BONUS 298: Future Infertility Research (Part 2)

February 19, 2021

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Today’s bonus episode guest is Dr. Carol Curchoe, the founder of ART Compass, a senior clinical embryologist at a fertility clinic and a board-certified technical supervisor in embryology.

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Dr. Curchoe and Heather discuss the second of the top 10 priorities for future infertility research:


Before we get to listener questions, there was a new study about low/moderate-degree mosaic embryos that you wanted to discuss. Tell us about that.


  • Can Day 3 embryos with a lot more than 8 cells (for example 16 cells) represent a good viable embryo, even if the cells are all nice and even with no fragmentation? (We recently transferred a fresh day 3 embryo with 16 cells and it was called “beautiful” by our doctor. It unfortunately ended in a chemical pregnancy. I have always read that it’s not a good sign if embryos grow “too fast,” which this one seems to have done. I was not able to find much information on an embryo with this many cells on day 3. How can it have had that many cells so quickly? It was my only embryo so no others to choose from. Thank you.)
  • What does it mean when an egg has smooth endoplasmic reticulum, and how can it be avoided? Does it suggest that the other eggs in the cohort are substandard, even if they do not have it? (For context, I had 4 eggs, all made it to day 3, and none made it to blast but my husband also has elevated DNA frag.)
  • Do visual clues help to diagnose egg problems? If my eggs appear grainy and grey-ish under the microscope, is that possibly why we have only gotten 1 blastocyst from 2 egg retrievals? Have you ever seen a patient’s eggs improve from one cycle to the next?
  • Do you recommend assisted hatching?
  • How far off is egg maturation as a regular process? (It seems like it would have major benefits for the people going through IVF. My understanding is that a stim cycle would no longer be needed since the antral follicles are collected instead.)


  • An article was published in Human Reproduction in November 2020 outlining the top future infertility-related research priorities. Before we dive into the specifics, can you tell us about the study design, methods, and limitations?
  • Research priority #2: What is the optimal treatment for women undergoing IVF who are poor responders to increase live birth rates?
    • Why is this a research priority?
      • Despite 40 years of research and clinical application, the average success rate of IVF today has been reported to be as low as 20-40%. Poor ovarian response in IVF cycles ranges from 10-20%, and this percentage decreases with advancing age.
      • An inadequate response to controlled ovarian stimulation leads to insufficient egg retrievals, poor quality and maturity oocytes, and reduced embryo quality
      • Preventing cycle cancelation due to poor ovarian response, empty follicle syndrome, miscarriage
  • What are the two main stimulation protocols?
    • Agonist and antagonist, each having numerous variations
  • What are the main clinical decisions?
    • Stop stimulation
    • Trigger cycle
    • Continue stimulation
    • Number of days to follow-up, any dose adjustment needed
  • What are the research questions?
    • How to determine the follicle-stimulating hormone (FSH) starting dose
    • New ovarian response variables; age, body mass index, day 3 serum FSH, AFC, ovarian volume, Doppler ovarian score, smoking status–but these are not good enough
      • For example: Gene polymorphisms in genes involved in FSH signaling, estrogen biosynthesis, folliculogenesis, folate metabolism and other aspects influence the response to exogenous gonadotropin administration–but the polymorphism FSHR Asn680Ser is practically the only genetic marker, together with ESR1 PvuII T/C, that can currently be clinically applied
    • Growth characteristics and steroidogenic activities of antral cohorts exhibit considerable cycle to cycle variations–WHY?
    • New predictive algorithms and artificial intelligence
  • What are the new technologies on the horizon for measuring follicle growth?
    • Follicle growth is so important for making these clinical decisions, yet ultrasound is such an inaccurate, not-sensitive technology
    • Computer-assisted image analysis and mathematical modeling of the dynamic changes within the ovary
    • Spectral, color-flow, and power Doppler imaging now facilitate physiologic interpretations of vascular dynamics over time
    • Magnetic resonance imaging (MRI) is emerging as a research tool in ovarian imaging
    • New technologies, such as 3D ultrasonography and MRI, ultrasound-based biomicroscopy and synchrotron-based techniques each have the potential to enhance our real-time picture of ovarian function to the near-cellular level
    • Remote patient monitoring
      • Home E2 saliva testing
      • Home sonography of follicle development (study 1, study 2)
    • Clinical applications of in vitro growth (IVG) of human ovarian follicles
  • Is there anything else you’d like to add?


What words of hope would you offer to infertility warriors with poor ovarian response?


Thanks for listening!

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