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,
I’m 34 with PCOS, an AFC of 30plus, and and a high AMH. I have 4 lives births under my belt, and 3 living children. I recently decided to pursue IVF for Gender Selection of a healthy XX. My first cycle produced 12 eggs at ER, 9 mature, all 9 fert….However none made it past Day 3. During this failed cycle my E2 never exceeded 900. I started with about 225 of GonalF—and at some point dropped down to 150. Could I have essentially fried my eggs?? With being fertile, and only using IVF for a healthy XX embryo to transfer…I’m just in shock that I didn’t get even one embryo to test. I should add that this was not at a Sher Clinic.
Thank you,
Laney
Based upon your high AFC and possible PCOS, you probably were considered to be a potentially high responder. I suspect that the protocol used for ovarian stimulation was selected with this possibility in mind. In my opinion, the protocol used for ovarian stimulation needs to be reviewed and revised. I am curious to know how you were triggered. Was hCG used or Lupron? See below.
Polycystic ovary syndrome (PCOS) is a common hormonal system disorder among women affecting between 5% and 10% of women of reproductive age worldwide. Women with PCOS may have enlarged ovaries that contain multiple small collections of fluid (subcapsular microcysts) that are arranged like a “string of pearls” immediately below the ovarian surface (capsule).interspersed by an overgrowth of ovarian connective tissue (stroma). The condition is characterized by abnormal ovarian function (irregular or absent periods, abnormal or absent ovulation and infertility, androgenicity (increased body hair or hirsutism, acne) and increased body weight –body mass index or BMI.
Women with PCOS are at increased risk that ovarian stimulation with gonadotropins will result in the, of development of severe ovarian hyperstimulation syndrome (OHSS), a life-endangering condition that is often accompanied by a profound reduction in egg “competency” and on fertilization often yield an inordinately high percentage of “incompetent” embryos which have a reduced potential to propagate viable pregnancies.
Concern and even fear that their PCOS patients will develop of OHSS often leads the treating RE to take measures aimed at reducing the risk of this life-endangering condition. One such measures is to “trigger” egg maturation prematurely in the hope of arresting further follicular growth and the other, is to initiate the “trigger” with a reduced dosage of hCG (i.ed. 5,000U rather than the usual 10,000U of of Pregnyl/Profasi/Novarel, to use or 250mcg rather than 500mcg of Ovidrel or to supplant the hCG “trigger” with a Lupron “trigger” which causes a prompt LH surge from the woman’s pituitary gland to take place. While such measures do indeed reduce the risk of OHSS to the mother, this often comes at the expense of egg quantity and “competency”. Fewer than the anticipated number of eggs are harvested and those that are retrieved are far more likely to be “immature” and chromosomally abnormal (aneuploid”), or “immature” , thereby significantly compromising IVF outcome.
Against this background, It is my considered opinion that when it comes to performing IVF in women with PCOS, the most important consideration must be the selection and proper implementation of an individualized or customized ovarian stimulation protocol. Thereupon, rather than prematurely initiating the “trigger” to arrest further follicle growth, administering a reduced dosage of hCG or “triggering with a GnRH agonist (e.g. Lupron/Buserelin) that can compromise egg “competency”….. use of one of the following techniques will often markedly reduce the risk of OHSS while at the same time protecting egg quality:
1. PROLONGED COASTING…my preferred approach: My preferred approach is to use a long pituitary down-regulation protocol coming off the BCP which during the last 3 days is overlapped with the agonist, Lupron/Buserelin/Superfact. The BCP is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling LH-induced ovarian androgen (predominantly, testosterone) production and release. I then stimulate my PCOS patients using a low dosage of recombinant FSH-(FSHr) such as Follistim/Gonal-F/Puregon. On the 3rd day of such stimulation a smidgeon of LH/hCG (Luveris/Menopur) is added. Thereupon, starting on day 7 of ovarian stimulation, I perform serial blood estradiol (E2) and ultrasound follicle assessments, watching for the number and size of the follicles and the blood estradiol concentration [E2]. I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. At this point, provided the [E2] reaches at least >2,500pg/ml, I stop the agonist as well as gonadotropin stimulation and track the blood E2 concentration daily. The [E2] will almost invariably increase for a few days. I closely monitor the [E2] as it rises, plateaus and then begins to decline. As soon as the [E2] drops below 2500pg/ml (and not before then), I administer a “trigger” shot of 10,000U Profasi/ Novarel/Pregnyl or 500mcg Ovidrel/Ovitrel. This is followed by an egg retrieval, performed 36 hours later. Fertilization is accomplished using intracytoplasmic sperm injection (ICSI) because “coasted” eggs usually have little or no cumulus oophoris enveloping them and eggs without a cumulus will not readily fertilize naturally. Moreover, they also tend to have a “hardened” envelopment (zona pellucida), making spontaneous fertilization problematic in many cases. All fertilized eggs are cultured to the blastocyst stage (up to day 5- 6 days) and thereupon are either vitrified and preserved for subsequent transfer in later hormone replacement cycles or (up to 2) blastocysts are transferred to the uterus, transvaginally under transabdominal ultrasound guidance. The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If started too early, follicle growth will arrest and the cycle will be lost. If commenced too late, too many follicles will be post-mature/cystic (>22mm) and as such will usually harbor abnormal or dysmature eggs. Use of “Coasting” almost always prevents the development of severe OHSS, optimizes egg/embryo quality and avoids unnecessary cycle cancellation. If correctly implemented, the worst you will encounter is moderate OHSS and this too is relatively uncommon.
2. EMBRYO FREEZING AND DEFERMENT OF EMBRYO TRANSFEDR (ET): OHSS is always a self-limiting condition. In the absence of continued exposure to hCG, symptoms and signs as well as the risk of severe complications will ultimately abate. Thus, in the absence of pregnancy, all symptoms, signs and risks associated with OHSS will disappear within about 10-14 days of the hCG trigger. Conversely, since early pregnancy is always accompanied by a rapid and progressive rise in hCG , the severity of OHSS will increase until about the 9th or tenth gestational week whereupon a transition from ovarian to placental hormonal dominance occurs, the severity of OHSS rapidly diminishes and the patient will be out of risk. Accordingly, in cases where in spite of best effort to prevent OHSS, the woman develops symptoms and signs of progressive overstimulation prior to planned ET, all the blastocysts should be vitrified and cryostored for FET in a subsequent hormone replacement cycle. In this way women with OHSS can be spared the risk of the condition spiraling out of control.
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.
·Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
·Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
·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?
·Taking A Fresh Look at Ovarian Hyperstimulation Syndrome (OHSS), its Presentation, Prevention and Management
·Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
·Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
·“Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
·The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
•.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.
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
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
Dr. Sher,
I am 39 yrs old with PCOS and had my left tube removed. I had two egg retrieval’s, 19-20 eggs retrieved both times. Both times I had 4 embryos tested, both times all 4 were abnormal with PGS.
I went ahead and transferred one just for the sake of trying and today I found out my beta was negative.
Is it worth trying again? I am afraid my embryos will be all abnormal again. Should I try another med protocol? Any suggestions?
Linda
Sorry to piggyback off my last message, is there any chance I could still conceive naturally?
With PCOS, and a high high responder, I suspect that the protocol used for ovarian stimulation was selected with this possibility in mind. In my opinion, the protocol used for ovarian stimulation needs to be reviewed and revised. I am curious to know how you were triggered. Was hCG used or Lupron? See below.
Polycystic ovary syndrome (PCOS) is a common hormonal system disorder among women affecting between 5% and 10% of women of reproductive age worldwide. Women with PCOS may have enlarged ovaries that contain multiple small collections of fluid (subcapsular microcysts) that are arranged like a “string of pearls” immediately below the ovarian surface (capsule).interspersed by an overgrowth of ovarian connective tissue (stroma). The condition is characterized by abnormal ovarian function (irregular or absent periods, abnormal or absent ovulation and infertility, androgenicity (increased body hair or hirsutism, acne) and increased body weight –body mass index or BMI.
Women with PCOS are at increased risk that ovarian stimulation with gonadotropins will result in the, of development of severe ovarian hyperstimulation syndrome (OHSS), a life-endangering condition that is often accompanied by a profound reduction in egg “competency” and on fertilization often yield an inordinately high percentage of “incompetent” embryos which have a reduced potential to propagate viable pregnancies.
Concern and even fear that their PCOS patients will develop of OHSS often leads the treating RE to take measures aimed at reducing the risk of this life-endangering condition. One such measures is to “trigger” egg maturation prematurely in the hope of arresting further follicular growth and the other, is to initiate the “trigger” with a reduced dosage of hCG (i.ed. 5,000U rather than the usual 10,000U of of Pregnyl/Profasi/Novarel, to use or 250mcg rather than 500mcg of Ovidrel or to supplant the hCG “trigger” with a Lupron “trigger” which causes a prompt LH surge from the woman’s pituitary gland to take place. While such measures do indeed reduce the risk of OHSS to the mother, this often comes at the expense of egg quantity and “competency”. Fewer than the anticipated number of eggs are harvested and those that are retrieved are far more likely to be “immature” and chromosomally abnormal (aneuploid”), or “immature” , thereby significantly compromising IVF outcome.
Against this background, It is my considered opinion that when it comes to performing IVF in women with PCOS, the most important consideration must be the selection and proper implementation of an individualized or customized ovarian stimulation protocol. Thereupon, rather than prematurely initiating the “trigger” to arrest further follicle growth, administering a reduced dosage of hCG or “triggering with a GnRH agonist (e.g. Lupron/Buserelin) that can compromise egg “competency”….. use of one of the following techniques will often markedly reduce the risk of OHSS while at the same time protecting egg quality:
1. PROLONGED COASTING…my preferred approach: My preferred approach is to use a long pituitary down-regulation protocol coming off the BCP which during the last 3 days is overlapped with the agonist, Lupron/Buserelin/Superfact. The BCP is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling LH-induced ovarian androgen (predominantly, testosterone) production and release. I then stimulate my PCOS patients using a low dosage of recombinant FSH-(FSHr) such as Follistim/Gonal-F/Puregon. On the 3rd day of such stimulation a smidgeon of LH/hCG (Luveris/Menopur) is added. Thereupon, starting on day 7 of ovarian stimulation, I perform serial blood estradiol (E2) and ultrasound follicle assessments, watching for the number and size of the follicles and the blood estradiol concentration [E2]. I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. At this point, provided the [E2] reaches at least >2,500pg/ml, I stop the agonist as well as gonadotropin stimulation and track the blood E2 concentration daily. The [E2] will almost invariably increase for a few days. I closely monitor the [E2] as it rises, plateaus and then begins to decline. As soon as the [E2] drops below 2500pg/ml (and not before then), I administer a “trigger” shot of 10,000U Profasi/ Novarel/Pregnyl or 500mcg Ovidrel/Ovitrel. This is followed by an egg retrieval, performed 36 hours later. Fertilization is accomplished using intracytoplasmic sperm injection (ICSI) because “coasted” eggs usually have little or no cumulus oophoris enveloping them and eggs without a cumulus will not readily fertilize naturally. Moreover, they also tend to have a “hardened” envelopment (zona pellucida), making spontaneous fertilization problematic in many cases. All fertilized eggs are cultured to the blastocyst stage (up to day 5- 6 days) and thereupon are either vitrified and preserved for subsequent transfer in later hormone replacement cycles or (up to 2) blastocysts are transferred to the uterus, transvaginally under transabdominal ultrasound guidance. The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If started too early, follicle growth will arrest and the cycle will be lost. If commenced too late, too many follicles will be post-mature/cystic (>22mm) and as such will usually harbor abnormal or dysmature eggs. Use of “Coasting” almost always prevents the development of severe OHSS, optimizes egg/embryo quality and avoids unnecessary cycle cancellation. If correctly implemented, the worst you will encounter is moderate OHSS and this too is relatively uncommon.
2. EMBRYO FREEZING AND DEFERMENT OF EMBRYO TRANSFEDR (ET): OHSS is always a self-limiting condition. In the absence of continued exposure to hCG, symptoms and signs as well as the risk of severe complications will ultimately abate. Thus, in the absence of pregnancy, all symptoms, signs and risks associated with OHSS will disappear within about 10-14 days of the hCG trigger. Conversely, since early pregnancy is always accompanied by a rapid and progressive rise in hCG , the severity of OHSS will increase until about the 9th or tenth gestational week whereupon a transition from ovarian to placental hormonal dominance occurs, the severity of OHSS rapidly diminishes and the patient will be out of risk. Accordingly, in cases where in spite of best effort to prevent OHSS, the woman develops symptoms and signs of progressive overstimulation prior to planned ET, all the blastocysts should be vitrified and cryostored for FET in a subsequent hormone replacement cycle. In this way women with OHSS can be spared the risk of the condition spiraling out of control.
I strongly recommend that you visit https://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.
· Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
· Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
· 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?
· Taking A Fresh Look at Ovarian Hyperstimulation Syndrome (OHSS), its Presentation, Prevention and Management
· Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
· Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.
· “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
· The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
• .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.
• Implications of “Empty Follicle Syndrome and “Premature Luteinization”
• Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
• Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
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
Hi Dr. Sher,
I am 45 years old with no children and one miscarriage at age 42. After trying unsuccessfully to get pregnant naturally, at age 44, I turned to IVF. On my first round of IVF, we had 10 eggs retrieved, 9 were mature, 8 were fertilized with ICSI, but none made it to the 5 day mark to get tested even though on day 3, 5 of them were rated excellent and the other 3 were good. After our first cycle, our clinic changed their policies and eliminated the 3 day check. Is it possible that checking the embryos on day 3 affected the outcome on day 5?
For our second round, the egg retrieval was a month before my 45th birthday. 9 eggs were retrieved, 8 were fertilized. We had 2 embryos make it to PGS testing this time. One came back chromisomally normal and on March 8, 2018 it was implanted. I am now pregnant. My question is in regards to the other embryo. It came back as having an extra chromosome 14. They told me it was not a viable embryo for life. However, after reading your blog, it sounds like this could self correct after implantation? What are your thoughts on an extra chromosome 14? Is it possible that could be a viable embryo for implantation in the future?
Thank you so much for this blog! It’s so helpful.
Atv 45y, you really need IVF with egg donation. The success rate with own eggs is very low. However, if in spite of this you still insist on using own eggs, then please consider the following:
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
Hi! I am writing because I’m so confused! I’m 34 and have low AMH (0.60), trying to conceive for 2 years and we are unexplained infertility. I have a 13 and 9 y/o. My husband has no bio children. I am very impatient so I skipped right over IUI’s and went straight to IVF. We did a micro dose Lupron cycle and birth control pills leading into it. I ended up responding extremely slow in terms of follicle growth and estrogen levels. I believe had 16 or 17 days of stims (menupur and gonal-F) and my final recorded estrogen was 2198 right before trigger. We retrieved 7 eggs and only 5 were mature with just one fertilizing and resulting in a slow growing, fragmented embryo. I agreed to go back to IUI with femara and ovidrel just to give it a shot. On the 3rd round we conceived but the pregnancy was found to be non-viable at the 7 week scan. A gestational sac was noted, with a large yolk sac and no embryo. We were so sad but a little encouraged that at least something happened. So now I just had another IUI on a Gonal F cycle, per my request. I was on 225 units x 5 days (cycle day 4-8). When I went in for my ultrasound on cycle day 9, my main follicles were at 20.5, 21, and 14.5 mm. My estrogen was 616. Lining was 12mm. I was told not to take Gonal F that day and to trigger 19 hours after that. Then IUI was 36 hours after trigger (cycle day 11). My question is, do you have any explanation as to why my ovaries would respond so slow with our IVF and now they are responding on the fast side? Does that have any implications for adjusting the protocol going forward, maybe even for an IVF cycle? Also, do I have any chance with this IUI that I just did or are the eggs probably compromised from stimming so fast? Thank you!
You clearly have diminished ovarian reserve and need a very individualized approach to ovarian stimulation. You do not have the time to waste on IUI. In my opinion, the protocol used for ovarian stimulation, against the backdrop of age, and ovarian reserve are the drivers of egg quality and egg quality is the most important factor affecting embryo “competency”.
Women 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 effect of DOR, certain ovarian stimulation regimes, by promoting excessive LH production (e.g. short agonist/Lupron- “flare” protocols, clomiphene and Letrozole), can in my opinion, 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 women 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 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, https://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
Dear Dr. Sher,
I’m a 28 year old female and my husband is 38 year old. We’ve been trying to conceive through the different techniques of IVF (ICSI, IMSI, PICSI..) for more than 7 years. We went through 12 fresh cycles in 4 different centers and all ended up with negative results (only 2 with chemical)!!!
The reason why we started IVF was my husband bad morphology (we discovered later on a problem with DFI. One of tests was 70%) but during the cycles we had issues related to egg low maturity rate and low fertilization rate. We were getting different number of embryos 4,3,2,1 even we got 0 three times because of bad egg quality.
We tried many protocols and many supplements like DHEA, Ubiquinol, Melatonin, Growth hormone … Many kinds of stimulations and trigger shots and I was taking most of the times prednisone with stimulation and innohep after retrieve. We had different number of eggs (6-20) with different maturation rate (0-40%) and the fertilization rates were no more than 40%.
A few months ago we went to a new reproductive center and the doctor there suggested a reason for our case. He thinks that I’m having an immune issue as a reaction to my husband’s high DNA fragmentation and he believes that a high NK cells rate at the end of the uterine tubes could affect eggs quality and it can kill also the embryos which are retrieved to my uterus. So we did some blood work for my NK cells because the test of NK cells in uterus is not available in our country. The test came up with the following results:
CD3-/CD56+/CD16+ = 7%
CD3-/CD56+/CD16- = 15%
CD3-/CD56-/CD16+ = 22% (high)
CD3-/CD57+/CD16+ = 4%
CD3-/CD57+/CD16- = 2%
CD3-/CD57-/CD16+ = 22% (high)
CD4+CD3(helper cell)=30%
CD8+CD3 (Cytotoxic cell)=40% (inversion ratio of CD4/CD8)
CD3 (T-Lymphocytes)= 70%
______
CD8= 40%
CD4= 30%
CD3= 70%
Anti- TCR a ß= 62%
Anti TCR ? d= 3%
CD56+/CD3+= 4%
CD57+/CD3+= 2%
CD16+/CD3+= 8%
CD56+/CD3-= 15%
CD16+/ CD3-= 22%
CD57+/CD3-= 2%
CD45= 100%
In light of this test we were sent to an immunology consultant and he in turns asked for more blood work and suggested an immune treatment 3 months prior to our next cycle which contains: intralipid, prednisone, asprin, black cumin oil, innohip and IVIG.
I’m really sorry for my long message, but do you think that we are on the right road or we should go back to our previous doctor opinion who thinks that my problem is a genetic problem that can’t be solved and we have only tiny hope to get a bfp.
I very respectfully seriously disagree with the proposed thesis that there is any link whatsoever between egg quality and uterine NK cell activation. Based upon your clear evidence of NKa, I am persuaded that you have an immunologic implantation dysfunction which is likely autoimmune in causation, but could be alloimmune. Since treatment would differ, it is in my opinion imperative that it be determined which causation before undergoing further treatment.
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.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
•The Fundamental Requirements for Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Blastocyst Embryo Transfers should be the Standard of Care in IVF
•IVF: How Many Attempts should be considered before Stopping?
•“Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
•IVF Failure and Implantation Dysfunction:
•The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
•Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
•Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
•Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
•Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
•Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
•Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•A personalized, stepwise approach to IVF
•How Many Embryos should be transferred: A Critical Decision in IVF?
•The Role of Nutritional Supplements in Preparing for IVF
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