Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
권호 표지
DOI QR코드

DOI QR Code

Do spontaneously decreasing estradiol levels prior to triggering of ovulation adversely impact in vitro fertilization outcomes?

  • Grin, Leonti (Department of Obstetrics and Gynecology and Infertility, Barzilai University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev) ;
  • Berkovitz-Shperling, Roza (Sackler Faculty of Medicine, Tel Aviv University) ;
  • Zohav, Eyal (Sackler Faculty of Medicine, Tel Aviv University) ;
  • Namazov, Ahmet (Department of Obstetrics and Gynecology and Infertility, Barzilai University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev) ;
  • Leyetes, Sophia (Department of Obstetrics and Gynecology, Wolfson Maternity Hospital, Wolfson Medical Center) ;
  • Friedler, Shevach (Department of Obstetrics and Gynecology and Infertility, Barzilai University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev)
  • Received : 2019.11.17
  • Accepted : 2020.02.20
  • Published : 2020.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: The aim of this study was to explore the potential adverse effect of spontaneously decreasing serum estradiol (SE) levels on in vitro fertilization (IVF) outcomes. Methods: This retrospective single-subject study analyzed IVF cycles conducted at a hospital IVF unit between 2010 and 2017. Overall, 2,417 cycles were analyzed. Only cycles with spontaneously decreasing SE before human chorionic gonadotropin (hCG) triggering were included. Each patient served as her own control, and subsequent cycles were analyzed for recurrent SE decreases. The main outcome was the number of oocytes retrieved. Results: Cycle characteristics were similar between the study (SE decrease) and control groups, with the exception of the median SE on the day of hCG triggering (899.7 pg/mL; interquartile range [IQR], 193-2,116 pg/mL vs. 1,566.8 pg/mL; IQR, 249-2,970 pg/mL; p< 0.001). The study group, relative to the control group, had significantly fewer total oocytes (5 [IQR, 2-9] vs. 7 [IQR, 3-11]; p= 0.002) and significantly fewer metaphase II (MII) oocytes (3 [IQR, 1-6] vs. 4 [IQR, 2-8]; p= 0.001) retrieved. The study group had fewer cleavage-stage embryos than the control cycles (3 [IQR, 1-6] vs. 4 [IQR, 2-7]; p= 0.012). Compared to cycles with a ≤ 20% SE decrease, cycles with a > 20% decrease had significantly fewer total and MII oocytes retrieved. SE decrease recurred in 12% of patients. Conclusion: A spontaneous decrease in SE levels adversely affected IVF outcomes, with a linear correlation between the percentage decrease and the number of oocytes retrieved. SE decrease can repeat in later cycles.

Keywords

References

  1. Phelps JY, Levine AS, Hickman TN, Zacur HA, Wallach EE, Hinton EL. Day 4 estradiol levels predict pregnancy success in women undergoing controlled ovarian hyperstimulation for IVF. Fertil Steril 1998;69:1015-9. https://doi.org/10.1016/S0015-0282(98)00059-4
  2. Sharma V, Riddle A, Mason BA, Pampiglione J, Campbell S. An analysis of factors influencing the establishment of a clinical pregnancy in an ultrasound-based ambulatory in vitro fertilization program. Fertil Steril 1988;49:468-78. https://doi.org/10.1016/s0015-0282(16)59775-1
  3. Corbett S, Shmorgun D, Claman P; Reproductive Endocrinology Infertility Committee; Special Contributor. The prevention of ovarian hyperstimulation syndrome. J Obstet Gynaecol Can 2014;36:1024-33. https://doi.org/10.1016/s1701-2163(15)30417-5
  4. Mitwally MF, Bhakoo HS, Crickard K, Sullivan MW, Batt RE, Yeh J. Estradiol production during controlled ovarian hyperstimulation correlates with treatment outcome in women undergoing in vitro fertilization-embryo transfer. Fertil Steril 2006;86:588-96. https://doi.org/10.1016/j.fertnstert.2006.02.086
  5. Johnson MH, Everitt BJ. Essential reproduction. 5th ed. Oxford: Blackwell Science; 2000.
  6. Dorrington JH, Moon YS, Armstrong DT. Estradiol-17beta biosynthesis in cultured granulosa cells from hypophysectomized immature rats; stimulation by follicle-stimulating hormone. Endocrinology 1975;97:1328-31. https://doi.org/10.1210/endo-97-5-1328
  7. Adashi EY, Hsueh AJ. Estrogens augment the stimulation of ovarian aromatase activity by follicle-stimulating hormone in cultured rat granulosa cells. J Biol Chem 1982;257:6077-83. https://doi.org/10.1016/S0021-9258(20)65107-9
  8. Erickson GF, Wang C, Hsueh AJ. FSH induction of functional LH receptors in granulosa cells cultured in a chemically defined medium. Nature 1979;279:336-8. https://doi.org/10.1038/279336a0
  9. Kessel B, Liu YX, Jia XC, Hsueh AJ. Autocrine role of estrogens in the augmentation of luteinizing hormone receptor formation in cultured rat granulosa cells. Biol Reprod 1985;32:1038-50. https://doi.org/10.1095/biolreprod32.5.1038
  10. Louvet JP, Vaitukaitis JL. Induction of follicle-stimulating hormone (FSH) receptors in rat ovaries by estrogen priming. Endocrinology 1976;99:758-64. https://doi.org/10.1210/endo-99-3-758
  11. Hillier SG, Reichert LE Jr, Van Hall EV. Control of preovulatory follicular estrogen biosynthesis in the human ovary. J Clin Endocrinol Metab 1981;52:847-56. https://doi.org/10.1210/jcem-52-5-847
  12. McNatty KP, Smith DM, Makris A, Osathanondh R, Ryan KJ. The microenvironment of the human antral follicle: interrelationships among the steroid levels in antral fluid, the population of granulosa cells, and the status of the oocyte in vivo and in vitro. J Clin Endocrinol Metab 1979;49:851-60. https://doi.org/10.1210/jcem-49-6-851
  13. Jones HW Jr, Acosta A, Andrews MC, Garcia JE, Jones GS, Mantzavinos T, et al. The importance of the follicular phase to success and failure in in vitro fertilization. Fertil Steril 1983;40:317-21. https://doi.org/10.1016/s0015-0282(16)47293-6
  14. The ganirelix dose-finding study group. A double-blind, randomized, dose-finding study to assess the efficacy of the gonadotrophin-releasing hormone antagonist ganirelix (Org 37462) to prevent premature luteinizing hormone surges in women undergoing ovarian stimulation with recombinant follicle stimulating hormone (Puregon). Hum Reprod 1998;13:3023-31. https://doi.org/10.1093/humrep/13.11.3023
  15. Fauser BC, Devroey P, Yen SS, Gosden R, Crowley WF Jr, Baird DT, et al. Minimal ovarian stimulation for IVF: appraisal of potential benefits and drawbacks. Hum Reprod 1999;14:2681-6. https://doi.org/10.1093/humrep/14.11.2681
  16. Felberbaum R, Diedrich K. Ovarian stimulation for in-vitro fertilization/intracytoplasmic sperm injection with gonadotrophins and gonadotrophin-releasing hormone analogues: agonists and antagonists. Hum Reprod 1999;14 Suppl 1:207-21. https://doi.org/10.1093/humrep/14.suppl_1.207
  17. Fisher S, Grin A, Paltoo A, Shapiro HM. Falling estradiol levels as a result of intentional reduction in gonadotrophin dose are not associated with poor IVF outcomes, whereas spontaneously falling estradiol levels result in low clinical pregnancy rates. Hum Reprod 2005;20:84-8. https://doi.org/10.1093/humrep/deh543
  18. Styer AK, Jackson KV, Hornstein MD, Racowsky C, Ginsburg ES, Gargiulo AR. Pregnancy outcomes in in vitro fertilization cycles with serum estradiol drop prior to human chorionic gonadotropin. Int J Gynaecol Obstet 2005;89:133-7. https://doi.org/10.1016/j.ijgo.2005.02.005
  19. Lindheim SR, Morales AJ. GnRH antagonists followed by a decline in serum estradiol results in adverse outcomes in donor oocyte cycles. Hum Reprod 2003;18:2048-51. https://doi.org/10.1093/humrep/deg407
  20. Ben-Rafael Z, Kopf GS, Blasco L, Flickinger GL, Tureck RW, Strauss JF, et al. Follicular maturation parameters associated with the failure of oocyte retrieval, fertilization, and cleavage in vitro. Fertil Steril 1986;45:51-7. https://doi.org/10.1016/s0015-0282(16)49096-5
  21. Hsueh AJ, Kawamura K, Cheng Y, Fauser BC. Intraovarian control of early folliculogenesis. Endocr Rev 2015;36:1-24. https://doi.org/10.1210/er.2014-1020
  22. Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev 1996;17:121-55. https://doi.org/10.1210/edrv-17-2-121
  23. Rodgers RJ, Irving-Rodgers HF. Formation of the ovarian follicular antrum and follicular fluid. Biol Reprod 2010;82:1021-9. https://doi.org/10.1095/biolreprod.109.082941
  24. Zuccotti M, Merico V, Cecconi S, Redi CA, Garagna S. What does it take to make a developmentally competent mammalian egg? Hum Reprod Update 2011;17:525-40. https://doi.org/10.1093/humupd/dmr009