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.
Hello, I just wanted to know your opinion on my situation. I am 41 years old and my fertility issue is fallopian tube related. I do not have a fallopian tube on the left side and the right side is completely blocked. I had my daughter naturally when I was 18 years old and then had a son via IVF in 2012 at 35 years old. I have been trying to conceive another child before my child bearing days are completely over but it has been difficult. I went back to the same clinic that I had my son with and last October when I was 40yrs old I did an IVF cycle which rendered 5 embryos all of which did not fertilize. Then in Feb of this year I did another cycle and only received 3 embryos this cycle. Only one of the embryos fertilized and it was a day later. That led to a BFN. So this time around the Dr. had me on Omnitrope 5.8 mg injecting 0.33 mg daily for about a month prior to my retrieval. I was on Gonal F 450 IU, Menopur 150 IU, Cetrotide 0.25 mg, prednisone 5 mg 2x daily during my IVF cycle. On the day of retrieval they got 3 embryos, 2 of which fertilized and they said they froze them on day 3. They said they were graded good. I just ovulated and I’m currently waiting to do an endometrium scratch next week. They then said they will do an FET next month after my menstrual cycle. My question to you is, in your experience have you had any luck with Omnitrope and your patients? I am scared of my FET being a failure due to them not surviving the thaw, them being 3 day embryos, or maybe the quality of my embryo will go from good to bad. Can you please give me your professional opinion on my case? Thank you so much.
Older women and those who have diminished ovarian reserve (DOR) have greater difficulty in conceiving naturally or through assisted reproductive technology (ART). This is largely due to an inevitable increase in egg aneuploidy (numerical chromosome irregularity). However, although less significant than the rising increase in egg aneuploidy, advancing age and DOR are both also associated with non-chromosomal egg deterioration involving a decline in mitochondrial activity as well as a progressive reduction in the ability of the granulosa cells that line the inside of the follicle to respond to FSH stimulation.
Getting older women and those with DOR to respond optimally to ovarian stimulation often represents a serious challenge. Many will fail to respond adequately to standard ovarian stimulation regimens, requiring any individualized and strategic approach to ovarian stimulation…. one that regulates and limits exposure of ovarian follicles and eggs to LH-induced local male hormones (predominantly testosterone). This, in my opinion is best addressed by using a modified long pituitary down regulation protocol with an agonist (e.g. Lupron/Buserelin/Superfact) coming off a birth control pill. Thereupon, as soon as the period starts, the agonist is supplanted by an antagonist (e.g. Cetrotide/Orgalutron/Ganirelix) and stimulation with recombinant FSH (Follistim/Gonal-F/Puregon) along with a small amount of menotropin (e.g. Menopur) until t optimal follicle development prompts initiation of the hCG trigger. More than 15 years ago, I reported on the observation that in some women with severe DOR, the addition of intramuscular administration of estradiol valerate (i.e. Delestrogen) prior to and during gonadotropin stimulation (i.e. “estrogen priming”) is capable of further enhancing follicle growth .
More recently, researchers have shown that the administration of human growth hormone (HGH), as an adjunct to ovarian stimulation, can enhance follicle response in older women and those with DOR. Two basic mechanisms have been proposed: a) enhanced response to FSH by up-regulating the FSH receptors on follicular granulosa cells and, b) through a direct effect of HGH on the egg itself whereby mitochondrial activity is enhanced. Human eggs do have receptors to HGH but eggs retrieved from older women show decreased expression of such receptors (as well as a reduced amount of functional mitochondria. It was recently observed that some such women treated with HGH, show a marked increase in egg functional mitochondria along with improved egg quality.
The older a woman becomes, the more likely it is that her eggs will be chromosomally/genetically “incompetent” (not have the potential upon being fertilized and transferred, to result in a viable pregnancy). That is why, the likelihood of failure to conceive, miscarrying and of giving birth to a chromosomally defective child (e.g. with Down Syndrome) increases with the woman’s advancing age. In addition, as women age beyond 35Y there is commonly a progressive diminution in the number of eggs left in the ovaries, i.e. diminished ovarian reserve (DOR). So it is that older women as well as those who (regardless of age) have DOR have a reduced potential for IVF success. Much of this is due to the fact that such women tend to have increased production of LH biological activity which can result in excessive LH-induced ovarian male hormone (predominantly testosterone) production which in turn can have a deleterious effect on egg/embryo “competency”.
While it is presently not possible by any means, to reverse the age-related effect on the woman’s “biological clock, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can make matters worse. Similarly, the amount/dosage of certain fertility drugs that contain LH/hCG (e.g. Menopur) can have a negative effect on the development of the eggs of older women and those who have DOR and should be limited.
I try to avoid using such protocols/regimes (especially) in older women and those with DOR, favoring instead the use of the agonist/antagonist conversion protocol (A/ACP), a modified, long pituitary down-regulation regime, augmented by adding supplementary human growth hormone (HGH). 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 by allowing them to to capitalize on whatever residual ovarian reserve and egg quality might still exist and thereby “make hay while the sun still shines” could significantly 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
If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .
*FYI
The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
Drar Dr. Sher,
My HCG only went from 29.000 (6w4d) to 63.000 (7w4d) over a 7 day period. Ultrasound on that day showed a 7.4 week baby with a heartbeat of 157. I haven´t been able to find any study or reliable information on doubling times later during the first semester. I had a stillbirth last year at 36 weeks, which makes me very nervous. Would you believe this is an omnious sign?
I appreciate your willingness to share your knowledge very much.
Best regards,
Maria
After around 6,000U the hCG level starts increasing progressively more slowly than earlier doubling every 48h.
Geoff Sher
Hi,
I just got off of an (unsuccessful IVF cycle). Had estrogen priming protocol and 7 follicles, 6 eggs retrieved, mature, only one fertilized normally. Estrogen priming was started day 21 prior cycle and continued through the entire Ivf cycle until my period came. It was 2mg Three times daily. Also estrace patches. Three days after my next cycle started, I began Femara. My FSH was only 4.0 when it’s usually 8-10. Estradiol was 43. Cycle day 13 I was triggered with an 18mm follicle and a 15mm. Had the IUI 26 hours later. Unsuccessful. This current cycle, my estradiol was 124 on cycle day 3. My doc had me start Femara. That night (cycle day 3), I had a positive OPK- it has never been positive until day 11 or 12- I have very regular 28 day cycles. My concern is that my estradiol in over a year of fertility treatments has always been between 40 and 44. I wonder if something has altered my hormones for this long, somehow. I got pregnant with IUI in November but had a blighted ovum so we are holding onto hope that one will work because we don’t want to keep doing IVF to just end up with one fair embryo each cycle out of 7-8 eggs. IUI doesn’t cost us anything. Thanks.
Copy and good luck!
Geoff Sher
Good afternoon Dr. Sher. I have had 5 miscarriages in the past 7 years the most recent was a moth ago. I recently found out that I have a double ace gene and the mthrf gene which I believe is the reason for the multiple miscarriages. Is this something that can be fixed?
There is to my knowledge no proven association between angiotensin-converting enzyme (ACE) gene mutation and the occurrence of first-trimester recurrent miscarriage.
Geoff Sher
Hi Dr. Sher,
My husband and I were found to have a partial DQ alpha match in presence of activated NK cells. Could you please interpret the severity of these results and if it would respond to treatment?
25:1 Native State – 19.9%
25:1 + IL-2 Stimulation – 21.6% (8.4% increase)
25:1 + intralipids- 18.6% (6.4% reduced)
25:1 + 12.5 mg IgG – 6.5% (67.5% reduced)
25:1 + 6.25 mg IgG – 10.8% (45.9% reduced)
NK activity assay:
50:1 Native – 26.3%
25:1 Native – 19.9%
12.5:1 Native- 10.5%
CD3+/56+ (NK T cells) – 15.8% (high)
Everything else under regarding immune tests were normal.
Please advise, thank you.
You clearly have an alloimmune implantation dysfunction. I strongly suggest we talk.
The implantation process begins six or seven days after fertilization of the egg. At this time, specialized embryonic cells (i.e., the trophoblast), which later becomes the placenta; begin growing into the uterine lining. When the trophoblast and the uterine lining meet, they, along with Immune cells in the lining, become involved in a “cross talk” through mutual exchange of hormone-like substances called cytokines. Because of this complex immunologic interplay, the uterus is able to foster the embryo’s successful growth. Thus, from the very earliest stage of implantation the trophoblast establishes a foundation for the future nutritional, hormonal and respiratory interchange between mother and baby. In this manner, the interactive process of implantation is not only central to survival in early pregnancy but also to the quality of life after birth.
Considering its importance, it is not surprising that failure of proper function of this immunologic interaction during implantation has been implicated as a cause of recurrent miscarriage, late pregnancy fetal loss, IVF failure, and infertility. A partial list of immunologic factors that may be involved in these situations includes anti-phospholipid antibodies (APA), antithyroid antibodies (ATA), and most importantly activation of uterine natural killer cells (NKa). Presently, these immunologic markers in the blood can be only adequately measured by a handful of highly specialized reproductive immunology laboratories in the United States. I personally use Reproductive Immunology Associates in Van Nuys, CA or Reprosource in Boston, MA.
The Central role of Natural Killer cells: After ovulation and during early pregnancy, NK cells comprise more than 70% of the immune cell population of the uterine lining. NK cells produce a variety of local hormones known cytokines. Uncontrolled, excessive release of certain cytokines (i.e. TH-1 cytokines) is highly toxic to the trophoblast (“root system”) of the embryo” leading to their programmed death (apoptosis) and, subsequently to failed or compromised/dysfunctional implantation. In the following situations NK cells become activated, and start to produce an excess of TH-1 cytokines:
•Autoimmune Implantation Dysfunction: This is most commonly seen in association with a personal or family history of autoimmune diseases such as ith conditions such as Rheumatoid arthritis, hypothyroidism endometriosis and Lupus Erythematosus, Scleroderma, Dermatomyositis etc. It is also encountered in one third of women who have endometriosis (regardless of its severity), and in cases of “unexplained infertility” as well as with recurrent pregnancy loss (RPL).
•Alloimmune implantation dysfunction where the male and female partners share specific genetic (DQ-alpha and/or HLA) similarities This is commonly seen in cases of RPL and in cases of secondary infertility
Activated NK cells (NKa) can be detected through the K-562 target cell blood test and (more recently) through uterine biopsy for TH-1 cytokine activity. Treatment involves selective use of Intralipid (IL) or immunoglobulin (IVIG) therapy combined with oral steroids, initiated more 10-14 days prior to embryo transfer and in most cases of alloimmune implantation dysfunction, the transfer of a single blastocyst at a time.
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.
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF:
•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!
•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
•How Many Embryos should be transferred: A Critical Decision in IVF.
•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
•Treating Ovarian Endometriomas with Sclerotherapy.
•Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options.
•Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
•Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s &
•Induction of Ovulation With Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its ue
•Clomiphene Induction of Ovulation: Its Use and Misuse!
If you are interested in my advice or medical services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD