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. DHEA supplementation 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.

CHR Explains

The use of a DHEA supplement prior to and during IVF cycles was introduced by CHR’s Dr. Norbert Gleicher and Dr. David H. Barad in 2004. Since then, CHR has been active in refining the DHEA IVF treatment protocol and understanding the physiological mechanism of DHEA, ovarian reserve, and female fertility.

Which Patients Should Use DHEA Supplement for IVF?

At CHR, we typically prescribe 6-8 weeks of DHEA supplementation prior to starting IVF 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 diminished ovarian reserve

The purpose of DHEA supplementation 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 supplement, and if the androgen levels do not reach the desired level, patients stay on DHEA supplementation for longer than the typical 6-8 weeks before they start their IVF cycles. One of the earlier CHR studies on DHEA and female fertility showed an impressive doubling of IVF pregnancy rates after DHEA supplementation.

How Many Weeks Does DHEA IVF Treatment Last?

The purpose of DHEA supplementation in hypo-androgenic infertile women is improvement of egg quantity and quality. Studies conducted at CHR and elsewhere have demonstrated that taking a DHEA supplement for at least 6 weeks is required before statistically significant improvements in female fertility can be observed. Peak effectiveness is typically reached between 16-20 weeks of DHEA supplementation. However, as noted above, the length of time is not necessarily the best indicator--what matters is that the woman’s androgen levels rise to about the upper ⅓ of the normal range.

Where time is of the essence, experts initially recommended that fertility treatments, like in vitro fertilization (IVF), be initiated after 6-8 weeks of DHEA supplementation, with the patients continuing supplementation uninterrupted until pregnancy (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, poorly convert DHEA to testosterone. One, therefore, cannot automatically assume that even excellent DHEA supplements always lead to satisfactory DHEA and testosterone levels within 6 weeks, and must rely on confirmed androgen level improvements in blood with concomitant declines in sex hormone binding globulin (SHBG) (which usually goes into opposite direction to testosterone levels). 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 DHEA IVF Treatment?

Egg Maturation Process and DHEA Effects during IVF

FSH promotes oocyte maturation

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.

DHEA supplementation can be initiated at any time. The reason is that 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 for maturing follicles 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 still maturing follicles produce eggs of poor quality.

Small growing follicles still 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, therefore, available in IVF cycles. This is the reason why pre-supplementation with DHEA must be initiated at least 6 weeks before IVF cycle start. If a DHEA supplement is given for shorter periods or only during ovarian stimulation with fertility drugs, the follicles receiving the treatment benefits are still weeks to months away from the gonadotropin-dependent stage of follicle maturation, and the follicles available in that DHEA IVF 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 produce in IVF cycles. 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 IVF cycle start improves egg quality and results in overall better IVF outcomes.

"DHEA is revolutionizing infertility care for older women and younger women with prematurely aging ovaries."

Center For Human Reproduction: Dr. Norbert Gleicher, best fertility specialist in the US Dr. Norbert Gleicher

CHR's recent DHEA fertility research and clinical experience have demonstrated that DHEA supplementation works by raising androgenandrogen levels in the ovaries to the normal level needed for healthy egg development. Based on this observation, CHR now starts IVF cycles after androgen levels rise to the appropriate levels with DHEA supplementation, in order to ensure that the eggs that are maturing for the DHEA IVF cycles have had a chance to develop in an androgen-rich environment.

By exploring and understanding the physiological mechanism of follicle and egg development and DHEA/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

infertility physician

Norbert Gleicher, MD, FACOG, FACS

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, 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.

Follow Dr. Gleicher on LinkedIn Center for Human Reproduction: Follow us on Google+. IVF center with best fertility options for each infertility patient. or watch his videos on YouTube Center for Human Reproduction: Follow us on Google+. IVF center with best fertility options for each infertility patient.

Last Updated: April 22, 2019

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