BONUS 306: Future Infertility Research Part 3

April 30, 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 third of the top 10 priorities for future infertility research:

Before we answer a few listener questions, Dr. Curchoe explains the recent ASRM review of best practices for rapid cooling vitrification.

LISTENER QUESTIONS

  • What are the risks of thawing, testing, and then refreezing untested embryos? Do the benefits outweigh the risks?
  • I’ve heard that a good vs. bad embryologist can make a big difference. What, specifically, does a good one do differently?
  • I have eggs frozen at a clinic with a worse lab than the clinic I’m working with now. How do I make the decision to thaw and fertilize the eggs at the clinic where they were frozen or to transfer them to the (apparently) better lab?
  • Should morphology of an embryo be used to make a decision on which embryo to transfer if they are PGT normal? Does the method of morphology grading differ greatly between clinics?

TOP RESEARCH PRIORITIES

  • An article was published in Human Reproduction in November 2020 outlining the top future infertility-related research priorities. Today we will be discussing research priority #3: What is the optimal method of sperm selection in IVF cycles?
  • Why is this a research priority?
    • The semen analysis is an incredibly important part of a fertility workup and it should be done FIRST. Before women undergo endless rounds of expensive and invasive testing, since 1/3 of infertility is solely due to male factor problems. Often, the sperm gets looked at last — yikes!
  • Let’s start with basic sperm biology.
    • Picture a garden hose — a tube with a thick wall. All jumbled up like a ball of yarn. That is the testicles — the site of sperm production.
    • Stem cells sit in the thick tissue of the seminiferous tubules. As the cells divide in meiosis, the mature sperm get pushed through the wall of the tube and drop into the center. That takes 64 days to happen and it happens over and over again asynchronously through the tube.
    • So let’s say each long section is in a different spot in that 64 day — then it sits in the epididymis, then the vas deferens. It takes a long time — much longer than people think. But the good news is that fresh sperm are constantly undergoing meiosis from stem cells! So you can change a LOT in one year.
  • Common problems with sperm production
    • Diet / lifestyle / obesity / environment / workplace exposure **recent article on BPA/ endocrine disrupters** (LINK??)
    • Genetic
    • Previous injury
    • Current medications
    • Varicocele
  • How does the vagina attack and select sperm?
    • Cervical selection
    • Site of fertilization of a human egg
    • Cumulus oophorus
    • Capacitation
    • Acrosome reaction
    • Binding with zona pellucida
  • What is embryonic genome activation?
    • What happens to the embryonic DNA in cell divisions 1-2 and 2-4
    • Why cleavage stage embryos fail to develop further at day 3
  • What are some fun facts about the origin of the Y chromosome?
  • Why process sperm and separate it from semen at all?
    • Current processing methods
    • Gradient / swim up / wash
    • ZyMot chips
  • How do embryologists catch the fastest, best-looking sperm in the ICSI dish?
    • Sperm motility
    • Sperm DNA fragmentation
    • Humans need the integrity of the spermatozoon to ordain the normal chromosomal segregation
  • Why do you love ICSI (intracytoplasmic sperm injection)?
    • Usual reasons: see and grade eggs and maturity AT retrieval for quality of STIM, and to reduce DNA contamination for PGT testing
    • ICSI bypasses all the initial steps of natural fertilization — penetration of the cumulus cells, binding to the zona pellucida, and fusion with the oolemma
  • What happens to the sperm tail that gets injected into the egg?
  • Why do you not like PICSI (physiologically selected intracytoplasmic sperm injection)?
    • The contact of sperm and egg plasma membranes is not a critical step for egg activation
    • Injecting sperm at various stages of spermiogenesis has demonstrated that elongating spermatids can activate eggs, whereas round spermatids and secondary spermatocytes cannot
    • The factor to activate the egg has nothing to do with zona binding — it is carried deep within the mature sperm head
  • What is IMSI (intracytoplasmic morphologically selected sperm injection)?
    • Not really available — and even less people trained
  • Artificial intelligence for sperm selection
    • What is AI?
    • How does it analyze images and use data to make predictions?
    • What will it actually take to have an AI that circles the sperm on screen?
  • Is there anything else you’d like to add?

WRAPPING UP

  • What words of hope would you offer to infertility warriors with male factor infertility?

References:

Thanks for listening!

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