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DOI QR Code

Ovarian Features after 2 Weeks, 3 Weeks and 4 Weeks Transdermal Testosterone Gel Treatment and Their Associated Effect on IVF Outcomes in Poor Responders

  • Kim, Chung-Hoon (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center) ;
  • Ahn, Jun-Woo (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Ulsan University Hospital) ;
  • Moon, Jei-Won (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center) ;
  • Kim, Sung-Hoon (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center) ;
  • Chae, Hee-Dong (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center) ;
  • Kang, Byung-Moon (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center)
  • Received : 2014.07.15
  • Accepted : 2014.08.04
  • Published : 2014.09.30

Abstract

This study was performed to investigate the effect of of transdermal testosterone gel (TTG) on controlled ovarian stimulation (COS) and IVF outcomes and ovarian morphology according to pretreatment duration in poor responders. A total of 120 women were recruited for this pilot study. They were randomized into control, 2 weeks, 3 weeks or 4 weeks TTG treatment groups. For three TTG treatment groups, 12.5 mg TTG was applied daily for 2 weeks, 3 weeks or 4 weeks in preceding period of study stimulation cycle. After 3 weeks of TTG pretreatment, significant increase of antral follicle count (AFC) and significant decreases of mean follicular diameter (MFD) and resistance index (RI) value of ovarian stromal artery were observed (p=0.026, p<0.001, p<0.01, respectively). The total dose of rhFSH administered for COS significantly decreased after 3 and 4 weeks TTG treatment both compared with control group (p<0.001, p<0.001). The numbers of oocytes retrieved and mature oocytes were significanty higher in 3 and 4 weeks TTG treatment groups than control group (p<0.001, p<0.001 in the number of oocytes retrieved; p<0.001, p<0.001 in the number of mature oocytes). The clinical pregnancy rate and live birth rate were increased only in 4 weeks TTG treatment group compared with control group (p=0.030 and p=0.042, respectively). These data demonstrated that TTG pretreatment for 3 to 4 weeks increases AFC and ovarian stromal blood flow, thereby potentially improving the ovarian response to COS and IVF outcome in poor responders undergoing IVF/ICSI.

Keywords

References

  1. Barad D, Gleicher N (2006) Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 21:2845-2849. https://doi.org/10.1093/humrep/del254
  2. Barbieri RL, Sluss PM, Powers RD, McShane PM, Vitonis A, Ginsburg E (2005) Association of body mass index, age, and cigarette smoking with serum testosterone levels in cycling women undergoing in vitro fertilization. Fertil Steril 83:302-308. https://doi.org/10.1016/j.fertnstert.2004.07.956
  3. Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE (2000) Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod 15:2129-2132. https://doi.org/10.1093/humrep/15.10.2129
  4. de los Santos MJ, Garcia-Laez V, Beltran D, Labarta E, Zuzuarregui JL, Alama P (2013) The follicular hormonal profile in low-responder patients undergoing unstimulated cycles: Is it hypoandrogenic? Hum Reprod 28:224-229. https://doi.org/10.1093/humrep/des349
  5. Fabregues F, Penarrubia J, Creus M, Manau D, Casals G, Carmona F (2009) Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial. Hum Reprod 24:349-359. https://doi.org/10.1093/humrep/den428
  6. Fanchin R, Frydman N, Even M, Berwanger da Silva AL, Grynberg M, Ayoubi JM (2011) Androgens and poor responders: are we ready to take the plunge into clinical therapy? Fertil Steril 96:1062-1065. https://doi.org/10.1016/j.fertnstert.2011.09.050
  7. Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L (2011) ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod 26:1616-1624. https://doi.org/10.1093/humrep/der092
  8. Frattarelli JL, Peterson EH (2004) Effect of androgen levels on in vitro fertilization cycles. Fertil Steril 81:1713-1714. https://doi.org/10.1016/j.fertnstert.2003.11.032
  9. Futterweit W, Deligdisch L (1986) Histopathological effects of exogenously administered testosterone in 19 female to male transsexuals. J Clin Endocrinol Metab 62:16-21. https://doi.org/10.1210/jcem-62-1-16
  10. Gonzalez-Comadran M, Duran M, Sola I, Fabregues F, Carreras R, Checa MA (2012) Effects of transdermal testosterone in poor responders undergoing IVF: systematic review and meta-analysis. Reprod Biomed Online 25:450-459. https://doi.org/10.1016/j.rbmo.2012.07.011
  11. Jonard S, Robert Y, Cortet-Rudelli C, Pigny P, Decanter C, Dewailly D (2003) Ultrasound examination of polycystic ovaries: is it worth counting the follicles? Hum Reprod 18:598-603. https://doi.org/10.1093/humrep/deg115
  12. Massin N, Cedrin-Durnerin I, Coussieu C, Galey-Fontaine J, Wolf JP, Hugues JN (2006) Effects of transdermal testosterone application on the ovarian response to FSH in poor responders undergoing assisted reproduction technique--a prospective, randomized, double-blind study. Hum Reprod 21:1204-1211. https://doi.org/10.1093/humrep/dei481
  13. Nielsen ME, Rasmussen IA, Kristensen SG, Christensen ST, Mollgard K, Wreford AE (2011) In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA. Mol Hum Reprod 17:63-70. https://doi.org/10.1093/molehr/gaq073
  14. Pache TD, Chadha S, Gooren LJ, Hop WC, Jaarsma KW, Dommerholt HB (1991) Ovarian morphology in longterm androgen-treated female to male transsexuals. A human model for the study of polycystic ovarian syndrome? Histopathology 19:445-452. https://doi.org/10.1111/j.1365-2559.1991.tb00235.x
  15. Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S (2003) Elevated serum level of antimullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab 88:5957-5962. https://doi.org/10.1210/jc.2003-030727
  16. Ryan KJ, Petro Z, Kaiser J (1968) Steroid formation by isolated and recombined ovarian granulosa and tehcal cells. J Clin Endocrinol Metab 28:355-358. https://doi.org/10.1210/jcem-28-3-355
  17. Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA (1998) Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest 101:2622-2629. https://doi.org/10.1172/JCI2081
  18. Vendola K, Zhou J, Wang J, Famuyiwa OA, Bievre M, Bondy CA (1999) Androgens promote oocyte insulinlike growth factor I expression and initiation of follicle development in the primate ovary. Biol Reprod 61:353-357. https://doi.org/10.1095/biolreprod61.2.353
  19. Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ (2004) Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 89:2085-2098. https://doi.org/10.1210/jc.2003-032006
  20. Weil SJ, Vendola K, Zhou J, Adesanya OO, Wang J, Okafor J (1998) Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations. J Clin Endocrinol Metab 83:2479-2485. https://doi.org/10.1210/jcem.83.7.4917
  21. Weil S, Vendola K, Zhou J, Bondy CA (1999) Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development. J Clin Endocrinol Metab 84:2951-2956. https://doi.org/10.1210/jcem.84.8.5929
  22. Zeleznik AJ, Little-Ihrig L, Ramasawamy S (2004) Administration of dihydrotestosterone to rhesus monkeys inhibits gonadotropin-stimulated ovarian steroidogenesis. J Clin Endocrinol Metab 89:860-866. https://doi.org/10.1210/jc.2003-031292