Dr. Geoffrey Sher on January 17, 2021 at 2:55 am

We really should talk!

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 15y 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
e.Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
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?
______________________________________________________
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

19,771 Comments

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Newer Comments →

Angela on January 18, 2021 at 5:34 am

Dear Dr Sher,
Can I please ask your thoughts on embyro glue.
Do you use it at your clinics?
Thank you
Angela
Jlcockrell on January 17, 2021 at 12:33 am

Good evening. I recently had a miscarriage and now have found out I’m pregnant again. Not sure how far along because we conceived between my miscarriage and first cycle. My hcg was at 7 on 1/6, 78 on 1/12 , and 138 on 1/14. My doctors nurse called panicked about the numbers. She said she would consult with the doctors about a new draw and call me back. She never called. Are these numbers worrisome?
- Dr. Geoffrey Sher on January 18, 2021 at 9:50 pm
  
  Only time will tell!
  
  I am hopeful for you though!
  
  Good luck!
  
  Geoff Sher
Melissa on January 16, 2021 at 10:39 pm

Hello Dr. Sher,

I’m 45, just completed donor egg IVF with PGT-A tested embryo. We transferred one tested embryo. I have adenomyosis (confirmed via MRI in 2019). The adenomyosis is localized. I went on Depot Lurpon for 3 months prior to the FET. We got pregnant from this cycle, HCG levels were multiplying, but only a sac was seen at 6 weeks 4 days. A repeat ultrasound at 7 weeks 3 days was done, and the gestational sac and yolk sac were seen, and only a flicker of a small embryo. The doctor has given me the option to miscarry naturally, do a D&C or take the Misoprostol.

I conceived naturally 3 years ago, but it was an ectopic pregnancy. Did two rounds of methotrexate.

I’m worried I will not be able to carry a baby to term. Could you please advise if I should get tested for Immunology? If so, what tests would you recommend? I reached out to Alan Beer Center but have been put on 4 month waiting list. If you can recommend any labs near me (in the Bay Area) that could speed up the process, that would be very helpful. I’m also willing to travel for testing.

Thank you very much,
Melissa
- Dr. Geoffrey Sher on January 17, 2021 at 2:55 am
  
  We really should talk!
  
  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 15y 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
  e.Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
  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?
  ______________________________________________________
  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
Rachel on January 16, 2021 at 12:26 pm

Thank you Dr. Sher-
My RE has determined that I have a mutation of my follicle receptors. My eggs do not mature sufficiently with a trigger shot. For IVF, I have used 10,000 Novarel. She wants to try a higher dose or wait 38 hours rather than 36 before retrieval. I can’t find very much information about this problem. Doe it sound familiar to you? Thank you!
- Dr. Geoffrey Sher on January 16, 2021 at 10:26 pm
  
  Respectfully, This does not sound familiar to me in any way!
  
  Geoff Sher
HAS on January 16, 2021 at 11:31 am

Hi, Dr.Sher

I had my LMP on 3rd December 2020. Tested a strong positive on 4th Jan on UPT. 5th Jan Bhcg level was 2443. 7th Jan Bhcg level was 6672. Had slight spotting yesterday. USG confirmed a single gestation sac in the uterus, a yolk sac of 3.3mm, fetal pole and a fetal heartbeat of 163bpm. USG dating put it at 6w+4d. Hcg levels now at 63672. On folic acid, Ecosprin and Pregcert 300SR. What could be the reason for this spotting. Is this a viable pregnancy??

Very worried since I had a miscarriage a year earlier at 5 weeks.

Thank you for your help.
- Dr. Geoffrey Sher on January 16, 2021 at 10:28 pm
  
  This actually looks quite promising to me!
  
  Good luck!
  
  Geoff Sher

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