DHEA and IVF: Improving Fertility with DHEA
IVF & DHEA Supplement
DHEA supplementation for women with diminished ovarian reserve (or DOR) has revolutionized the practice of in vitro fertilization, since CHR introduced this treatment into fertility practice. It has vastly improved pregnancy outcomes for women who suffer from premature ovarian aging (or POA) as well as women over 40 whose ovarian reserve is declining as a part of the natural aging process. In fact, one of the earlier CHR studies on DHEA and female fertility showed an impressive doubling of pregnancy rates.
The use of DHEA supplementation leading up to, and during, IVF cycles was first introduced by CHR’s Dr. Norbert Gleicher and Dr. David H. Barad in 2004. Since then, CHR has been active in refining the treatment protocol and understanding the physiological mechanism of DHEA, ovarian reserve, and female fertility.
Which Patients Benefit?
At CHR, we typically prescribe 6-8 weeks of supplementation before cycle start for the following groups of women:
- All women over 40
- Younger women whose ovarian reserve parameters (such as FSH and AMH) indicate that they have DOR
The purpose here is to raise the androgen levels in the ovarian environment to its “youthful” normal range, which has been shown to improve the number and quality of eggs available for retrieval. Therefore, CHR physicians closely monitor the androgen levels while women are on DHEA supplements, and if the androgen levels do not reach the desired level, patients continue supplementation for longer than the typical 6-8 weeks until they are ready to start their IVF cycles.
How Many Weeks to Stay on Supplementation?
The purpose of DHEA supplementation in hypo-androgenic infertile women (i.e., women with infertility due to low androgen levels) is improvement of egg quantity and quality. Studies conducted at CHR and elsewhere have demonstrated that taking a DHEA supplement for at least 6-8 weeks is required before statistically significant improvements in female fertility can be observed. Peak effectiveness is typically reached between 16 and 20 weeks. However, as noted above, the length of time is not necessarily the best indicator--what matters is that the woman’s androgen (testosterone) levels rise to about the upper ⅓ of the normal range.
Where time is of the essence, experts initially recommended that fertility treatments be initiated after 6-8 weeks of DHEA supplementation, with the patients continuing supplementation uninterrupted until pregnancy (diagnosed based on rising hCG levels) or until patients decide to discontinue treatment attempts with use of their own eggs.
More recent recommendations, however, suggest that the timing of the start of a post-DHEA IVF cycle should not only be based on a pre-fixed interval of time with DHEA supplementation, but also on measured improvements in androgen levels from pretreatment baseline levels.
The principal reason for the latter recommendation was the observation that a small minority of women, mostly for a variety of genetic reasons, don’t convert DHEA to testosterone very well. Therefore, we cannot automatically assume that a sufficient length of supplementation always leads to satisfactory testosterone levels. This is why physicians at CHR look out for confirmed androgen level improvements in blood with concomitant declines in sex hormone binding globulin (SHBG), which usually goes into opposite direction to testosterone levels. It appears that women of African descent are more affected by poor DHEA-to-testosterone conversions than either Caucasian or Asian women.
When is the Best Time to Begin Treatment?
Egg Maturation Process and DHEA Effects during IVF
DHEA for IVF is most effective when eggs are going through the early stages of maturation in the ovary. In the image, these early stages correspond to the pre-antral follicle stage to early antral follicle stage, which can take 2-3 months.
Supplementation can be initiated at any time. The reason is that well-functioning ovaries constantly recruit fresh follicles out of the so-called resting follicle pool, to start a 3-4 months-long journey of maturation. The time periods when good testosterone levels are of crucial importance are the so-called small growing follicle stages, ranging from primary follicles to small antral follicles. If, at those stages, the microenvironment of ovaries does not offer follicles adequate testosterone levels, follicle maturation slows down, and even the follicles that are still maturing produce eggs of poor quality.
Small growing follicles require at least 6-8 weeks of further maturation before reaching the so-called gonadotropin-dependent stage, where they finally become responsive to fertility drugs and, therefore, available for retrieval in IVF cycles. This is the reason why pre-supplementation with DHEA must be initiated at least 6 weeks before an IVF cycle starts. If it is given for a shorter period or only during ovarian stimulation with fertility drugs, the follicles receiving the treatment benefits are still weeks or even months away from the gonadotropin-dependent stage of follicle maturation, and the follicles available in the current treatment cycle will not have received significant benefits from the supplementation.
How DHEA Supplementation Improves IVF Success Rates
DHEA’s beneficial effects on IVF pregnancy rates primarily come from the higher quality and quantity of eggs that women’s ovaries produce. Without intervention, women with diminished ovarian reserve tend to have a very small number of poor-quality eggs. Poor-quality eggs frequently fail to fertilize, and when they do fertilize, they often develop into poor-quality embryos that stop growing before embryo transfer, fail to implant, or stop developing in the uterus and end in miscarriages. Adding a DHEA supplement for at least 6-8 weeks before the start of an IVF cycle improves egg quality and results in overall better outcomes. These beneficial effects on the eggs appear to be exerted through androgen receptors that are on the cells—called granulosa cells—that surround and support the developing eggs.
DHEA is revolutionizing infertility care for older women and younger women with prematurely aging ovaries.
By exploring and understanding the physiological mechanism of follicle and egg development, and androgen’s effects on the process, CHR has been able to vastly improve IVF outcomes for women with DOR. Our center is now recognized as the “center of last resort” for women with severely diminished ovarian reserve, and as a result, 70% of our patients—who come from all over the world—are now 40 years or older, with about 40% of them being over 44. Practically all of our patients, even those in their twenties or thirties, have some degree of DOR. Even in this difficult-to-treat patient population, our center’s IVF pregnancy rates are quite remarkable, partially because of the way our physicians integrate DHEA supplementation into a comprehensive fertility treatment paradigm designed specifically for each individual patient.
Read more about DHEA Treatment
Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.