the possibility of an endometriosis-associated immunologic implantation dysfunction…see the articles below.
Please visit my new Blog on this very site, http://www.GeoffreySherIVF.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)
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•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 Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Why did my IVF Fail?
•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
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•The Role of Nutritional Supplements in Preparing for IVF
•Endometriosis and Infertily
•Treating Ovarian Endometriomas with Sclerotherapy.
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
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
Simone,
I had a dominant follicle issue for my first two failed cycles. I did estrogen priming (along with Human Growth Hormone) for an ENTIRE CYCLE before stimming (30-45 days). I then did lower dose stims (225 Follistim, Femara 5mg, and 10 units hcg-LH). I also added: neupogen, prednisone, intralipids at retrieval, and LDN. I had my best response yet: only 7 retrieved (but that was the most for me) and all 7 fertilized! I transferred two at day 5 (bfn) but 4 of the remaining 5 made it to blast and are frozen at pretty good grades. Just wanted to share this protocol in case you wanted to try something new.
I will be doing my first FET (post-lap where not much was found at all) in a few weeks and I am adjusting my intralipids to the way Dr Sher recommends (once 10-14 days before transfer and then once at bfp). I will double neupogen (to 20 units), prednisone (to 10mg), and LDN (to 3.o mg) as well. Baby dust!
I keep hearing and reading about auto correction of pgs abnormal embryos ….
I also recently heard about a study that took multiple biopsies of a batch of embryos and sent them to different pgs testing centers and they all gave different results…
Now there is this whole mosaics situation .., had a discussion with Braver,an about this and they just completed another study with large amounts of women getting pg with abnormal embryos and delivering healthy babies???
Not sure how to process this as I am embryo banking with pgs ?
Now I am scared to destroy embryos that are abnormal .
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).”.
Please visit my new Blog on this very site, 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)
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Frozen Embryo Transfer (FET): What Does it Involve?
•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 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?
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, your clinic is clearly the preeminent authority with regards to treatment of immune-mediated implantation failure. I am concerned that my RE’s protocol differs from yours. He starts prednisolone on CD7 and gives intralipid only 2-3 days prior to ET and again 2-3 days post. He claims there is little evidence to guide practice. My question to you would be : what evidence basis underpins your protocol (I have found the article re timing of NKC activation in vivo; is there anything else you can refer me to?). I have no doubt that internationally, your clinics would probably have the largest patient numbers, so any unpublished audit data would be compelling in the absence of published papers (I know there aren’t any RCTs going around, so we are probably in the realms of professional opinion/audit). Ditto for the agonist/antagonist conversion protocol and stim doses exceeding 300- I need some data to show my RE as he won’t contemplate this for me. I have DOR and autoimmune implantation failure and am running out of time to convince him – anything you can throw me would be so greatly appreciated! Thank you so much for your time.
I think both of your questions are best answered by an article I recently wrote and which is to appear on this blog in a day or two…..
………………………..herewith:
The dictionary defines “evidence based medicine” i as follows:
“The practice of medicine in which the physician finds, assesses, and implements methods of diagnosis and treatment on the basis of the best available current research, their clinical expertise, and the needs and preferences of the patient…….
This definition does not suggest that adoption of new advances be confined to only that which has been proven through “gold standard” statistical analyses.
Self-proclaimed IVF authorities often glibly assert that acceptance of new methods be predicated upon results obtained through “evidence-based gold standard” analyses (usually randomized controlled studies). Yet, most advances in the field of assisted reproduction have come through tried and tested experience-based evaluations.
In the field of medicine and particularly when it comes to Reproductive Medicine the vast majority of clinical advances have resulted from experience-based (longitudinal) implementation of tried-and-tested methods rather than through randomized studies. Let me here cite but a few indisputable examples in the field of assisted reproductive medicine:
1. IVF has emerged as a more effective method than surgery, to treat tubal damage.
2. IVF is more successful than surgical tubal reversal in the treatment of women who have had a prior tubal ligation.
3. IVF (and ICSI) rather than intrauterine insemination is a preferred method for treating infertility due to male factor and moderately severe and severe cases of endometriosis
4. IVF is more successful than gamete or zygote intrafallopian tube transfer (GIFT or ZIFT.
5. Ultrasound guided embryo transfer is superior to blind embryo transfers.
6. Intracytoplasmic sperm injection (ICSI) is a much more successful way to achieve pregnancy in cases of male infertility than alternatives such as sub-zonal insemination (SUZI).
7. Artificial insemination (AI) is best conducted using concentrated (seminal plasma-free) sperm rather than whole sperm and should be delivered as intrauterine insemination (IUI) rather than being deposited in the upper vagina. ( I was the first to publish on the use of IUI as far back as in 1984)
8. Success rates with embryo freezing performed through vitrification are far better than when conventional (slow) freezing is used.
9. The transfer of embryos subjected to full chromosomal analyses using preimplantation genetic sampling (PGS) ,particularly when it comes to women >35Y of age, enhances IVF outcome as compared with conventional IVF
10. Next generation gene sequencing has emerged as a superior method for performing PGS.
Consider the fact that in order for randomized controlled studies to be properly conducted and be reliably requires that all variables (other those being evaluated) have to be kept stable. Only then, through randomly assigning cases to one or other leg of the study can variations in the tested variables be determined. However, when it comes to reproductive medicine, it is impossible to stabilize and control the non-tested variables, thereby virtually negating liable interpretation of results. You see, IVF involves an interplay between a multitude of variables all of which are subject to variation and profoundly affect IVF outcome. Here are but a few examples of such variables. :
• Maternal and paternal age
• Egg and sperm “competency”
• Ovarian reserve
• The medications and protocols used for ovarian stimulation and their implementation
• Monitoring of ovarian stimulation
Just consider the following: By far, the most important variable that influences IVF outcome is “embryo competency”. This is largely (but not exclusively) a function of the egg’s (rather than the fertilizing sperm’s) chromosomal integrity. For an embryo to be able to propagate a normal healthy baby, it must be euploid (i.e. it must have precisely 46 chromosomes). If there is even one more/less than 46 chromosomes present in its cells (a condition known as “aneuploidy”), such an embryo would be “incompetent” and would either fail to attach to the uterine lining, miscarry, or result in a child with a birth defect such as Down Syndrome.
If we were to dismiss any innovation that had not been proven through gold standard trials, the field of Reproductive Medicine would not have progressed to the point it has reached today. I and the team I have assembled around me over the last 34 years have been responsible for a number of such innovations. Here are but a few examples of innovations we have introduced, none of which (for the reasons cited above) were proven through gold standard testing, yet most of which have since been adopted by many, into the main-stream of IVF practice.
• Individualized protocols for ovarian stimulation.
• The agonist/antagonist conversion protocol (A/ACP) with and without estrogen priming to selectively improve follicle/egg development.
• The role activated endometrial natural killer cells in causing embryo implantation dysfunction and the importance of down-regulating such activity with intravenous immunoglobulin-G (IVIG)/Intralipid/steroid/heparin therapy in the treatment of Implantation failure.
• Intrauterine (artificial) insemination (IUI) of processed or “washed” (spun down) sperm which I was the first to introduce and publish on (Fertility and Sterility) in 1984.
• Ultrasound measurement of endometrial thickness to assess implantation potential.
• Use of Vaginal Viagra to improve the uterine lining.
• “Prolonged coasting” to prevent severe ovarian hyperstimulation syndrome (OHSS).
• Measurement of HLA-g in the media surrounding developing embryos to assess their quality.
• Complete chromosomal embryo karyotyping to identify the most “competent” embryos for transfer.
• Complete chromosomal egg karyotyping to identify the most “competent” eggs for egg banking.
The fact that more than 70% of IVF failures and miscarriages are due to embryo aneuploidy, and that prior to CGH, most such chromosomal irregularities went unrecognized means that this important variable was unaccounted for in virtually all studies that used IVF outcome as the end point. This effectively negates the interpretation of most prior statistical evaluations in IVF.
IVF is a classic example of an “art-science blend”. While one can control scientific concepts, you cannot control the “art-side” of things. The latter involves the enormous interpersonal and intrapersonal variation in approach, judgment, skill-set and execution of technical tasks involved in the preparation for, and implementation of, IVF treatment. This renders the using controlled randomized studies in the IVF setting largely pointless. In fact, were an IVF text book to be compiled of only those processes, procedures or treatments that were absolutely proven in this manner…….. it would at best be a single page in length.
Please visit my new Blog on this very site, 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)
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Why did my IVF Fail?
• Recurrent Pregnancy Loss (RPL): Why do I keep losing my Pregnancies?
• 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)
• Traveling for IVF from Out of State/Country–
• A personalized, stepwise approach to IVF
• The Role of Nutritional Supplements in Preparing for IVF
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