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Why Failed IVF Occurs Even With “Normal” Embryos

So, you've been through an IVF cycle. Your doctors have retrieved a good number of eggs with a good number reaching the blastocyst stage. Having counseled about the advantages of SMART IVF, you agreed to have the embryos biopsied and the cells analyzed for chromosomal abnormalities (preimplantation genetic screening (PGS) or preimplantation genetic diagnosis (PGD)). The results showed a good number of “normal” (euploid) embryos. You then underwent embryo transfer of a single cryopreserved (frozen) euploid embryo. Everything seemed to be going well, but then, the pregnancy test result was negative! It is reasonable to ask, "Why did I have a failed IVF cycle when we transferred 'normal' embryos?"

Background

Between 30% and 70% of human embryos are chromosomally abnormal. The number can be 100% in older patients. With SMART IVF, we are able to screen out these “abnormal” (aneuploid) embryos (sometimes, the best-looking embryos will be abnormal and vice versa). At InVia Fertility Specialists, we currently have a 70% pregnancy rate with the transfer of a single euploid embryo. But that also means that 30% of the time, patients will have to try again. To understand why even SMART IVF fails, it helps to look at data from a paper by Dr. David Meldrum at the University of California at San Diego, in Fertility and Sterility (in press):

Cytoplasmic Factors

failed ivf understanding cell structure

A cell consists of a nucleus, which contains chromosomes. The nucleus in turn is surrounded by a thick fluid, which fills the cell and is called cytoplasm. The cytoplasm consists of several organelles that are essential for the cell to survive. One such organelle is the mitochondria which supplies energy to the cell. Cytoplasmic quality may be sufficient to support normal chromosomal division but not to result in a fully capable embryo. As the embryo divides, each blastomere receives a smaller and smaller share of everything the egg has managed to accumulate. The embryo is not capable of adding cytoplasmic factors till it starts dividing (cleavage stage) and more mitochondria do not form till the blastocyst stage.

Mitochondrial energy is critically important for chromosomes to segregate and for cells to divide. Mitochondrial energy declines with age.

“Stressed” embryos appear to compensate by producing more mitochondrial DNA. A recent study by Simon, et al., of the University of Valencia, Spain, showed that increased mitochondrial DNA levels were associated with poor embryo capacity to implant.

Emotional Stress

Emotional stress can have a negative impact on egg quality. The “fight or flight” response associated with stress mobilizes blood flow to the heart, muscles and brain at the expense of “inessential” organs such as the ovary. The quality of blood flow to the follicles strongly correlates to pregnancy outcome. The introduction of a “mind-body” program improved IVF outcomes at a large IVF clinic in Boston run by Dr. Alice Domar.

What can be done to improve outcomes?

Stress reduction

  • Lifestyle changes. Both smoking and obesity have a negative impact on embryo quality. Quitting smoking and weight loss are steps in the right direction. At InVia, we offer the Ideal Protein Diet program to help our patients with weight loss.
  • Acupuncture, yoga, psychological counseling can all help to reduce stress.
  • Anti-oxidants such as CoQ10 400 mg orally daily can reduce oxidate stress.

These can take 3 – 6 months before they have an optimal effect.

Other medications

  • Testosterone: Egg quality may improve with the use of testosterone. DHEA 25 mg orally three times a day for 2 – 3 months or Androgel 1% used transdermally for 3 weeks may help.
  • Growth hormone: The use of growth-hormone has been advocated to improve egg quality. Growth hormone levels fall with age, and follicular fluid levels are lower in poor responders and women who fail to conceive with IVF. We have had good success at InVia with the use of growth hormone in select patients (poor responders and older patients).

Optimizing stimulation protocols

Using too much or too little of stimulation medications can impact egg quality. The use of “mild” stimulation protocols in poor responders is currently being investigated at InVia.

Optimizing laboratory conditions.

It is very important that conditions be optimal in the embryology laboratory.

To work with a fertility clinic that uses a state-of-the art laboratory to achieve exceptional success rates, make an appointment at one of InVia's four Chicago area fertility clinics.


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Dr. Vishvanath Karande

Dr. Vishvanath Karande

Dr. Karande is Board Certified in the specialty of Obstetrics and Gynecology as well as the subspecialty of Reproductive Endocrinology and Infertility. He is a Fellow of the American College of Obstetricians and Gynecologists and Member of the American Society for Reproductive Medicine.

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