Advertisement

Journal of Assisted Reproduction and Genetics

, Volume 35, Issue 3, pp 475–482 | Cite as

Estrogen treatment in infertile women with premature ovarian insufficiency in transitional phase: a retrospective analysis

  • Sara Pinelli
  • Paolo Giovanni Artini
  • Stefano Basile
  • Maria Elena Rosa Obino
  • Claudia Sergiampietri
  • Diana Giannarelli
  • Giovanna Simi
  • Vito Cela
Assisted Reproduction Technologies
  • 302 Downloads

Abstract

Purpose

During the transitional phase of premature ovarian insufficiency (POI), sporadic resumption of ovulation is possible because of fluctuation of hormonal levels but the chance of spontaneous pregnancy is low, and the main perspective of childbearing in these women is egg donation or adoption. The purpose of the study was to verify whether treatment with estrogens in POI patients in transitional phase could reduce FSH levels and to evaluate if this pre-treatment could improve reproductive outcomes of in vitro fertilization (IVF).

Methods

Study patients (26) were administered with valerate estradiol 2 mg daily adding dihydrogesterone 10 mg daily during luteal phase for 3 months before IVF. Control group (26 patients) did not receive any pre-treatment. Ovarian stimulation was conducted in both groups with the same short GnRH-antagonist protocol. Clinical and laboratory data of patients were retrospectively analyzed.

Results

In the study group, 4/26 POI patients became spontaneously pregnant during pre-treatment. In the remaining patients, the mean level of FSH after the pre-treatment was significantly reduced compared with baseline. Levels of circulating estradiol on the day of hCG administration were significantly higher in the study group. The total number of MII oocytes retrieved and fertilized oocytes was significantly higher in the study group, as well as the number of embryos transferred for pickup and clinical pregnancy rate.

Conclusions

Treatment with estrogens in infertile POI patients in transitional phase reduces circulating FSH levels, hence causing potential spontaneous conception. Moreover, in these patients, estrogen pre-treatment seems to improve IVF outcomes in a GnRH-antagonist short protocol compared to no pre-treatment.

Keywords

Premature ovarian insufficiency IVF POF Estrogens Infertility 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

References

  1. 1.
    Woad KJ, Watkins WJ, Prendergast D, Shelling AN. The genetic basis of premature ovarian failure. Aust N Z J Obstet Gynaecol. 2006;46(3):242–4.CrossRefPubMedGoogle Scholar
  2. 2.
    De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010;376(9744):911–21.CrossRefPubMedGoogle Scholar
  3. 3.
    Coulam B, Adamson C, Annegers F. Incidence of premature ovarian failure. Obstet Gynecol. 1986;67(4):604–6.PubMedGoogle Scholar
  4. 4.
    Lumsden MA, Davies M, Sarri G. Diagnosis and management of menopause: the National Institute of Health and Care Excellence (NICE) guideline. JAMA Intern Med. 2016;176(8):1205–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Webber L, et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926–37.CrossRefPubMedGoogle Scholar
  6. 6.
    Knauff EAH, et al. Anti-mullerian hormone, inhibin B, and antral follicle count in young women with ovarian failure. J Clin Endocrinol Metab. 2009;94(3):786–92.CrossRefPubMedGoogle Scholar
  7. 7.
    Welt CK. Primary ovarian insufficiency: a more accurate term for premature ovarian failure. Clin Endocrinol. 2008;68(4):499–509.CrossRefGoogle Scholar
  8. 8.
    Shestakova IG, Radzinsky VE, Khamoshina MB. Occult form of premature ovarian insufficiency. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2016;32(sup2):30–2.Google Scholar
  9. 9.
    Cox L, Liu JH. Primary ovarian insufficiency: an update. Int J Womens Health. 2014;6:235–43.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Maclaran K, Panay N. Current concepts in premature ovarian insufficiency. Womens Health. 2015;11(2):169–82.Google Scholar
  11. 11.
    Soave I, Lo Monte G, Marci R. POI: premature ovarian insufficiency/pregnancy or infertility? North Am J Med Sci. 2013;5(1):71.CrossRefGoogle Scholar
  12. 12.
    Ben-Nagi J, Panay N. Premature ovarian insufficiency: how to improve reproductive outcome? Climacteric. 2014;17(3):242–6.CrossRefPubMedGoogle Scholar
  13. 13.
    McNatty KP, Makris A, DeGrazia C, Osathanondh R, Ryan KJ. The production of progesterone, androgens, and estrogens by granulosa cells, thecal tissue, and stromal tissue from human ovaries in vitro. J Clin Endocrinol Metab. 1979;49(5):687–99.CrossRefPubMedGoogle Scholar
  14. 14.
    Fisch JD, Keskintepe L, Sher G. Gonadotropin-releasing hormone agonist/antagonist conversion with estrogen priming in low responders with prior in vitro fertilization failure. Fertil Steril. 2008;89(2):342–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Keltz M, Sauerbrun-Cutler M-T, Breborowicz A. Managing poor responders in IVF. Expert Rev Obstet Gynecol. 2013;8(2):121–34.CrossRefGoogle Scholar
  16. 16.
    Cooper TG, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–45.CrossRefPubMedGoogle Scholar
  17. 17.
    Determina n. 1073/2016 Agenzia Italiana Del Farmaco (AIFA), nota 745. Gazzetta Ufficiale Serie Generale n.201 del 29-08-2016.Google Scholar
  18. 18.
    Simi G, Obino MER, Casarosa E, Litta P, Artini PG, Cela V. Different stimulation protocols for oocyte cryropreservation in oncological patients: a retrospective analysis of single university centre. Gynecol Endocrinol. 2015;31(12):966–70.CrossRefPubMedGoogle Scholar
  19. 19.
    Artini PG, et al. DHEA supplementation improves follicular microenviroment in poor responder patients. Gynecol Endocrinol. 2012;28(9):669–73.CrossRefPubMedGoogle Scholar
  20. 20.
    Veeck LL. Morphological estimation of mature oocytes and their preparation for insemination. In: Jones Jr HW, Jones GS, Hodgen GD, Rosenwaks Z, editors. In vitro fertilization, Norfolk. Baltimore: Williams and Wilkins; 1986. p. 81–93.Google Scholar
  21. 21.
    Ferraretti AP, La Marca A, Fauser BCJM, 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. Oxf. Engl. 2011;26(7):1616–24.CrossRefGoogle Scholar
  22. 22.
    Cohen J, Chabbert-Buffet N, Darai E. Diminished ovarian reserve, premature ovarian failure, poor ovarian responder—a plea for universal definitions. J Assist Reprod Genet. 2015;32(12):1709–12.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Anasti JN. Premature ovarian failure: an update. Fertil Steril. 1998;70(1):1–15.CrossRefPubMedGoogle Scholar
  24. 24.
    Santoro N. Research on the mechanisms of premature ovarian failure. J Soc Gynecol Investig, vol. 8, no. 1 Suppl Proceedings, pp. S10–2, 2001.Google Scholar
  25. 25.
    Schoemaker J. Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy. Hum Reprod Update. 1999;5(5):483.CrossRefPubMedGoogle Scholar
  26. 26.
    Check JH, Nowroozi K, Chase JS, Nazari A, Shapse D, Vaze M. Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea. Fertil Steril. 1990;53(5):811–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Fernandes AMDS, Arruda MDS, Bedone AJ. Twin gestation two years after the diagnosis of premature ovarian failure in a woman on hormone replacement therapy; a case report. J Reprod Med. 2002;47(6):504–6.PubMedGoogle Scholar
  28. 28.
    Zargar AH, Salahuddin M, Wani AI, Bashir MI, Masoodi SR, Laway BA. Pregnancy in premature ovarian failure: a possible role of estrogen plus progesterone treatment. J Assoc Physicians India. 2000;48(2):213–5.PubMedGoogle Scholar
  29. 29.
    Taylor AE, Adams JM, Mulder JE, Martin KA, Sluss PM, Crowley WF. A randomized, controlled trial of estradiol replacement therapy in women with hypergonadotropic amenorrhea. J Clin Endocrinol Metab. 1996;81(10):3615–21.PubMedGoogle Scholar
  30. 30.
    Tartagni M, Cicinelli E, De Pergola G, De Salvia MA, Lavopa C, Loverro G. Effects of pretreatment with estrogens on ovarian stimulation with gonadotropins in women with premature ovarian failure: a randomized, placebo-controlled trial. Fertil Steril. Apr. 2007;87(4):858–61.CrossRefPubMedGoogle Scholar
  31. 31.
    Popat VB, Vanderhoof VH, Calis KA, Troendle JF, Nelson LM. Normalization of serum luteinizing hormone levels in women with 46,XX spontaneous primary ovarian insufficiency. Fertil Steril. 2008;89(2):429–33.CrossRefPubMedGoogle Scholar
  32. 32.
    Serna J, Cholquevilque JL, Cela V, Martínez-Salazar J, Requena A, Garcia-Velasco JA. Estradiol supplementation during the luteal phase of IVF-ICSI patients: a randomized, controlled trial. Fertil Steril. 2008;90(6):2190–5.CrossRefPubMedGoogle Scholar
  33. 33.
    Check JH, Wilson C, DiAntonio G, DiAntonio A. In vitro fertilization (IVF) outcome in women in overt menopause attempting to induce follicular maturation by follicle stimulating hormone (FSH) receptor down-regulation. Clin Exp Obstet Gynecol. 2016;43(2):181–3.CrossRefPubMedGoogle Scholar
  34. 34.
    Tartagni R, Damiani R, Di Naro R, Persiani R, Crescini R, Loverro R. Pregnancy in a woman with premature ovarian insufficiency undergoing intracytoplasmic sperm injection after pretreatment with estrogens followed by therapy with estrogens associated with ovarian stimulation with gonadotropins: remarks about oocyte and embryo quality. Menopause. 2011;18(8):932–4.CrossRefPubMedGoogle Scholar
  35. 35.
    Sonigo C, Dray G, Roche C, Cédrin-Durnerin I, Hugues J-N. Impact of high serum progesterone during the late follicular phase on IVF outcome. Reprod BioMed Online. 2014;29(2):177–86.CrossRefPubMedGoogle Scholar
  36. 36.
    Venetis CA, et al. Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles. Hum Reprod Oxf Engl. 2015;30(3):684–91.CrossRefGoogle Scholar
  37. 37.
    Ulug U, Ben-Shlomo I, Turan E, Erden HF, Akman MA, Bahceci M. Conception rates following assisted reproduction in poor responder patients: a retrospective study in 300 consecutive cycles. Reprod BioMed Online. 2003;6(4):439–43.CrossRefPubMedGoogle Scholar
  38. 38.
    Vural B, Cakiroglu Y, Vural F, Filiz S. Hormonal and functional biomarkers in ovarian response. Arch Gynecol Obstet. 2014;289(6):1355–61.CrossRefPubMedGoogle Scholar
  39. 39.
    Iliodromiti S, Anderson RA, Nelson SM. Technical and performance characteristics of anti-müllerian hormone and antral follicle count as biomarkers of ovarian response. Hum Reprod Update. 2015;21(6):698–710.CrossRefPubMedGoogle Scholar
  40. 40.
    La Marca A, et al. Possibilities and limits of ovarian reserve testing in ART. Curr Pharm Biotechnol. 2012;13(3):398–408.CrossRefPubMedGoogle Scholar
  41. 41.
    Parry JP, Koch CA. Ovarian reserve testing, in Endotext, L. J. De Groot, G. Chrousos, K. Dungan, K. R. Feingold, A. Grossman, J. M. Hershman, C. Koch, M. Korbonits, R. McLachlan, M. New, J. Purnell, R. Rebar, F. Singer, and A. Vinik, Eds. South Dartmouth (MA): MDText.com, Inc., 2000.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology OncologyUniversity of PisaPisaItaly
  2. 2.Biostatistics UnitRegina Elena National Cancer InstituteRomeItaly

Personalised recommendations