Email this article Use of androgens and aromatase inhibitors in poor responders undergoing in vitro fertilization
- Authors: Merkulova A.I.1, Dzhemlikhanova L.K.1,2, Niauri D.A.1,2, Gzgzyan A.M.1,2, Kogan I.Y.1,2, Krikheli I.O.2, Tapilskaya N.I.2,3, Mekina I.D.2, Lesik E.A.2, Komarova E.M.2
-
Affiliations:
- Saint Petersburg State University
- The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
- Saint Petersburg State Pediatric Medical University
- Issue: Vol 68, No 6 (2019)
- Pages: 37-46
- Section: Original Research
- URL: https://journals.rcsi.science/jowd/article/view/16294
- DOI: https://doi.org/10.17816/JOWD68637-46
- ID: 16294
Cite item
Full Text
Abstract
Hypothesis/aims of study. Poor ovarian response is still considered one of the most challenging tasks in reproductive medicine. Poor responders have decreased circulating androgens during spontaneous cycles. Androgens are known to play an important role in follicular growth and development. Hence, the use of various androgens and androgen inhibitors in poor responders undergoing ovarian stimulation for IVF has been proposed to improve efficacy of treatment. This study was aimed to examine the efficacy of aromatase inhibitors and androgens in infertility treatment in patients with poor response.
Study design, materials and methods. This prospective cohort-controlled clinical trial included 204 patients under 42 years of age with infertility and poor response to ovarian stimulation. In vitro fertilization treatment with an antagonist FSH/hMG protocol with letrozole (5 mg/day) was administered in the first group of patients (n = 26) during the first 5 days of stimulation. Patients of the second group (n = 38) were applied testosterone (25 mg/day) transdermally, starting from the 5th day of the menstrual cycle preceding controlled ovarian stimulation for in vitro fertilization. The third group of patients (n = 18) was administered dehydroepiandrosterone (100 mg/day) for 3 months prior to controlled ovarian stimulation for in vitro fertilization.
Results. Improved response to FSH stimulation with letrozole co-treatment was evidenced, with parameters of stimulation efficacy and embryo development being better in the testosterone group. No significant improvement in ovarian response markers, ovarian response to gonadotrophin stimulation and in vitro fertilization outcomes were found in poor responders receiving pre-treatment dehydroepiandrosterone.
Conclusion. Further studies are necessary to improve approaches of testosterone and aromatase inhibitors use in poor responders undergoing in vitro fertilization.
Full Text
##article.viewOnOriginalSite##About the authors
Alexandra I. Merkulova
Saint Petersburg State University
Author for correspondence.
Email: merkulova.alexandra@gmail.com
ORCID iD: 0000-0001-5555-2425
SPIN-code: 5109-0816
MD, Postgraduate student. The Department of Obstetrics, Gynecology, and Reproductive Sciences, Medical Faculty
Russian Federation, Saint PetersburgLyailya Kh. Dzhemlikhanova
Saint Petersburg State University; The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: dzhemlikhanova_l@mail.ru
ORCID iD: 0000-0001-6842-4430
SPIN-code: 1691-6559
MD, PhD, Associate Professor. The Department of Obstetrics, Gynecology, and Reproductive Sciences, Medical Faculty; the Department of Assisted Reproductive Technologies
Russian Federation, Saint PetersburgDariko A. Niauri
Saint Petersburg State University; The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: d.niauri@mail.ru
ORCID iD: 0000-0003-1556-248X
SPIN-code: 4384-9785
MD, PhD, DSci (Medicine), Professor, the Head of the Department of Obstetrics, Gynecology, and Reproductive Sciences, Medical Faculty; Leading Researcher. The Gynecological Department with the Operation Unit
Russian Federation, Saint PetersburgAlexander M. Gzgzyan
Saint Petersburg State University; The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: agzgzyan@mail.ru
ORCID iD: 0000-0003-3917-9493
SPIN-code: 6412-4801
MD, PhD, DSci (Medicine), Professor. The Department of Obstetrics, Gynecology, and Reproductive Sciences, Medical Faculty; the Head of the Department of Assisted Reproductive Technologies
Russian Federation, Saint PetersburgIgor Yu. Kogan
Saint Petersburg State University; The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: ikogan@mail.ru
ORCID iD: 0000-0002-7351-6900
SPIN-code: 6572-6450
MD, PhD, DSci (Medicine), Professor, Corresponding Member of RAS. The Department of Obstetrics, Gynecology, and Reproductive Sciences, Medical Faculty; Director
Russian Federation, Saint PetersburgInna O. Krikheli
The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: ikrikhely@gmail.com
ORCID iD: 0000-0002-5439-1727
SPIN-code: 7356-6189
MD, PhD, Senior Researcher. The Department of Assisted Reproductive Technologies
Russian Federation, Saint PetersburgNatalya I. Tapilskaya
The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott; Saint Petersburg State Pediatric Medical University
Email: tapnatalia@yandex.ru
ORCID iD: 0000-0001-5309-0087
SPIN-code: 3605-0413
MD, PhD, DSci (Medicine), Professor, Leading Researcher; Professor. The Department of Obstetrics and Gynecology with the Course of Pediatric and Adolescent Gynecology
Russian Federation, Saint PetersburgIrina D. Mekina
The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: iagmail@ott.ru
ORCID iD: 0000-0002-0813-5845
SPIN-code: 4682-8590
PhD, Senior Researcher. The Department of Assisted Reproductive Technologies
Russian Federation, Saint PetersburgElena A. Lesik
The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: iagmail@ott.ru
PhD, Senior Researcher. The Department of Assisted Reproductive Technologies
Russian Federation, Saint PetersburgEvgenia M. Komarova
The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott
Email: iagmail@ott.ru
ORCID iD: 0000-0002-9988-9879
SPIN-code: 1056-7821
PhD, Researcher. The Department of Assisted Reproductive Technologies
Russian Federation, Saint PetersburgReferences
- Haahr T, Esteves SC, Humaidan P. Individualized controlled ovarian stimulation in expected poor-responders: an update. Reprod Biol Endocrinol. 2018;16(1):20. https://doi.org/10.1186/s12958-018-0342-1.
- Chai J, Lee VC, Yeung TW, et al. Live birth and cumulative live birth rates in expected poor ovarian responders defined by the Bologna criteria following IVF/ICSI treatment. PLoS One. 2015;10(3):e0119149. https://doi.org/10.1371/journal.pone.0119149.
- Polyzos NP, Nwoye M, Corona R, et al. Live birth rates in Bologna poor responders treated with ovarian stimulation for IVF/ICSI. Reprod Biomed Online. 2014;28(4):469-474. https://doi.org/10.1016/j.rbmo.2013.11.010.
- Goldfarb JM. Cumulative pregnancy rates in women with poor ovarian response. Fertil Steril. 2018;109(6):1004-1005. https://doi.org/10.1016/j.fertnstert.2018.02.011.
- Jeve YB, Bhandari HM. Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis. J Hum Reprod Sci. 2016;9(2):70-81. https://doi.org/10.4103/0974-1208.183515.
- Busnelli A, Somigliana E. Prognosis and cost-effectiveness of IVF in poor responders according to the Bologna Criteria. Minerva Ginecol. 2018;70(1):89-98. https://doi.org/10.23736/S0026-4784.17.04132-6
- Prizant H, Gleicher N, Sen A. Androgen actions in the ovary: balance is key. J Endocrinol. 2014;222(3):R141-151. https://doi.org/10.1530/JOE-14-0296.
- van der Stege JG, Groen H, van Zadelhoff SJ, et al. Decreased androgen concentrations and diminished general and sexual well-being in women with premature ovarian failure. Menopause. 2008;15(1):23-31. https://doi.org/10.1097/gme.0b013e3180f6108c.
- Gleicher N, Kim A, Weghofer A, et al. Hypoandrogenism in association with diminished functional ovarian reserve. Hum Reprod. 2013;28(4):1084-1091. https://doi.org/10.1093/humrep/det033.
- Ferraretti AP, La Marca A, Fauser BC, et al. ESHRE consensus on the definition of “poor responseˮ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26(7):1616-1624. https://doi.org/10.1093/humrep/der092.
- Tao J, Tamis R, Fink K, et al. The neglected morula/compact stage embryo transfer. Hum Reprod. 2002;17(6):1513-1518. https://doi.org/10.1093/humrep/17.6.1513.
- Bastu E, Buyru F, Ozsurmeli M, et al. A randomized, single-blind, prospective trial comparing three different gonadotropin doses with or without addition of letrozole during ovulation stimulation in patients with poor ovarian response. Eur J Obstet Gynecol Reprod Biol. 2016;203:30-34. https://doi.org/10.1016/j.ejogrb.2016.05.027.
- Cortinez A, De Carvalho I, Vantman D, et al. Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients. Fertil Steril. 2005;83(1):110-115. https://doi.org/10.1016/ j.fertnstert.2004.05.099.
- Palomba S. Aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab. 2015;100(5):1742-1747. https://doi.org/10.1210/jc.2014-4235.
- Pavone ME, Bulun SE. Clinical review: The use of aromatase inhibitors for ovulation induction and superovulation. J Clin Endocrinol Metab. 2013;98(5):1838-1844. https://doi.org/10.1210/jc.2013-1328.
- Cantor A, Tannus S, Son WY, et al. A comparison of two months pretreatment with GnRH agonists with or without an aromatase inhibitor in women with ultrasound-diagnosed ovarian endometriomas undergoing IVF. Reprod Biomed Online. 2019;38(4):520-527. https://doi.org/10.1016/j.rbmo.2018.12.028.
- Ozmen B, Sonmezer M, Atabekoglu CS, Olmus H. Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols. Reprod Biomed Online. 2009;19(4):478-485. https://doi.org/10.1016/j.rbmo.2009.05.007.
- Mol BW, Bossuyt PM, Sunkara SK, et al. Personalized ovarian stimulation for assisted reproductive technology: study design considerations to move from hype to added value for patients. Fertil Steril. 2018;109(6):968-979. https://doi.org/10.1016/j.fertnstert.2018.04.037.
- Bosdou JK, Venetis CA, Dafopoulos K, et al. Transdermal testosterone pretreatment in poor responders undergoing ICSI: a randomized clinical trial. Hum Reprod. 2016;31(5):977-985. https://doi.org/10.1093/humrep/dew028.
- Guo J, Zhang Q, Li Y, et al. Predictive value of androgens and multivariate model for poor ovarian response. Reprod Biomed Online. 2014;28(6):723-732. https://doi.org/10.1016/j.rbmo.2014.02.009.
- Polyzos NP, Davis SR, Drakopoulos P, et al. Testosterone for poor ovarian responders: lessons from ovarian physiology. Reprod Sci. 2018;25(7):980-982. https://doi.org/10.1177/1933719116660849.
- Vaiarelli A, Cimadomo D, Ubaldi N, et al. What is new in the management of poor ovarian response in IVF? Curr Opin Obstet Gynecol. 2018;30(3):155-162. https://doi.org/10.1097/GCO.0000000000000452.
- Rosner W, Auchus RJ, Azziz R, et al. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab. 2007;92(2):405-413. https://doi.org/10.1210/jc.2006-1864.
Supplementary files
