Effect of DHEA on Patients With Poor Ovarian Responds

NCT02432248 | Unknown

• 1 other identifier: S00056W9
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the effect of DHEA for treatment of subfertile patients with poor ovarian reserve and post-treatment evaluation of IVF outcome.

Conditions

Subfertility

Keywords

DHEA; live birth rate; poor ovarian responder

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  Compare the live birth rate between DHEA group and placebo group

  Participants will be followed for live birth rate up to 1 year.

Secondary Outcomes (1)

• Pregnancy rate

  Participants will be followed for pregnancy rate up to 1 year.

Study Arms (2)

Dehydroepiandrosterone

EXPERIMENTAL

DHEA is considered as health supplement and is available over the counter. Side effects are minimal at present dosage (25mg or 50mg tds).

Drug: Dehydroepiandrosterone

Placebo

PLACEBO COMPARATOR

Medical starch is considered as medicine components. Side effects are minimal at present dosage.

Other: placebo(medical starch)

Interventions

Dehydroepiandrosterone DRUG

75mg/day, PO for 90 days

Also known as: DHEA

Dehydroepiandrosterone

placebo(medical starch) OTHER

75mg/day, PO for 90 days

Placebo

Eligibility Criteria

• Age: 21 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Indicated for IVF treatment according to our standard department protocol
• Age \< 42
• Regular menstrual cycles (21-35 days)
• Poor ovarian responders are defined according to the Bologna criteria fulfilling 2 out of 3 of the following:
• Advanced maternal age (≥40) or any other genetic or acquired risk factor for POR
• Previous poor ovarian response (POR) (≤3 oocytes with a conventional stimulation protocol using at least 150IU gonadotrophins per day)
• Abnormal ovarian reserve test (i.e. AFC \< 5-7 or AMH \< 0.5-1.1ng/ml). Alternatively, two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal ORT.

You may not qualify if:

• Previous chemotherapy or pelvic irradiation
• Polycystic ovarian syndrome or polycystic ovaries
• On hormonal supplementation for any indication at the time of recruitment (e.g. estrogen, testosterone or DHEA)

Sponsors & Collaborators

• The Affiliated Hospital of Inner Mongolia Medical University: lead
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• Renmin Hospital of Wuhan University: collaborator

Study Sites (1)

The Affiliated Hospital of Inner Mongolia Medical University

Inner Mongolia, China

RECRUITING

Related Publications (32)

• Ubaldi FM, Rienzi L, Ferrero S, Baroni E, Sapienza F, Cobellis L, Greco E. Management of poor responders in IVF. Reprod Biomed Online. 2005 Feb;10(2):235-46. doi: 10.1016/s1472-6483(10)60946-7.

  PMID: 15823231 BACKGROUND

• Arlt W, Justl HG, Callies F, Reincke M, Hubler D, Oettel M, Ernst M, Schulte HM, Allolio B. Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression. J Clin Endocrinol Metab. 1998 Jun;83(6):1928-34. doi: 10.1210/jcem.83.6.4850.

  PMID: 9626121 BACKGROUND

• Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, Burki RE, Ginsburg ES, Rosen RC, Leiblum SR, Caramelli KE, Mazer NA. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000 Sep 7;343(10):682-8. doi: 10.1056/NEJM200009073431002.

  PMID: 10974131 BACKGROUND

• Gleicher N, Weghofer A, Barad DH. The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment? Reprod Biol Endocrinol. 2011 Aug 17;9:116. doi: 10.1186/1477-7827-9-116.

  PMID: 21849061 BACKGROUND

• Zhang HH, Xu PY, Wu J, Zou WW, Xu XM, Cao XY, Wei LZ. Dehydroepiandrosterone improves follicular fluid bone morphogenetic protein-15 and accumulated embryo score of infertility patients with diminished ovarian reserve undergoing in vitro fertilization: a randomized controlled trial. J Ovarian Res. 2014 Oct 21;7:93. doi: 10.1186/s13048-014-0093-3.

  PMID: 25330837 BACKGROUND

• Gleicher N, Weghofer A, Barad DH. Defining ovarian reserve to better understand ovarian aging. Reprod Biol Endocrinol. 2011 Feb 7;9:23. doi: 10.1186/1477-7827-9-23.

  PMID: 21299886 BACKGROUND

• Casson PR, Santoro N, Elkind-Hirsch K, Carson SA, Hornsby PJ, Abraham G, Buster JE. Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor-I and decreases high-density lipoprotein: a six-month trial. Fertil Steril. 1998 Jul;70(1):107-10. doi: 10.1016/s0015-0282(98)00121-6.

  PMID: 9660430 BACKGROUND

• Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.

  PMID: 21505041 BACKGROUND

• Mutlu MF, Erdem M, Erdem A, Yildiz S, Mutlu I, Arisoy O, Oktem M. Antral follicle count determines poor ovarian response better than anti-Mullerian hormone but age is the only predictor for live birth in in vitro fertilization cycles. J Assist Reprod Genet. 2013 Jun;30(5):657-65. doi: 10.1007/s10815-013-9975-3. Epub 2013 Mar 19.

  PMID: 23508679 BACKGROUND

• Gleicher N, Barad DH. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod Biol Endocrinol. 2011 May 17;9:67. doi: 10.1186/1477-7827-9-67.

  PMID: 21586137 BACKGROUND

• Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod. 2000 Oct;15(10):2129-32. doi: 10.1093/humrep/15.10.2129.

  PMID: 11006185 BACKGROUND

• Mamas L, Mamas E. Dehydroepiandrosterone supplementation in assisted reproduction: rationale and results. Curr Opin Obstet Gynecol. 2009 Aug;21(4):306-8. doi: 10.1097/gco.0b013e32832e0785.

  PMID: 19610174 BACKGROUND

• Sunkara SK, Pundir J, Khalaf Y. Effect of androgen supplementation or modulation on ovarian stimulation outcome in poor responders: a meta-analysis. Reprod Biomed Online. 2011 Jun;22(6):545-55. doi: 10.1016/j.rbmo.2011.01.015. Epub 2011 Feb 17.

  PMID: 21493151 BACKGROUND

• Gleicher N, Weghofer A, Barad DH. Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS). Reprod Biol Endocrinol. 2010 Nov 10;8:140. doi: 10.1186/1477-7827-8-140.

  PMID: 21067609 BACKGROUND

• Ferrario M, Secomandi R, Cappato M, Galbignani E, Frigerio L, Arnoldi M, Fusi FM. Ovarian and adrenal androgens may be useful markers to predict oocyte competence and embryo development in older women. Gynecol Endocrinol. 2015 Feb;31(2):125-30. doi: 10.3109/09513590.2014.964639. Epub 2014 Sep 26.

  PMID: 25259725 BACKGROUND

• Weissman A, Horowitz E, Ravhon A, Levran D. Administration of DHEA augments progesterone production in a woman with low ovarian reserve being transplanted with cryopreserved ovarian tissue. J Assist Reprod Genet. 2014 Nov;31(11):1565. doi: 10.1007/s10815-014-0358-1. Epub 2014 Oct 3. No abstract available.

  PMID: 25278174 BACKGROUND

• Pediaditakis I, Iliopoulos I, Theologidis I, Delivanoglou N, Margioris AN, Charalampopoulos I, Gravanis A. Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors. Endocrinology. 2015 Jan;156(1):16-23. doi: 10.1210/en.2014-1596.

  PMID: 25330101 BACKGROUND

• Cecconello AL, Trapp M, Hoefel AL, Marques CV, Arbo BD, Osterkamp G, Kucharski LC, Ribeiro MF. Sex-related differences in the effects of high-fat diets on DHEA-treated rats. Endocrine. 2015 Apr;48(3):985-94. doi: 10.1007/s12020-014-0396-6. Epub 2014 Oct 10.

  PMID: 25300783 BACKGROUND

• Buster JE. Transvaginal dehydroepiandrosterone: an unconventional proposal to deliver a mysterious androgen that has no receptor or target tissue using a strategy with a new name: hormone precursor replacement therapy (HPRT). Menopause. 2009 Sep-Oct;16(5):858-9. doi: 10.1097/gme.0b013e3181ae1fca. No abstract available.

  PMID: 19574935 BACKGROUND

• Artini PG, Simi G, Ruggiero M, Pinelli S, Di Berardino OM, Papini F, Papini S, Monteleone P, Cela V. DHEA supplementation improves follicular microenviroment in poor responder patients. Gynecol Endocrinol. 2012 Sep;28(9):669-73. doi: 10.3109/09513590.2012.705386. Epub 2012 Jul 26.

  PMID: 22835219 RESULT

• Barad D, Brill H, Gleicher N. Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function. J Assist Reprod Genet. 2007 Dec;24(12):629-34. doi: 10.1007/s10815-007-9178-x. Epub 2007 Dec 11.

  PMID: 18071895 RESULT

• Gleicher N, Ryan E, Weghofer A, Blanco-Mejia S, Barad DH. Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study. Reprod Biol Endocrinol. 2009 Oct 7;7:108. doi: 10.1186/1477-7827-7-108.

  PMID: 19811650 RESULT

• Gleicher N, Weghofer A, Barad DH. Improvement in diminished ovarian reserve after dehydroepiandrosterone supplementation. Reprod Biomed Online. 2010 Sep;21(3):360-5. doi: 10.1016/j.rbmo.2010.04.006. Epub 2010 Apr 18.

  PMID: 20638339 RESULT

• Wiser A, Gonen O, Ghetler Y, Shavit T, Berkovitz A, Shulman A. Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study. Hum Reprod. 2010 Oct;25(10):2496-500. doi: 10.1093/humrep/deq220. Epub 2010 Aug 21.

  PMID: 20729538 RESULT

• Yilmaz N, Uygur D, Inal H, Gorkem U, Cicek N, Mollamahmutoglu L. Dehydroepiandrosterone supplementation improves predictive markers for diminished ovarian reserve: serum AMH, inhibin B and antral follicle count. Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(2):257-60. doi: 10.1016/j.ejogrb.2013.04.003. Epub 2013 May 9.

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• Singh N, Zangmo R, Kumar S, Roy KK, Sharma JB, Malhotra N, Vanamail P. A prospective study on role of dehydroepiandrosterone (DHEA) on improving the ovarian reserve markers in infertile patients with poor ovarian reserve. Gynecol Endocrinol. 2013 Nov;29(11):989-92. doi: 10.3109/09513590.2013.824957. Epub 2013 Sep 4.

  PMID: 24004296 RESULT

• Gleicher N, Kim A, Weghofer A, Shohat-Tal A, Lazzaroni E, Lee HJ, Barad DH. Starting and resulting testosterone levels after androgen supplementation determine at all ages in vitro fertilization (IVF) pregnancy rates in women with diminished ovarian reserve (DOR). J Assist Reprod Genet. 2013 Jan;30(1):49-62. doi: 10.1007/s10815-012-9890-z. Epub 2012 Dec 5.

  PMID: 23212832 RESULT

• Yeung TW, Li RH, Lee VC, Ho PC, Ng EH. A randomized double-blinded 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 Jan;98(1):380-8. doi: 10.1210/jc.2012-3071. Epub 2012 Nov 8.

  PMID: 23144466 RESULT

• Yeung TW, Chai J, Li RH, Lee VC, Ho PC, Ng EH. A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders. Fertil Steril. 2014 Jul;102(1):108-115.e1. doi: 10.1016/j.fertnstert.2014.03.044. Epub 2014 May 3.

  PMID: 24796766 RESULT

• Xu B, Li Z, Yue J, Jin L, Li Y, Ai J, Zhang H, Zhu G. Effect of dehydroepiandrosterone administration in patients with poor ovarian response according to the Bologna criteria. PLoS One. 2014 Jun 16;9(6):e99858. doi: 10.1371/journal.pone.0099858. eCollection 2014.

  PMID: 24932478 RESULT

• Barad D, Gleicher N. Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod. 2006 Nov;21(11):2845-9. doi: 10.1093/humrep/del254. Epub 2006 Sep 22.

  PMID: 16997936 RESULT

• Jirge PR, Chougule SM, Gavali VG, Bhomkar DA. Impact of dehydroepiandrosterone on clinical outcome in poor responders: A pilot study in women undergoing in vitro fertilization, using bologna criteria. J Hum Reprod Sci. 2014 Jul;7(3):175-80. doi: 10.4103/0974-1208.142477.

  PMID: 25395742 RESULT

MeSH Terms

Conditions

Infertility

Interventions

Dehydroepiandrosterone

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 17-Ketosteroids; Ketosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Yu Wang, PHD

  The Affiliated Hospital of Inner Mongolia Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yu Wang, PHD

CONTACT

86-18604718958; wuai1544@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: May 4, 2015
• Study Start: February 1, 2015
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: July 20, 2023

Record last verified: 2023-07

Locations

CN (1)