Conceivability_What I Learned Exploring the Frontiers of Fertility

by Elizabeth L. Katkin

  35. J. Chang, S. L. Boulet, G. Jeng, et al., “Outcomes of In Vitro Fertilization with Preimplantation Genetic Diagnosis: An Analysis of the United States Assisted Reproductive Technology Surveillance Data, 2011–2012,” Fertility and Sterility 105, no. 2 (February 2016): 394–400.

  36. G. Murugappan, L. Shahine, C. Perfetto, et al., “Intent to Treat Analysis of In Vitro Fertilization and Preimplantation Genetic Screening Versus Expectant Management in Patients with Recurrent Pregnancy Loss,” Human Reproduction 31, no. 8 (August 1, 2016): 1668–74.

  37. SART 2014 National Summary Report, https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx.

  38. G. L. Harton, S. Munné, M. Surrey, et al., “Diminished Effect of Maternal Age on Implantation after Preimplantation Genetic Diagnosis with Array Comparative Genomic Hybridization,” Fertility and Sterility 100, no. 6 (December 2013):1695–703.

  39. SART 2014; Munné “Appraisal of PGS Outcome-Data” presentation.

  40. Jacques Cohen, “Design and quality control of future IVF laboratories,” presentation at 2016 ART World Congress, October 14, 2016.

  Chapter 8

  1. Kate Wighton, “Miscarriage and Ectopic Pregnancy May Trigger Post-Traumatic Stress Disorder,” Imperial College London, November 2, 1016, http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_1-11-2016-17-15-45.

  2. March of Dimes, “Miscarriage,” http://www.marchofdimes.org/complications/miscarriage.aspx.

  3. For an exceptional examination of miscarriage, see Jon Cohen, Coming to Term: Uncovering the Truth About Miscarriage (New Brunswick, NJ: Rutgers University Press, 2007). The statistics cited herein can be found on page 16.

  4. Mark Hughes, “Molecular Diagnostic Technologies” presentation.

  5. Together with Lord Robert Winston and Dr. Alan Handyside.

  6. Murugappan et al., “Intent to Treat Analysis.”

  7. See chapter 13, particularly “Improving Egg Quality through Hormones: The Pregmama Story,” for an in-depth discussion of research into improving egg quality.

  8. Diethylstilbestrol, a synthetic estrogen known as DES, became a popular treatment for the prevention of miscarriage from the late 1940s to the early 1970s, despite a lack of controlled studies demonstrating its efficacy or serious investigation of its safety for mother or child. Amid mounting concern about both, in 1971, the FDA advised doctors to stop prescribing DES to pregnant women. Beginning in the 1970s, significant research emerged revealing a troubling number of serious problems: DES caused clear cell adenocarcinoma in some women who took it; uterine abnormalities in as many as a third of the daughters born to mothers who took it, which led to devastatingly high miscarriage and infertility rates; an increased risk of breast cancer among mothers who took it; and rubbing salt in the wound, actually increased the risk of miscarriage in mothers who took it. For a thorough examination of the history and effects of DES, see Jon Cohen, Coming to Term, 116–29.

  9. While a certain genetic problem called a “balanced translocation” in either parent is also known to cause recurrent miscarriage, there is unfortunately no treatment for this condition, and intended parents who are diagnosed with this are advised to seek genetic counseling.

  10. Jon Cohen, Coming to Term, 113.

  11. R. Rai, M. Backos, F. Rushworth, and L. Regan, “Polycystic Ovaries and Recurrent Miscarriage—A Reappraisal,” Human Reproduction 15, no. 3 (March 1, 2000): 612–15.

  12. J. X. Wang, M. J. Davies, and R. J. Norman, “Polycystic Ovarian Syndrome and the Risk of Spontaneous Abortion Following Assisted Reproduction Technology Treatment,” Human Reproduction 16 (2001): 2606–9.

  13. R. S. Legro, H. X. Barnhart, W. D. Schlaff, et al., “Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome,” New England Journal of Medicine, February 356, no. 6 (2007): 551–66.

  14. E. Moll, P. M. Bossuyt, J. C. Korevaar, et al., “Effect of Clomifene Citrate Plus Metformin and Clomifene Citrate Plus Placebo on Induction of Ovulation in Women with Newly Diagnosed Polycystic Ovary Syndrome: Randomised Double Blind Clinical Trial,” BMJ 332, no. 7,556 (Jun 24):1485.

  15. E. Vanky, S. Stridsklev, R. Heimstad, et al., “Metformin versus Placebo from First Trimester to Delivery in Polycystic Ovary Syndrome: A Randomized, Controlled Multicenter Study,” Journal of Clinical Endocrinology & Metabolism 95, no. 12 (December 2010): e448–55.

  16. V. De Leo, M. C. Musacchio, P. Piomboni, et al., “The Administration of Metformin During Pregnancy Reduces Polycystic Ovary Syndrome Related Gestational Complications,” European Journal of Obstetrics and Gynecology and Reproductive Biology 157, no. 1 (July 2011): 63–66. See also F. H. Nawaz, R. Khalid, T. Naru, and J. Rizvi, “Does Continuous Use of Metformin throughout Pregnancy Improve Pregnancy Outcomes in Women with Polycystic Ovarian Syndrome?,” Journal of Obstetrics and Gynaecology Research 34, no. 5 (October 2008): 832–37.

  17. T. B. Mesen and S. L. Young, “Progesterone and the Luteal Phase: A Requisite to Reproduction,” Obstetrics and Gynecology Clinics of North America 42, no. 1 (March 2015): 135–51; P. Miller and M. Soules, “Luteal Phase Deficiency: Pathophysiology, Diagnosis and Treatment,” Global Library of Women’s Medicine, May 2009.

  18. Jon Cohen, Coming to Term, 108.

  19. R. M. Oates-Whitehead, D. Haas, and J. Carrier, “Progesterone for Preventing Miscarriage,” Cochrane Database of Systematic Reviews, no. 4 (October 20, 2003): article ID CD003511. Updated by D. M. Haas and P. S. Ramsey, “Progesterone for Preventing Miscarriage,” Cochrane Database of Systematic Reviews, no. 2 (April 16, 2008): article ID CD003511, and D. M. Haas and P. S. Ramsey, “Progesterone for Preventing Miscarriage,” Cochrane Database of Systematic Reviews, no. 10 (October 31, 2013): article ID CD003511.

  20. A. Coomarasamy, H. Williams, E. Truchanowicz, et al., “PROMISE: First-Trimester Progesterone Therapy in Women with a History of Unexplained Recurrent Miscarriages—a Randomised, Double-Blind, Placebo-Controlled, International Multicentre Trial and Economic Evaluation,” Health Technology Assessment 20, no. 41 (May 2016): 1–92.

  21. Mayo Clinic, “Cervical Cerclage,” March 17, 2015, http://www.mayoclinic.org/tests-procedures/cervical-cerclage/basics/definition/prc-20012949.

  22. S. M. Althuisius, G. A. Dekker, P. Hummel, and H. P. van Gejin, “Cervical Incompetence Prevention Randomized Cerclage Trial: Emergency Cerclage with Bed Rest versus Bed Rest Alone,” American Journal of Obstetrics & Gynecology 189, no. 4 (October 2003): 907–10.

  23. See A. O. Rust, R. O. Atlas, K. J. Jones, et al., “A Randomized Trial of Cerclage versus No Cerclage among Patients with Ultasonographically Detected Second-Trimester Peterm Dilation of the Internal Os,” American Journal of Obstetrics & Gynecology 183 (October 2000): 830–85; A. J. Drakeley, D. Roberts, and Z. Alfirevic, “Cervical Cerclage for Prevention of Preterm Delivery: Meta-analysis of Randomized Trials,” Obstetrics & Gynecology 102, no. 3 (September 2003): 621–27.

  24. V. Berghella, T. J. Rafael, J. M. Szychowski, et al., “Cerclage for Short Cervix on Ultrasonography in Women with Singleton Gestations and Previous Preterm Birth: A Meta-analysis,” Obstetrics & Gynecology 117, no. 3 (March 2011): 663–71.

  25. T. J. Rafael, V. Berghella, and Z. Alfirevic, “Cervical Stitch (Cerclage) for Preventing Preterm Birth in Multiple Pregnancy,” Cochrane Database of Systematic Reviews, no. 9 (September 2014): article ID CD009166.

  26. APS Support UK, “About APS—Pregancy,” accessed December 11, 2017, http://www.aps-support.org.uk/about-aps/pregnancy.php.

  27. R. S. Rai, L. Regan, K. Clifford, et al., “Immunology: Antiphospholipid Antibodies and β2-Glycoprotein-I in 500 Women with Recurrent Miscarriage: Results of a Comprehensive Screening Approach, Human Reproduction 10, no. 8 (August 1, 1995): 2001–5.

  28. R. Rai, H. Cohen, M. Dave, and L. Regan, “Randomised Controlled Trial of Aspirin and Aspirin Plus Heparin in Pregnant Women with Recurrent Miscarriage Associated with Phospholipid Antibodies (or Antiphospholipid Antibodies),” BMJ 314, no 7,706 (Janu
ary 25, 1997):253–57.

  29. Megan Brooks, “Pravastatin Shows Promise in Pregnant Women with Antiphospholipid Syndrome,” Reuters Health, August 1, 2016, https://www.consultant360.com/story/pravastatin-shows-promise-pregnant-women-antiphospholipid-syndrome.

  30. Reproductive Immunology Associates, “Miscarriages Can Be Prevented,” accessed December 11, 2017, http://www.rialab.com/fertility-services/reproductive-immunology/multiple-miscarriages-can-be-prevented.php; Braverman IVF & Reproductive Immunology, “Patients with 5 or more miscarriages have an outstanding 80% chance of having a successful pregnancy with our treatment protocols (all pregnancies delivered or currently past 20 weeks). A review of 30 cases at Braverman IVF & Reproductive Immunology,” posted on June 23, 2015, http://www.preventmiscarriage.com/patients-with-5-or-more-miscarriages-have-an-out.html.

  31. Jon Cohen, Coming to Term, 64–66.

  32. Peter Castro and Giovanna Breu, “Injection of Hope,” People, October 28, 1996, http://people.com/archive/injection-of-hope-vol-46-no-18/.

  33. Jerry Adler, Susan Katz, Elisa Williams, and Vicki Quade, “Learning from the Loss,” Newsweek, March 24, 1986, 66.

  34. B. Stray-Pedersen and S. Stray-Pedersen, “Etiologic Factors and Subsequent Reproductive Performance in 195 Couples with a Prior History of Habitual Abortion,” American Journal of Obstetrics & Gynecology 148, no. 2 (January 15, 1984):140–46. See also Jon Cohen, Coming to Term, 175–77.

  35. H. S. Liddell, N. S. Pattison, and A. Zanderigo, “Recurrent Miscarriage—Outcome After Supportive Care in Early Pregnancy,” Australian and New Zealand Journal of Obstetrics and Gynaecology 31, no. 4 (November 1991): 320–22.

  36. C. Ober, T. Karrison, R. Odem, et al., “Mononuclear-cell immunisation in prevention of recurrent miscarriages: a randomised trial,” The Lancet 354, no. 9176 (July 31, 1999): 365–69.

  37. Department of Health and Human Services, Public Health Service, Food and Drug Administration, “Lymphocyte Immune Therapy (LIT) Letter,” January 30, 2002, https://wayback.archive-it.org/7993/20170406072912/https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm105848.htm.

  38. A. Moffett, L. Regan, and P. Braude, “Natural Killer Cells, Miscarriage, and Infertility,” BMJ 329, no. 7,477 (November 27, 2004): 1283–85.

  39. L. F. Wong, T. Porter, and J. R. Scott, “Immunotherapy for Recurrent Miscarriage,” Cochrane Database of Systematic Reviews, no. 10 (2014): article ID CD000112.

  40. Geoffrey Sher, “IVIG & Intralipid Therapy in IVF: Interpreting Natural Killer Cell Activity for Diagnosis and Treatment,” Doctors Blog, Sher Fertility, https://haveababy.com/fertility-information/ivf-authority/ivig-intralipid-therapy-in-ivf-natural-killer-cell-activity-for-diagnosis-and-treatment. In the interest of full disclosure, my daughter, Alexandra, was conceived under the care of Dr. Batzofin at Sher Fertility, although without immunology treatment.

  41. Braverman IVF & Reproductive Immunology, “IVIG Treatment for Miscarriages” accessed December 11, 2017, http://www.preventmiscarriage.com/intravenous-immunoglobulin-ivig-.html.

  42. Alan E. Beer, Julia Kantecki, and Jane Reed, Is Your Body Baby Friendly?: “Unexplained” Infertility, Miscarriage & IVF Failure (Leesburg, VA: AJR Publishing, 2006), 4.

  43. A. J. Wilcox, C. R. Weinberg, J. F. O’Connor, et al., “Incidence of Early Loss of Pregnancy,” New England Journal of Medicine 319, no. 4 (July 28, 1988) 189–94; R. M. Lee and R. M. Silver, “Recurrent Pregnancy Loss: Summary and Clinical Recommendations,” Seminars in Reproductive Medicine 18, no. 4 (2000): 433–40. See also “Getting Pregnant—Pregnancy After Miscarriage: What You Need to Know,” Mayo Clinic, http://www.mayoclinic.org/healthy-lifestyle/getting-pregnant/in-depth/pregnancy-after-miscarriage/art-20044134; “After a Miscarriage: Getting Pregnant Again,” American Pregnancy Association, http://americanpregnancy.org/pregnancy-loss/after-miscarriage-getting-pregnant-again/.

  Chapter 9

  1. E. Scott Sills, ed., Handbook of Gestational Surrogacy: International Clinical Practice and Policy Issues (Cambridge, UK: Cambridge University Press, 2016), 1.

  2. W. H. Utian, L. A. Sheean, J. M. Goldfarb, and R. Kiwi, “Successful Pregnancy After In Vitro Fertilization and Embryo Transfer from an Infertile Woman to a Surrogate,” New England Journal of Medicine 313, no. 21 (November 21, 1985):1351–52.

  3. For a detailed exploration of laws in different countries, see Sills, Handbook.

  4. The Surrogacy Experience, “U.S. Surrogacy Laws by State,” http://www.thesurrogacyexperience.com/u-s-surrogacy-law-by-state.html.

  5. Alexandra Sifferlin, “Battle Over Paid Surrogacy Opens New Front,” Time, January 28, 2015, http://time.com/3666606/battle-over-paid-surrogacy-opens-new-front/; Anemona Hartocollis, “And Surrogacy Makes 3: In New York, a Push for Compensated Surrogacy,” New York Times, February 19, 2014, https://www.nytimes.com/2014/02/20/fashion/In-New-York-Some-Couples-Push-for-Legalization-of-Compensated-Surrogacy.html?_r=0.

  6. Quoted in A. S. Persky, “Reproductive Technology and the Law,” Washington Lawyer, July/August 2012, https://www.dcbar.org/bar-resources/publications/washington-lawyer/articles/july-august-2012-reproductive-tech.cfm.

  7. Ibid.

  Chapter 10

  1. Jacqueline Mroz, “One Sperm Donor, 150 Offspring,” New York Times, September 5, 2011, http://www.nytimes.com/2011/09/06/health/06donor.html?_r=0. For an excellent discussion of this and other aspects of sperm donation, see Jacqueline Mroz, Scattered Seeds: In Search of Family and Identity in the Sperm Donor Generation (Berkeley, CA: Seal Press, 2017).

  2. Mroz, “One Sperm Donor.”

  3. Mroz, Scattered Seeds, 177.

  4. A. Tanaka, M. Nagayoshi, I, Tanaka, et al., “Controversy Over Rights of Children Born from Oocyte Donations, Is Full Disclosure of Donor’s Identity Necessary?,” Fertility and Sterility 104, no. 3 (September 2015): e231

  5. Kristen Riggan, “Regulation (or Lack Thereof) of Assisted Reproductive Technologies in the U.S. and Abroad,” Center for Bioethics & Human Dignity, March 4, 2011, https://cbhd.org/content/regulation-or-lack-thereof-assisted-reproductive-technologies-us-and-abroad. See also Mroz, Scattered Seeds, 164.

  6. D. A. Greenfeld and S. C. Klock, “Disclosure Decisions among Known and Anonymous Oocyte Donation Recipients,” Fertility and Sterility 81, no. 6 (June 2004): 1565–71.

  7. Dr. Joan Manheimer, interview with the author, April 1, 2016.

  8. Nancy Hass, “To Tell, or Not to Tell, Your Egg Donor Baby?” Elle, August 20, 2015, http://www.elle.com/life-love/sex-relationships/news/a29904/whose-life-is-it-anyway/.

  9. Quoted in Hass, “To Tell.”

  10. Wendy Kramer, “The Ethical Sperm Bank: An All-Open Sperm Bank. An Idea Whose Time Has Come,” The Blog, Huffington Post, July 22, 2015, updated July 22, 2016, https://www.huffingtonpost.com/wendy-kramer/the-ethical-sperm-bank-an_b_7841180.html.

  11. Donor Sibling Registry statistics, as of October 13, 2017, found at https://donorsiblingregistry.com.

  12. Mroz, “One Sperm Donor.” See also Mroz, Scattered Seeds, chapter 8.

  13. Wendy Kramer, “A Brief History of Donor Conception,” The Huffington Post, May 10, 2016, https://www.huffingtonpost.com/wendy-kramer/a-brief-history-of-donor-conception_b_9814184.html; Mroz, Scattered Seeds, 79–85.

  14. Mroz, Scattered Seeds, 77–78, 89–103.

  15. At the Sperm Bank of California, which tracks its donor-conceived births, 60 percent of the children are born to lesbian parents and 20 percent to single mothers. Mroz, Scattered Seeds, 109.

  16. Tamar Lewin, “Sperm Banks Accused of Losing Samples and Lying About Donors,” New York Times, July 21, 2016, https://www.nytimes.com/2016/07/22/us/sperm-banks-accused-of-losing-samples-and-lying-about-donors.html?_r=0.

  17. Ibid.

  18. Ibid.

  19. Theresa Boyle, “U.S. Sperm Bank Admits It Doesn’t Verify Donor Information,” The Star, April 9, 2015, https://www.thestar.com/life/health_wellness/2015/04/09/us-sperm-bank-sued-by-canadian-couple-says-it-didnt-verify-donor-information.htm
l.

  20. Mroz, Scattered Seeds, 176–77.

  21. “Success Stories,” Donor Sibling Registry, https://donorsiblingregistry.com/success-stories.

  22. Mroz, Scattered Seeds, 56–63.

  23. Hass, “To Tell.”

  Chapter 11

  1. Arkansas, California, Connecticut, Hawaii, Illinois, Louisiana, Maryland, Massachusetts, Montana, New Jersey, New York, Ohio, Rhode Island, Texas, and West Virginia. See “Coverage by State,” Resolve: The National Infertility Association, accessed December 11, 2017, http://resolve.org/what-are-my-options/insurance-coverage/coverage-state/.

  2. Arkansas, Hawaii, Maryland, and Texas. Ibid.

  3. The Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA, or Public Law 102-493) requires that clinics performing ART annually provide data for all procedures performed to the CDC. The CDC is required to use these data to report and publish clinic-specific success rates and certification of embryo laboratories.

  4. US Department of Health and Human Services Centers for Disease Control and Prevention, 2006 Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic Reports (Atlanta: CDC, 2008).

  5. See Riggan, “Regulation (or Lack Thereof).”

  6. PBS Frontline interview with Dr. Mark Sauer, accessed December 11, 2017, http://www.pbs.org/wgbh/pages/frontline/shows/fertility/interviews/sauer.html.

  7. See J. Johnston, M. K. Gusmano, and P. Patrizio, “Preterm Births, Multiples, and Fertility Treatment: Recommendations for Changes to Policy and Clinical Practices,” Fertility and Sterility 102, no. 1 (July 2014): 36–39.

  8. Ibid, 36.

  9. Ibid, 38.

  10. Sumathi Reddy, “Fertility Study Warns of Risks from Multiple Births,” Wall Street Journal, April 28, 2014, https://www.wsj.com/articles/fertility-study-warns-of-risks-from-1398726124; Bernice Yeung and Jonathan Jones, “When Pregnancy Dreams Become IVF Nightmares,” Reveal: from the Center for Investigative Reporting, https://www.revealnews.org/article/when-pregnancy-dreams-become-ivf-nightmares/.