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 Mr. Sher,
I’m very grateful that you provide this kind of support to all of us worldwide- I can easily say that I have gained most valuable knowledge through your webpage.I have an urgent question hope that you can support.
Me and my husband (F 41 age, M 44 age) we are married since 8 years. My husband has advanced varicosele, both sides. He never wanted to try naturally (he believed his sperm morphology will cause miscarriages). He also didn’t agree on varicosele operation. Instead, after many years of waiting, in 2016 we have started our IVF journey. But during this period (one of the reason was his alcohol addiction and smoking) sperm count went to just around 1ml, 0% motility and 0% morphology.
We both started using a lot of supplements (to ensure egg quality and sperm count) and planned for ICSI, microchip techniques. In total we have done 4 rounds of egg retrieval (in just 9 months) each time between 9 and 17 eggs collected, and his sperm count and motility seems to be increased, but still 0% morphology. Each round we have got several blastocyst embryos and these were sent to NGS (next generation sequencing for embryos). We endup with just 1 embryo all 24 chromosomes normal, 1 monosomy 14 and all the others with more advances issues.
Now I’m preparing for the first time embryo transfer for next week. We have done hysteroscopy (even though no issue shown on HGS), ERA and endometrium biopsy (CD56 is normal).
My RE recommended to transfer the normal embryo together with the other embryo with monosomy 14. I guess he is worried a bit about the quality of the normal one. Both of them are from the same cycle. During that cycle we had 3 blast embryos were sent to NGS test. He said he will not know about the quality until the transfer day which is next week.
I have read some articles about monosomic embryos. They may correct if they implant (unless the issue is on the X-Y chromosome, ours is monosomy 14). My question is that if we will transfer it together with the chromosomally normal one do we decrease the chance for implementation for the normal one? Is it better to transfer just the normal one?
Thanks a lot,
Demi
I agree with the strategy to transfer both. If you do conceive I strongly would advocate that you do CVS or amniocentesis to asses the chromosomal integrity of the conceptus!
Good luck!
Geoff Sher
Dear Dr. Sher,
Thank you so much for you website and all the great information.
I have done 5 cycles of traditional IVFs for egg retrieval. I got 18 eggs total, 7 embryos an did genetic testing. 3 came back normal. 2 of them day-5 grade good and one day-6 grade fair.
They transferred the day-6 embryo and it didn’t work.
To me it was an odd choice for them to choose the less quality embryo.
We decided not to touch the left embryos in a fear of losing them.
Our hope is to try to see if we can get more embryos and if not we use a surrogate for the left embryos.
I was told that mini IVF might be a better route for me as I have low egg quantity (3-4 each cycle)
I am 37 years old with stage 4 endo and AMH 0.4
Do you think mini IVF is a better choice and might help getting better quality eggs?
Respectfully, I do not advocvate mini-IVF. Thew number and quality of eggs/embryos so propagated will likely be less than opytimal. In addition, endometriosis is also a “red flag.”.
Endometriosis and implantation dysfunction:
More than half of women who have endometriosis harbor antiphospholipid antibodies (APA) that can compromise development of the embryo’s root system (trophoblast). In addition and far more serious, is the fact that in about one third of cases endometriosis, regardless of its severity is associated with NKa and cytotoxic uterine lymphocytes (CTL) which can seriously jeopardize implantation. This immunologic implantation dysfunction (IID) is diagnosed by testing the woman’s blood for APA, for NKa (using the K-562 target cell test or by endometrial biopsy for cytokine activity) and, for CTL (by a blood immunophenotype). Activated NK cells attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in rejection of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or an early miscarriage. As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.
Women who harbor APA’s often experience improved IVF birth rates when heparinoids (Clexane/Lovenox) are administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy. NKa is treated with a combination of Intralipid (IL) and steroid therapy: 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.IL 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%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating NKa.
The therapeutic effect of IL/steroid therapy is likely due to an ability to suppress pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. IL/steroids down-regulates NKa within 2-3 weeks of treatment the vast majority of women experiencing immunologic implantation dysfunction. In this regard IL is just as effective as Intravenous Gamma globulin (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.
The toxic pelvic environment caused by endometriosis, profoundly reduces natural fertilization potential. As a result normally ovulating infertile women with endometriosis and patent Fallopian tubes are much less likely to conceive naturally, or by using fertility agents alone (with or without intrauterine (IUI) insemination. The only effective way to bypass this adverse pelvic environment is through IVF. I am not suggesting here that all women who have endometriosis require IVF! Rather, I am saying that in cases where the condition is further compromised by an IID associated with NKa and/or for older women(over 35y) who have diminished ovarian reserve (DOR) where time is of the essence, it is my opinion that IVF is the treatment of choice.
Mini-IVF
Mini-IVF is a procedure that involves ovarian stimulation using low dosage medications (often oral drugs like clomiphene and letrozole) under the premise that it is a “safer” and less expensive than conventional gonadotropin stimulation regimes while yielding comparable success. …….. Nothing could be further from the truth. The fact is that success rates per fresh mini-IVF cycle ranges between 10% and 12%s (i.e., about one third of that which reported national average for conventional IVF performed on women under 39y of age) ). And when it comes to older women and those with diminished ovarian reserve (DOR), the success rate with mini-IVF is usually much lower still.
There can be little doubt that aside from a woman’s age, the method used for ovarian stimulation represents the most important determinant of egg/embryo quality and thus of IVF outcome. There is no single stimulation protocol that is suitable for all IVF patients. It must be individualized…. especially when it comes to women who, regardless of their age have diminished ovarian reserve (DOR) and for women over >40y of age. The reason for this is that in such cases, the pituitary gland often over-produces LH which in turn causes the ovarian stroma/theca (connective tissue) to thicken (stromal hyperplasia/hyperthecosis) and over-produce male hormones (mainly testosterone). This in turn adversely influences egg and follicle growth, resulting in poor egg/embryo “competency” and compromised IVF outcome.
So let us examine the validity of the claims made in support of mini-IVF:
1.Milder stimulation using oral agents such as clomiphene, letrozole (alone or in combination with low dosage gonadotropins (Follistim/Gonal-F/Puregon/Menopur) reduces stress on the ovaries and overall risk associated with IVF. This argument while perhaps having some merit when applied to mini-IVF conducted in younger women who also have normal ovarian reserve, does not hold water for older women and those with DOR who (s stated above) often already have excessive LH-induced ovarian testosterone production. Furthermore, addition of clomiphene and letrozole by further increasing pituitary LH (and thus ovarian testosterone) only serves to add “fuel to the fire” in such cases and Menopur which contains both LH and hCG ( that both have similar effects on ovarian testosterone production), if administered in large amounts (>75U per day) can also do harm in my opionion.
2.Women with DOR will respond better to “milder stimulation” and egg quality will so be enhanced. This assertion borders on the ridiculous. It is like saying that applying less force to a heavier object will increase the likelihood of moving it”. That is simply not how FSH stimulates follicle development. You see…the cell membranes that envelop the follicular granulosa cells that line the inside surface of ovarian follicles have on their surfaces, a finite number of FSH receptors. FSH molecules attach to these receptors and mediate intracellular events that lead to granulosa cell proliferation with production of estradiol and the concurrent development of the egg (oogenesis) that is attached to the inner wall of the follicle. Once all the FSH receptors on the cell membranes are saturated, any residual FSH is discarded. This is why, when it comes to older women and women with DOR whose granulose cell membranes harbor fewer FSH receptors, it is virtually impossible to overstimulate them. Excessive FSH will simply be rejected and discarded.
3. Use of fewer drugs translates into lower cost. This would be true, were it not for the fact that success rates with mini-IVF across the board are much lower than with conventional ovarian stimulation. More important is the fact that the cost of IVF should be expressed in terms of “the cost of having a baby” rather than “cost per cycle of treatment”. When this is taken into account the cost associated with mini-IVF will b be significantly higher than conventional IVF. Then there is the additional emotional cost associated with a much higher IVF failure rate with mini-IVF.
4.Mini-IVF is less technology driven, less stressful and easier to execute. This assertion is in my opinion also without merit. Aside from reduced cost of medications, the same monitoring and laboratory procedures are needed for mini-IVF as with conventional treatment.
What is the best approach? When it comes to older women and those with DOR, it is in my opinion preferable to use a long pituitary down-regulation protocol with conversion from an I.M agonist (e.g. Lupron or Buserelin) to an antagonist such as Cetrotide/Orgalutron or Ganirelix (the agonist/antagonist conversion protocol) augmented with human growth hormone (HGH) and/or estrogen priming and combing this “embryo banking” over several cycles. In such cases preimplantation genetic screening (PGS) can be incorporated to help select the most “competent” embryos for transfer.
What about younger women with normal or increased ovarian reserve? If mini-IVF has any role at all, it could be in young women who have normal or increased ovarian reserve. I do not o not advocate aggressively stimulating the ovaries of younger women who have normal or increased ovarian reserve (as assessed by basal FSH, AMH and estradiol) simply to try and access more eggs. In fact, such an approach is neither safe nor acceptable. In such women it is often wiser to use lower dosage stimulation to try and prevent the development of severe ovarian hyperstimulation syndrome (OHSS) which aside from putting the woman at severe risk of (sometimes) life-endangering complications, can also compromise egg/embryo quality. However, it is my fervent belief that in such women, the preferred approach to ovarian stimulation is through the use of low dosage FSHr-dominant gonadotropins (rather than oral agents such as clomiphene or letrozole and/or high dosage Menopur). This approach is referred to as Micro-I
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.
•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
•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
•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
•A Thin Uterine Lining: Vaginal Viagra is Often the Answer (update)
•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.
•Avoiding High Order Multiple Pregnancies (Triplets or Greater) with IVF
•The Role of Nutritional Supplements in Preparing for IVF
•Endometriosis and Infertily
•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.
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
In my opinion, such testing is to your advantage because it would help decide whether/how to proceed with ET to your uterus.
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 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.
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
In my opinion and others might not concur), I definitely would advise testing for alloimmune factors such as DQ alpha/HLA matching. If there were to be a match I would yse IL+prednisone therapy and do s single blastocyst transfer of a PGS-normal blastocyst.
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
Dr Sher, what’s the benefit of BCP with lupron overlap over of d21 lupron start? Do they achieve the exact same baseline hormone levels before menses or is one better than the other? Just curious the reason for your preference.
Most important is that it allows for timing of the onset of stimulation to the benefit and convenience of all and it does so without any down-side….in my opinion. In addition, by lowering ovarian LH-induced male hormone (predominantly testosterone activity) for longer, it could (in my opinion) enhance egg quality, especially oin women with DOR.
One often hears the expressed opinion that the BCP suppresses response to ovarian stimulation. This is not the case, provided that the BCP is overlapped with administration of an agonist (e.g. Lupron, Buserelin, Superfact) for several days leading up to the start of menstruation and the initiation of ovarian stimulation cycle with gonadotropin drugs. If the latter precaution is not taken, and the cycle of stimulation is initiated coming directly off the BCP the response will often be blunted and subsequent egg quality could be adversely affected. The explanation for this is that in natural (unstimulated) as well as in cycles stimulated with fertility drugs, the ability of follicles to properly respond to FSH stimulation is dependent on their having developed FSH-responsive receptors . Pre-antral follicles (PAF) do not have such primed FSH receptors and thus cannot respond properly to FSH stimulation with gonadotropins. The acquisition of FSH receptor responsivity requires that the pre-antral follicles be exposed to FSH, for a number of days (5-7) during which time they attain “FSH-responsivity” and are now known as antral follicles (AF). These AF’s are now able to respond properly to stimulation with administered FSH-gonadotropins. In regular menstrual cycles, the rising FSH output from the pituitary gland insures that PAFs convert tor AF’s. The BCP (as well as prolonged administration of estrogen/progesterone) suppresses FSH. This suppression needs to be countered by artificially causing blood FSH levels to rise in order to cause PAF to AF conversion prior to COS commencing, otherwise pre-antral-to –antral follicle conversion will not take place in an orderly fashion, the duration of ovarian stimulation will be prolonged and both follicle and egg development may be compromised. GnRH agonists (e.g. Lupron, Buserelin, Superfact) , cause an immediate surge in release of FSH by the pituitary gland thus causing conversion from PAF to SAF. This is why, women who take a BCP to launch a cycle of COS need to have an overlap of the BCP with an agonist. By overlapping the BCP with an agonist for a few days prior to menstruation the early recruited follicles are able to complete their developmental drive to the AF stage and as such, be ready to respond appropriately to optimal ovarian stimulation. Using this approach, the timing of the initiation of the IVF treatment cycle can readily and safely be regulated and controlled by varying the length of time that the woman is on the BCP.
Since optimizing follicular response to COS requires that prior to stimulation with gonadotropins, FSH-induced conversion from PAF to AF’s first be completed and the BCP suppresses FSH, it follows when it comes to women launching COS coming off a BCP something needs to be done to cause a rise in FSH for 5-7 days prior to menstruation heralding the cycle of CO S.This is where overlapping the BCP with an agonist (e.g. Lupron/Superfact/Buserelin) comes in. The agonist causes FSH to be released by the pituitary gland and if overlapped with the BCP for several days and this will (within 2-5 days) facilitate PAF to AF conversion…. in time to start COS with the onset of menstruation. Initiating ovarian stimulation in women taking a BCP, without doing this is suboptimal
I believe it to be essential regardless of the protocol of COS protocol being contemplated, for women who launching ovarian stimulation coming off a BCP to overlap with an agonist for several days in advance of initiating ovarian stimulation with the onset of menstruation,
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.
•Human Growth Hormone Administration in IVF: Does it Enhances
•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
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