Conceivability_What I Learned Exploring the Frontiers of Fertility

by Elizabeth L. Katkin

  18. Hua Liu, Jian-Yang Xu, Lin Li, et al., “fMRI Evidence of Acupoints Specificity in Two Adjacent Acupoints,” Evidence-Based Complementary and Alternative Medicine 2013 (2013): 5 pages, article ID 932581.

  19. Sela et al., “Acupuncture and Chinese Herbal Treatment.”

  20. Pei et al., “Quantitative Evaluation.”

  21. G. Franconi, L. Manni, L. Aloe, et al., “Acupuncture in Clinical and Experimental Reproductive Medicine: A Review,” Journal of Endocrinological Investigation 34, no. 4 (April 2011): 307–11.

  22. Ibid. Also, in 2002, a group of German researchers discovered that adding acupuncture to the traditional IVF treatment protocols substantially increased pregnancy success, finding that nearly half of women receiving just two twenty-five-minute sessions of acupuncture, one prior to having the fertilized embryos transferred into their uteri, and one directly afterward, had success getting pregnant, compared to just over a quarter of those who received no acupuncture treatments. W. E. Paulus, M. Zhang, E. Strehler, et al., “Influence of Acupuncture on the Pregnancy Rate in Patients Who Undergo Assisted Reproduction Therapy,” Fertility and Sterility 77, no. 4 (April 2002): 721–24; S. Dieterle, G. Ying, W. Hatzmann, and A. Neuer, “Effect of Acupuncture on the Outcome of In Vitro Fertilization and Intracytoplasmic Sperm Injection: A Randomized, Prospective, Controlled Clinical Study,” Fertility and Sterility 85, no. 5 (May 2006): 1347–51.

  Yet the research is not entirely clear. Although a meta-analysis of seven trials found that acupuncture treatments on the same day as embryo transfer increased the odds of clinical pregnancy by 65 percent (Manheimer et al., “Effects of Acupuncture”), later trials indicated that similar protocols of acupuncture treatments on the day of embryo transfer did not improve pregnancy rates compared with control groups. Y. C. Cheong, S. Dix, E. Hung Yu Ng, et al., “Acupuncture and Assisted Reproductive Technology,” Cochrane Database of Systematic Reviews, no. 7 (July 26, 2013): article ID CD006920. A small American study that duplicated the German methodology did not find any improvement in pregnancy rates with acupuncture.

  23. Quoted in Gordon, “Acupuncture May Boost.”

  24. For instance, a group of clinicians and researchers in Oregon designed the first comprehensive study to compare the results of IVF cycles carried out in conjunction with whole-systems TCM against the IVF results of cycles paired with just two acupuncture treatments on the day of embryo transfer and cycles that involved only the usual IVF care without any TCM intervention. Hullender Rubin et al., “Impact of Whole Systems.” Their findings that an increased number of acupuncture treatments led to greater pregnancy and live birth outcomes echo the results of earlier studies on specific outcomes resulting from repetitive acupuncture sessions. For example, blood flow to the uterus was found to improve with eight electroacupuncture sessions (Stener-Victorin et al., “Reduction of Blood Flow”), serum cortisol and prolactin were increased with a corresponding increase in IVF outcomes after nine electroacupuncture sessions (Magarelli et al., “Changes in Serum Cortisol”), and women with polycystic ovaries experienced improved menstrual regularity and reduced androgen levels after fourteen electro-acupuncture treatments (E. Jedel, F. Labrie, A. Oden, et al., “Impact of Electro-acupuncture and Physical Exercise on Hyperandrogenism and Oligo/Amenorrhea in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial,” American Journal of Physiology-Endocrinology and Metabolism 300, no. 1 (January 2011): e37–45.

  Chapter 4

  1. For further information on toxoplasmosis and its potential effects on pregnancy, see the CDC, Parasites-Toxoplasmosis (Toxoplasma infection) at https://www.cdc.gov/parasites/toxoplasmosis/gen_info/pregnant.html.

  2. One study found the frequency of chromosomal abnormalities to be 69.4 percent. M. Ohno, T. Maeda, and A. Matsunobu, “A Cytogenetic Study of Spontaneous Abortions with Direct Analysis of Chorionic Villi,” Obstetrics & Gynecology 77, no. 3 (March 1991): 394–98. Another study found that 70 to 90 percent of miscarriages occur due to chromosomal abnormalities. See IVF1, “Miscarriage History Raises Risk for Baby Chromosome Abnormalities,” July 30, 2008, http://www.ivf1.com/miscarriage-risk/. For a more detailed discussion of the role of chromosomal abnormalities in miscarriage, please see chapter 8 and its notes.

  Chapter 5

  1. A typical round of IUI in the United States costs anywhere from $500 to $1,000 (up to $2,500 to $4,000, with medications and ultrasound monitoring); expensive, but a drop in the bucket when compared to $12,000 to $25,000 for an IVF cycle.

  Chapter 6

  1. “What people worry about is that this is the first step on the road to Gattaca [referring to gender selection],” said Dr. Matt Wynia, the director of the University of Colorado Center for Bioethics and Humanities. “Letting parents choose the height, eye color, IQ, etc. When you start thinking about those things being very expensive, you can imagine some future world in which only the wealthy can have a healthy, tall baby made to order,” quoted in Jaclyn Allen, “Boy or Girl? More and More Colorado Parents Are Choosing Their Baby’s Gender,” Denver Channel, updated May 13, 2017, http://www.thedenverchannel.com/money/science-and-tech/boy-or-girl-more-and-more-colorado-parents-are-chosing-their-babys-gender. See also “Chrissy Teigen and John Legend Already Know the Gender of Their Second Baby—and Here’s How,” Vogue, November 21, 2017, https://www.vogue.com/article/chrissy-teigen-ivf-gender-selection-controversy-explained; and M. L. McGowan, and R. R. Sharp, “Justice in the Context of Family Balancing,” Science, Technology & Human Values 38, no. 2 (March 1, 2013): article ID 10.1177/0162243912469412.

  2. Margot Peppers, “The Rise of ‘Social’ Surrogacy: The Women Choosing Not to Carry Their Own Babies for Fear of Hurting Their Careers or Ruining Their Bodies, Daily Mail (UK), April 16, 2014, http://www.dailymail.co.uk/femail/article-2606101/the-rise-social-surrogacy-the-women-choosing-not-carry-babies-fear-hurting-careers-ruining-bodies.html#ixzz4t4OcD1ca. See also Sarah Elizabeth Richards, “Should a Woman Be Allowed to Hire a Surrogate Because She Fears Pregnancy Will Hurt Her Career?,”Elle, April 17, 2014, http://www.elle.com/life-love/a14424/birth-rights/.

  3. Critics fear the successful birth of a baby with three genetic parents, in a procedure performed to eliminate the possibility of passing on Leigh syndrome, an inherited genetic disorder, “could open the door to the creation of so-called designer babies.” Rob Stein, “New York Fertility Doctor Says He Created Baby With 3 Genetic Parents,” All Things Considered, NPR News, September 27, 2016, http://www.npr.org/sections/thetwo-way/2016/09/27/495668299/new-york-fertility-doctor-says-he-created-baby-with-3-genetic-parents.

  4. Olivia Blair, “Chrissy Teigen Defends Selecting Gender of Her Baby During IVF After Backlash,” The Independent (UK), February 24, 2016, http://www.independent.co.uk/news/people/chrissy-teigen-john-legend-baby-ivf-a6893621.html.

  5. Interestingly, although many women I have spoken with shared this feeling, it is certainly not universal. Diana felt that the hardest part was getting herself and her husband to a fertility clinic; she was relieved to just follow their instructions. Paula, on the other hand, had quite a different reaction to her first visit to a nationally recognized fertility specialist. “It was just a load of BS,” she told me, still indignant years later, recalling her response to the diagnosis and advice she received. “I decided I was just going to wait and see what happened.”

  6. The first baby conceived with IVF using preimplantation genetic testing was born in 1990, and the technology has progressed dramatically in the last ten to fifteen years. For a more detailed discussion of the evolution of preimplantation genetic testing, see chapter 7, and Jason Franasiak and Richard T. Scott Jr., “A Brief History of Preimplantation Genetic Diagnosis and Preimplantation Genetic Screening,” Virtual Academy of Genetics, http://www.ivf-worldwide.com/cogen/oep/pgd-pgs/history-of-pgd-and-pgs.html.

  7. I had thought at the time that the Puregon contained synthetic FSH but have since learned that the solution for injection contains the active substance follitropin beta, prod
uced by genetic engineering of a Chinese hamster ovary (CHO) cell line. See http://www.medicines.org.uk/emc/medicine/15946.

  8. Also known as Pregnyl, Ovidrel, Novarel and others, all brand names for human chorionic gonadotropin (HCG).

  9. Anna Magee, “Why Are So Many British Women Travelling Abroad for Fertility Treatment?,” The Telegraph (UK), March 28, 2015, http://www.telegraph.co.uk/women/mother-tongue/11482483/fertility-treatment-why-british-women-are-travelling-abroad.html. M. Rezazadeh Valojerdi, P. Eftekhari-Yazdi, L. Karimian, et al., “Vitrification Versus Slow Freezing Gives Excellent Survival, Post Warming Embryo Morphology and Pregnancy Outcomes for Human Cleaved Embryos,” Journal of Assisted Reproduction and Genetics 26, no. 6 (June 2009), 347–54.

  Chapter 7

  1. I injected 250 IUs of Puregon daily, up from 150 IUs.

  2. At the time, Dr. Ashby referred to it as preimplantation genetic diagnosis (PGD) a more common term for both types of technology in 2004. As the technology has evolved, the terminology has correspondingly become more specific, and the type of genetic testing she was referring to is now known as PGS. In order to avoid confusion, I refer to PGS, here and throughout, as it is generally used in 2017. A more detailed discussion of PGS and PGD can be found later in this chapter in the section entitled “Preimplantation Genetic Diagnosis (PGD) and Screening (PGS)”.

  3. For this cycle, I was prescribed Puregon, a form of FSH, plus Menopur, synthetic FSH combined with LH, as opposed to just FSH.

  4. Viagra has been shown to increase the thickness of the uterine lining by increasing blood flow and estrogen delivery to the lining. See Geoffrey Sher, “Viagra as a Treatment to Thicken Uterine Lining,” April 11, 2016, http://drgeoffreysherivf.com/viagra-treatment-thicken-uterine-lining/; R. D. Firouzabadi, R. Davar, F. Hojjat, and M. Mahdavi, “Effect of sildenafil citrate on endometrial preparation and outcome of frozen-thawed embryo transfer cycles: a randomized clinical trial,” Iranian Journal of Reproductive Medicine 11, no. 2 (February 2013): 151–58.

  5. Dr. Gillian Lockwood, the medical director of Midland Fertility Services, quoted in Magee, “British Women Travelling.”

  6. FertilityIQ, “Finding an IVF Doctor Is Total Hell,” accessed December 11, 2017, https://www.fertilityiq.com/fertilityiq-data-and-notes/finding-an-ivf-doctor-is-total-hell.

  7. Dr. Laura Rienzi, “How to Improve Embryos’ Quality in the IVF Lab,” presentation at the 24th World Congress on Controversies in Obstetrics, Gynecology & Infertility (COGI), Amsterdam, Netherlands, November 11, 2016.

  8. Q. Lai, H. Zhang, G. Zhu, et al., “Comparison of the GnRH Agonist and Antagonist Protocol on the Same Patients in Assisted Reproduction During Controlled Ovarian Stimulation Cycles,” International Journal of Clinical and Experimental Pathology 6, no. 9 (August 15, 2013):1903–10.

  9. Richard Sherbahn and Michelle Catenacci, “High Live Birth Rates in IVF High Responders Using Either a Lupron Trigger Alone (Agonist Trigger) or Using a Dual Trigger if Intensive Luteal Support Is Given,” research study presented by Richard Sherbahn, MD, at the 70th Annual Meeting of the American Society for Reproductive Medicine, Honolulu, October 2014.

  10. A 2007 study indicated that early embryos were no better off in the uterus than in the incubator. G. Sher, L. Keskintepe, M. Keskintepe, et al., “Oocyte Karyotyping by Comparative Genomic Hybrydization Provides a Highly Reliable Method for Selecting ‘Competent’ Embryos, Markedly Improving In Vitro Fertilization Outcome: A Multiphase Study,” Fertility and Sterility 87, no. 5 (May 2007): 1033–40.

  11. At one top clinic in Chicago, for example, 68.9 percent of women aged thirty-eight to forty became pregnant and 52 percent had a live birth following a blastocyst transfer, as opposed to a 40.9 percent pregnancy rate and 27.4 percent birth rate resulting from an embryo transfer. Among women just a couple of years older, aged forty-one to forty-two, the blastocyst transfers resulted in a 59.5 percent pregnancy and 37 percent live birth rate, as compared to 24.6 percent and 15.8 percent, respectively, for those who had an embryo transfer. Richard Sherbahn, “IVF Success Rates with 5 Day Blastocyst Transfers at the Advance Fertility Center of Chicago,” Advanced Fertility Center of Chicago, accessed December 11, 2017, www.advancedfertility.com/blastocystpregnancyrates.htm.

  12. John Rock, “Conception in a Watch Glass,” New England Journal of Medicine 217, no. 678 (October 21, 1937).

  13. A. H. Handyside, E. H. Kontogianni, K. Hardy, and R. M. Winston, “Pregnancies from Biopsied Human Preimplantation Embryos Sexed by Y-specific DNA Amplification,” Nature 344, no. 6,268 (April 19, 1990): 768–70.

  14. A. H. Handyside, J. G. Lesko, J. J. Tarin, et al., “Birth of a Normal Girl After In Vitro Fertilization and Preimplantation Diagnostic Testing for Cystic Fibrosis,” New England Journal of Medicine 327, no. 13 (September 24, 1992): 905–9.

  15. Ibid.

  16. Mark Hughes, “Current and Future Molecular Diagnostic Technologies for PGS and PGD,” presentation at ART World Congress, October 13, 2016.

  17. Ibid.

  18. L. Rienzi, A. Capalbo, M. Stoppa, et al., “No Evidence of Association Between Blastocyst Aneuploidy and Morphokinetic Assessment in a Selected Population of Poor-Prognosis Patients: A Longitudinal Cohort Study,” Reproductive BioMedicine Online 30, no. 1 (January 2015): 57–66; R. R. Angell, A. A. Templeton, and R. J. Aitken, “Chromosome Studies in Human In Vitro Fertilization,” Human Genetics 72, no. 4 (April 1986): 333–39.

  19. See S. Mastenbroek, M. Twisk, J. van Echten-Arends, et al., “In Vitro Fertilization with Preimplantation Genetic Screening,” New England Journal of Medicine, no. 357 (2007): 9–17.

  20. Ibid.

  21. Santiago Munné and Dagan Wells, “Detection of Mosaicism at Blastocyst Stage with the Use of High-Resolution Next-Generation Sequencing,” Fertility and Sterility 107, no. 5 (May 2017): 1085–91.

  22. S. Munné, “Preimplantation Genetic Diagnosis for Aneuploidy and Translocations Using Array Comparative Genomic Hybridization,” Current Genomics 13, no. 6 (September 2012): 463–70. The first baby conceived in the UK after using aCGH was born in 2010. University of Oxford, “First IVF Babies Born Using New Chromosome Counting Technique,” February 4, 2011, http://www.ox.ac.uk/news/2011-02-04-first-ivf-babies-born-using-new-chromosome-counting-technique.

  23. Analysis of 15,033 embryos biopsied showed 47.3 percent to be normal (euploid), 39 percent to be abnormal (aneuploid), and 13.7 percent to be mosaic, with nearly 5 percent of the mosaics showing low levels of mosaicism and therefore treated as normal, and just under 9 percent showing high levels of abnormality. Ibid. A further analysis of data from Reprogenetics and Genesis Genetics through March 2016 regarding 33,236 embryos showed a range of mosaic embryos from 11 percent to 22 percent, depending on the age group, and a range of aneuploidy embryos from 16 percent to 42 percent. Approximately 30 percent of blastocyst-stage embryos are mosaic. Munné and Wells, “Detection of Mosaicism.”

  24. Hughes, “Molecular Diagnostic Technologies” presentation. Similarly, an embryo indicated as normal using aCGH was found to be a high-level mosaic, with 70 percent of its cells having trisomy 16. Santiago Munné, “An Appraisal of PGS Outcome-Data from the Two Largest PGS Providers,” presentation at ART World Congress, October 13, 2016.

  25. Ibid.

  26. E. Greco, M. G. Minasi, and F. Florentino, “Healthy Babies After Intrauterine Transfer of Mosaic Aneuploid Blastocysts,” New England Journal of Medicine no. 373 (2015): 2089–90.

  27. Reprogenetics and Recombine, a company founded by Dr. Munné that provides carrier screening tests for couples planning to conceive, were acquired in 2015 and 2016, respectively, by CooperSurgical, and are now part of CooperGenomics, where Dr. Munné serves as chief scientific officer.

  28. Stephen S. Hall, “A New Last Chance: There Could Soon Be a Baby-Boom Among Women Who Thought They’d Hit an IVF Dead End,” The Cut, New York Magazine, September 17, 2017, https://www.thecut.com/2017/09/ivf-abnormal-embryos-new-last-chance.html.

  29. Ibid.

 
; 30. Evidence that mosaic embryos implant less than those that are euploid comes from a recent study in which mosaic embryos, as determined with the use of hrNGS, resulted in 30.1 percent initial implantations and 15.4 percent ongoing pregnancies, significantly less than a well-matched nonmosaic euploid control group (55.8 percent implantations, 46.2 percent ongoing pregnancies). Another study showed a miscarriage rate of 55.6 percent for blastocysts classified as mosaic, versus 17.2 percent for euploid control samples (Munné and Wells, “Detection of Mosaicism”).

  31. Ibid.

  32. Pasquale Patrizio, head of fertility medicine at Yale University, and Sherman Silber of St. Luke’s Hospital in St. Louis, quoted in Hall, “New Last Chance.”

  33. Z. Yang, J. Liu, G. S. Collins, et al., “Selection of Single Blastocysts for Fresh Transfer Via Standard Morphology Assessment Alone and with Array CGH for Good Prognosis IVF Patients: Results from a Randomized Pilot Study,” Molecular Cytogenetics 5, no. 1 (May 2, 2012): 24; R. T. Scott, K. M. Upham, E. J. Forman, et al., “Blastocyst Biopsy with Comprehensive Chromosome Screening and Fresh Embryo Transfer Significantly Increases In Vitro Fertilization Implantation and Delivery Rates: A Randomized Controlled Trial,” Fertility and Sterility 100, no. 3 (September 2013): 697–703; E. J. Forman et al., “In Vitro Fertilization with Single Euploid Blastocyst Transfer: A Randomized Controlled Trial,” Fertility and Sterility 100, no. 1 (July 2013): 100–7.

  34. E. M. Dahdouh, J. Balayla, and J. A. Garcia-Velasco, “Impact of Blastocyst Biopsy and Comprehensive Chromosome Screening Technology on Preimplantation Genetic Screening: A Systematic Review of Randomized Controlled Trials,” Reproductive BioMedicine Online 30, no. 3 (March 2015): 281–89; E. Lee, P. Illingworth, L. Wilton, and G. M. Chambers, “The Clinical Effectiveness of Preimplantation Genetic Diagnosis for Aneuploidy in All 24 Chromosomes (PGD-A): Systematic Review,” Human Reproduction 30, no. 2 (February 2015): 473–83.