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, hoping you can help me out.
– do you ever recommend a Pill Antagonist without an overlap of an Agonist for a 40 year old who does not have DOR
– what point in the cycle do you measure LH levels?
– Does the timing of the trigger only impact the ratio of mature vs immature eggs. Or could it also impact the quality?
– what level of HGH do you recommend for a 40 year old?
– do you ever recommend a Pill Antagonist without an overlap of an Agonist for a 40 year old who does not have DOR
A: An antagonist is given by injection and yes, it can be used without a preceding BCP.
– what point in the cycle do you measure LH levels?
A: Before the cycle starts. I do not measure LH routinely in-cycle.
– Does the timing of the trigger only impact the ratio of mature vs immature eggs. Or could it also impact the quality?
A: Both
– what level of HGH do you recommend for a 40 year old?
Thye protocols we use differ. I would be willing to discuss this with you, if and when we consult.
Geoff Sher
800-780-7437
Thank you Dr Sher.
By “planning the trip before you take the ride”, when do you recommend doing bloods to influence the protocol?
By way of example, on a pill long down reg, should the bloods (basel FSH, E2, LH) on Day 3 and bloods post Pill help determine the dosage of gonadotropins for that cycle? Or is that too late too?
Many thanks again. This blog is amazing and much appreciated.
They can be measured on days 1-4 of the menstrual cycle…preferably when the woman is not on a BCP.
Geoff Sher
Hi Doctor Sher. My partner and I are both 34. My partner has a low sperm count so we use icsi. I also have low grade endometriosis and elevated natural killer cells. We’ve been through 3 stim cycles and 5 transfers. The first stim cycle we transferred 1 embryo with negative result. The second cycle we transferred a blastocyst with the same outcome. The third cycle we froze 8 embryos at day 3. The first double transfer failed, so I had a hysteroscopy and laparoscopy where they removed low grade endometriosis. The next double transfer resulted in a pregnancy but I miscarried at 8 weeks. We had the embryo tested and was told it was a trisomy 16 defect. We have just got a negative result from our third double embryo transfer (fifth transfer overall). We have two more frozen embryos which we will transfer this month. Is it worth doing chromosome testing? Should we start looking at other options? Donor embryos? If I’ve had a miscarriage is it more likely an embryo problem than implantation issue? I question the quality of our embryos with so many negative results. Thanks in advance.
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 a decade 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
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.
•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
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
•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.
•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
•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
•Treating Ovarian Endometriomas with Sclerotherapy.
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
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.
Dr Sher, After conceiving my daughter naturally in 2011, we’ve been struggling to have another child since. My husband has no issues. My main fertility issue is a blocked tube due to an ectopic in 2009, and although my right tube appears open with a dye test, we didn’t want to waste time and decided to go down the IVF route in Oct 2014 after 6 months of trying naturally. It’s wasn’t a great cycle – 7 follicles but only three eggs and we transferred the best 2 x 3 day 8 cell embryos – nothing to freeze. I got pregnant, initially with twins but at the 12 week scan they found a third baby – triplets. Unfortunately I suffered PROMs at 20 weeks and lost the pregnancy within days. Post mortem didn’t detect any problems with babies just bad luck and the result of multiples. In 2015, we tried another round of IVF. Much better cycle (double trigger as I have a higher BMI) resulted in 9 follicles, 7 eggs, 5 fertilised and 5 excellent/good quality blastocysts. Due to triplets we opted to transfer one at a time. Fresh cycle with perfect embryo failed. 1st FET in November 2015 resulted in blighted ovum at 8 weeks, 2nd FET lead to a chemical in Feb 2016. Dr added in a scratch and intra-lipids infusion in prep for 3rd FET in March (with a perfect day 6 blasto), It worked and everything was perfect until the 22 week scan where they diagnosed Complete Agenises of the Corpus Callosum and Tallipes of the right foot. After an amnio (which was negative) and an MRI, we were advised to terminate. I delivered a little girl at 23w6d in July this year. I transferred the last FET two weeks ago but it hasn’t worked. I’m at a loss on what to do next. I’m not ready to give up – I’ve just turned 39 so I know the clock is ticking but all the advice I read says not to consider egg donation till 42+. My question is, are we just unlucky (what all our Drs are saying) or are there egg quality issues at play?? I’m happy to move forward with a fresh cycle, but is there any point? Would you suggest testing? The ACC wouldn’t have been picked up as amnio was clear, I just want our best chance and would really appreciate your expert opinion. Many thanks, Angela Magny
This is very likely a case of very bad luck! Have careful genetic counseling and then consider trying Staggered IVF with PGS testing. I would suggest however that you have your cervix carefully examined to exclude cervical incompetency. Also for the next stimulation, might I recommend the use an agonist/antagonist conversion protocol (A/ACP) which is a modified, long pituitary down-regulation regime and thatbthis be augmented by adding supplementary human growth hormone (HGH)….see below. I further recommend that such women be offered access to embryo banking of PGS (next generation gene sequencing/NGS)-selected normal blastocysts, the subsequent selective transfer of which would enhance the opportunity to achieve a viable pregnancy
Please visit my new Blog on this very site, http://www.DrGeoffreySherIVF.com, find the “search bar” and type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
•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)
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•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
•Frozen Embryo Transfer (FET) versus “Fresh” ET: How to Make the Decision
•Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting 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.
•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
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF.
•The Role of Nutritional Supplements in Preparing for IVF
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•IVF Egg Donation: A Comprehensive Overview
I invite you to arrange to have a Skype or an in-person consultation with me to discuss your case in detail. If you are interested, please contact Julie Dahan, at:
Email: Julied@sherivf.com
OR
Phone: 702-533-2691
800-780-7437
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.
Hi Dr. Sher,
I have an elevated ANA, APA, and NK Cells (RIP test is normal). In addition to my current protocol of prednisone and baby aspirin (which was successful 2 years ago when I learned I ONLY had an elevated ANA level…I did have a baby after that through IVF). Now I had just recently had a failed FET and they redid my immunology testing which found elevated levels for all these other things… so in addition to the 10mg of prednisone, I am being told I will have to do IVIG. Is there anything else that I should consider adding to my protocol to make this next transfer successful? Also, are there any other health (diet, acupuncture, etc.) steps I can take to lowering my levels? Thank you.
Dr. Sher… this is Stefanie. I wanted to add to my post just now that this last FET I did prednisone AND intralipid infusion 2 weeks before my transfer… and it implanted but then it was a chemical pregnancy and failed just a week after my transfer. It was a chromosomally normal embryo.
Hi Stefanie,
IVIG works but it is very expensive and the risk of side effects , quite high. In my opinion, it can be supplanted by using Intralipid (IL) without compromising success, at a much lower cost, and with a lower incidence of side effects. However, whether IVIG or IL is used, it needs to be combined with steroid therapy to be optimally effective. Another thing…you need to know upfront whether yours is an autoimmune or an alloimmune implantation dysfunction because the treatment is different.
Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid. It is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid), 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).
Possible Mode of Action:
It is thought that fatty acids within the emulsion serve as ligands to activate peroxisome proliferator-activated receptors (PPARs) expressed by the NK cells. This is believed to decrease NK cytotoxic activity, and thereby enhance implantation A growing number of IVF programs, including ours, perform egg retrieval under conscious sedation using Propofol, a short acting hypnotic agent. Interestingly, similar to Intralipid 1% Propofol also contains the same concentration of soybean oil, and purified egg phospholipid, with glycerin. Perhaps its use offers a fringe benefit in cases of immunologic implantation dysfunction.
Whatever the exact mechanism of action might be, IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating cytotoxic /activated natural killer cells (NKa). This effect is enhanced through the concomitant administration of corticosteroids such as dexamethasone, prednisolone and prednisone which in my opinion do so by immune modulation of T cells . The combined effect of IL + steroid therapy is thought to suppresses pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha, produced in excess by activated NK cells and cytotoxic T cells.
IL will in about 80% of cases, successfully down-regulats activated natural killer cells (NKa) within 2-3 weeks. In this regard it is likely to be just as effective as IVIg but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.
Can in-vitro (laboratory) tests assess for an immediate benefit of IL on Nka?
Since the down-regulation of NKa through IL (or IVIg) therapy can take several weeks to become detectable, it follows that there is really no benefit in trying to assess the potential efficacy of such treatment by retesting NKa in the laboratory after adding IL (or IVIg) to the cells being tested.
Treatment of NKa Using IL:
•Autoimmune Implantation Dysfunction: When it comes to NKa in IVF cases complicated by autoimmune implantation dysfunction, the combination of daily oral dexamethasone commencing with the onset of ovarian stimulation and continuing until the 10th week of pregnancy, combined with an initial infusion of IL (100ml, 20% Il dissolved in 500cc of saline solution, 10-14 days prior to embryo transfer and repeated once more (only), as soon as the blood pregnancy test is positive), the anticipated chance of a viable pregnancy occurring within 2 completed IVF attempts (including fresh + frozen ET’s) in women under 39Y (who have normal ovarian reserve) is approximately 80%.
•Alloimmune Implantation Dysfunction
oPartial DQ alpha match: IVF patients who have NKa associated with a partial alloimmune implantation dysfunction (DQ alpha match between partners) we use the same IL, infusion as with autoimmune-NKa, only here we prescribe oral prednisone rather than dexamethasone until the 10th week of pregnancy and IL infusions are repeated every 2-4 weeks following the chemical diagnosis of pregnancy until the 24th week. Additionally, (as alluded to elsewhere) in such cases we transfer only a single embryo at a time. This is because in such cases, the likelihood is that one out of two embryos will “match” and we are fearful that if we transfer >1 embryo, and one transferred embryos “matches” it could cause further activation of uterine NK cells and so prejudice the implantation of all transferred embryos. Since we presently have no way of determining which embryo carries the matching paternal DQ alpha gene and thus would transfer only one embryo at a time, it follows that the anticipated viable pregnancy rate per cycle will be much lower than with autoimmune implantation dysfunction. It also follows the only way to improve success with a single embryo being transferred would be to perform PGS on the embryos in advance of ET and then selectively transfer a “chromosomally normal-euploid (“competent”) embryos.
oTotal (complete) DQ alpha Match: In cases where the partners have a total alloimmune (DQ alpha) match with accompanying NKa the chance of a viable pregnancy occurring or (if it does) resulting in a live birth at term, is so small as to be an indication for using a non-matching sperm donor or resorting to gestational surrogacy would in our opinion be preferable by far.
Contra-Indications and Cautions with Intralipid Infusion:
IL is only contraindicated in conditions associated with severely disordered fat metabolism (e.g. severe liver damage, acute myocardial infarction and shock,
Rarely, hypersensitivity has been observed in patients allergic to soybean protein, egg yolk and egg whites and where fat metabolism may be disturbed (e.g. renal insufficiency, uncontrolled diabetes, certain metabolic disorders and in cases oif severe infection (sepsis) sepsis
Adverse Reactions During Infusions of IL (rare):
Adverse reactions (rare) reported to occur during and/or following infusion of Intralipid include: transient fever, chills, nausea, vomiting, headache, back or chest pain with dyspnea and cyanosis.
In cases of verified or suspected liver insufficiency, liver function must be closely followed. If increased levels of transaminases, alkaline phosphatases or bilirubin appear, infusion of Intralipid should be withheld or postponed, until normalization is achieved.
Very rare cases of hypersensitivity have been observed in patients allergic to soybean protein, egg yolk and egg whites.
Fat metabolism may be disturbed in conditions such as renal insufficiency, uncompensated diabetes, certain forms of liver insufficiency, metabolic disorders and sepsis.
Administration:
The drip rate is adjusted to 500 ml of a 20% solution should be infused over about 3 hours. The infusion should be started at half the infusion rate during the first 30 minutes, under supervision.
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.
•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)
•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:
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437
Geoff Sher
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.