There is much debate in the fertility profession about the inhibin hormones, which could be an indicator of egg abundance and quality. Research has found Inhibin B to be an good indicator of the number of follicles recruited for the current menstrual cycle. The higher Inhibin B is, the great number of follicles is present for selection to become the dominant follicle at ovulation.
Currently there is much contemplation about how to integrate Inhibin B into the baseline testing. According to Resolve the FDA has not approve the test and the test is only offered by a few laboratories due to how complicated it is. Plus, doctors have varying interpretations of Inhibin B baselines and what determines normal secretion.
What is Inhibin A? Inhibin A is a hormone is secreted by the corpus luteum and regulates the pituitary from releasing follicle stimulating hormone (FSH) during the luteal phase. The hormone decreases the secretion of FSH to stop follicular recruitment and ovulation during the luteal phase. Thus inhibin A is low in the early follicular phase and rises rapidly with ovulation, peaking during the midluteal phase. As the corpus luteum degrades late in the luteal phase, Inhibin A will decrease allowing the pituitary to increase the secretion of FSH.
What is Inhibin B? Inhibin B is a hormone is secreted by the early antral follicles during the early part of the menstrual cycle and into the development/selection of a dominant follicle. The hormone is secreted by the follicular granulosa cells in response to FSH/LH. Inhibin B regulates the pituitary to decrease FSH, allowing the selection of a single dominant follicle. During the menstrual cycle inhibin B will be low since the follicles are not mature and less granulosa cells are present. As FSH increases and follicles mature, granulosa cells proceed to multiply resulting in a rise in inhibin B. Research has found Inhibin B levels are level with estradiol secretion in the pre- and perimenopausal years and they reflect follicular function.
From a Chinese point of view, Inhibin is yin in nature and balances the yang nature of FHS. For fertility to be successful, yin must strong and abundant before yang can activate the growth of a follicle. If the follicles are like flowers, FSH would be the sunshine that encourages the flower to bloom. Inhibin would act as cloud cover when the moisture (being consumed by the sunshine) is depleted. As FSH warms the flower, inhibin would signal to cover the sun to stop the flower from wilting (i.e.: too many follicle or early ovulation). As women age the lower quality follicles are poorly formed flowers, which the body believes require more sunshine to grow. Yet, as the sun bakes the flower, all the moisture leaves it. Without moisture the flower can not open and be receptive for pollination. Dryness would be a sign in (especially in an older woman) that decreased yin has affected the quality of the DNA and it will be harder to conceive.
It’s interesting that “Inhibins levels after stimulation by exogenous FSH did not reflect fertilization that resulted in high quality embryos”. Why? Well from a Chinese view, inhibin and FSH play a balancing act between yin and yang, which is easily thrown off by aggressive stimulation. If a woman does not have enough yin stored in her body, the yang in FSH can produce follicles but ones which are dry can not form into embryos.
Anti-Müllerian hormone substance from follicular fluid is positively associated with success in oocyte fertilization during in vitro fertilization
Fertility and Sterility, March 2008
Chie Takahashi, MD and all
Anti-Müllerian hormone (AMH), also known as Müllerian inhibiting substance, has become known as one of the most important markers of ovarian reserve. Anti-Müllerian hormone is a member of the transforming growth factor-beta (TGF-β) superfamily. The TGF-β superfamily members inhibin A, inhibin B, and activin are related to ovarian follicle development. Furthermore, it has become clear that AMH also plays an important role in ovarian function, especially follicle development and follicle selection. In females, the ovaries produce AMH after 36 weeks’ gestational age. In ovaries from adult rats, the colocalization of AMH and anti-Müllerian hormone receptor II (AMHR II) messenger RNA (mRNA) in the granulosa cells of specific follicle types suggest that the actions of AMH via AMHRII are autocrine in nature. Both AMH and AMHRII mRNA are expressed mainly by granulosa cells of preantral and small antral follicles. Corpora lutea, large antral follicles, primordial follicles, oocytes, and thecal and interstitial cells express little or no AMH or AMHRII mRNA. After menopause, AMH and AMHRII mRNA expression decreases.
Age, serum basal follicle-stimulating hormone (FSH) levels, and serum basal estradiol (E2) levels are known as markers for ovarian reserve. Antral follicle count, serum inhibin B levels, and ovarian volume have also been studied as markers of ovarian reserve. It has been reported that AMH is strongly associated with ovarian follicular development, and may be a new marker for ovarian aging, since levels correlate with the number of antral follicles and age. AMH levels evaluated in patients with premature ovarian failure were significantly lower (or undetectable). Levels of AMH significantly decrease over time in young normal ovulatory women, whereas other markers associated with ovarian aging do not change.
AMH levels are useful for predicting ovarian response in women undergoing IVF treatment. Lack of success in IVF, indicative of a diminished ovarian reserve, is associated with reduced AMH concentrations. Under the stimulated cycle for IVF, AMH levels are strongly related to the number of retrieved oocytes. AMH levels may positively correlate with ovarian response in IVF treatment, but whether AMH is a prediction factor for pregnancy is unknown. Some studies have reported that AMH can predict pregnancy, but others have reported that it cannot. Moreover, there have been few studies on the correlation between follicular fluid (FF) AMH levels and follicle quality. One study reported a possible association between AMH and follicle quality. Our study was designed to investigate whether AMH levels from follicular fluid and serum on the day of oocyte retrieval are associated with successful fertilization for IVF.
Patients
Serum samples were collected on the day of oocyte retrieval. The follicular fluid was not collected from follicles if the follicular diameter was less than 17 mm. We selected one follicular fluid sample from a single follicle in each patient. The follicular fluid samples were obtained from the largest follicle up to 24 mm in diameter.
Group 1: 21 patients comprised samples from patients whose oocytes from follicular fluid samples achieved fertilization, and we examined the follicular fluid of the follicle from which the obtained oocyte had achieved fertilization.
Group 2: 12 patients comprised samples from patients whose oocytes from follicular fluid samples did not achieve fertilization.
Results
There were no statistically significant differences between the fertilized (group 1) and the nonfertilized group (group 2). Moreover, there was no difference in the fertility evaluations between the two groups. There were no differences between the two groups in the number of follicles and oocytes, the average diameter of follicles, and hMG/FSH administration days. The concentrations of estradiol, progesterone, FSH, and inhibin B in serum and follicular fluid measured on the day of oocyte retrieval have no significant difference.
Discussion
We showed that the AMH levels in follicular fluid from women undergoing IVF whose oocytes became fertilized were statistically significantly higher than in the follicular fluid of those whose oocytes did not become fertilized. In our study, there was no statistically significant difference between the fertilized and the nonfertilized groups in inhibin B and estradiol levels in follicular fluid. These results suggest that AMH plays a more important role in the development and fertilization of oocytes than either inhibin B or estradiol.
Markers from follicular fluid that directly indicate embryo quality have not been discovered. Elevated follicular fluid levels of inhibin B and estradiol have been reported to be associated with ovarian response, high quality of oocytes, and high fertilization and pregnancy rates, but the reverse also has been reported by some studies. In our study, the follicular fluid levels of inhibin B, estradiol, and progesterone were not statistically significantly different in the fertilized group and the nonfertilized group. The follicular fluid levels of inhibin B, estradiol, and progesterone also may not be sensitive markers for predicting embryo quality.
We found no statistically significant correlation between serum AMH on the day of oocyte retrieval and the ratio of the formed high quality embryo. The quality of the embryo is an important predictor for IVF treatment, as high quality embryos lead to a high pregnancy ratio. In serum, basal AMH levels from the early follicular phase have been reported to be a predictor of follicular quality during controlled ovarian stimulation in IVF treatment. The result in our study indicates that serum AMH levels do not reflect high quality fertilization after stimulation by exogenous FSH.
We also found no statistically significant correlation between serum AMH levels after stimulation by exogenous FSH on the day of oocyte retrieval and the number of the oocytes, though serum basal AMH has been recognized as a positive marker of ovarian response in IVF stimulation. However, serum estradiol and inhibin B levels on the day of oocyte retrieval statistically significantly correlated with the number of the oocytes. These results indicate that exogenous FSH does not positively correlate with serum AMH levels, but estradiol and inhibin B do strongly, positively correlate with exogenous FSH.
The mechanism of association between AMH and growing follicles is complicated and still unclear, although many reports have been published. It has been reported that serum basal AMH levels among stimulated IVF patients correlated highly with the number of antral follicles and the numbers of oocytes retrieved. There is a negative relationship between serum basal AMH levels and poor ovarian response. In another study, serum basal AMH levels were found to be higher in patients with five or more retrieved oocytes than in patients with fewer than five. However, it is clear that one of the roles of AMH is as an inhibitor of follicle recruitment; AMH directly inhibited follicular growth during these early stages of primordial folliculogenesis.
The mechanism of AMH secretion is different in a normal ovulatory cycle and during FSH stimulation in an IVF cycle. A recent study demonstrated that AMH levels were mainly constant throughout a normal menstrual cycle.
Many reports have showed that serum basal AMH levels correlate positively with the number of follicles after FSH stimulation during an IVF cycle. It has been reported that exogenous FSH administration causes a significant reduction in AMH levels. During the luteal phase, under controlled ovarian hyperstimulation, AMH levels initially decline, presumably as an effect of follicle luteinization, and then increase during the midluteal phase. Our study found that serum AMH after FSH stimulation did not correlate with the number of follicles and oocytes, though serum inhibin B and estradiol strongly correlated with these. These results would indicate that exogenous FSH may have some effect on AMH in folliculogenesis, but there is no distinct correlation between exogenous FSH and AMH.
Our study found that follicular fluid AMH appears to be an important indicator of fertilization. High follicular fluid AMH levels positively correlated with successful oocyte fertilization, which indicates that follicular fluid AMH may play a more important role in the development of oocytes and fertilization than inhibin B, estradiol, or progesterone. However, the serum AMH levels after stimulation by exogenous FSH did not reflect fertilization that resulted in high quality embryos.