Ovarian Reserve Testing for Prognosis

ReproSource. This commercial publication has been modified for this web site. The application of this assay to an individual patient should be discussed with her physician. The test may be of interest to women in their early to mid 30’s who are considering when to have a baby. A normal test result may be reassuring for the time being.In an IVF clinic, this test will be most useful before going through the first cycle of treatment. It gives an index number based on blood hormone levels which are known to relate to the likelihood of success. The test is based on comparing test results to outcomes in numbers of eggs retrieved at the time of IVF. It explains that the FSH test, the AMH and inhibin tests are all measuring different indirect biochemical aspects of ovarian reserve. The report takes all the data from these tests, factors in the woman’s age and produces a single number. This index number is called the Egg Retrieval ScoreTM and the higher the score up to 20, the better. Some patients will have unexpectedly low scores. This information could influence the treatment plan by the physician and modify expectations on the part of the patient.An advantage of the test is that it does not vary widely from month to month. Just as important is the fact that it is done in a national standardized lab. The FSH and other tests vary in results from lab to lab. This has been a problem for years. Another test of ovarian reserve is the antral follicle count, a count by ultrasound of the early follicle numbers which is another indicator of the potential to become pregnant from IVF treatment. See the Antral Follicle Count article on this web site regarding prognosis for more information.

More Babies…sooner through proactive diagnostics

The Ovarian Assessment Report™ (OAR)
The New Standard for Ovulatory Egg Supply Testing

A growing need for proactive egg supply assessment

The vast majority of women have sufficient eggs to have their own children before the age of 30, but subsequently, it is highly variable when an individual’s egg supply is depleted.   Women often wait too long to address their inability to conceive and miss their window for a successful treatment with reproductive technologies.  Without an easily available test for assessing egg supply, women have had to make decisions about when to have children with little or no information about their personal risk of depleted egg supply.  Woman experiencing difficulty having children can benefit from earlier proactive testing that can identify their risk for poor egg supply allowing these women to get help before it is too late.The OAR: a new, more accurate diagnostic for ovulatory egg supply; based upon two scientific breakthroughs:

1) Ovarian follicles discovered to produce hormones measurable in blood

AMH (Anti-Müllerian) hormone and Inhibin B are produced in the ovaries by the egg-bearing follicles 1-3.  Several recent clinical studies show that the blood levels of these hormones relate directly to the remaining egg supply 4-7. ReproSource, in collaboration with international leaders in fertility medicine, has helped solidify the link between these hormones and egg supply in the fertile and infertile populations.

2) Mathematical formula provides superior accuracy

The OAR provides the most accurate available assessment of a woman’s ovulatory egg supply using a single blood sample.  The OAR combines age with blood serum levels of various ovary related hormones such as AMH and FSH into a proprietary mathematical algorithm to provide the Egg Retrieval Score (ERS) which has been calibrated to the most definitive available measure of ovulatory egg supply: number of eggs retrieved through ovarian stimulation.Indications:  Any woman who is:

  • experiencing infertility
  • being evaluated as a potential egg donor
  • considering egg preservation

The Biology Behind The Breakthrough

Unlike FSH, AMH and Inhibin B are directly related to egg supply

FSH is a hormone from the pituitary gland and its measurement of ovarian function is very indirect. Previously, FSH was the only widely available test in use for assessing egg supply, despite the fact that it has poor accuracy and usually is only abnormal once a woman has significantly depleted her egg supply.  Recent discoveries have revealed that the hormones AMH (anti-Müllerian hormone) and Inhibin B are secreted by the granulosa cells that surround each egg in the young follicles.  For the first time, blood measurements that directly assess egg supply are now possible.

AMH and Inhibin B provide different information

AMH is named for its role in embryonic development which prevents the female system from developing in males.  Research has shown that AMH is also produced by ovarian follicles first by the single layer of flattened pre-granulosa cells surrounding the egg at the primordial follicle stage.  AMH production is thought to be fairly constant from the granulosa cells in each follicle until ceasing when a follicle reaches the pre-antral stage 9. Inhibin B expression is believed to begin later as follicle begins to grow10.  Inhibin B is thought to provide a more functional assessment of the egg pool as it is produced by follicles only in response to FSH and therefore may demonstrate the potential of the eggs to perform as expected.

The OAR™ Algorithm  –  Greater Accuracy, Greater Reliability

The Egg Retrieval Score (ERS), compared with other tests such as FSH, AMH or Inhibin B, has superior accuracy in predicting “ovulatory egg supply” (the supply of eggs available for ovulation).  Using number of eggs per retrieval from 454 egg retrievals from 244 women (including 79 egg donors, 26 female partners of males requiring TESA, and 139 infertile women), an analysis  demonstrated superior sensitivity and specificity of the ERS in identifying women with 4 eggs or fewer retrieved.

The Research Behind the OAR™: Egg Retrieval Score Predicts Egg Supply

Objective: Establish the Egg Retrieval Score™, an index value which combines age with blood levels of AMH, inhibin B, FSH, and estradiol, as a useful predictor of egg supply.
Methods: Under IRB approval, frozen menstrual cycle day three serum samples along with  medical information were obtained from 283 women undergoing 454 egg retrievals following ovarian stimulation..  The test population included women likely to have excellent egg supply (79 egg donors and 26 female partners of men with azoospermia) as well as women with possible poor egg supply (139 infertile women).  Samples were sent to ReproSource for determination of AMH, inhibin B, FSH, LH, and estradiol levels.  Laboratory results with Egg Retrieval Scores and corresponding clinical outcomes data were analyzed.
Results/Conclusions:  The Egg Retrieval Score™ is highly correlated with the number of eggs obtained through ovarian stimulation and can be a useful tool for initial ovarian assessment of women being considered for this procedure.

The Ovarian Assessment Report™: The Complexity of Ovarian Reserve Made Patient Friendly

The results of the tests are plotted on a chart with age. The results are categorized according to the chances to obtain at least 5 eggs at retrieval after IVF. The scale ranges from reduced to excellent.  An example is:

References

1. de Vet, A., et al., Antimüllerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril, 2002. 77(2): p. 357-62.2. Fanchin, R., et al., Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. Hum Reprod, 2003. 18(2): p. 323-7.3. van Rooij, I.A., et al., Serum anti-Müllerian hormone levels: a novel measure of ovarian reserve. Hum Reprod, 2002. 17(12): p. 3065-71.4. Bancsi, L.F., et al., Predictors of poor ovarian response in in vitro fertilization: a prospective study comparing basal markers of ovarian reserve. Fertil Steril, 2002. 77(2): p. 328-36.5. Erdem, M., et al., Comparison of basal and clomiphene citrate induced FSH and inhibin B, ovarian volume and antral follicle counts as ovarian reserve tests and predictors of poor ovarian response in IVF. J Assist Reprod Genet, 2004. 21(2): p. 37-45.6. Fabregues, F., et al., Ovarian reserve test with human menopausal gonadotropin as a predictor of in vitro fertilization outcome. J Assist Reprod Genet, 2000. 17(1): p. 13-9.7. Ficicioglu, C., et al., The role of inhibin B as a basal determinant of ovarian reserve. Gynecol Endocrinol, 2003. 17(4): p. 287-93.8. Leader, B et al ?Ovarian Reserve Index (ERS) predicts number of oocytes at retrieval in fertile and infertile women? Abstract submitted ESHRE 2008.9. Feyereisen, E., et al., Anti-Müllerian hormone: clinical insights into a promising biomarker of ovarian follicular status.Reproductive Biomedicine Online, 2006. 12(6): p. 695-703.10. Wang, Y., et al., Gonadotropin control of inhibin secretion and the relationship to follicle type and  number in the
hpg mouse. Biol Reprod, 2005. 73(4): p. 610-8.11. http://www.fda.gov/cdrh/oivd/guidance/1610.pdf.  (last accessed:  1/29/2008)