Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Hello Doctor,
I had my 3rd IVF lite retrieval
1st attempt 5 eggs and 1 empty follicle
2nd attempt 1 egg and 3 empty follicles
3rd attempt 0 eggs and 4 empty follicles.
The sizes of all these follicles were around or more than 18 mm but still empty.
My age is 36 and I’m not sure the reason for this and what should be my next step And if there is a solution to avoid empty follicles
There is in my opinion no such entity as “Empty Follicle Syndrome”. All follicles contain eggs. Failure to access those eggs at ER can often be a result of the protocol used for controlled ovarian stimulation (COS.
Not infrequently, when following vigorous and often repeated flushing of follicles at egg retrieval they fail to yield eggs, it is ascribed to the “empty follicle syndrome”. This is a gross misnomer because all follicles contain eggs so it did not happen because the follicles were “empty”. Most likely it was because they would/could not yield the eggs they harbored. This situation is most commonly seen in older women, women who have severely diminished ovarian reserve and in women with polycystic ovarian syndrome and in my opinion, it often preventable when an optimal, individualized and strategic protocol for controlled ovarian stimulation (COS) is employed and the correct timing and dosage is applied to the “hCG trigger” shot.
Normally, following optimal ovarian stimulation, the hCG “trigger shot” is given for the purpose of it triggering meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG “trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse such that the egg can detach and readily be captured at egg retrieval (ER). Ordinarily, normal eggs (and even those with only one or two chromosomal irregularities) will readily detach and be captured with the very first attempt to empty of a follicle. Eggs that have several chromosomal numerical abnormalities (i.e., are “complex aneuploid”) are often unable to facilitate this process. This explains why when the egg is complex aneuploid its follicle will not yield an egg…and why, when it requires repeated flushing of a follicle to harvest an egg, it is highly suggestive of it being aneuploid and thus “incompetent” (i.e., incapable of subsequently propagating a normal embryo).
Older women, women with diminished ovarian reserve and those with polycystic ovarian syndrome, tend to have more biologically active LH in circulation. LH cause production of male hormone (androgens, predominantly testosterone, by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced oogenesis’ (egg development. Too much LH activity compromises the latter and eggs so affected, are far more likely to be aneuploid, following meiosis. Women with the above conditions have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH elevations or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the “hCG trigger” leading to failed and the so called “empty follicle syndrome”
Since the developing eggs of women who have increased LH activity [older women, women with diminished ovarian reserve (DOR) and those with PCOS] are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Also, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole) and drugs that contain LH or hCG (e.g., Menopur; or protocols of ovarian stimulation the provoke increase exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols” and the use of “late pituitary blockade (antagonists) protocols can be prejudicial. The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used and the timing of its administration in such cases, cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG(hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG can by compromising meiosis, increase the risk of egg aneuploidy and thus of IVF outcome.
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.
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
•Premature Luteinization (“the premature LH surge): Why it happens and how it can be prevented.
•Fertility Preservation (FP) Through Freezing/Banking Human Eggs
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•The “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)
•Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
•Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
•Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
•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?
•Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of 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.
•IVF: Selecting the Best Quality Embryos to Transfer
•Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
•PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
•PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
•IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.
•IVF: The first Choice for Infertile Women 40 to 43 Years of Age!
•IVF Egg Donation: A Comprehensive Overview
______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.
Patients are encouraged to share the information I provide, with their treating Physicians and/or to avail themselves of my personal hands-on services, provided through batched IVF cycles that I conduct every 3 months at Los Angeles IVF (LAIVF) Clinic, Century City, Los Angeles, CA.
If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).
PLEASE SPREAD THE WORD ABOUT SFS!
Geoff Sher
Hi Dr. Sher,
A two-parter, if you don’t mind.
1. What are your thoughts on 2-3 months of lupron treatment between the egg retrieval and embryo transfer for women with possible endometriosis?
2. After our first (failed) embyro transfer, between our two beta HCGs, I was awoken in the middle of the night with 30 minutes of lower pelvic pain that was so bad, I would have gone to the ER if it continued. Our second beta HCG showed good doubling, but the night after that test I had the same thing happen. About 3-4 days later, I started miscarrying. I assumed it was all related, but three weeks after the loss it happened again. Our doctor was stumped, and nothing abnormal appeared on a fluid ultrasound or hysteroscopy. Is this something you’ve seen? Should we be concerned?
1. What are your thoughts on 2-3 months of lupron treatment between the egg retrieval and embryo transfer for women with possible endometriosis?
A: I personally am not in favor because it can suppress subsequent response to stimulation and by chronically lowering blood estradiol might cause the uterine lining not to thicken optimally.
2. After our first (failed) embyro transfer, between our two beta HCGs, I was awoken in the middle of the night with 30 minutes of lower pelvic pain that was so bad, I would have gone to the ER if it continued. Our second beta HCG showed good doubling, but the night after that test I had the same thing happen. About 3-4 days later, I started miscarrying. I assumed it was all related, but three weeks after the loss it happened again. Our doctor was stumped, and nothing abnormal appeared on a fluid ultrasound or hysteroscopy. Is this something you’ve seen? Should we be concerned?
A: you may have ruptured a corpus luteum cyst of early pregnancy.
Good luck !
Geoff Sher
Hi Dr Sher
What are your thoughts about Human Growth Hormone? I’m 37 in June with low ovarian reserve and poor egg quality. My partner’s sperm had been deemed ok. Not sure if relevant but my period has only ever lasted 1 normal flow day and 0.5 light flow day. I’ve done 4 IVF cycles and only walked away with one embryo:
Cycle 1 – Gonal F, 8 eggs, 3 fertilised, 1 blastocyst (graded 3BB with fragments) and this was transferred but failed
Cycle 2 – Menopur, only 1 egg big enough so cycle cancelled
Cycle 3 – long cycle with Synarel nose spray and Gonal F, only 1 egg big enough so cycle cancelled
Cycle 4 – long cycle with Testogel, DHEA and Gonal F, 4 eggs collected, none fertilised
I’m looking at cycle 5 and my doctor is suggesting DHEA alongside Gonal F plus Pergoveris to add LH hormone to cycle as that is a bit low. I asked about Human Growth Hormone but my doc doesn’t think there is evidence this helps. If this is not going to help, do you have any suggestions for improving egg quality / outcome? I’m feeling very overwhelmed!
Thank you
Here is my opinion!
Older women and those who have diminished ovarian reserve (DOR) have greater difficulty in conceiving naturally or through assisted reproductive technology (ART). This is largely due to an inevitable increase in egg aneuploidy (numerical chromosome irregularity). However, although less significant than the rising increase in egg aneuploidy, advancing age and DOR are both also associated with non-chromosomal egg deterioration involving a decline in mitochondrial activity as well as a progressive reduction in the ability of the granulosa cells that line the inside of the follicle to respond to FSH stimulation.
Getting older women and those with DOR to respond optimally to ovarian stimulation often represents a serious challenge. Many will fail to respond adequately to standard ovarian stimulation regimens, requiring any individualized and strategic approach to ovarian stimulation…. one that regulates and limits exposure of ovarian follicles and eggs to LH-induced local male hormones (predominantly testosterone). This, in my opinion is best addressed by using a modified long pituitary down regulation protocol with an agonist (e.g. Lupron/Buserelin/Superfact) coming off a birth control pill. Thereupon, as soon as the period starts, the agonist is supplanted by an antagonist (e.g. Cetrotide/Orgalutron/Ganirelix) and stimulation with recombinant FSH (Follistim/Gonal-F/Puregon) along with a small amount of menotropin (e.g. Menopur) until t optimal follicle development prompts initiation of the hCG trigger. More than 15 years ago, I reported on the observation that in some women with severe DOR, the addition of intramuscular administration of estradiol valerate (i.e. Delestrogen) prior to and during gonadotropin stimulation (i.e. “estrogen priming”) is capable of further enhancing follicle growth .
More recently, researchers have shown that the administration of human growth hormone (HGH), as an adjunct to ovarian stimulation, can enhance follicle response in older women and those with DOR. Two basic mechanisms have been proposed: a) enhanced response to FSH by up-regulating the FSH receptors on follicular granulosa cells and, b) through a direct effect of HGH on the egg itself whereby mitochondrial activity is enhanced. Human eggs do have receptors to HGH but eggs retrieved from older women show decreased expression of such receptors (as well as a reduced amount of functional mitochondria. It was recently observed that some such women treated with HGH, show a marked increase in egg functional mitochondria along with improved egg quality.
Geoff Sher
702-533-2691
dr sher how do we have intralipid? two and half hours for 100ml lipid after that two and half hour 500cc isotonic solution iv, is it okay?
First Intralipid infusion is done 10-14 days prior to anticipated ET. It is combined with corticosteroid (dexamethasone 0.75mg or prednisone 10mg daily).
500 ml of a 20% IL solution should be infused over about 3 hours. The infusion should be started at half the infusion rate during the first 30 minutes, under supervision. For women who have an autoimmune cause of immunologic implantation dysfunction (IID) with Nka+, one additional infusion is doen at the time of a +ve blood beta hCG test. The steroid is continued to the 8th week of pregnancy and then tailed off over 2-3 weeks. Alternatively, corticosteroid is tailed off if pregnancy does not occur or is lost. Women who have alloimmune IID (DQ alpha/HLA matching), continue to receive IL infusions every 2 weeks until the 24th week of pregnancy. However, the steroid is discontinued after the i11th week as for autoimmune IID cases.
Geoff Sher
Hi Dr! I went to er sunday 1/12.. Ruptured ovarian cyst with internal bleeding caused need for emergency laparoscopic procedure. Also found out at that time my hcg levels were 200! LMP was 12/16. Dr did not seem very hopeful. Wed. 1/15 hcg levels were 1200. Were terrified as the dr doesnt seem hopeful and really stressed how high risk the surgery was… She wont schedule me for another exam for a month off still. Should i be worried?!
I would be guardedly optimistic. Ruptrure of a corpus luteum cyst in earlb pregnancy does not preclude continuation to viability.
Good luck!
Geoff Sher