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Fertility Facts

Fertility Facts. Four common topics that may come up in your office ( and why IVF is not just a money grab ). Dr. Carol Redmond Hannam Fertility Centre, Toronto November 2014. The Questions. “Can you check my fertility?” “Can I freeze my eggs?”

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Fertility Facts

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  1. Fertility Facts Four common topics that may come up in your office (and why IVF is not just a money grab) Dr. Carol Redmond Hannam Fertility Centre, Toronto November 2014

  2. The Questions • “Can you check my fertility?” • “Can I freeze my eggs?” • “I’m not getting pregnant, can I just take Clomid?” • “If Clomid doesn’t work, what does help? How does IVF work?”

  3. “Can you check my fertility?” • History • AGE • Regular cycles • History of STI • Family history of early menopause • Symptoms of endometriosis http://whattoexpectwhenyouarenot.wordpress.com/

  4. Ultrasound Endometrioma Submucosal Fibroid PCO occur in 1/3 of women without PCOS http://www.fornewyou.com/Endometrioma-Cyst http://www.medscape.com/viewarticle/491677_2 http://tatjana-mihaela.hubpages.com/hub/polycysticOS

  5. Age • Egg quality declines with age • Egg quality is the gate keeper to fertility • If all else is normal, egg quality decides cycle fecundity and success rates with ART http://nymag.com/news/features/mothers-over-50-2011-10/

  6. Myths and Misconceptions • “My cycles are regular so my fertility is fine” • “I’ve stayed fit and healthy so my fertility has been maintained” • “My day 3 FSH is good so my fertility is still fine” • “All the women in my family get pregnant easily over age 40” • “I got pregnant easily the first time so I will be fine”

  7. Age • Daniluk surveyed 1021 women age 20-40 (2010) • Most expected to have more than 1 child in their 3rd or 4th decade • 70% expected to start after age 30 • 60% wanted 2 children • 20% wanted more than 2 children • Most thought health was a better predictor of fertility than age

  8. Age • The first sign of aging of the eggs is infertility • There are no other clinical or biochemical signs • The first clinical sign of aging is a shortening of the cycle (Lambalk, 2009)

  9. Odds of Natural Conception Age of marriage and percentage of women not using contraception but childless (Menken, 1986) Estimated age-related chances of conception within 12 months resulting in live birth (Leridon, 2004) Age Age

  10. Age • So if eggs are the gate keeper, can we assess egg quality? NO!

  11. Age • Egg quality can only be assessed at the time of IVF • What is “ovarian reserve testing” testing then? • This is testing egg quantity • Egg quantity declines with age • If number of eggs is declining, it is a reasonable assumption that another aging process – declining egg quality – is also ongoing

  12. Tests of Ovarian Reserve • AMH • AFC (AntralFollicle Count) • Day 3 FSH

  13. Tests of Ovarian Reserve • AMH • Produced by pre-antral and small antral follicles • The serum level reflects the number of small follicles in the ovaries • The absolute level does not predict fertility • The ideal range is 15-30 pmol/L

  14. Does Low AMH Level Matter? • 1/3 of young women (age 21) will have an AMH level <12 pmol/L (Lund Kristensen, 2012) • 26% of potential egg donors showed an AMH level in the low range (Gleicher, 2010) • I surveyed 94 women presenting to HFC for donor sperm

  15. How Do We Use AMH Levels? • Changes in AMH may matter • A dropping AMH level suggests declining egg numbers, which indicates ovarian aging, which suggests egg aging • AMH predicts ovarian responsiveness • AMH is a good predictor of the ability of the ovary to “superovulate”

  16. Tests of Ovarian Reserve • Antral follicle count • Also measures the reserve of small follicles, but very observer dependent • FSH • This is the last thing to change as the ovary ages • Significant decline in ovarian reserve can occur in the presence of a normal FSH level • High FSH level strongly predicts an inability of the ovary to “superovulate”

  17. “How can I tell if I’m fertile?” • Try to get pregnant • A low AMH level at any age does not preclude pregnancy • A normal AMH level does not imply normal fertility http://pregnancytips.org/getting-pregnant/how-to-get-pregnant/trying-to-get-pregnant/

  18. “Can I freeze my eggs to be safe?” • Egg freezing is now a reliable technology with the advent of egg vitrification • Most of the babies are from frozen donor eggs • A survey in 2012 of the 7 USA Commercial Egg Banks revealed that 8780 frozen eggs had generated 602 pregnancies (6.8%) (Quaas, 2013) http://retrievefreezerelax.com/egg-freezing-basics/

  19. Egg Freezing • We can expect a thaw rate of 86% • And a fertilization rate of 76% • So 10 eggs on average will generate 3 blastocysts • Implantation rate per embryo from fresh eggs: • SART data, 2012, (n=165,172 cycles)

  20. Egg Freezing • The success rate will depend on the quality of the eggs being frozen • This will decline with age • Chang,2013

  21. Egg Freezing • This is where AMH levels fit in • The AMH level is a reasonable predictor of egg yield with IVF • A 37 year old with an AMH of 7? • Maybe 3 eggs to freeze, which may make 1 embryo, if all three eggs thaw and fertilize, with IR of 27%

  22. Egg Freezing • Things to consider: • Effort – requires ovarian stimulation and egg retrieval • Very little data yet on thawing and pregnancy rates (CCRM has had 47 thaws of non donor frozen eggs in the past few years (personal communication, 2014) http://www.bodyconfidential.co.uk/Health/Egg-Freezing-A-21st-Century-Dilemma

  23. Egg Freezing • Things to consider (cont): • Cost!

  24. Embryo Banking • This is a more certain option • Proceed with IVF, fertilize eggs, make embryos, screen embryos with PGS for aneuploidy • Each euploid embryo has a 60-70% chance of a live birth – independent of age at transfer http://www.biopoliticaltimes.org/article.php?id=5833

  25. “I’m not getting pregnant, can’t I just take Clomid?” The Miracle Drug Clomid • First get a diagnosis • Ovulation • Semen analysis • Sonohysterogram to check uterus and tubal patency http://www.kinetic-international.net/Oral_clomid50.html

  26. Myths and Misconceptions • “We didn’t havesex on exactly the right day” • “I know it’s because I’ve been stressed” • “The sperm leaks out” • “I need to lie there for ½ hour” • “We are having sex too often/not often enough” • “It doesn’t matter that we smoke – all our friends do and they have kids” http://raspberrytruffles.org/trying-is-fun/

  27. Clomid • Estrogen receptor blocker • Can induce the development of more than 1 egg per month (40% of cycles) • 40% of women have anti-estrogenic side effects (thin endometrium, poor cervical mucus) which impede pregnancy • Nuisance side effects: headaches, visual flashes, hot flushes, moodiness

  28. Clomid • How well does it work? • Not very… Clinical Pregnancy Rate Per Cycle

  29. What Does Work? Hannam Fertility Center, 2014

  30. What Does Work? Age IUI Cycle # Hannam Fertility Center, 2014

  31. FSH Superovulation and IUI • FSH • Daily injections for 10-13 days • Daily monitoring with blood & USS • Costly • 20% of pregnancies are twins • 1% are triplets

  32. IVF • Two multi-centre prospective randomized trials in a population of patients with unexplained infertility and unsuccessful Clomid and IUI looked at proceeding to FSH and IUI then IVF as needed, or straight to IVF • Both showed a higher pregnancy rate achieved in fewer cycles and at a lower cost if the patients proceeded directly to IVF • (FORT-T trial, 2014, & FASTT trial, 2010)

  33. IVF • 272 women COH & IUI • CLBR after 2 cycles 27% • Twins 13% • 1 triplets • 1 quadruplet • 176 women IVF • LBR after 1 cycle 39% • Twins 10% • (Chambers, 2010) http://www.co-parentmatch.com/In-Vitro-Fertilization-IVF.aspx

  34. IVF Hannam Fertility Center, 2014

  35. IVF • National Health Service funded IVF • < 40 years of age, 3 IVF cycles • Took less than 2 years to achieve 3 cycles (Goswami, 2013)

  36. IVF with PGS • PGS = pre-implantation genetic screening for aneuploidy • Euploidy rate • 56% if excellent blastocyst morphology • 39% if good blastocyst morphology • 42% if average blastocyst morphology • 25% if poorblastocyst morphology • (Capalbo, 2014)

  37. IVF & PGS Case Studies • 39-40 year old woman with unexplained infertility • Over 4 IVF cycles she generated • 33 year old woman with unexplained infertility • Over 1 IVF cycle she generation

  38. IVF & PGS Case Studies • 40 year old trying for 2 years

  39. IVF & PGS • Recurrent implantation failure • (Greco, 2014)

  40. IVF & PGS & Miscarriage • PGS is the answer to most miscarriage (Benner, 2012)

  41. IVF & PGS & Miscarriage Case Study • 40 year old TDI X 8 • IVF

  42. IVF • Women for donor sperm over age 40 • Nearly all successful IVF was in first attempt • Single IVF = 6 cycles of TDI • (De Brucker, 2013)

  43. Summary • Age remains the best predictor of fertility • AMH levels do not predict fertility • Serial AMH levels may have value • Egg freezing is great technology (when applied to young women) • If you are sub-fertile, there is no simple approach that also has a great success rate • IVF, particularly with PGS, if highly effective, but not simple or natural

  44. Questions? You are invited to contact me anytime at carol.redmond@hannamfertility.com http://www.cartoonstock.com/directory/i/infertility.asp

  45. References • Benner, A. 2012. Evaluation of 571 IVF cycles and 4873 embryos using 23-chromosome SNP (single nucleotid polymorphism) microarray PGS. Fertil & Steril 97(3)Supp:S23. • Capalbo, A., Rienzi, L., Cimadomo, C, Maggiulli, R., Elliott, T., Wright, G., Nagy, Z., & Ubaldi, F. 2014. Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum. Reprod29(11):234-9. • Chambers, G., Sullivan, E., Shanahan, M., Ho, M., Priester, K., & Chapman, M. 2010. Is in vitro fertilisation more effective than stimulated intrauterine insemination as a first-line therapy for subfertility? A cohort analysis. Aust N Z J ObstetGynaecol 50(3):280-8. • Chang , C., Elliott, T., Wright, G., Shapiro, D., Toledo, A., & Nagy, Z. 2013. Prospective controlled study to evaluate laboratory and clinical outcomes of oocyte vitrification obtained in in vitro fertilization patients aged 30 to 39 years. Fertil & Steril99(7):1891-7. • Daniluk, J. Koert, E., & Cheung, A.2011. Childless women’s knowledge of fertility and assisted human reproduction: identifying the gaps. Fertil & Steril97(2):420-6.

  46. References • De Brucker, M., Camus, M., Haentjens, P., Verheyen, G., Collins, G., & Tournaye, H. 2013. Assisted reproduction using donor spermatozoa in women aged 40 and above: the high road or the low road? Repro BioMed Online 26(6):577-85. • Gleicher, N. Can egg donor selection be improved - a pilot study. ReprodBiolEndocrinol8:76. • Goswami, M., Hyslop, L., & Murdoch, A. 2013. NHS-funded IVF: consequences of NICE implementation. Hum Fertil16(2):121-7. • Greco, E., et al. 2014. Comparative genomic hybridization selection of blastocysts for repeated implantation failure treatment: a pilot study. Biomed Res Int. 2014:457913. • Lambalk, C. Van Disseldorp, J., De Koning, C., & Broekmans, F. 2009. Testing ovarian reserve to predict age at menopause. Maturitas 63(4):280-91. • LeridonH. 2004. Can assisted reproductive technlogy compensate for the natural decline in fertility with age? A model assessment. Hum Reprod19:1548-53.

  47. References • Lund Kristensen, S. 2012. The association between circulating levels of AMH and follicle number, androgens, and menstrual cycle characteristics in young women. Fertil & Steril 97(3):779-785. • Menken J., Trussell, J., & Larsen, U. 1986. Age and infertility. Science 233:1389-94. • Quaas, A., Melamed, A., Chung, K., Bendikson, K., & Paulson, R. 2013. Egg banking in the United States: current status of commercially available cryopreserved oocytes. Fertil & Steril 99(3):827-31.

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