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Follicular Waves in the Human Ovary: A New Physiological Paradigm for Novel Ovarian Stimulation Protocols

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Abstract

Ovulation induction (OI) is a cornerstone of human assisted reproduction treatments (ART). Current OI protocols are based on the human follicular dynamics model known as propitious moment theory (PMT), by which follicles continuously grow from the primordial pool without any pattern, and follicular fate depend on the occurrence of a gonadotropin surge. Recently, a new paradigm of human follicular dynamics called follicular waves was revealed using sequential ultrasound examination of 1 interovulatory interval. Instead of random growth, follicles develop in coordinated groups or waves, occurring 2 to 3 times during an interovulatory interval. Follicular waves are common in several other mono-ovulatory species, like equines and bovines. In fact, this model was applied to the development of several OI protocols in veterinary medicine, especially in cows. It has been shown that synchronization of OI with the emergence of a follicular wave increases substantially success rates in animals, even with single embryo transfer. Veterinarians have already developed mechanisms to control wave emergence through mechanical or chemical ablation of the dominant follicle or corpus luteum. Considering the follicular dynamics similarities between humans and bovines regarding the follicular wave phenomenon, we hypothesize that synchronization of follicular wave emergence with ovarian stimulation produces more competent oocytes and embryos and will enhance ART efficiency in humans. At the end of this article, we propose 2 theoretical approaches to induce the emergence of a follicular wave in women: (1) a mechanical strategy by aspiration of the dominant follicle and (2) a pharmacological strategy by administering estradiol and progesterone.

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References

  1. Center for Disease Control. 2005. Assisted Reproductive Technology (ART) Report. Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Division of Reproductive Health. Atlanta, 98 pages.

  2. Adams GP, Jaiswal R. Follicular dynamics in cattle: Historical overview and research update. Acta Scientiae Veterinariae. 2008;36:387–396.

    Google Scholar 

  3. Gougeon A. Some aspects of the dynamics of ovarian follicular growth in the human. Acta Eur Fertil. 1989;20(4):185–192.

    CAS  PubMed  Google Scholar 

  4. Gougeon A. Dynamics of follicular growth in the human: a model from preliminary results. Hum Reprod. 1986;1(2):81–87.

    Article  CAS  PubMed  Google Scholar 

  5. Baerwald AR, Adams GP, Pierson RA. Characterization of ovarian follicular wave dynamics in women. Biol Reprod. 2003;69(3):1023–1031.

    Article  CAS  PubMed  Google Scholar 

  6. Ginther OJ, Gastal EL, Gastal MO, Bergfelt DR, Baerwald AR, Pierson RA. Comparative study of the dynamics of follicular waves in mares and women. Biol Reprod. 2004;71(4):1195–1201.

    Article  CAS  PubMed  Google Scholar 

  7. Ginther OJ, Beg MA, Donadeu FX, Bergfelt DR. Mechanism of follicle deviation in monovular farm species. Anim Reprod Sci. 2003;78(3–4):239–257.

    Article  CAS  PubMed  Google Scholar 

  8. McCorkell R, Woodbury M, Adams GP. Ovarian follicular and luteal dynamics in wapiti during the estrous cycle. Theriogenology. 2006;65(3):540–556.

    Article  PubMed  Google Scholar 

  9. Skidmore JA, Adams GP, Billah M. Synchronisation of ovarian follicular waves in the dromedary camel (Camelus dromedarius). Anim Reprod Sci. 2009;114(1–3):249–255.

    Article  CAS  PubMed  Google Scholar 

  10. Baruselli PS, Mucciolo RG, Visintin JA, et al. Ovarian follicular dynamics during the estrous cycle in buffalo (Bubalus bubalis). Theriogenology. 1997;47(8):1531–1547.

    Article  CAS  PubMed  Google Scholar 

  11. Adams GP, Sumar J, Ginther OJ. Effects of lactational and reproductive status on ovarian follicular waves in llamas (Lama glama). J Reprod Fertil. 1990;90(2):535–545.

    Article  CAS  PubMed  Google Scholar 

  12. Buratini J, Rosa e Silva AA, Barros CM, Papa FO, Caldas MC, Meira C. Follicular dynamics in Mangalarga mares. Equine Vet J Suppl. 1997;25:7–11.

    Google Scholar 

  13. Sirois J, Fortune JE. Ovarian follicular dynamics during the estrous cycle in heifers monitored by real-time ultrasonography. Biol Reprod. 1988;39(2):308–317.

    Article  CAS  PubMed  Google Scholar 

  14. Ginther OJ, Knopf L, Kastelic JP. Ovarian follicular dynamics in heifers during early pregnancy. Biol Reprod. 1989;41(2):247–254.

    Article  CAS  PubMed  Google Scholar 

  15. Rathbone MJ, Kinder JE, Fike K, et al. Recent advances in bovine reproductive endocrinology and physiology and their impact on drug delivery system design for the control of the estrous cycle in cattle. Adv Drug Deliv Rev. 2001;50(3):277–320.

    Article  CAS  PubMed  Google Scholar 

  16. Ginther OJ, Beg MA, Gastal EL, Gastal MO, Baerwald AR, Pierson RA. Systemic concentrations of hormones during the development of follicular waves in mares and women: a comparative study. Reproduction. 2005;130(3):379–388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003;80(1):116–122.

    Article  PubMed  Google Scholar 

  18. Wallach EE. Physiology of menstruation. Clin Obstet Gynecol. 1970;13(2):366–385.

    Article  CAS  PubMed  Google Scholar 

  19. McCorkell R, Woodbury MR, Adams GP. Ovarian follicular and luteal dynamics in wapiti during seasonal transitions. Theriogenology. 2007;67(7):1224–1232.

    Article  CAS  PubMed  Google Scholar 

  20. Chaves MG, Aba M, Aguero A, Egey J, Berestin V, Rutter B. Ovarian follicular wave pattern and the effect of exogenous progesterone on follicular activity in non-mated llamas. Anim Reprod Sci. 2002;69(1–2):37–46.

    Article  CAS  PubMed  Google Scholar 

  21. Adams GP. Comparative patterns of follicle development and selection in ruminants. J Reprod Fertil Suppl. 1999;54:17–32.

    CAS  PubMed  Google Scholar 

  22. van Wagtendonk-de Leeuw AM. Ovum pick up and in vitro production in the bovine after use in several generations: a 2005 status. Theriogenology. 2006;65(5):914–925.

    Article  PubMed  Google Scholar 

  23. Adams GP. Control of ovarian follicular wave dynamics in cattle: implications for synchronization and superstimulation. Theriogenology. 1994;41(1):19–24.

    Article  Google Scholar 

  24. Nasser LF, Adams GP, Bo GA, Mapletoft RJ. Ovarian superstimulatory response relative to follicular wave emergence in heifers. Theriogenology. 1993;40(4):713–724.

    Article  CAS  PubMed  Google Scholar 

  25. Mapletoft RJ, Bo GA, Baruselli PS. Control of ovarian function for assisted reproductive technologies in cattle. Anim Reprod. 2009;6(1):114–124.

    Google Scholar 

  26. Wiltbank JN, Kasson CW. Synchronization of estrus in cattle with an oral progestational agent and an injection of an estrogen. J Anim Sci. 1968;27(1):113–116.

    Article  CAS  PubMed  Google Scholar 

  27. Bo GA, Adams GP, Nasser LF, Pierson RA, Mapletoft RJ. Effect of estradiol valerate on ovarian follicles, emergence of follicular waves and circulating gonadotropins in heifers. Theriogenology. 1993;40(2):225–239.

    Article  CAS  PubMed  Google Scholar 

  28. Bo GA, Adams GP, Pierson RA, Mapletoft RJ. Effect of progestogen plus estradiol-17beta treatment on superovulatory response in beef cattle. Theriogenology. 1996;45(5):897–910.

    Article  CAS  PubMed  Google Scholar 

  29. Kohram H, Twagiramungu H, Bousquet D, Durocher J, Guilbault LA. Ovarian superstimulation after follicular wave synchronization with GnRH at two different stages of the estrous cycle in cattle. Theriogenology. 1998;49(6):1175–1186.

    Article  CAS  PubMed  Google Scholar 

  30. Wock JM, Lyle LM, Hockett ME. Effect of gonadotropin releasing hormone compared to estradiol 17-beta at the beggining of a superstimulation protocol on the superovulatory response and embryo quality. Reprod Fertil Dev. 2008;20(1):228–228.

    Article  Google Scholar 

  31. Adams GP, Nasser LF, Bo GA, Garcia A, Del Campo MR, Mapletoft RJ. Superovulatory response of ovarian follicles of wave 1 versus wave 2 in heifers. Theriogenology. 1994;42(7):1103–1113.

    Article  CAS  PubMed  Google Scholar 

  32. Ginther OJ, Knopf L, Kastelic JP. Temporal associations among ovarian events in cattle during oestrous cycles with two and three follicular waves. J Reprod Fertil. 1989;87(1):223–230.

    Article  CAS  PubMed  Google Scholar 

  33. Gastal EL, Gastal MO, Beg MA, Ginther OJ. Interrelationships among follicles during the common-growth phase of a follicular wave and capacity of individual follicles for dominance in mares. Reproduction. 2004;128(4):417–422.

    Article  CAS  PubMed  Google Scholar 

  34. Bergfelt DR, Bo GA, Mapletoft RJ, Adams GP. Superovulatory response following ablation-induced follicular wave emergence at random stages of the oestrous cycle in cattle. Anim Reprod Sci. 1997;49(1):1–12.

    Article  CAS  PubMed  Google Scholar 

  35. Baruselli PS, de Sa Filho MF, Martins CM, et al. Superovulation and embryo transfer in Bos indicus cattle. Theriogenology. 2006;65(1):77–88.

    Article  PubMed  Google Scholar 

  36. Ginther OJ, Bergfelt DR, Beg MA, Kot K. Follicle selection in cattle: relationships among growth rate, diameter ranking, and capacity for dominance. Biol Reprod. 2001;65(2):345–350.

    Article  CAS  PubMed  Google Scholar 

  37. Vlahos NF, Giannakikou I, Vlachos A, Vitoratos N. Analgesia and anesthesia for assisted reproductive technologies. Int J Gynaecol Obstet. 2009;105(3):201–205.

    Article  PubMed  Google Scholar 

  38. El-Shawarby S, Margara R, Trew G, Lavery S. A review of complications following transvaginal oocyte retrieval for in-vitro fertilization. Hum Fertil (Camb). 2004;7(2):127–133.

    Article  PubMed  Google Scholar 

  39. Vaskivuo TE, Ottander U, Oduwole O, et al. Role of apoptosis, apoptosis-related factors and 17beta-hydroxysteroid dehydrogenases in human corpus luteum regression. Mol Cell Endocrinol. 2002;194(1–2):191–200.

    Article  CAS  PubMed  Google Scholar 

  40. Bolt HM. Metabolism of estrogens—natural and synthetic. Pharmacol Ther. 1979;4(1):155–181.

    Article  CAS  PubMed  Google Scholar 

  41. Fabregues F, Penarrubia J, Vidal E, Casals G, Vanrell JA, Balasch J. Oocyte quality in patients with severe ovarian hyperstimulation syndrome: a self-controlled clinical study. Fertil Steril. 2004;82(4):827–833.

    Article  PubMed  Google Scholar 

  42. Delvigne A, Rozenberg S. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002;8(6):559–577.

    Article  CAS  PubMed  Google Scholar 

  43. De VA, Steenholdt C, Risco CA. Pregnancy rates and milk production in natural service and artificially inseminated dairy herds in Florida and Georgia. J Dairy Sci. 2005;88(3):948–956.

    Article  Google Scholar 

  44. Peixoto MG, Bergmann JA, Suyama E, Carvalho MR, Penna VM. Logistic regression analysis of pregnancy rate following transfer of Bos indicus embryos into Bos indicus x Bos taurus heifers. Theriogenology. 2007;67(2):287–292.

    Article  CAS  PubMed  Google Scholar 

  45. Macklon NS, van der Gaast MH, Hamilton A, Fauser BC, Giudice LC. The impact of ovarian stimulation with recombinant FSH in combination with GnRH antagonist on the endometrial transcriptome in the window of implantation. Reprod Sci. 2008;15(4):357–365.

    Article  CAS  PubMed  Google Scholar 

  46. Horcajadas JA, Minguez P, Dopazo J, et al. Controlled ovarian stimulation induces a functional genomic delay of the endometrium with potential clinical implications. J Clin Endocrinol Metab. 2008;93(11):4500–4510.

    Article  CAS  PubMed  Google Scholar 

  47. Haouzi D, Assou S, Mahmoud K, et al. Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. Hum Reprod. 2009;24(6):1436–1445.

    Article  CAS  PubMed  Google Scholar 

  48. Baerwald AR. Human antral folliculogenesis: what we have learned from the bovine and equine models. Animal Reproduction. 2009;6:20–29.

    Google Scholar 

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Correspondence to Paulo Homem de Mello Bianchi MD.

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de Mello Bianchi, P.H., Serafini, P., Monteiro da Rocha, A. et al. Follicular Waves in the Human Ovary: A New Physiological Paradigm for Novel Ovarian Stimulation Protocols. Reprod. Sci. 17, 1067–1076 (2010). https://doi.org/10.1177/1933719110366483

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