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DHEA & IVF. Is dehydroepiandrosterone supplementation something to consider?

4 fertility expert(s) answered this question

Answer from: Maria Arquè, MD, PhD

Gynaecologist, Reproductive Specialist

DHEA is a supplement that might be used for IVF cycles. It might be considered for patients who have a low ovarian reserve, and we classify them as poor responders. Usually, these are patients who have low levels of testosterone.

There are some trials, and there is some evidence published saying that patients who take testosterone or DHEA during some months previous to the IVF cycle might benefit from taking these medications and might have a better ovarian response. Even though we have to be aware that DHEA is a supplement that might have some adverse effects, for example, it can have an impact on the function of the liver.

Therefore, I’d not advise any patient to use it without medical supervision. You should always check that the liver is functioning properly before we can consider administrating DHEA.

Answer from: Ruth Sánchez, MD

Gynaecologist, Fertility Specialist PreGen (UR Vistahermosa)

DHEA, which is an endogenous steroid that has originated in the reticularis zone of the adrenal cortex and the ovarian theca cell. It is an essential prohormone in ovarian follicular steroidogenesis. DHEA supplements have beneficial effects in ovarian stimulations on patients with a poor ovarian response. There is still speculation regarding its mechanism of action. It is known that oral administration of DHEA increases serum levels of an insulin growth factor which ought to have a positive effect on follicular development and oocyte quality.

But what do we mean when we talk about a poor ovarian response? Most of the studies consider a poor ovarian response by the presence of at least 2 of the 3 following criteria: patients older than 40 years of age, antral follicle count lower than 5, or decreased AMH, or a deficient prior ovarian response. A recent review, published in 2018, included 5 studies comparing pregnancy rates in patients undergoing IVF ICSI and in patients who received DHEA before ovarian stimulation. All the patients had a poor ovarian response and met at least 2 of the 3 criteria described. The primary objective was the clinical pregnancy rate per an initiated cycle. Secondary objectives were: average oocyte retrieval and miscarriage frequency. DHEA was administered in 25 mg doses, 3 times a day – between 6 and 16 weeks before IVF ICSI cycles. The findings indicated that the use of DHEA is associated with a better pregnancy rate and a lower frequency of miscarriages, but without affecting the average oocyte retrieval.

This implies that an improved clinical pregnancy rate might be due to the improvement in the oocyte quality. The findings of a lower rate of miscarriage in the DHEA groups give some further support to this. Whether DHEA improves oocyte quality or endometrium receptivity is yet to be enunciated – however, this might be translated into an improved pregnancy rate and a decreased miscarriage rate.

The use of DHEA before ovarian stimulation in women with a poor ovarian response is associated with an improvement in prognosis, and given that DHEA is a well-tolerated drug, it can be a good recommendation that should be included in the treatment of patients with a poor ovarian response.
Anyway, more studies are needed to support this recommendation.

Answer from: Iryna Kotsiubska, MD

Gynaecologist, Fertility Specialist Reproduction Center – Parens Ukraine

Dehydroepiandrosterone supplementation improves IVF outcomes of poor ovarian responders, especially in women with low serum concentrations of DHEA-S. DHEA supplementation has vastly improved pregnancy outcomes in women who suffer from premature ovarian ageing, as well as, women over 40 whose ovarian reserve is declining as a part of the natural ageing process.

DHEA supplementation is typically prescribed 6-8 weeks before starting the IVF cycle for all women over 40. Also, younger women whose ovarian reserve parameters such as FSH and AMH indicate that they have diminished ovarian reserve.

The purpose of DHEA supplementation is to raise the androgen levels in the ovarian environment to the normal range, which has been shown to improve the numbers and the quality of eggs available for retrieval.
Before the prescription of DHEA, the level of androgen is monitored, and then, when the woman is on DHEA, it is further monitored. If androgen levels do not reach the desired range, the patient stays on the DHEA supplementation for longer.

The purpose of DHEA supplementation in hypo-androgenic infertile women is the improvement of egg quantity and quality. Studies have demonstrated that taking a DHEA supplement for at least 6 weeks is required before statistically significant improvements in female fertility can be observed. Greater effectiveness is typically reached between 16-20 weeks of DHEA supplementation. But the length of time is not the best indicator – what matters is that the woman’s androgen levels rise to about the upper one-third of the normal range.

Experts initially recommended fertility treatments like IVF to be initiated after 6-8 weeks of the DHEA supplementation. The supplementation is to be continued uninterrupted until pregnancy or until a patient decides to discontinue treatment attempts with the use of her own eggs. According to recent recommendations, the timing of the start of a post-DHEA IVF cycle should not only be based on the prefixed interval of the time with DHEA supplementation but also the mentioned improvements in androgen levels.

DHEA supplementation can be initiated at any time. Small growing follicles require at least 6-8 weeks of further maturation after small growing stages before reaching the so-called gonadotropin-dependent stage, where they finally become responsive to fertility drugs and available in IVF cycles. This is the reason why pre-supplementation with DHEA must be initiated at least 6 weeks before the IVF cycle start.

DHEA supplementation is contraindicated in patients with a history of sex hormones sensitive cancers such as breast, ovarian, endometrial, and PCOS patients. DHEA fertility research and clinical experience have demonstrated that DHEA supplementation works by raising androgen levels in the ovaries to the normal level needed for healthy egg development and improved IVF results. Adding a DHEA supplement for at least 6-8 weeks before the IVF cycle starts, improves egg quality and results in overall better IVF outcomes.

Answer from: Bogna Sobkiewicz, MD

Gynaecologist, Fertility Specialist Salve Medica

DHEA is known as dehydroepiandrosterone (or prasterone in the US). It is a steroid hormone produced in the adrenal glands. It has many functions, but in fertility programs, it is a precursor to testosterone and estrogen. We use it in women who are expected to be poor responders and whose ovarian reserve is low. It is not beneficial to use it in normal responders.

DHEA improves the number of retrieved oocytes, the embryo quality, and thus – pregnancy rates. There is a new concept saying that it is the ovarian environment that influences the oocyte quality, and IVF treatment success rates. We use 75 mg of DHEA per day, in 3 doses. Generally, we should start the supplementation 6, 8, or 12 weeks before the beginning of ovarian stimulation with gonadotropin. However, it is said that 12 weeks is the shortest period during which DHEA should be supplemented.

Now, we have new ESHRE guidelines for ovarian stimulation that say it is not beneficial to use DHEA in women who are poor responders. However, we know that more than one-third of fertility centres still use this type of supplementation for their patients successfully. It is important to note that we are not 100% sure if DHEA has a beneficial impact on IVF or not. But as it is financially available to our patients, we use it to improve success rates as much as we can.

About this question:

Should you consider DHEA? How can dehydroepiandrosterone supplementation improve fertility?

In what cases DHEA is useful? Can it have a bad influence in some cases? How does it work, and who can benefit from it?

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