If you have been diagnosed with high FSH, often doctors view this as predictor of depleted ovarian reserve and poor egg quality. This article focuses its’ research behind the correlation of high FSH and miscarriage. Modern medicine believes most early miscarriages (i.e.: chemical pregnancies or miscarriages within the first several weeks) are related to aneuploidy resulting in DNA fragmentation and chromosomal defects.
What is aneuploidy and why is it important? (From the website www.ourstolenfuture.org)
Aneuploidy is an error in cell division that results in the "daughter" cells having the wrong number of chromosomes. In some cases there is a missing chromosome, while in others an extra.
Most cases of "meiotic" aneuploidy result in spontaneous miscarriage of the fetus. Babies that survive to birth after aneuploidy have birth defects, including Down Syndrome. Meiotic aneuploidy causes 10-20% of birth defects in people. Another type of aneuploidy, "mitotic" aneuploidy, is associated with virtually all solid tumor cancers.
Having the correct number of chromosomes in a cell is key, because chromosomes contain the body’s DNA, and DNA is the chemical in which genes are encoded. When a cell is missing a particular chromosome, or has an extra copy, it doesn’t have the proper mix of genes. Many cellular errors result, with the details depending upon which chromosome is absent (or present in surplus).
I often experience that clients are informed their FSH is elevated will result in poor egg quality and their reoccurring miscarriage. The researchers (of the below article) came to an important theory; high FSH (especially in women under the age of 35) is not reliable indicator of poor egg quality. From a Chinese medicine view, high FSH is only an indicator of an energetic imbalance and the hormonal elevation is improperly cueing follicular recruitment and growth. But yet there is a chance (with treatment) to lower FSH and improve hormonal cues for conception. Eastern medicine views conception as delicate interaction between many hormones, nutrients, and organ function – something not solely based on one hormone. As new research discovers how complicated the body is, maybe modern medicine will not base all assumptions on one player.
Basal follicle-stimulating hormone as a predictor of fetal aneuploidy
Fertility and Sterility December 2008 Volume 9
Jamie A.M. Massie, M.D., Richard O. Burney, M.D., Amin A. Milki, M.D., Lynn M. Westphal, M.D., Ruth B. Lathi, M.D.
The risk of fetal aneuploidy increases with advancing maternal age, and the majority of this risk is believed to be secondary to errors arising at meisois I in the oocyte. Two prominent theories have developed to explain this observation—one highlights the influence of chronologic ovarian aging, whereas the “limited pool hypothesis” emphasizes the role of biologic signals on ovarian aging. Several lines of evidence support the impact of chronologic ovarian aging on fetal aneuploidy risk. Meiotic error rates in oocytes are higher in women with advancing maternal age, a finding that may result from the prolonged time that oocytes spend arrested in meiosis I before ovulation. Meiotic spindle morphology has also been found to change deleteriously with advancing maternal age.
Finally, the risk of maternal sex chromosome nondisjunction increases with maternal age.
On the other hand, the limited pool hypothesis holds that ovarian aging rather than chronologic aging contributes to fetal aneuploidy risk. This concept was first proposed by investigators who noted that unilateral oophorectomy in mice not only advanced cessation of reproduction, but also increased the incidence of trisomic offspring. The human correlate to this observation in mice would imply that women conceiving trisomic pregnancies experience menopause at an earlier age than the population at large. Women with a known trisomic pregnancy enter menopause about 1 year earlier than do those with a chromosomally normal index pregnancy. Likewise, mothers of Down syndrome individuals were significantly more likely than controls to have a reduced ovarian complement, either as a result of ovarian surgery or because of congenital absence of one ovary.
The treatment of infertility and reduction of aneuploidy risk require an ability to identify the highest quality oocytes. Several modalities currently exist for evaluating oocyte quality after retrieval, including early embryonic cleavage, multinucleation, morphology of the polar body, and preimplantation genetic diagnosis. Unfortunately, a reliable, noninvasive predictor of oocyte quality before oocyte retrieval has yet to be identified.
An elevated basal FSH concentration is used clinically as a marker for diminished ovarian reserve. Yet, the correlation between basal FSH and oocyte quality is less clear. It has been hypothesized that increased FSH levels toward the end of reproductive life may correlate with the increased aneuploidy rates seen in oocytes retrieved from older women. Elevations in basal FSH levels are also seen in younger women whose reduction in oocyte pool is a result of premature ovarian failure (POF). A role for basal FSH as a marker of oocyte quality in these populations has been suggested. An age-independent relationship between elevated basal FSH level and reduced oocyte quality/aneuploidy risk would lend support to the limited pool hypothesis. Clinically, such an association would impact the preconceptual counseling of the younger patient with an elevated basal FSH as to her miscarriage and fetal aneuploidy risks.
In this study, we sought to determine whether an elevated basal FSH concentration is an independent predictor of fetal aneuploidy, as assessed by karyotyping of spontaneous abortions (SAB).
Analysis revealed basal FSH not to be independently predictive of an aneuploid gestation when analyzed as a continuous variable. However, when analyzed as a categorical variable, basal FSH ≥14 mIU/mL was found to be significantly associated with karyotypically normal pregnancies (P=.029). When maternal age was evaluated as a continuous variable, no statistically significant association with fetal aneuploidy was identified. However, when advanced maternal age was analyzed as a categorical variable (age ≥35 years), the association with fetal aneuploidy nearly reached statistical significance (P=.064). A separate analysis including 46XX karyotypes in the euploid group was also performed and no significant association between basal FSH and aneuploid gestation was demonstrated (data not shown).
This study was designed to determine whether an elevated basal serum FSH level is associated with fetal aneuploidy risk. Because maternal age has a known association with increased meiotic error rates, as well as gradually increasing FSH levels, we sought to determine whether FSH acts as an independent marker for increased aneuploidy risk. Using a cutoff of 35 years, a nearly significant association between advanced maternal age (≥35 years) and increased fetal aneuploidy rate was found (P=.064), a trend consistent with other studies.
Other studies have assessed the value of basal FSH as a marker for oocyte quality as measured by fetal aneuploidy. The results of these studies suggested an inverse relationship between basal FSH and oocyte quality, with a significantly greater proportion of age-matched women with abnormally elevated FSH values experiencing miscarriages with abnormal fetal karyotypes. Other investigators have reported an increased risk of Down syndrome in women with elevated basal FSH concentrations measured preconceptually. These studies would seem to support the limited pool hypothesis of ovarian aging, in that diminished ovarian reserve and advanced biologic ovarian aging are better predictors of aneuploidy risk than is chronological age.
However, more recent studies contradict this conclusion. Havryliuk et al showed no correlation between basal FSH level and fetal trisomy risk in poor prognostic IVF patients. A separate study found that premature decline in ovarian function, as evidenced by history of ovarian resistance or an elevated basal FSH level, was not associated with an increased risk of aneuploidy. Other investigators have reported basal FSH to be particularly poor at predicting aneuploidy risk in younger women. In sum, it appears that elevated basal FSH concentration is a consistent marker for decreased ovarian reserve, but a poor indicator of oocyte quality, especially in younger women with premature decline in ovarian reserve.
Interestingly, our study revealed that spontaneous abortuses in women with a basal FSH level of ≥14 mIU/mL were more likely to be euploid (5/27) than aneuploid (6/107), and this finding reached statistical significance (P=.029). Logistic regression treating both basal FSH and maternal age as categorical variables (cutoffs as discussed previously) confirmed an association between elevated basal FSH and euploid karyotype of miscarriage products. Thus, women with a basal serum FSH ≥14 mIU/mL who conceive and experience miscarriage are less likely to have conceived an aneuploid gestation. A subset analysis was attempted to further investigate this finding; however, due to small sample size, no meaningful conclusions could be reached. It is possible that factors other than fetal aneuploidy were responsible for miscarriages within in this group. Such factors could include immunologic, endocrine, and hematologic processes not accounted for within the scope of this study.
An elevated basal FSH level has been associated with recurrent pregnancy loss and this association was assumed to be consequent to an increase in fetal aneuploidy. Yet our findings suggest that an elevated basal FSH level may be associated with an abnormality not detectable by conventional karyotype or an altogether nongenetic (i.e., hormonal) abnormality that deleteriously impacts fecundity.
In summary, our data do not appear to support the hypothesis that a reduced oocyte pool is associated with an increased meiotic error rate. Continued investigations to identify reliable, noninvasive methods for predicting oocyte and fetal aneuploidy are necessary.