Hi Dr. Sher, I have a child conceived naturally at 39 and then two early miscarriages also natural conception (first loss at 6 weeks and second loss at 7 weeks prior to heartbeat being detected) at age 42 and age 43 which were attributed to likely chromosomal abnormalities. Since that time I’ve had one failed round of own egg IVF where none of the fertilized eggs made it blastocyst and one frozen donor egg round where 4 of 6 fertilized eggs made it to blastocyst and three were chromosomally normal. My first FET transfer was a hormonal replacement cycle that resulted in a chemical pregnancy. My second FET was a modified natural transfer that was negative for pregnancy, and now my last transfer was modified natural with autoimmune protocol (baby aspirin, 10 mg Prednisone daily, Claritin 10 mg daily, famotidine 20 mg twice a day, 5 mg estrace starting week of transfer and progesterone 200 mg suppository twice a day for luteal support.) What do you advise should be done next to increase chance of next donor FET transfer being successful? Will add that all my pregnancies have been with my husband who had sperm analysis done with good total sperm count, but less than 2% normal so advised IVF would be best. Thank you.
3 failed pgs donor fet transfers
This is highly likely to at least in part, be due to a secondary implantation dysfunction (see below). While not definitive, I suspect an immunologic implantation dysfunction (IID). The fact that you have had a child already means that it if an IID exists, it is possibly alloimmune in origin (see below). You mentioned treatment you received empirically for an IID , however, what you described would in my opinion not have been optimal (see below).
Implantation dysfunction is unfortunately often overlooked as an important cause of IVF failure. In the pursuit of optimizing outcome with IVF, the clinician has a profound responsibility to meticulously assess and address this important issue if IVF success is to be optimized. This is especially relevant in cases of “unexplained IVF failure, Recurrent Pregnancy Loss (RPL) and in women suspected of having underlying anatomical and immunologic factors. Doing so will not only maximize the chance of a viable pregnancy but enhancing placentation, will at the same time promote the noble objective of optimizing the quality of life after birth.”
IVF success rates have been improving over the last decade. The average live birth rate per embryo transfer in the U.S.A for women under 40y using their own eggs , is currently better than 1:3 women. However, there is still a wide variation from program to program for IVF live birth rates, ranging from 20% to near 50%. Based upon these statistics, the majority of women undergoing IVF in the United States require two or more attempts to have a baby. IVF practitioners in the United States commonly attribute the wide dichotomy in IVF success rates to variability in expertise of the various embryology laboratories. This is far from accurate. In fact, other factors such as wide variations in patient selection and the failure to develop individualized protocols for ovarian stimulation or to address those infective, anatomical and immunologic factors that influence embryo implantation are at least equally important.
About 80% of IVF failures are due to “embryo incompetency” that is largely due to an irregular quota of chromosomes (aneuploidy) which is usually related to advancing age of the woman and is further influenced by other factors such as the protocol selected for ovarian stimulation, diminished ovarian reserve (DOR)m and severe male factor infertility. However in about 20% of dysfunctional cases embryo implantation is the cause of failure.
This blog article will focus on implantation dysfunction and IVF failure due to:
- Anatomical abnormalities in the uterine cavity (polyps/scarring/internal fibroids)
Several studies performed both in the United States and abroad have confirmed that a dye X-Ray or hysterosalpingogram (HSG) will fail to identify small endouterine surface lesions in >20% of cases. This is significant because even small uterine lesions have the potential to adversely affect implantation. Hysteroscopy is the traditional method for evaluating the integrity of the uterine cavity in preparation for IVF. It also permits resection of most uterine surface lesions, such as submucous uterine fibroids (myomas), intrauterine adhesions and endometrial or placental polyps. All of these can interfere with implantation by producing a local “inflammatory- type” response similar in nature to that which is caused by an intrauterine contraceptive device. Hysterosonography (syn; HSN/ saline ultrasound examination) and hysteroscopy have all but supplanted HSG to assess the uterine cavity in preparation for IVF. HSN which is less invasive and far less expensive than is than hysteroscopy involves a small amount of a sterile saline solution is injected into the uterine cavity, whereupon a vaginal ultrasound examination is performed to assess the contour of the uterine cavity.
- Endometrial Thickness: As far back as in 1989 I first reported on the finding that ultrasound assessment of the late proliferative phase endometrium following ovarian stimulation in preparation for IVF, permits better identification of those candidates who are least likely to conceive. We noted that the ideal thickness of the endometrium at the time of ovulation or egg retrieval is >9 mm and that a thickness of less than 8 mm bodes poorly for a successful outcome following IVF.
Then in 1993, I demonstrated that sildenafil (Viagra) introduced into the vagina prior to hCG administration can improve endometrial growth in many women with poor endometrial development. Viagra’s mechanism of action is improvement in uterine blood flow with improved estrogen delivery…thereby enhancing endometrial development.
- Immunologic factors: These also play a role in IVF failure. Some women develop antibodies to components of their own cells. This “autoimmune” process involves the production of antiphospholipid, antithyroid, and/or anti-ovarian antibodies – all of which may be associated with activation of Natural Killer (NK) cells in the uterine lining. Activated NK cells (NKa) release certain cytokines (TH-I) that if present in excess, often damage the trophoblast (the embryo’s root system) resulting in immunologic implantation dysfunction (IID). This can manifest as “infertility” or as early miscarriages). In other cases (though less common), the problem is due to “alloimmune” dysfunction. Here the genetic contribution by the male partner renders the embryo “too similar” to the mother. This in turn activates NK cells leading to implantation dysfunction. These IID’s are treated using combinations of medications such as heparin, Clexane, Lovenox, corticosteroids and intralipid (IL).
I strongly recommend that you visit www.SherIVF.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.
- A Fresh Look at the Indications for IVF
- 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.
- Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
- IVF and the use of Supplementary Human Growth Hormone (HGH) : Is it Worth Trying and who needs it?
- 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
- Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
- IVF: Approach to Selecting the Best Embryos for Transfer to the Uterus.
- Fresh versus Frozen Embryo Transfers (FET) Enhance IVF Outcome
- Frozen Embryo Transfer (FET): A Rational Approach to Hormonal Preparation and How new Methodology is Impacting IVF.
- Genetically Testing Embryos for IVF
- Staggered IVF
- Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
- 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
- Endometrial Receptivity Array (ERA): Is There an actual “There, There”?
- IVF Failure and Implantation Dysfunction:
- Diagnosing and Treating Immunologic Implantation Dysfunction (IID)
- 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
- A Thin Uterine Lining: Vaginal Viagra is Often the Answer (update)
- Cervical Ureaplasma Urealyticum Infection: How can it Affect IUI/IVF Outcome?
- The Role of Nutritional Supplements in Preparing for IVF
- The Basic Infertility Work-Up
- Defining and Addressing an Abnormal Luteal Phase
- Male Factor Infertility
- Routine Fertilization by Intracytoplasmic Sperm Injection (ICSI): An Argument in Favor
- Hormonal Treatment of Male Infertility
- Hormonal Treatment of Male Infertility
- Antisperm Antibodies, Infertility and the Role of IVF with Intracytoplasmic Sperm Injection (ICSI)
- Endometriosis and Infertily
- Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF
- Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice.
- Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options
- Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination) and Reproductive Surgery Versus IVF
- Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
- Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s & Con’s!IUI-Reflecting upon its Use and Misuse: Time for a Serious “Reality Check
- Mode of Action, Indications, Benefits, Limitations and Contraindications for its ue
- Clomiphene Induction of Ovulation: Its Use and Misuse!
I am attaching online links to two E-books which I recently co-authored with my partner at SFS-NY (Drew Tortoriello MD)……. for your reading pleasure:
1.From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) “
- “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link
To set up an online consultation with me, please contact my assistant, Patti Converse at 702-533-2691 or by email: concierge@sherIVF.com
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