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 am wondering if you can provide me with some advice. I just had a medicated FET cycle cancelled as my lining shrunk. It went from 4.6mm on CD9 to 6.6mm on CD14, to 5.4mm on CD17. Is it likely that my body doesn’t like synthetic oestrogen?
I know that my lining isn’t great in a natural cycle – around 6-7mm on day of my LH surge.
What would you recommend for a future natural FET to try and improve my lining? In an IVF cycle my lining is generally 8-9mm on day of trigger so it does respond well to high levels of natural oestrogen.
Many thanks in advance
Natalie
Frankly, I am not a fan of natural cycle FET’s. I prefer hormone medicated cycles because it broadens the window of implantation, is more manageable and predictable.
It was as far back as 1989, when I first published a study that examined the correlation between the thickness of a woman’s uterine lining (the endometrium), and the subsequent successful implantation of embryos in IVF patients. This study revealed that when the uterine lining measured <8mm in thickness by the day of the “hCG trigger” (in fresh IVF cycles), or at the time of initiating progesterone therapy (in embryo recipient cycles, e.g. frozen embryo transfers-FET, egg donation-IVF etc.) , pregnancy and birth rates were substantially improved. Currently, it is my opinion, that an ideal estrogen-promoted endometrial lining should ideally measure at least 9mm in thickness and that an endometrial lining measuring 8-9mm is “intermediate”. An estrogenic lining of <8mm is in most cases unlikely to yield a viable pregnancy.
A “poor” uterine lining is usually the result of the innermost layer of endometrium (the basal or germinal endometrium from which endometrium grows) ) not being able to respond to estrogen by propagating an outer, “functional” layer thick enough to support optimal embryo implantation and development of a healthy placenta (placentation). The “functional” layer ultimately comprises 2/3 of the full endometrial thickness and is the layer that sheds with menstruation in the event that no pregnancy occurs.
The main causes of a “poor” uterine lining are:
1.Damage to the basal endometrium as a result of:
a.Inflammation of the endometrium (endometritis) most commonly resulting from infected products left over following abortion, miscarriage or birth
b.Surgical trauma due to traumatic uterine scraping, (i.e. due to an over-aggressive D & C)
2.Insensitivity of the basal endometrium to estrogen due to:
a.Prolonged , over-use/misuse of clomiphene citrate
b.Prenatal exposure to diethylstilbestrol (DES). This is a drug that was given to pregnant women in the 1960’s to help prevent miscarriage
3.Over-exposure of the uterine lining to ovarian male hormones (mainly testosterone): Older women, women with diminished ovarian reserve (poor responders) and women with polycystic ovarian syndrome -PCOS tend to have raised LH biological activity.. This causes the connective tissue in the ovary (stroma/theca) to overproduce testosterone. The effect can be further exaggerated when certain methods for ovarian stimulation such as agonist (Lupron/Buserelin) “flare” protocols and high dosages of menotropins such as Menopur are used in such cases.
4.Reduced blood flow to the basal endometrium:
Examples include;
a.Multiple uterine fibroids - especially when these are present under the endometrium (submucosal)
b.Uterine adenomyosis (excessive, abnormal invasion of the uterine muscle by endometrial glands).
“The Viagra Connection”
Eighteen years ago years ago, after reporting on the benefit of vaginal Sildenafil (Viagra) for to women who had implantation dysfunction due to thin endometrial linings I was proud to announce the birth of the world’s first “Viagra baby.” Since the introduction of this form of treatment, thousands of women with thin uterine linings have been reported treated and many have gone on to have babies after repeated prior IVF failure.
For those of you who aren’t familiar with the use of Viagra in IVF, allow me to provide some context. It was in the 90’s that Sildenafil (brand named Viagra) started gaining popularity as a treatment for erectile dysfunction. The mechanism by which it acted was through increasing penile blood flow through increasing nitric oxide activity. This prompted me to investigate whether Viagra administered vaginally, might similarly improve uterine blood flow and in the process cause more estrogen to be delivered to the basal endometrium and thereby increase endometrial thickening. We found that when Viagra was administered vaginally it did just that! However oral administration was without any significant benefit in this regard. We enlisted the services of a compound pharmacy to produce vaginal Viagra suppositories. Initially, four (4) women with chronic histories of poor endometrial development and failure to conceive following several advanced fertility treatments were evaluated for a period of 4-6 weeks and then underwent IVF with concomitant Viagra therapy. Viagra suppositories were administered four times daily for 8-11 days and were discontinued 5-7 days prior to embryo transfer in all cases.
Our findings clearly demonstrated that vaginal Viagra produced a rapid and profound improvement in uterine blood flow and that was followed by enhanced endometrial development in all four cases. Three (3) of the four women subsequently conceived. I expanded the trial in 2002 and became the first to report on the administration of vaginal Viagra to 105 women with repeated IVF failure due to persistently thin endometrial linings. All of the women had experienced at least two (2) prior IVF failures attributed to intractably thin uterine linings. About 70% of these women responded to treatment with Viagra suppositories with a marked improvement in endometrial thickness. Forty five percent (45%) achieved live births following a single cycle of IVF treatment with Viagra The miscarriage rate was 9%. None of the women who had failed to show an improvement in endometrial thickness following Viagra treatment achieved viable pregnancies.
Following vaginal administration, Viagra is rapidly absorbed and quickly reaches the uterine blood system in high concentrations. Thereupon it dilutes out as it is absorbed into the systemic circulation. This probably explains why treatment is virtually devoid of systemic side effects
It is important to recognize that Viagra will NOT be effective in improving endometrial thickness in all cases. In fact, about 30%-40% of women treated fail to show any improvement. This is because in certain cases of thin uterine linings, the basal endometrium will have been permanently damaged and left unresponsive to estrogen. This happens in cases of severe endometrial damage due mainly to post-pregnancy endometritis (inflammation), chronic granulomatous inflammation due to uterine tuberculosis (hardly ever seen in the United States) and following extensive surgical injury to the basal endometrium (as sometimes occurs following over-zealous D&C’s).
Combining vaginal Viagra Therapy with oral Terbutaline;
In my practice I sometimes recommend combining Viagra administration with 5mg of oral terbutaline. The Viagra relaxes the muscle walls of uterine spiral arteries that feed the basal (germinal) layer of the endometrium while Terbutaline, relaxes the uterine muscle through which these spiral arteries pass. The combination of these two medications interacts synergistically to maximally enhance blood flow through the uterus, thereby improving estrogen delivery to the endometrial lining. The only drawback in using Terbutaline is that some women experience agitation, tremors and palpitations. In such cases the terbutaline should be discontinued. Terbutaline should also not be used women who have cardiac disease or in those who have an irregular heartbeat.
About 75% of women with thin uterine linings see a positive response to treatment within 2-3 days. The ones that do not respond well to this treatment are those who have severely damaged inner (basal/germinal) endometrial linings, such that no improvement in uterine blood flow can coax an improved response. Such cases are most commonly the result of prior pregnancy-related endometrial inflammation (endometritis) that sometimes occurs post abortally or following infected vaginal and/or cesarean delivery.
Viagra therapy has proven to be a god send to thousands of woman who because of a thin uterine lining would otherwise never have been able to successfully complete the journey “from infertility to family”.
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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. I’ve just gone through my first round of ivf at a uk clinic and wasn’t successful. I am 40 years old and have an amh of 4.2. I had prostap followed by 14 days of ovaleap 375 IU daily (6000 IU in total). My trigger was ovitreille at day 14 an I took this at 10.45pm as instructed and was due egg collection at 10.45am 36hours later. At my final scan they said I had 6 good sized follicles some at 22mm and a few around 18/19mm. My egg collection was an hour and 10 minutes late (11.55am) due to complications with the previous patient and the Dr said he was disappointed that some of the follicles were empty and they only collected 2 eggs. After doing a blood test they think I might have ovulated early. 2 eggs fertilised with both reaching day 3 and one reached to day 5. They kept it until day 6 as growth was slow and then sadly it didn’t survive. I want another opinion as to whether the late egg collection could have caused me to have ovulated early and why I only got 2 eggs? Thanks
I do not believe that the 1.5h delay explains your so called “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
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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.
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. I had a FET. Day 10 HCG was 607 and day 20 was 10680. Is this TOO high?
Looks good to me but if >1 embryo was transferred, it could be a multiple!
GS
My lmp is 27 july 2021 ac to lmo i shoul be 9 weeks today but gestational age shows 7 weeks and my hcg is 14000 no heart beat dr said its missed miscarriage, is it? Plz tell i am too much worried.
Sadly,
I do not hold out much hope, given this information!
Sorry,
Geoff Sher
Hello, I had a faint positive home pregnancy test 4 days ago at 12dpo and went in for my first HCG two days later. I ovulated early, so my period is still not due for two days.
14dpo hcg 77 progesterone 125
16 Dpo hcg 70 prohesterone 91
I think falling almost certainly means a chemical pregnancy, but is there any hope if it’s only two tests.
Unfortunately, this does not look promising!
Geoff Sher