My IVF Cycle Failed – What Went Wrong? Question #17: Why Didn’t I Get Pregnant When I Used a Young Egg Donor and Had Good Quality Embryos?

30 Aug
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This is #17 in a series of answers to common questions about failed IVF.

For women whose advancing age and/or ovarian resistance make having a baby with their own eggs unfeasible or unlikely, IVF using donated eggs from a young donor (under 35 years) is an excellent option and is statistically highly successful – with approximately 60% conceiving following embryo transfer. The main reason why IVF with egg donation is so highly successful resides in the improved number and quality of a younger woman’s eggs:

  1. Younger women usually have a healthy ovarian reserve and are thus capable of yielding numerous eggs at the time of egg retrieval (ER).
  2. Since age is the major determinant of egg chromosomal integrity (the rate limiting factor in human reproduction), the eggs of younger women are far more likely to be “competent,” meaning that upon fertilization, they are capable of propagating chromosomally normal (“competent”) embryos. Such embryos are the ones that are most likely to develop into normal, healthy babies.

Women choosing to undergo egg donation understandably have high expectations of a successful outcome, and when they fail to conceive, they are often bewildered, angry and feel betrayed. But there are explanations as to why IVF with egg donation can and does fail.

  1. Even younger women can have diminished ovarian reserve that goes undetected. In other cases, in spite of best effort on the part of the treating medical team, an egg donor will have a low yield of eggs.
  2. Less than half the eggs of younger women are euploid (have a normal number of chromosomes) and abnormal (“aneuploid”) eggs cannot develop into competent embryos.
  3. The eggs derived from very young donors (in their late teens or early 20’s) are often of poorer quality and may produce more “incompetent” embryos. That is why, in my opinion, the ideal age of an egg donor is between 26 and 35 years.
  4. In addition, very young donors are much more prone to ovarian hyperstimulation on fertility drugs. In such cases, egg quality can also be compromised.
  5. On the other side of the equation, there is the reality that some embryo recipients may have embryo implantation dysfunction(usually undiagnosed). This can be due to:o Inadequate endometrial (uterine lining) thickness(more common in post menopausal women who have had prolonged estrogen deprivation).o Previously undetected/unaddressed uterine surface lesions that interfere with implantation (submucous fibroids, scar tissue or polyps)o Immunologic implantation dysfunction which often goes unsuspected, undetected, undiagnosed and untreated.
  6. Hitherto unrecognized male factor infertility.

Unless such issues are addressed, even the transfer of the very best quality donor embryos will often not propagate viable pregnancies.

The answer (as always) lies in the fact that each egg donation candidate and her partner must be thoroughly evaluated before embarking on a cycle of IVF with donated eggs, and each egg donor must be carefully selected and evaluated for ovarian reserve.

In my opinion, the ideal egg donor is 26-34 years of age, has regular ovulatory cycles, has had no prior difficulty in achieving pregnancy and (ideally) will in the past have successfully donated eggs which propagated one or more viable pregnancies. True, it is rare to find all these attributes in most egg donors, but knowing the “best case” criteria can help a couple more effectively evaluate their donor choices and optimize their chances of IVF success.


  • Caryn says:

    Hi Dr. Sher,
    I had an IVF baby in 2014 and then 4 failed cycles in an attempt to have another. We decided to go with a donor egg (29 year old with 2 children) and ended up with 8 embryos, transferred 2 fresh, failed, then 2 thawed, failed again. I had polyps removed prior to this, and we waited an extra week to thicken my lining. After I stopped breastfeeding my baby, I was diagnosed with celiac disease but have been gluten and symptom free for 2 years. What could the issue be? Autoimmune? I have 4 more frozen embryos. Should (or can) I try a different IVF clinic or ask for different testing? My doctor just says to try again but I don’t want to waste good embryos by doing the same thing with the same negative results. What do you recommend?

  • Lynda says:

    Hi Dr. Sher

    My husband and I have a very complicated infertility history (6 years). We have had 2 donor egg cycles with the same donor (20/21 yo). First cycle we had 10 eggs. Only 3 made it to blastocyst. Did a fresh and frozen transfer into me. First fresh was a 5 week miscarriage of a ‘perfect’ embryo. Second transfer (FET) was the last 2 blasts (3bb & 4 not sure). This resulted in again, another pregnancy but with slow to rise hcg levels. We did a second retrieval with same donor. 13 eggs retrieved, 10 mature, and 7 blastocysts. For this cycle, my husband had taken antioxidants for 3 months prior due to previously having a DFI of 20%. We believe this is why we got some many more blastocysts that time. I did a fresh 3 day transfer of two of those embryos and this resulted in a chemical. We then found a GC and did 2 more transfers with her. First one was an eSET of a 5aa blastocyst. This was a negative result. Second transfer of another single great quality blast resulted in identical twins that had no heartbeats at 9 weeks. The POC were tested and found to be ‘normal’. So then our clinic acquired the ability to biopsy our last frozen blasts (4 of them). 2 of them expanded enough to biopsy when thawed. These 2 were euploid. I then did another FET with the highest quality ‘normal’ one. That resulted in another negative cycle. Then we found another gestational carrier. We transfered the euploid (poor grade though-a 5cc, and the non-tested one a 4-can’t remember). This resulted in another slow rising beta roller coaster. My question: 3 different women have had these blastocysts transfered and no live birth has resulted. I should also add that 3 of the transfers to me (1 fresh and 2 frozen), I did immune treatment for positive ANA, & APAs. Treatments were IVIG, predisone, lovenox. My 2 carriers did not do any immune treatments and were not tested for immune issues. Is this a donor egg issue? A sperm issue? A carrier issue? My clinic is throwing their hands up. I have since found a new egg donor. Are we crazy to try again?

    • Geoffrey Sher says:

      I will be hosting a webinar on recurrent pregnancy loss in this site tomorrow at 5.30PM (PST). I encourage you to enroll and participate.

      When it comes to reproduction, humans are the poorest performers of all mammals. In fact we are so inefficient that up to 75% of fertilized eggs do not produce live births, and up to 30% of pregnancies end up being lost within 10 weeks of conception (in the first trimester). RPL is defined as two (2) or more failed pregnancies. Less than 5% of women will experience two (2) consecutive miscarriages, and only 1% experience three or more.
      Pregnancy loss can be classified by the stage of pregnancy when the loss occurs:
      • Early pregnancy loss (first trimester)
      • Late pregnancy loss (after the first trimester)
      • Occult “hidden” and not clinically recognized, (chemical) pregnancy loss (occurs prior to ultrasound confirmation of pregnancy)
      • Early pregnancy losses usually occur sporadically (are not repetitive).
      In more than 70% of cases the loss is due to embryo aneuploidy (where there are more or less than the normal quota of 46 chromosomes). Conversely, repeated losses (RPL), with isolated exceptions where the cause is structural (e.g., unbalanced translocations), are seldom attributable to numerical chromosomal abnormalities (aneuploidy). In fact, the vast majority of cases of RPL are attributable to non-chromosomal causes such as anatomical uterine abnormalities or Immunologic Implantation Dysfunction (IID).
      Since most sporadic early pregnancy losses are induced by chromosomal factors and thus are non-repetitive, having had a single miscarriage the likelihood of a second one occurring is no greater than average. However, once having had two losses the chance of a third one occurring is double (35-40%) and after having had three losses the chance of a fourth miscarriage increases to about 60%. The reason for this is that the more miscarriages a woman has, the greater is the likelihood of this being due to a non-chromosomal (repetitive) cause such as IID. It follows that if numerical chromosomal analysis (karyotyping) of embryonic/fetal products derived from a miscarriage tests karyotypically normal, then by a process of elimination, there would be a strong likelihood of a miscarriage repeating in subsequent pregnancies and one would not have to wait for the disaster to recur before taking action. This is precisely why we strongly advocate that all miscarriage specimens be karyotyped.
      There is however one caveat to be taken into consideration. That is that the laboratory performing the karyotyping might unwittingly be testing the mother’s cells rather than that of the conceptus. That is why it is not possible to confidently exclude aneuploidy in cases where karyotyping of products suggests a “chromosomally normal” (euploid) female.
      Late pregnancy losses (occurring after completion of the 1st trimester/12th week) occur far less frequently (1%) than early pregnancy losses. They are most commonly due to anatomical abnormalities of the uterus and/or cervix. Weakness of the neck of the cervix rendering it able to act as an effective valve that retains the pregnancy (i.e., cervical incompetence) is in fact one of the commonest causes of late pregnancy loss. So also are developmental (congenital) abnormalities of the uterus (e.g., a uterine septum) and uterine fibroid tumors. In some cases intrauterine growth retardation, premature separation of the placenta (placental abruption), premature rupture of the membranes and premature labor can also causes of late pregnancy loss.
      Much progress has been made in understanding the mechanisms involved in RPL. There are two broad categories:
      1. Problems involving the uterine environment in which a normal embryo is prohibited from properly implanting and developing. Possible causes include:
      • Inadequate thickening of the uterine lining
      • Irregularity in the contour of the uterine cavity (polyps, fibroid tumors in the uterine wall, intra-uterine scarring and adenomyosis)
      • Hormonal imbalances (progesterone deficiency or luteal phase defects). This most commonly results in occult RPL.
      • Deficient blood flow to the uterine lining (thin uterine lining).
      • Immunologic implantation dysfunction (IID). A major cause of RPL. Plays a role in 75% of cases where chromosomally normal preimplantation embryos fail to implant.
      • Interference of blood supply to the developing conceptus can occur due to a hereditary clotting disorder known as Thrombophilia.
      2. Genetic and/or structural chromosomal abnormality of the embryo.Genetic abnormalities are rare causes of RPL. Structural chromosomal abnormalities are slightly more common but are also occur infrequently (1%). These are referred to as unbalanced translocation and they result from part of one chromosome detaching and then fusing with another chromosome. Additionally, a number of studies suggest the existence of paternal (sperm derived) effect on human embryo quality and pregnancy outcome that are not reflected as a chromosomal abnormality. Damaged sperm DNA can have a negative impact on fetal development and present clinically as occult or early clinical miscarriage. The Sperm Chromatin Structure Assay (SCSA) which measures the same endpoints are newer and possibly improved methods for evaluating.

      Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA).
      But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States.
      Alloimmune IID, i.e., where antibodies are formed against antigens derived from another member of the same species, is believed to be a relatively common immunologic cause of recurrent pregnancy loss.
      Autoimmune IID is often genetically transmitted. Thus it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage.

      Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction.
      However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated NK cells and CTL in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.
      In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients.
      Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include:

      • Karyotyping (chromosome analysis) both prospective parents
      • Assessment of the karyotype of products of conception derived from previous miscarriage specimens
      • Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.)
      • Hysterosalpingogram (dye X-ray test)
      • Hysteroscopic evaluation of the uterine cavity
      • Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.)
      • Immunologic testing to include:
      a) Antiphospholipid antibody (APA) panel
      b) Antinuclear antibody (ANA) panel
      c) Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
      d) Reproductive immunophenotype
      e) Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
      f) Alloimmune testing of both the male and female partners
      Treatment for Anatomic Abnormalities of the Uterus: This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated.
      Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin.
      Sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures.

      Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.
      Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: Modalities such as IL/IVIg, heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction.
      The Use of IVF in the Treatment of RPL
      In the following circumstances, IVF is the preferred option:
      1. When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed.
      2. In cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.
      The reason for IVF being a preferred approach in such cases is that in order to be effective, the immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative
      Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic diagnosis (PGD), with tests such as CGH, can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGD requires IVF to provide access to embryos for testing.
      There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha matching where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy.
      The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.

      Please go to the home page of When you get there look for a “search bar” in the upper right hand column. Then type in the following subjects into the bar, click and this will take you to all the relevant articles I posted there.
      1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)

      2. Ovarian Stimulation for IVF: The most important determinant of IVF Outcome” (Nov. 2103)

      3. “Agonist/Antagonist Conversion Protocol”

      4. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

      5. “Thyroid Autoimmune Disease and IVF”

      6. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)

      7. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)

      8.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)

      9. “IVF success: Factors that influence outcome”

      10. “Use of the Birth Control Pill in IVF”

      9.”Staggered IVF”

      10.“Frozen Embryo Transfer (FET)”

      11.“Next Generation Gene Sequencing (NGS)”

      Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype with me so we can discuss your case in detail.

      Finally, perhaps you would be interested in accessing my new book (recently released). It is the 4th edition (and a re-write) of “In Vitro Fertilization, the ART of Making Babies”. The book is available through “” as a down-load or in book form. It can also be obtained from most bookstores.

      Geoff Sher

      P.S: Please go to
      To view a video-tutorial by Linda Vignapiano RN, Clinical Manager at SIRM-Las Vegas.

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