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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)

  • ASSISTED REPRODUCTION TECHNOLOGIES
  • Published:
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Abstract

Purpose

To investigate whether androgen conversion rates after supplementation with dehydroepiandrosterone (DHEA) differ, and whether differences between patients with diminished ovarian reserve (DOR) are predictive of pregnancy chances in association with in vitro fertilization (IVF).

Methods

In a prospective cohort study we investigated 213 women with DOR, stratified for age (≤38 or >38 years) and ovarian FMR1 genotypes/sub-genotypes. All women were for at least 6 weeks supplemented with 75 mg of DHEA daily prior to IVF, between initial presentation and start of 1st IVF cycles. Levels of DHEA, DHEA-sulfate (DHEAS), total T (TT) and free T (FT) at baseline (BL) and IVF cycle start (CS) were then compared between conception and non-conception cycles.

Results

Mean age for the study population was 41.5 ± 4.4 years. Forty-seven IVF cycles (22.1 %) resulted in clinical pregnancy. Benefits of DHEA on pregnancy rates were statistically associated with efficiency of androgen conversion from DHEA to T and amplitude of T gain. Younger women converted significantly more efficiently than older females, and selected FMR1 genotypes/sub-genotypes converted better than others. FSH/androgen and AMH/androgen ratios represent promising new predictors of IVF pregnancy chances in women with DOR.

Conclusions

DOR at all ages appears to represent an androgen-deficient state, benefitting from androgen supplementation. Efficacy of androgen supplementation with DHEA, however, varies depending on female age and FMR1 genotype/sub-genotype. Further clarification of FMR1 effects should lead to better individualization of androgen supplementation, whether via DHEA or other androgenic compounds.

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Abbreviations

AMH:

Anti-Müllerian hormone

AMHR:

Anti-Müllerian hormone receptor

AR:

Androgen receptor

BL :

Baseline

CS :

Cycle start

DHEA:

Dehydroepiandrosterone

DHEAS:

Dehydroepiandrosterone sulfate

DOR:

Diminished functional ovarian reserve

FMR1 :

Fragile X mental retardation 1

FOR:

Functional ovarian reserve

FSH:

Follicle stimulating hormone

FSHR:

Follicle stimulating hormone receptor

het :

Heterozygous

IVF:

In vitro fertilization

hom :

Homozygous

norm :

Normal

PCO:

Polycystic ovary

PCOS:

Polycystic ovary syndrome

POA:

Premature ovarian aging

T:

Testosterone

FT:

Free testosterone

TT:

Total testosterone

Δ:

Change

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Financial disclosure

NG, AW and DHB have received research and grant support, travel funds and speaker honoraria from various pharmaceutical and medical device companies, none, however, related to here presented topics. NG and DHB are listed as inventors on two already awarded and other still pending United States patents, claiming beneficial effects on diminished ovarian reserve (DOR) and embryo ploidy from dehydroepiandrosterone (DHEA) or from other androgen supplementations. NG is owner of CHR, where this research was conducted. NG and DHB are also listed as co-inventors on a number of pending United States patents, claiming diagnostic relevance for the assessment of triple CGG repeats on the FMR1 gene in determining risk towards DOR and related issues. At time of this submission only two United States user patents with relevance to this manuscript, both DHEA-related, have been awarded (November 10, 2009; #7615544 and November 29, 2011; #8067400) The first claims benefits from supplementation of DHEA/androgens on ovarian reserve and IVF pregnancy rates in women with DOR; and the second claims decreased aneuploidy (and, therefore, miscarriage rates) and improved pregnancy rates. Among FMR1-related pending patent applications, one describes ovarian genotypes and sub-genotypes, as used in this manuscript, and claims that these genotypes and sub-genotypes reflect different ovarian aging patterns. All patent applications filed by researchers at CHR are 50 % owned by CHR and 50 % by the investigators who did the research that led to the application. A full list of all patent information can be provided on request.

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Authors and Affiliations

  1. Center for Human Reproduction, New York, NY, 10021, USA

    Norbert Gleicher, Ann Kim, Andrea Weghofer, Aya Shohat-Tal, Emanuela Lazzaroni, Ho-Joon Lee & David H. Barad

  2. Foundation for Reproductive Medicine, New York, NY, 10021, USA

    Norbert Gleicher & David H. Barad

  3. Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University Vienna, 1090, Vienna, Austria

    Andrea Weghofer

  4. The CHR, 21 East 69th Street, New York, NY, 10021, USA

    Norbert Gleicher

Authors
  1. Norbert Gleicher
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  2. Ann Kim
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  3. Andrea Weghofer
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  4. Aya Shohat-Tal
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  5. Emanuela Lazzaroni
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  6. Ho-Joon Lee
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  7. David H. Barad
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Corresponding author

Correspondence to Norbert Gleicher.

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Contributions to authorship

N.G. and D.H.B. contributed equally to the manuscript. N.G. contributed to study design and data analysis, and wrote the manuscript, A.K. and D.H.B. performed data analyses and statistical analyses, A.W. contributed to study design. All authors approved the final manuscript

Capsule

This study suggests a strong statistical association between improving androgen levels and IVF pregnancy chances.

Funded by extramural funds from the Foundation for Reproductive Medicine and intramural funds from The Center for Human Reproduction (CHR) both New York, New York. Both funding organizations had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript with the following caveats: Authors, NG and DHB, are members of the Board of the Foundation for Reproductive Medicine, and author, NG, is owner of The Center for Human Reproduction (CHR), a for-profit fertility center.

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Gleicher, N., Kim, A., Weghofer, A. et al. 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 30, 49–62 (2013). https://doi.org/10.1007/s10815-012-9890-z

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  • DOI: https://doi.org/10.1007/s10815-012-9890-z

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