The use of androgen priming in infertile women with diminished ovarian reserve undergoing assisted reproductive technology (IVF/ICSI)


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective: To study the effectiveness of androgen priming in infertile women with diminished ovarian reserve (DOR) undergoing assisted reproductive technology (ART) treatment. Materials and methods: A prospective cohort study included infertile women with DOR undergoing in vitro fertilization (IVF) treatment. According to the ESHRE criteria (Bologna Criteria, 2011), the study group included 305 women; among them there were 203 patients who received androgen priming during one month prior to the IVF/ICSI program. The hormonal study including the androgen fractions in the blood serum was carried out using immunochemiluminescent assay (ICMA) in all women. Results: The use of androgen priming in infertile women with DOR led to statistically significant improvements in the parameters of oogenesis and embryogenesis. The use of dehydroepiandrosterone (DHEA) revealed statistically significant differences in the number of oocytes from 2.9 (0.3) to 4.4 (0.3), including mature oocytes from 1.8 (1) to 3.3 (1.05), zygotes from 1.2 (0.6) to 2.1 (0.7), blastocysts from 0.8 (0.4) to 1.4 (0.6), and the frequency of blastula formation from 27.6% to 31.8% (p<0.001). There was an increase in the pregnancy rate from 8.6% to 11.4% (p=0.32). The use of testosterone-containing gel also revealed statistically significant differences in the number of oocytes from 3.0 (0.5) to 4.1 (0.5) and mature oocytes from 1.74 (0.5) to 3.4 (0.6), zygotes from 1.1 (0.4) to 2.2 (0.6), blastocysts from 0.6 (0.3) to 1.5 (0.7), the frequency of blastula formation from 20.0% to 36.6% and pregnancy rate as well (p<0.001); however, pregnancy rate was found to be higher (14%) in this group after receiving therapy compared to the DHEA group. Conclusion: A decrease in the level of androgens in the blood serum is associated with impaired folliculogenesis, oogenesis, embryogenesis and leads to reduced effectiveness of the IVF/ICSI program. The study demonstrated an increase in the number of mature oocytes, the percentage of fertilization and the number of blastocysts of good and excellent quality, which can be the main factors leading to the clinical effectiveness of ART programs; however, there was no statistically significant difference in the pregnancy rate between the groups of patients who received treatment.

Full Text

Restricted Access

About the authors

Alla A. Gavisova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: gavialla@yandex.ru
Ph.D., Senior Researcher at the lst Gynecological Department.

Nail S. Kamaletdinov

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: sunsh86@mail.ru
Embryologist at the ist Gynecological Department

Tatiana A. Nazarenko

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: t_nazarenko@oparina4.ru
Dr. Med. Sci., Professor, Director of the Institute of Reproductive Medicine

Natalia V. Dolgushina

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_dolgushina@oparina4.ru
Dr. Med. Sci., Professor, Deputy Director - Head of the Department of Organization of Scientific Activities

References

  1. Jeve Y., Bhandari H. Effective treatment protocol for poor ovarian response: a systematic review and meta-analysis. J. Hum. Reprod. Sci. 2016; 9(2):70-81. 9(2):70-81. https://dx.doi.org/10.4103/0974-1208.183515.
  2. Ferraretti A.P., La Marca A., Fauser B.C.J.M., Tarlatzis B., Nargund G., Gianaroli L. ESHRE consensus on the definition of “poor response” to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum. Reprod. 2011; 26(7): 1616-24. https://dx.doi.org/10.1093/humrep/der092.
  3. MacLaughlin D.T., Donahoe P.K. Sex determination and differentiation. N. Engl. J. Med. 2004; 350(4): 367-78. https://dx.doi.org/10.1056/NEJMra022784.
  4. Neves A.R., Montoya-Botero P., Polyzos N.P. The role of androgen supplementation in women with diminished ovarian reserve: time to randomize, not meta-analyze. Front. Endocrinol. (Lausanne). 2021; 12: 653857. https://dx.doi.org/10.3389/fendo.2021.653857.
  5. Richardson A., Jayaprakasan K. The use of androgen priming in women with reduced ovarian reserve undergoing assisted reproductive technology. Semin. Reprod. Med. 2021; 39(5-06): 207-19. https://dx.doi.org/10.1055/s-0041-1735646.
  6. Astapova O., Minor B.M.N., Hammes S.R. Physiological and pathological androgen actions in the ovary. Endocrinology. 2019; 160(5): 1166-74. https://dx.doi.org/10.1210/en.2019-00101.
  7. Ryan K.J., Petro Z., Kaiser J. Steroid formation by isolated and recombined ovarian granulosa and tehcal cells. J. Clin. Endocrinol. Metab. 1968; 28(3): 355-8. https://dx.doi.org/10.1210/jcem-28-3-355.
  8. Horie K., Takakura K., Fujiwara H. Immunohistochemical localization of androgen receptor in the human ovary throughout the menstrual cycle in relation to oestrogen and progesterone receptor expression. Hum. Reprod. 1992; 7(2): 184-90. https://dx.doi.org/10.1093/oxfordjournals.humrep.a137614.
  9. Suzuki T., Sasano H., Kimura N., Tamura M., Fukaya T., Yajima A., Nagura H. Immunohistochemical distribution of progesterone, androgen and oestrogen receptors in the human ovary during the menstrual cycle: relationship to expression of steroidogenic enzymes. Hum. Reprod. 1994; 9(9): 1589-95. https://dx.doi.org/10.1093/oxfordjournals.humrep.a138757.
  10. Hillier S.G., Tetsuka M., Fraser H.M. Location and developmental regulation of androgen receptor in primate ovary. Hum. Reprod. 1997; 12(1): 107-11. https://dx.doi.org/10.1093/humrep/12.1.107.
  11. Weil S.J., Vendola K., Zhou J., Adesanya O.O., Wang J., Okafor J., Bondy C.A. Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations. J. Clin. Endocrinol. Metab. 1998; 83(7): 2479-85. https://dx.doi.org/10.1210/jcem.83.7.4917.
  12. Harlow C.R., Shaw H.J., Hillier S.G., Hodges J.K. Factors influencing follicle-stimulating hormone-responsive steroidogenesis in marmoset granulosa cells: effects of androgens and the stage of follicular maturity. Endocrinology. 1988; 122(6): 2780-7. https://dx.doi.org/10.1210/endo-122-6-2780.
  13. Shaw H.J., Hillier S.G., Hodges J.K. Developmental changes in luteinizing hormone/human chorionic gonadotropin steroidogenic responsiveness in marmoset granulosa cells: effects of follicle-stimulating hormone and androgens. Endocrinology. 1989; 124(4): 1669-77. https://dx.doi.org/10.1210/endo-124-4-1669.
  14. Hillier S.G., Ross G.T. Effects of exogenous testosterone on ovarian weight, follicular morphology and intraovarian progesterone concentration in estrogen-primed hypophysectomized immature female rats. Biol. Reprod. 1979; 20(2): 261-8.
  15. Billig H., Furuta I., Hsueh J.W. Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis. Endocrinology. 1993; 133(5): 2204-12. https://dx.doi.org/10.1210/endo.133.5.8404672.
  16. Vendola K.A., Zhou J., Adesanya O.O., Weil S.J., Bondy C.A. Androgens stimulate early stages of follicular growth in the primate ovary. J. Clin. Invest. 1998; 101(12): 2622-9. https://dx.doi.org/10.1172/JCI2081.
  17. Spinder T., Spijkstra J., Van Den Tweel J. The effects of long term testosterone administration on pulsatile luteinizing hormone secretion and on ovarian histology in eugonadal female to male transsexual subjects. J. Clin. Endocrinol. Metab. 1989; 69(1): 151-7. https://dx.doi.org/10.1210/jcem-69-1-151.
  18. Jonard S., Robert Y., Cortet-Rudelli C., Pigny P., Decanter C., Dewailly D. Ultrasound examination of polycystic ovaries: is it worth counting the follicles? Hum. Reprod. 2003; 18(3): 598-603. https://dx.doi.org/10.1093/humrep/deg115.
  19. Pigny P., Merlen E., Robert Y., Cortet-Rudelli C., Decanter C., Jonard S., Dewailly D. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J. Clin. Endocrinol. Metab. 2003; 88(12): 5957-62. https://dx.doi.org/10.1210/jc.2003-030727.
  20. Gervasio C.G., Bernuci M.P., Silva-de-Sa M.F., de Rosa-e-Silva A.C.J.S. The role of androgen hormones in early follicular development. ISRN Obstet. Gynecol. 2014; 2014 : 818010. https://dx.doi.org/10.1155/2014/818010.
  21. Casson PR., Lindsay M.S., Pisarska M.D., Carson S.A., Buster J.E. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum. Reprod. 2000; 15(10): 2129-32. https://dx.doi.org/10.1093/humrep/15.10.2129.
  22. Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum. Reprod. 2011; 26(6):1270-83. https://dx.doi.org/10.1093/humrep/der037.
  23. Slater C.C., Souter I., Zhang C., Guan C., Stanczyk F.Z., Mishell D.R. Pharmacokinetics of testosterone after percutaneous gel or buccal administration. Fertil. Steril. 2001; 76(1): 32-7. https://dx.doi.org/10.1016/s0015-0282(01)01827-1.
  24. Davison S.L., Bell R., Donath S., Montalto J.G., Davis S.R. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J. Clin. Endocrinol. Metab. 2005; 90(7): 3847-53. https://dx.doi.org/10.1210/jc.2005-0212.
  25. Nagels H.E., Rishworth J.R., Siristatidis C.S., Kroon B. Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction. Cochrane Database Syst. Rev. 2015; 11: CD009749.
  26. Neves A.R., Montoya-Botero P., Polyzos N.P. Androgens and diminished ovarian reserve:the long road from basic science to clinical implementation. A comprehensive and systematic review with meta-analysis. Am. J. Obstet. Gynecol. 2022; 227(3): 401-413.e18. https://dx.doi.org/10.1016/j.ajog.2022.03.051.
  27. Yeung T.W.Y., Li R.H.W., Lee V.C.Y., Ho P.C., Ng E.H.Y. A randomized doubleblinded placebo-controlled trial on the effect of dehydroepiandrosterone for 16 weeks on ovarian response markers in women with primary ovarian insufficiency. J.,. Clin. Endocrinol. Metab. 2013; 98(1): 380-8. https://dx.doi.org/10.1210/jc.2012-3071.
  28. Singh A.B., Lee M.L., Sinha-Hikim I., Kushnir M., Meikle W., Rockwood A. et al. Pharmacokinetics of a testosterone gel in healthy postmenopausal women. J. Clin. Endocrinol. Metab. 2006; 91(1): 136-44. https://dx.doi.org/10.1210/jc.2005-1640.
  29. Fabregues F., Penarrubia J., Creus M., Manau D., Casals G., Carmona F., Balasch J. Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial. Hum. Reprod. 2009; 24(2): 349-59. https://dx.doi.org/10.1093/humrep/den428.
  30. Kim C.H., Howles C.M., Lee H.A. The effect of transdermal testosterone gel pretreatment on controlled ovarian stimulation and IVF outcome in low responders. Fertil. Steril. 2011; 95(2): 679-83. https://dx.doi.org/10.1016/j.fertnstert.2010.07.1077.
  31. Kim C.H., Ahn J.W., Moon J.W., Kim S.H., Chae H.D., Kang B.M. Ovarian features after 2 weeks, 3 weeks and 4 weeks transdermal testosterone gel treatment and their associated effect on IVF outcomes in poor responders. Dev. Reprod. 2014; 18(3): 145-52. https://dx.doi.org/10.12717/DR.2014.18.3.145.
  32. Amirikia H., Savoy-Moore R.T., Sundareson A.S., Moghissi K. The effects of long-term androgen treatment on the ovary. Fertil. Steril. 1986; 45(2): 202-8. https://dx.doi.org/10.1016/s0015-0282(16)49155-7.
  33. Burger H.G. Androgen production in women. Fertil. Steril. 2002; 77(Suppl. 4): S3-5. 1 https://dx.doi.org/10.1016/s0015-0282(02)02985-0.

Supplementary files

Supplementary Files
Action
1. JATS XML

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies