CHR's Prematurely Aging Ovaries Program
Here at CHR, we have a special interest in the “older women pregnancy and the aging ovary,” and have been conducting considerable research on this topic. Indeed, older women (those above age 38), and younger women with so-called prematurely aging ovaries (POA), will often find it harder to get pregnant. As reported in the CHR Voice, (our newsletter that provides ongoing updates on the progress of our research and our patients' results), we have been leading the way in exploring and implementing ways to treat prematurely aging ovaries
DHEA Beneficial Effects
The investigators at CHR have been using the mild male hormone dehydroepiandrosterone DHEA now for a number of years very successfully in women with diminished ovarian reserve (DOR), whether their ovarian impairment is due to advanced age or premature ovarian aging (POA). In doing so, we have been able to demonstrate that in such women DHEA supplementation has quite remarkable beneficial effects (see Table 1), which all can be summarized as rejuvenating ovarian function.
Table 1: EFFECTS OF DHEA IN WOMEN WITH DOR
Increases egg (oocyte) and embryo counts
Improves egg and embryo quality
Increases number of embryos available for embryo transfer
Increases euploid (chromosomally normal) embryos available
Speeds up time to pregnancy in fertility treatment
Increases spontaneously conceived pregnancies
Improves IVF pregnancy rates
Improves cumulative pregnancy rates in patients under treatment
Decreases spontaneous miscarriage rates
likely reduces aneuploidy (chromosomal abnormalities ) in embryos
Table 2: POSITIVE SIDE EFFECTS OF DHEA
Improved overall feeling
Improved sex drive
During all that time of DHEA use at CHR, we have carefully monitored side effects of the medication and have been impressed by how rarely even the most common side effects, such as oily skin, acne and hair loss, seem to occur.We, however, have been even more surprised that quite often what we really heard were anything but side effects; indeed, many more patients than complained about side effects, commented to us how much better overall DHEA supplementation makes them feel. Table 2 summarizes some of the specifics.Now comes a study, reported in the prestigious Journal of Clinical Endocrinology and Metabolism (Davis et al. 2008; 93:801-8), in which investigators from Australia report that DHEA appears to improve cognitive functions in women. Specifically, they noted that higher endogenous DHEA levels are independently and favorably associated with executive function, concentration and working memory. It seems our patients knew all along what they were talking about!
Overview of CHR's Research
We have known for quite some time that many centers around the world have routinely started using DHEA. One of these centers has been Toronto West Fertility Associates, in Toronto, Canada. We have intermittently heard from them that anecdotally they had similar results to ours, but last December they were kind enough to send us their whole, meticulously kept data bank on DHEA usage at their center.Their pregnancy experience results were, indeed, very similar to ours. What we, however, were most interested in this time was not pregnancy, but miscarriage rates. As we have repeatedly noted in our UPDATEs, we have come to believe that DHEA supplementation may reduce the number of chromosomally abnormal embryos (aneuploidy). We reached this conclusion after making two observations: (1) In a small number of women who underwent PGD after they had been treated with DHEA, we found lower aneuploidy rates than in women without DHEA supplementation. Unfortunately, women in need of DHEA usually have small embryo numbers and, therefore, only very rarely qualify for PGD. This kind of data accumulation is, therefore, very slow and we so far have not reached statistically robust enough numbers. (2) Our second, related observation was that we noted a surprisingly low miscarriage rate in DHEA pregnancies.
Since miscarriages, especially in older women, are mostly due to chromosomal abnormalities, this observation, too, suggested the possibility that DHEA may reduce aneuploidy rates. To reach statistically robust conclusions, once again relatively large (pregnancy) numbers were required and we therefore, up to this point, have been cautious to not over interpret our own data.This is why the timing of the arrival of the Toronto data was so exciting; these data not only confirmed the high pregnancy rate in very unfavorable patients with diminished ovarian reserve, but demonstrated an identical reduction in miscarriage rate to the one observed by us (when compared to national IVF data). Since the combined data sets between CHR and the Toronto center involve an adequate size patient sample, we are now confident to state that DHEA supplementation significantly decreases the miscarriage rate in women with diminished ovarian reserve.Indeed, we even can go beyond this statement: While a reduction in miscarriage rates is seen in women of all ages, the reduction is smaller in women below age 35 than in women above age 35 years, where the reduction often exceeds 50 percent. This, of course, should not surprise since miscarriages are known to increase with advancing female age. Most of these miscarriages are, however, due to aneuploidy and this observation brings us back to where we started from: Our new data, on the decrease in miscarriage rates after DHEA supplementation especially in older women above age 35, strongly support that DHEA, indeed, reduces chromosomal abnormalities (aneuploidy rates) in embryos.The importance of this observation cannot be overemphasized. Since older women represent in the USA the most rapidly growing age group of women having babies, our findings may have significance far beyond those older women who require fertility treatment. Indeed, if confirmed by further studies, DHEA may become a supplement to be given, like prenatal vitamins, to all (older) women contemplating pregnancy.
Treatment history summary - 2007
Probably the most exciting news in our continuous efforts to investigate the beneficial effects of DHEA supplementation on the ovary, is that the prospectively, double blinded, randomized study, which we started at the beginning of the year in collaboration with a number of European centers, is progressing well. Our European colleagues are, indeed, succeeding in enrolling patients into this placebo-controlled trial and we expect, at least preliminary results, by year end.Since this study was formally registered as a clinical trial, we received innumerable requests from U.S.-based women to participate. Unfortunately, this study is, for cost reasons, only conducted in Europe. Patients, who wish to be considered for DHEA treatment in the U.S., have to become our patients. The potential advantage here, of course, is that you do not run a 50% risk of being treated with placebo.Those of you, who have recently looked at CHRs 2006 IVF cycle outcomes, will already be fully aware of the dramatic improvement we experienced in pregnancy rates in women above age 40. With an overall clinical pregnancy rate of 23.5% in women at ages 40-45, we in statistically significant terms exceeded our pregnancy rates in these age groups for the years 2003-2005. The only change that had taken place in 2006 was the addition of DHEA supplementation in a systematic way to all women who had failed at least one prior IVF attempt. All in all, only 43% of women above age 40, therefore, received DHEA supplementation; yet, pregnancy rates still improved dramatically.Based on these findings, we have now instituted DHEA supplementation for all women above age 40. As a consequence, we fully expect a further improvement in our 2007 pregnancy rates in women of these age groups. Our second declared goal for the year 2007 is to expand our treatment successes in older women beyond age 45. We, therefore, encourage older women, above that age, who are still interested in pursuing conception with their own oocytes, to contact us. We have gotten very close to breaking the 46-year barrier, but are so-far still approximately one month shy.Our third goal for the year is to attempt DHEA supplementation in women with outright premature ovarian failure (POF). Amongst women with POF, some still demonstrate significant follicular activity, though their follicles fail to mature. Such patients now can be identified via their anti-Mullerian hormone levels and we suspect that, in these selected cases, DHEA may be helpful. Whether this, indeed, will be the case is, at the present time, still unknown; but we feel it is worthwhile investigating.
There are many more studies here,
7 years ago