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.
I have undergone ivf and my embryo transfer was a day 5 transfer.I got total 6 oocytes.out of that 2 are immatured.finally 2 got fertilised out of which 1 is from immaturrd one.of that one is 1aa and other is moderate.on day 4 after my embyro transfer my e2 level was 121pghl and progesterone was 56.01ng/ ml.Is this level correct for day 4 after transfer and will this predict any thing of my ivf result??please reply me as soon as possible
The estrogen is on the low side but the P4 is fine. Only time will tell. You need to await the blood hCG measurements.
Good luck and Happy New Year!
Geoff Sher
Hi Dr Sher,
Happy new year and thank you for sharing your knowledge with individuals like me on this forum.
I now have my first blastocyst at age 44 after utilising your advice on starting antagonist medication earlier in the cycle than day 6 and supplementing with recombinant human growth hormone having had to persuade my RE to tweak my protocol.
The blastocyst I have frozen only progressed to the early blastocyst stage on day 6 and was frozen on day 7; do you have any thoughts on the viability of blasts frozen on day 7?
Hi Tunde,
Embryos that reach blastocyst by day 5-6 have a reasonable, aged-related chance. I am not for freezing on day 7 but from your description, your embryo reached blastocyst by day 6. So since embryos that reach blastocyst by day 5-6 have a reasonable, aged-related chance, I think you do a have a shot…but I suggest you prepare for the worst while hoping for the best.
Good luck, G-d bless and happy new year.
Geoff Sher.
Hi Dr. Sher,
I’m 37 and with PCOS. I have had 2 failed FETs on 3 non-tested embryos. I have 2 non-tested embryos left (this 1st retrieval batch, I had over-stimulation with 38 eggs and 5 blasts making it to day 6). I’ve gotten 2 opinions suggesting either a new retrieval (with PGS) and/or then the ERA test. Do you recommmend PGS for someone under 39 because they have PCOS? Do you recommend the ERA test? I’m so confused by what our course of action should be. I also don’t know if I should go ahead and transfer the last 2 un-tested embryos; I feel up against the clock if i shall need another retrieval.
Neither PGS nor ERA can improve the likelihood of embryo competency. Rather, what matters most is the protocol used for ovarian stimulation and its implementation, especially when it comes to PCOS where egg quality is more likely to be at risk.
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. MULTIPLE FOLLICLE ASPIRATION: In some cases, in spite of best effort, you inadvertently find mean follicle size to exceed 16mm, thereby leaving too little time to implement “coasting”. On other occasions, “coasting” fails to effectively lower the [E2} below 2,500pg/ml within 3 days. In such case the number of developing follicles can effectively and drastically reduced (culled) through selective transvaginal aspiration prior to initiating the “trigger” with 10,000U hCG. This will almost invariably be accompanied by a rapid and significant drop in the plasma estradiol concentration along with a drastic reduction in the risk of OHSS occurring without significantly compromising egg/embryo quality. Upon completing surgical follicular reduction, the surviving follicles can be allowed to continue their full development, at which point the hCG “trigger” can be implemented. The drawback associated with this approach is that it unfortunately interjects an additional surgical intervention into an already complex and stressful situation.
3. 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
Hello Dr Sher. I am 40.2 yo and have very low AMH and very low, almost undetectable, DHEA and testosterone levels. I know DHEA/testosterone is bad, but given mine are very low, would it be worthwhile to supplement with micronised DHEA for a few months and then do the A/ACP ivy cycle in the hope of recruiting more follicles?
Dehydroepiandrosterone (DHEA), is steroid hormone produced by the adrenal glands and ovary. It is involved in producing the male hormones, androstenedione testosterone and also estrogen. DHEA blood levels tend to decline naturally with age.
Under the effect if luteinizing hormone (LH), DHEA is metabolized to testosterone in ovarian connective tissue (theca/stroma). Thereupon the testosterone is transported to the granulosa cells that form the innermost layer of the ovarian follicles where, under the influence of follicle stimulating hormone (FSH)-induced desmolase and aromatase enzymatic activity the testosterone is converted to estradiol. As this happens, granulosa cells multiply, follicle fluid volume increases along with estrogen output and egg development is promoted.
It is recognition of the essential/indispensable role that male hormones (mainly testosterone) play in follicle and egg development that prompted the belief that by giving DHEA and boosting ovarian testosterone production might benefit follicle/egg development. This belief was given some credence by an Israeli study that in 2010 reported on improved fertility when a group of infertile women were given the administration of 75mg of oral DHEA for 5 months. However, this study was seriously flawed by the fact that it did not separate out women who had diminished ovarian reserve, older women and those with PCOS, all of whom have increased LH-induced production of testosterone. In fact, we recently completed a study (currently being processed for publication) where we conclusively showed that when follicular fluid testosterone levels exceeded a certain threshold, egg quality was seriously prejudiced as evidenced by a marked increase in the incidence of egg chromosomal defects (aneuploidy).
Consider the following: Ovarian testosterone is needed for follicular development. However, the amount required is small. Too much ovarian testosterone spills over into the follicular fluid and has a deleterious effect on egg/follicle development. Some women (women with diminished ovarian reserve –DOR, older women and those with polycystic ovarian syndrome-PCOS) who tend to have increased LH biological activity, already over-produce testosterone. To such women, the administration of DHEA to such women, by “adding fuel to the fire” can be decidedly prejudicial, in my opinion. Young women with normal ovarian reserve do not over produce LH-induced ovarian testosterone, and are thus probably not at significant risk from DHEA supplementation. It is noteworthy that to date, none of the studies that suggest a benefit from DHEA therapy have differentiated between young healthy normal women with normal ovarian reserve on the one hand and older women, those with DOR and women with PCOS on the other hand.
In Some countries DHEA treatment requires a medical prescription and medical supervision. Not so in the U.S.A where it can be bought over the counter. Since DHEA is involved in sex hormone production, including testosterone and estrogen, individuals with malignant conditions that may be hormone dependent (certain types of breast cancer or testicular cancer) should not receive DHEA supplementation. Also, if overdosed with DHEA some “sensitive women” might so increase their blood concentrations of testosterone that they develop increased aggressive tendencies or male characteristics such as hirsuites (increased hair growth) and a deepening voice. DHEA can also interact other medications, such as barbiturates, corticosteroids, insulin and with other oral diabetic medications.
BUT the strongest argument against the use of routine DHEA supplementation is the potential risk of compromising egg quality in certain categories of women and since there is presently no convincing evidence of any benefit, why take the risk in using it on anyone.
Finally, for those who in spite of the above, still feel compelled to take DHEA, the best advice I can give is to consult their health care providers before starting the process.
Addendum: One potential advantage of DHEA therapy if used appropriately came from a study conducted by Washington University School of Medicine in St. Louis, MI and reported in the November 2004 issue of the “Journal of the American Medical Association” which showed that judicious (selective) administration of 50mg DHEA daily for 6 months resulted in a significant reduction of abdominal fat and blood insulin in elderly women.
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”.
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”.
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?
•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
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
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 book,”In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
Hi Dr Sher. Happy new year!!
I am usually a poor responder, but on the protocol you recommend, I had my AFC scan (on day 2) and there were 14 follicles!! Should I get excited or are follicles seen this early on not indicative of anything? Do follicles appear and then disappear?
I think you have reason for guarded optimism.
Geoff Sher