Should you consider DHEA? How dehydroepiandrosterone supplementation can improve fertility?
In what cases DHEA is useful? Can it have bad influence in certain cases? How does it work and for whom it’s advised?
All of it is explained by our experts in 3on1 #IVFANSWERS:
- Dr Ruth Sánchez – Gynecologist at PreGen, The Reproduction Unit at Clinica Vistahermosa
- Dr Bogna Sobkiewicz – Fertility Specialis at Salve Medica
- Dr Iryna Kotsiubska – Head Doctor, obstetrician-gynaecologist Parens IVF Center
Answer from embryologist Sánchez
DHEA an endogenous steroid originated in the reticularis zone of the adrenal cortex and in 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 a 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 the 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 prior to 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 prior to 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 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 prior to 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 Dr Sobkiewicz
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 has influence on 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 with 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 beneficial impact on IVF or not. But as it is financially available to our patients, we use it in order to improve success rates as much as we can.
Answer from Dr Kotsiubska
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 prior to starting the IVF cycle for all women over 40 and 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 no reach the desired range, the patient stays on the DHEA supplementation for longer.
The purpose of DHEA supplementation in hypo-androgenic infertile women is 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 on 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 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 IVF cycle start.
DHEA supplementation is contraindicated in patients with the history of sex hormones sensitive cancers such as breast, ovarian, endometrial and in patients with PCOS. DHEA fertility research and clinical experience have demonstrated that the 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 IVF cycle start improves egg quality and results in overall better IVF outcomes.