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’m 45 years old. I had a miscarriage back in 2021 & just gave up on trying. However I want to try again. I don’t want to do the Donor Eggs. I was hoping you can please, please help me. I do suffer from PCOS & I think I have an issue with ovulation. Can you please tell me would you be able to do the necessary blood work, an ultra sound & or all the other necessary test to tell me if I’m still able to conceive a child. I was hoping if my levels come back okay, maybe I can be put on the oral or injection medication to help me ovulate. I really want to do all the required testing that you can do before being told that because of my age I have to do Donor Eggs. I want to try to see if I can conceive my own child with my partner. He’s 33 & like I said I know my age is up there.. but who knows I might catch a miracle. Please help me.
Hi Kayla,
It is important that we talk this through. I would need much more information to respond authoritatively.
Please contact Patti Converse (my assistant) at 702-533-2691 and set up an online consultation with me.
Geoff Sher
Dr. Sher,
I watched you on the egg whisper show on the topic of recurring pregnancy loss. I would like to discuss with you my fertility situation and would like to understand your medical opinion on next steps. I am providing a detailed summary of all fertility treatment, so you are able to get a complete picture of fertility treatment thus far.
At age 34, I got pregnant naturally with my son who was born 36 weeks and 1 day. I was able to get pregnant within 5 months of trying. During this time, I had a subserosal fibroid that grew to 8cm throughout the pregnancy, but shrunk to 4cm after delivery. My uterus is retroverted. I was also on Synthroid 50mg during the pregnancy as my TSH was elevated during the pregnancy. I had an expanded carrier screening at this time, and I was negative for all items tested. I had a vaginal assisted vacuum delivery, with an episiotomy and third degree tear.
After 1 year at age 35.5, my husband and I tried again for 6-7 months after my period returned (I was breastfeeding for 1 year), and I was unable to get pregnant. I went to a fertility clinic January 2021 and an initial bloodwork was done, and the diagnosis was male factor infertility. My husband’s semen analysis was abnormal with respect to morphology (2%). My AMH level was 1.3 at this time, and HSG reported clear tubes. I still had the subserosal fibroid approx. 4cm. I went and proceeded with 4 IUI treatments from March – June 2021 (age 36), all resulting in failures. 3 medicated IUIs (2.5mg of Letrozle, with Ovidrel HCG – 1 cycle 3 follicles (thin lining), 2 cycles lining greater than 7), and one natural IUI (no medication, lining greater than 8). Doctor suggested that I also take Levothyroxine 25mg daily because TSH not high enough for fertility. July 2021, I had my husband do a sperm DNA fragmentation analysis with a reproductive urologist and it was normal (fragmentation approx. 25). Reproductive urologist did a second semen analysis which was abnormal for sperm count (5.5M), but morphology and motility normal. July 2021, my AMH was tested again and it was at 0.318 (diminished ovarian reserve).
Sept 2021 – February 2022 proceeded with IVF protocol.
Sept – Oct 2021. IVF Cycle 1.
Prior to starting IVF cycle, my doctor did endometrial biopsy and saline infused sonogram, and all looked normal.
IVF cycle 1 – Age 37 – I did ovarian PRP treatment prior to the procedure (2 weeks prior to IVF cycle start). My doctor suggested that I do gentle IVF because of diminished ovarian reserve. I also did 6 sessions of Ozone Sauna Therapy prior to egg retrieval. Protocol: estrogen priming (2mg daily) for 2 weeks, then 2 tablets of clomid (100mg), 2 tablets of letrozole (5mg) and Gonal F 150 units for 7 days, and then lupron trigger. Thin lining on day of egg retrieval. I was able to get 3 mature follicles, each with an egg and inseminated via ICSI. Of 3 follicles 1 made it to Day 5 blastocyst, and PGT-A euploid. Lining less than 7 on egg retrieval. The other 2 embryos did not make it to blastocyst by day 7, so were discarded. Prescribed birth control pills for 10 days after egg retrieval. My husband had another semen analysis done, and this time motility and count were normal, but morphology abnormal (2%).
Oct 2021 – IVF Cycle 2 – gentle stimulation IVF protocol.
Protocol: BCP 8 days, then for 10 days 100 mg clomid, 5mg Letrozole, 75 units Gonal F, then 100mg clomid, Gonal F 150 units 7 days. Dominant follicle absorbed all medication, and turned into cyst (40cc), so cycle cancelled. Thin lining. Progesterone 200mg daily for 10 days.
Nov 2021 – IVF cycle 3 – gentle stimulation IVF protocol.
Protocol: BCP for 10 days, clomid 50mg for 3 days, then clomid 100mg for 4 days. Thin lining. Cycle cancelled because I got COVID-19.
December 2021 – January 2022 – IVF cycle 4 – gentle stimulation IVF protocol
Protocol. Ovarian PRP done 2 weeks prior to egg retrieval. Estrace priming (2mg) for 7 days, then Clomid 50mg, Letrozole 2.5mg, 75 units Gonal-F for 5 days, then Clomid 50mg, 75 units Gonal-F 1 day, then Clomid 50mg, Gonal F 225 units for 1 day. Lupron trigger. Thin lining on day of egg retrieval. 4 follicles, 2 contained eggs. 1 egg mature on day of retrieval, 1 egg immature on day of retrieval. Egg immature, was matured in the lab and inseminated via ICSI second day. Egg inseminated via ICSI on day 0, degenerated on day 3. Egg inseminated on second day reached blastocyst on Day 5, and tested PGS-A euploid.
February 2022 – Frozen embryo transfer cycle.
Starting on Day 3 of cycle, estrogen 4mg daily 7 days and Intralipid infusion on day 7. Then estrogen 6mg daily for 5 days (lining 7.8mm), then estrogen 6mg, progesterone 800 mg (vaginal insertion), prednisone 10mg, lovenox 40 units, baby aspril 81mg, for 5 days. Then estrogen 6mg, progesterone 1000 mg (vaginal insertion and 200mg by mouth), prednisone 10mg, lovenox 40 units, baby aspirin for next 11 days. Intralipid infusion on and uterine PRP on day 18. Day 5 Frozen embryo transfer on Day 20 (of cycle) with embryo glue. Day 27 (2/18/2022) tested pregnancy Hcg 21.2 positive. Day 30 (2/21/2022) intralipid infusion, Hcg 3.9. Doctor informed me that no longer pregnant, and stop all medications. Dr. specified that this was immune protocol to help women with recurrent miscarriages and failed implantation. We also only had 2 embryos (both PGT-A Day 5 blastocyst – euploid), so Dr. specified this was the best protocol for implantation. I have not yet received my period, and doctor specified to call with next period. Dr. specified that prior to attempting another transfer we need to do a hysteroscopy.
I only have 1 embryo PGT-A euploid embryo remaining, and I do not want to do any additional transfers until we identify the problem. Based on the information provided above, do you suggest a hysteroscopy and ERT? Do you know what could have possibly caused this pregnancy loss? Do you think the subscerosal fibroid could have had any impact? I am devastated and am looking for answers. Any guidance you have would be very helpful.
Hi Annet,
There are so many factors involved in your case history, including but not limited to your repeated failures, your diminished ovarian reserve, a thyroid factor, the protocols used in your case band and the likelihood of an underlying implantation dysfunction,.
I cannot do you justice through a brief written response. We really need to talk.
Please call Patti Converse (702-533-2691), my assistant and set up an online consultation with me. I will be abroad until March 17th. Ask Patti to set this up ASAP after my return.
In the interim, please see below!
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
Dear Dr Sher,
I’m hoping for some advice on immune protocols for a future FET. I’ve recently had a chemical pregnancy following a euploid transfer. We have one euploid left and then we will stop as I’m now 44. My blood results this round showed raised NK 50:1 at 22 and raised Cytokines TNF-a:IL-10 (CD3+CD4+) at 40.3. My Endometrial immune profile from biopsy was normal. As a result my consultant was unwilling to give me steroids which he felt might make my uterine environment under-active so we just had intralipids prior to transfer. I’ve had ERA, Emma, Alice, saline sonogrophy and all normal/receptive. I am seeking further immune advice at my consultant’s suggestion.
I’m particularly interested to hear how you would approach a situation in which the uterine biopsy was normal but the bloods were not. Would you recommend any additional immune treatment for a future FET? I’ve previously had a successful pregnancy with no immune treatment (aged 3), IVF failure with IVIG (untested embryo) and a miscarriage (untested) at 9 weeks with intralipids at week 6.
Thank you
Vicky
Hi Vicky,
Welcome to this forum. First off, I commend your RE for using Intralipid therapy because you clearly have an immunologic implantation dysfunction (IID). However, very respectfully, in my opinion the omission of steroid therapy is a big mistake. Results are in my opinion MUCH poorer when steroids are not added.
Unless tests for immunologic implantation dysfunction (IID) are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U.S.A. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented. I recommend that my patients be tested by ReproSource Reproductive Immunology Reference Laboratory, Boston, MA.
WHO SHOULD UNDERGO IID TESTING?
When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:
•A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy)
•A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
•“Unexplained” infertility
•Recurrent pregnancy loss (RPL)
•A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
•Unexplained IVF failure
• “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby
What Parameters should be tested?
In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.
The parameters that require measurement include:
oFor Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6, Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity (in my opinion).
oFor Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).
How should results be interpreted?
Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. The most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit. Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.
There exists a pervasive but blatant misconception on the part of many, that the addition of Intralipid (IL) /immunoglobulin-G IVIG) can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.
Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
•The Fundamental Requirements for Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
•Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
•Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
•Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID) Why did my IVF Fail
•Recurrent Pregnancy Loss (RPL): Why do I keep losing my PregnanciesGenetically Testing Embryos for IVF
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
•Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
•IVF: Selecting the Best Quality Embryos to Transfer
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
•Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
•Intralipid (IL) Administration in IVF: It’s Composition how it Works Administration Side-effects Reactions and Precautions
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
•Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
•A personalized, stepwise approach to 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
My 2nd egg retrieval failed miserably. My 1st I had 6 retrieved 6 mature 6 fertilized with ICSI. On day 3 all were rated good quality and on day 6 we had 5 blasts and 3 had good grades and were frozen. 1 tested PGT normal.
This 2nd retrieval BOMBED. I had 12 retrieved 6 mature 3 fertilized with ICSI. I wasn’t surprised about the 50% maturity rate because we were only seeing 5-6 good size follicles, I think my doctor just went for everything she could get. But going from 100% to 50% fertilization with ICSI? Then on day 3, 2 were rated poor and 1 was fair with fragmentation. Doesn’t sound like any will make it.
I’m so confused by the drastically different results. Last cycle I was told I must have good egg quality to have 0% attrition through day 3 and good ratings across the board. This time the embryologist said it looks like bad egg quality. He said when they got the eggs some were fractured, some post-mature, and overall just sounds like the eggs were terrible.
Could it have been my protocol? 1st time I did BCP priming + antagonist and stimmed for 8 days with 225 Gonal and 150 Menopur. 2nd time I did estrogen & testosterone priming + antagonist but had a slow response so stimmed for 12 days and they had to increase to 300 Gonal and 150 Menopur. Added Omnitrope the last 4 days of stims. Also supplemented with DHEA before the cycle started. Follicles were around 15-20mm both times day of trigger.
I’m heartbroken and so confused. I’m praying it’s the protocol and not that my egg quality plummeted in 2 months.
I’m scared to do another retrieval and repeat the terrible results. Should I just go back to the 1st protocol? The reason we switched was because the doctor was hoping to retrieve more (closer to my AFC of 10). But clearly I’d prefer quality over quantity at this point.
Thank you!
Hi Allison!
Yes indeed, the protocol used for ovarian failure could be a factor here. However there could ber other issues as well. I really think we should talk. Please call 702-533-2691 and setup an online consultation with me to discuss in detail.
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?
Dear Dr Sher,
I have been pregnant twice (first a missed miscarriage at 11 weeks, fetal pole was seen but measured 6 weeks and the second at 5.5 weeks). We haven’t been able to conceive since (approx 1.5 years). We are both 34.
In my first pregnancy I developed weird symptoms and was diagnosed with MS and my MS seems to flare when I am pregnant.
We moved to IVF and I’ve had 3 transfers now (albeit two of the embryos weren’t the best quality) but none have stuck. I’ve done NK testing and have raised NK cells so take steroids (20mg) during treatment. Cytokine levels were normal. I’ve also recently done an ERA and need to take some antibiotics before my next transfer.
My question is, with my immune background, I feel that my immune system may be the issue. Would you recommend more testing before my next transfer and possibly adding intralipids?
Thank you
This sounds very much like an implantation dysfunction. WE should talk. I suggest you contact my assistant, Patti Converse at 702-533-2691 and set up an online consultation with me.
In the interim, please see below:
Implantation dysfunction is unfortunately often overlooked as an important cause of IVF failure. In the pursuit of optimizing outcome with IVF, the clinician has a profound responsibility to meticulously assess and address this important issue if IVF success is to be optimized. This is especially relevant in cases of “unexplained IVF failure, Recurrent Pregnancy Loss (RPL) and in women suspected of having underlying anatomical and immunologic factors. Doing so will not only maximize the chance of a viable pregnancy but enhancing placentation, will at the same time promote the noble objective of optimizing the quality of life after birth.”
IVF success rates have been improving over the last decade. The average live birth rate per embryo transfer in the U.S.A for women under 40y using their own eggs , is currently better than 1:3 women. However, there is still a wide variation from program to program for IVF live birth rates, ranging from 20% to near 50%. Based upon these statistics, the majority of women undergoing IVF in the United States require two or more attempts to have a baby. IVF practitioners in the United States commonly attribute the wide dichotomy in IVF success rates to variability in expertise of the various embryology laboratories. This is far from accurate. In fact, other factors such as wide variations in patient selection and the failure to develop individualized protocols for ovarian stimulation or to address those infective, anatomical and immunologic factors that influence embryo implantation are at least equally important.
About 80% of IVF failures are due to “embryo incompetency” that is largely due to an irregular quota of chromosomes (aneuploidy) which is usually related to advancing age of the woman and is further influenced by other factors such as the protocol selected for ovarian stimulation, diminished ovarian reserve (DOR)m and severe male factor infertility. However in about 20% of dysfunctional cases embryo implantation is the cause of failure.
Anatomical Endo-uterine Lesions: This blog article will focus on implantation dysfunction and IVF failure due to:
•Anatomical abnormalities in the uterine cavity (e.g. scarring, polyps and encroaching fibroid tumors)
•A thin endometrial lining
•Immunologic rejection of the embryos
Several studies performed both in the United States and abroad have confirmed that a dye X-Ray or hysterosalpingogram (HSG) will fail to identify small endouterine surface lesions in >20% of cases. This is significant because even small uterine lesions have the potential to adversely affect implantation. Hysteroscopy is the traditional method for evaluating the integrity of the uterine cavity in preparation for IVF. It also permits resection of most uterine surface lesions, such as submucous uterine fibroids (myomas), intrauterine adhesions and endometrial or placental polyps. All of these can interfere with implantation by producing a local “inflammatory- type” response similar in nature to that which is caused by an intrauterine contraceptive device. Hysterosonography (syn HSN/ saline ultrasound examination) and hysteroscopy have all but supplanted HSG to assess the uterine cavity in preparation for IVF. HSN which is less invasive and far less expensive than is than hysteroscopy involves a small amount of a sterile saline solution is injected into the uterine cavity, whereupon a vaginal ultrasound examination is performed to assess the contour of the uterine cavity.
Endometrial Thickness: As far back as in 1989 I first reported on the finding that ultrasound assessment of the late proliferative phase endometrium following ovarian stimulation in preparation for IVF, permits better identification of those candidates who are least likely to conceive. We noted that the ideal thickness of the endometrium at the time of ovulation or egg retrieval is >9 mm and that a thickness of less than 8 mm bodes poorly for a successful outcome following IVF.
Then in 1993, I demonstrated that sildenafil (Viagra) introduced into the vagina prior to hCG administration can improve endometrial growth in many women with poor endometrial development. Viagra’s mechanism of action is improvement in uterine blood flow with improved estrogen delivery…thereby enhancing endometrial development.
Immunologic factors: These also play a role in IVF failure. Some women develop antibodies to components of their own cells. This “autoimmune” process involves the production of antiphospholipid, antithyroid, and/or anti-ovarian antibodies – all of which may be associated with activation of Natural Killer (NK) cells in the uterine lining. Activated NK cells (NKa) release certain cytokines (TH-I) that if present in excess, often damage the trophoblast (the embryo’s root system) resulting in immunologic implantation dysfunction (IID). This can manifest as “infertility” or as early miscarriages). In other cases (though less common), the problem is due to “alloimmune” dysfunction. Here the genetic contribution by the male partner renders the embryo “too similar” to the mother. This in turn activates NK cells leading to implantation dysfunction. These IID’s are treated using combinations of medications such as heparin, Clexane, Lovenox, corticosteroids and intralipid (IL).
I strongly recommend that you visit http://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.
•A Fresh Look at the Indications for IVF
•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.
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•IVF and the use of Supplementary Human Growth Hormone (HGH) : Is it Worth Trying and who needs it?
•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
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•IVF: Approach to Selecting the Best Embryos for Transfer to the Uterus.
•Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
•Genetically Testing Embryos for IVF
•Staggered IVF
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
•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
•Endometrial Receptivity Array (ERA): Is There an actual “There, There”?
•IVF Failure and Implantation Dysfunction:
•Diagnosing and Treating Immunologic Implantation Dysfunction (IID)
•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
•A Thin Uterine Lining: Vaginal Viagra is Often the Answer (update)
•Cervical Ureaplasma Urealyticum Infection: How can it Affect IUI/IVF Outcome?
•The Role of Nutritional Supplements in Preparing for IVF
•The Basic Infertility Work-Up
•Defining and Addressing an Abnormal Luteal Phase
•Male Factor Infertility
•Routine Fertilization by Intracytoplasmic Sperm Injection (ICSI): An Argument in Favor
•Hormonal Treatment of Male Infertility
•Hormonal Treatment of Male Infertility
•Antisperm Antibodies, Infertility and the Role of IVF with Intracytoplasmic Sperm Injection (ICSI)
•Endometriosis and Infertily
•Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF
•Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice.
•Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options
•Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination) and Reproductive Surgery Versus IVF
•Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
•Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & Con’s!IUI-Reflecting upon its Use and Misuse: Time for a Serious “Reality Check
•Mode of Action, Indications, Benefits, Limitations and Contraindications for its ue
•Clomiphene Induction of Ovulation: Its Use and Misuse!