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.
Dear Dr Sher,
Firstly thank you so much for your articles and wonderful resources on fertility. I’ve started reading up on various topics but it is hard for me to put all the pieces together so I was hoping you could provide some advice on any recommended improvements to my IVF cycle protocols.
I am in the midst of our 12th ivf cycle and recently turned 45yo. We never found an actual infertility cause other than leaving things too late. Our very first cycle when I was 39yo ended in a miscarriage and was the only cycle to produce 2 frozen embryos (one of which later miscarried at 6-8 weeks and the other unsuccessful). Thankfully one subsequent cycle gave us a live birth, but no further success over the past 3years. Since then all the cycles were similar antagonist cycles with relatively low FSH dosages ranging from 66 to 100iu (current one at 87iu produced 8eggs with 5fertilised, currently awaiting progress of embryos). The cycles with low FSH doses attempted to target low egg number (1 or 2) in the hope of improved quality, and most embryos transferred at Day 3 as they seem to always deteriorate by Day 5.
Only one cycle earlier this year was different – it was a long cycle with Provera and Lucrin starting around Day 19 before start of new cycle, and 250iu of FSH – and it ended up with 19eggs with 11fertilised but no better outcome at the end. But extra tests done prior to that cycle for the first time found high NK cells (biopsy looked normal late last year but abnormally high 4months later in 2nd biopsy) as well as high ANA, for which I took Prednisolone and Clexane, plus Intralipid Infusion for good measure. I realise my age is now a problem but it’s a pity I didn’t know about these implantation impediments earlier as I don’t feel we gave ourselves a fair chance without treating for them in past cycles.
We hadn’t given up just yet as I still have good ovarian reserve and respond well to the FSH (actually easily overstimulate). Could I have your thoughts about finishing our current cycle – are we best to opt for Day 3 transfer, when is best time to have remaining Intralipids (first one was done 6 days before egg collection), and is daily 15mcg Prednisolone /40mg Clexane / 2Crinone gels reasonable? Most importantly, how many embryos is best to transfer (I was planning for at least 2 embryos to transfer (numbers permitting) but remember reading about other risks of them attacking each other but wasnt sure if that was a specific condition apart from high NK Cells and ANA. I do also have slightly underactive thyroid for which I take a 50mcg tablet 4 times per week).
Your advice would be greatly appreciated, particularly if this is our last try at IVF, to ensure we make the most of it. Do you think given all the factors there is any point trying again after this? And if so, what would be the best protocol? Once we complete this current cycle I would be happy to have a Skype appointment if a more detailed discussion is warranted.
Thanking you in advance,
Ollie
It is a pity that the immunologic implantation dysfunction (IID) was not detected at an earlier age because now, although it is likely that this icould be a relevat factor whether your eggs or donor eggs are used (see below), there can be little doubt that yourage and its impact on egg genetic/chromosomal integrity, is the most important consideration. At 45y, while it is possible to have an IVFsuccess using own eggs, it is highly unlikely that IVF with own eggs will be successful. Undoubtedly, egg donor-IVF is the only rational solution provided that if there is a seconary IID, this is dealt with simultaneously. Since this came after having a child before (secondary), while the IID could be autoimmune in origin, an alloimmune cause needs to be carefully considered (see below). Consider the following:
Older women as well as those who (regardless of age) have diminished ovarian reserve (DOR) tend to produce fewer and less “competent” eggs, the main reason for reduced IVF success in such cases. The compromised outcome is largely due to the fact that such women tend to have increased LH biological activity which often results in excessive LH-induced ovarian testosterone production which in turn can have a deleterious effect on egg/embryo “competency”.
Certain ovarian stimulation regimes either promote excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), augment LH/hCG delivered through additional administration (e.g. high dosage menotropins such as Menopur), or fail to protect against body’s own/self-produced LH (e.g. late antagonist protocols where drugs such as Ganirelix/Cetrotide/Orgalutron that are first administered 6-7 days after ovarian stimulation has commenced).
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of a modified, long pituitary down-regulation protocol (the agonist/antagonist conversion protocol-A/ACP) augmented by adding supplementary human growth hormone (HGH). I further recommend Staggered IVF with embryo banking of PGS (next generation gene sequencing/NGS)-normal blastocysts in such cases. This type of approach will in my opinion, optimize the chance of a viable pregnancy per embryo transfer procedure and provide an opportunity to capitalize on whatever residual ovarian reserve and egg quality still exists, allowing the chance to “make hay while the sun still shines”.
AS for a day 3 versus day 5 transfer at 45Y, all I can say is that if an embryo fails to make it to blastocyst, the overwhelming likelihood is that it is “incompetent” and wereit to have been transferred earlier, it would not have propagated a pregnancy anyway. So I personally would favor stoccpiling (banking) biopsies embryos and then subsequently transferring PGS-normal ones selectively.
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 Aproach
•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)
•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
•Why did my IVF Fail
•Secondary Infertility: Addressing the Root Causes
•Blastocyst Embryo Transfers Done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
•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
•IVF Egg Donation: A Comprehensive Overvie
Good luck!!
If in the future you would like my input , 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.
Hi Dr Sher
Have followed your blog for many years. For my first successful pregnancy I required prednisone 35mg clexane asprin and lipids pre embryo transfer and had low rising hcgs and lots bleeding but thankfully my child held on and was born healthy. I’ve managed to fall pregnant naturally and only took prednisone 15mg from ovulation with asprin and clexane and then had an intralipids at 12 days post ovulation with a positive pregnancy test. I’m 6 weeks and so far good hcg rise no bleeding and pregnancy is holding. I also upped my prednisone to 30mg on positive beta. Do you find after a successful pregnancy the uterus can be more favourable to a pregnancy ? It’s just I read you post that for intralipids to properly supress nk cell activation they need to be delivered pre implantation so will my immune treatment be ineffective as started later. Lastly what is the maximum therapeutic dose of prednisone you put your patients on and do you start weaning from 12 weeks?
Kind Regards
Jacinta
It is unquestionably better to start IL infusions with steroids (dexamethasone/prednisone) 10-14 days pre-emryo transfer/pre-implantation. But it sometimes works if you start later and that is definitely better than not taking it at all. I use 0.75mg dexamethasone daily or 10mg prednisone and I stazrt weaning off the steroids at 8 weeks with complete cessation by the 10th gestational week.
Good luck!
Geoff Sher
Hi Dr Sher,
My wife and I (37), have been naturally trying for baby number x2 for three years. In April we opted for our first round of assisted fertility. 17 eggs were retrieved, 16 were good quality. On my request 8 underwent IVF, 8 underwent ICSI, 4 from each side fertilised, on day three 1 viable mid range size and quality (with fragmentation present) was avalible from the IVF batch, and 2 from ICSI (same quality). The two ICSI embryos were transferred, and unfortunately resulted in no pregnancy. We have been advised that for our next cycle we should go only for ICSI, I have a preference for IVF – just because I feel there is more of a natural selection process and perhaps there are very minimal increase risk factors with ICSI. Only other thing to mention is my seamen morphology is scoring low at 1-2% normal on strict scale, all other parameters good. I would really appreciate your opinion. Thanks
Intracytoplasmic Sperm Injection ICSI which began in 1992 as a treatment for severe male factor infertility, involves the direct injection of a single sperm into each egg under direct microscopic vision.
Soon after the turn of the 20th century it was reported that while the diagnosis of a male factor infertility had remained static, the use of ICSI had markedly increased and that indications for ICSI had expanded from solely male infertility (for which it had primarily been developed) to a wide variety of other indications such as “unexplained infertility, unexplained IVF failure, polycystic Ovarian Syndrome (PCOS) and cases where the woman’s eggs had become more resistant to conventional fertilization. ICSI was also being used in cases where sperm was absent (or virtually absent) from the ejaculate due to congenital or traumatic or medically acquired obstruction of the main collecting ducts (vasa deferentia), testicular failure and in cases where for traumatic, neurologic, or psychologi reasons (impotency) no semen/sperm was being ejaculated. In such cases, sperm obtained through Testicular Sperm Extraction (TESE), or aspiration (TESA) was being successfully used for ICSI. Today in the United states more than 70% of all IVF fertilizations are being conducted using ICSI with high fertilization and pregnancy rates being reported, regardless of sperm concentration, motility or morphology.
Clearly ICSI is increasingly replacing conventional insemination due to its many benefits and lack of definable drawbacks. In fact, pregnancy rates achieved by this method of fertilization are at least as high as those of conventional IVF performed in cases of non-male-factor infertility. Indeed, ICSI is associated with high fertilization and pregnancy rates regardless of sperm concentration, motility or morphology.
Notwithstanding, the above, the proposition that ICSI be preferentially used as the routine method for fertilizing eggs in IVF continues to meet with resistance. Die hards argue that about 1-3% of pregnancies resulting from ICS are associated with congenital developmental and genetic defects that affect the offspring. They cite conditions such as *Beckwith-Wiedemann syndrome, *Angelman syndrome, *hypospadias, sex chromosome abnormalities, a slightly increased miscarriage rate and the fact that male offspring resulting fom ICSI pregnancies are themselves at risk of subsequently developing male infertility in later life.
What you do not often hear from nay-sayers is that those studies that site the above mentioned risks do not distinguish between cases where ICSI is/was mandated for male infertility )and cases where ICSI is/was done for other (non-male infertility) reasons. If this was done, what in my opinion would emerge is that the above mentioned birth defects and developmental conditions are largely confined to the underlying male factor for which ICSI was indicated and are not due to the ICSI process itself. In fact a relatively recent study performed in Sweden demostrated this well. Here 542 children who were conceived naturally were compared with 941 children conceived through IVF (440 by conventional IVF & 541via ICSI) The babies/children were assessed at birth and during the first 5 years of life: The findings revealed that while the incidence of birth and developmental defects was indeed higher in ICSI babies, this only applied to cases where ICSI had been done for male infertility. It did not apply to cases where ICSI was done in the absence of male factor infertility.
Another very important consideration that supports the routine fertilization of eggs by ICSI is the fact that good quality IVF relies heavily on an ability to adequately assess egg maturation immediately following egg retrieval. To do this requires removal of layers of cumulus oophoris (CO) cells that cover the egg envelopment (zona pellucida). Only after the CO is stripped can the 1st polar body (PB-1) which is located immediately under the zona pellucida be identified and it is the presence of PB-1 signifies that indicates that the egg has gone through meiosis (reproductive division) and is thus mature (M2) and overwhelmingly, successful fertilzation and viable embryo development requires that the fertilized egg was mature (M2). This assessment for the presence of PB-1 cannot be reliably done without first removing the cumulus oophoris cells attached to the outer surface of the zona pellucida. The problem is that stripping the cumulus oophoris cells away, markedly reduces natural fertilization potential, leaving ICSI as the only alternative by which to subsequently achieve viable embryo propagation. The only way by which to avoid fertilization by ICSI would be to bypass the important step of assessing egg maturation and this in my opinion would compromize IVF outcome significantly. Thus optimization of the entire IVF process virtually mandates routine ICSI in IVF.
For the above reasons, I proudly count myself among a growing majority of IVF practitioners who support the routine use of ICSI for all IVF patients
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 Aproach
•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
•Blastocyst Embryo Transfers Done 5-6 Days Following Fertilization are Fast Replacing Earlier day 2-3 Transfers of Cleaved Embryos.
•Why did my IVF Fail
•Male Factor Infertility
•Hormonal Treatment of Male Infertility
•Antisperm Antibodies, Infertility and the Role of IVF with Intracytoplasmic Sperm Injection?
•Varicocele and Male Infertility: When and how should it be treated.
•The Sperm Chromatin Structure Assay (SCSA): A Measure of the Potential of Sperm to Help Propagate a Viable Pregnancy
•IVF for Women Who Have Previously Conceived (Secondary Infertility).
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.
Hi Dr. Sher,
I’m 34 years old. I was diagnosed with PCOS when I started this journey over 2 years ago. I started IVF in February 2014. I was fortunate in the fact that they retrieved around 25 eggs and I ended up with 16 good quality embryos. I developed OHSS after the egg retrieval so did not do a fresh transfer. Instead, did a frozen transfer of 2 embryos and I got pregnant with one baby and gave birth on November 26, 2014. Then I decided in September 2015 to start trying for the second one. I had another hysteroscopy before getting started and everything was normal. My doctor had me on Estrace and Minnevelle patches. Unfortunately, my lining would not thicken past 6 mm so he canceled that cycle and then started me on stim medicines — menopur and gonal f. I did that for about a week, my lining thickened to around 7.8 – 8 mm so we started the progesterone shots and had the transfer 5 days later. My blood test confirmed a pregnancy but then we never got a heartbeat. I had a D&C. This happened in December 2015. I decided to try again in March, my doctor did the same protocal — stim medicines — my lining was about the same and I did not get pregnant. I went back in May and tried again. This time we did PGS on 8 embryos, came back with 5 chromosomally normal embryos. I followed the same protocol of stim medicines, my lining again was not above 8, we transferred one of the normal embryos and I just found that I’m not pregnant. Based on your article about viagra, I’m wondering if that would help my lining issues — or if you think my lining is the issue? Also, should I be using the stim medicines if I have PCOS? I just want to try something different. We’ve now tried the same thing 3 times and it failed. When I got pregnant the first time, I was just on estrace pills and patches and he did show me that my lining was only at 7.8 mm, which further leads me to believe that the stim medicine is not the best choice. What are your thoughts?
Thank you for your time.
Jessica Monford
I have little doubt that the main issue for you is an implantation dysfunction. Clearly the most likely explanation is a thin lining (<8mm) but there could also be an immunologic implantation dysfunction.
If it is a thin lining causation then vaginal Viagra might help. However there are causes of this that have to do with endometrial receptivity to estrogen. The latter can be caused by a protocol of ovarian stimulation that evoked an LH-induced exaggerated release of ovarian male hormones such as Testosterone which can desensitize the endometruium to estrogen. And tis is quite common in association with PCOS. If the thin lining is due to this cause, Viagra will not likely resolve the issue. There would instead be a need to review and revise the protocol used for ovarian stimulation and uterine preparation.
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 Aproach
•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
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
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,
Have you ever come across a case where thyroid antibodies were the cause / potential cause in your opinion of unexplained infertility when NK KIller cells are not activated – in depth testing completed on both sides – 5 failed fresh, 2 failed frozen, no implantation – only other issue low Morphology.
If so, Is there any treatment in such cases to treat antibodies?
Thoughts on significance of isolated low morphology?
Thanks,
J
In ,my opinion no! I do not treat thyroid antibodies in the absence of NKa.
Geoff Sher