Can DHEA Supplementation Improve IVF Outcomes In Patients With Normal Ovarian Function?

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Dehydroepiandrosterone (DHEA) has been found to improve pregnancy rates in patients with diminished ovarian reserve.  However, the question of whether older patients with normal ovarian reserve will also benefit from DHEA supplementation, has not been addressed.  A recent study conducted at the University of Bari School of Medicine in Italy suggests that miscarriage rates are lower and IVF pregnancy rates are higher in patients treated with DHEA supplements before undergoing IVF treatment.

 

In recent years there has been a great interest in the use of dehydroepiandrosterone (DHEA) as a nutritional supplement aimed at improving ovarian function in women with advanced reproductive age.  DHEA is a naturally occurring hormone produced by the adrenal cortex and the certain cells that line the interior of ovarian follicles.  Studies done over the past decade have suggested that supplementation with DHEA in women with diminished ovarian reserve results in improved rates of spontaneous and treatment induced pregnancies.  Most of the research published thus far has focused on women who have significantly elevated follicle stimulating hormone (FSH) levels and/or diminished anti-mullerian (AMH) levels.  A recent study by Tartagni, Cicinelli, et al. published in Reproductive Biology and Endocrinology in March 2015, investigated the effects of DHEA supplementation in women of advanced reproductive age, but with normal FSH and AMH levels. 

 

One hundred and nine infertile patients undergoing IVF were recruited for the study.  All were 36-40 years of age and had normal FSH and AMH levels.  Fifty-three of the patients were randomized to receive 8 weeks of pre-treatment with DHEA 75mg/day and 56 patients were given a placebo for 8 weeks prior to IVF treatment.

 

The DHEA treated group demonstrated the following statistically significant findings:

 

1)   Shorter duration of ovarian stimulation (11 vs. 13.1 days)

2)   Higher estradiol levels at the end of the ovarian stimulation (3478 vs. 2051)

3)   Thicker uterine lining (10.4 vs. 9.1)

4)   Improved live birth rate (22 vs. 13)

 

The DHEA treated group demonstrated the following non-significant findings:

 

1)   Greater number of eggs retrieved (8.9 vs. 8.2)

2)   Greater number of mature eggs (6.1 vs. 5.8)

3)   Greater number of embryos transferred (2.5 vs. 2.3)

4)   Greater number of clinical pregnancies (22 vs. 18)

 

Other noteworthy findings of this study:

 

1)   No miscarriages among the 22 pregnant patients in the DHEA treated group

2)   Five miscarriages in the Non-DHEA group

 

The mechanism of action of DHEA is uncertain at this time. One current theory is that DHEA improves the production of steroid hormones from the ovary.  DHEA is the precursor to testosterone that is present in the follicular fluid.  It is believed that enhancing the amount of male hormone in follicular fluid early in the cycle results in improved egg and embryo quality. 

 

One of the important findings of this study was the reduced miscarriage rate among patients pre-treated with DHEA. Since the majority of miscarriages are believed to be the result of chromosomal abnormalities, it is possible that chromosomal abnormalities of the egg (specifically aneuploidy) may be somehow decreased through DHEA supplementation.  Others (Gleicher et al.) have demonstrated reduced aneuploidy in DHEA supplemented women who had been found to have diminished ovarian reserve.

 

This study suggests that DHEA pre-treatment improves fertility in a group of women with advanced reproductive age, but with normal ovarian reserve indicators.  

Voorhees, New Jersey

Dr. Louis R. Manara

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