Ovarian reserve refers to the number of ovarian follicles (fluid-filled sacs) containing healthy eggs. In a spontaneous ovulatory cycle a single dominant follicle containing a single mature egg normally ovulates. However, ovaries of reproductive age women also contain a number of smaller follicles which can potentially grow and produce mature eggs. In general women with better ovarian reserve have higher success rate with in vitro fertilization.
Women whose ovaries possess good ovarian reserve typically respond to ovarian hyper-stimulation with FSH (What is Ovulation Induction?) by developing multiple growing follicles and mature eggs capable of establishing a healthy pregnancy. Women with reduced reserve typically develop very few follicles even with higher doses of FSH injections. Even more importantly, multiple studies have established that women with diminished ovarian reserve (DOR) are much less likely to achieve a live birth than women with other infertility factors when undergoing IVF and other fertility therapies.
The graph below clearly illustrates that women with diminished ovarian reserve (low reserve in red bar) had about half the live birth rates achieved by patients with most other diagnoses (adapted from the national CDC Reports on ART for 2004-08). Thus, next to the age factor, which itself is closely related to ovarian reserve (What is Age Factor?), reduction in ovarian reserve is the greatest determinant of the success of infertility treatment in women using their own eggs.
Live birth rate per IVF cycle start in women with different infertility factors
Accurate assessment of ovarian reserve may involve multiple hormonal tests as well as a high resolution vaginal ultrasound. Traditionally a baseline cycle day 2,3 or 4 FSH and Estradiol blood tests have been used to estimate ovarian reserve. FSH levels above 10 mIU/mL and/or Estradiol levels above 80 pg/mL are indicative of reduction in ovarian reserve. However, FSH/Estradiol levels tend to vary from one cycle to the next making interpretation tricky.
AMH (Anti-Mullerian Hormone) is secreted by the small follicles in the ovaries so it is more constant on different days of the menstrual cycle and and thus can be measured on any day in the cycle. AMH can be determined even in patients taking oral contraceptives, during pregnancy or breastfeeding. Thus AMH has rapidly gained popularity and is particularly useful in identifying women with PCOS who are at risk of ovarian hyperstimulation during IVF. AMH is of great value in women considering fertility preservation procedures such as egg cryo-preservation.
High resolution vaginal ultrasound of the ovaries provides the antral follicle count (AFC) which is an anatomical correlate of ovarian reserve. Unless small antral follicles are present within the ovaries, fertility medications cannot make them grow and the woman will not exhibit the multi-follicular response which is key to the success of IVF and other treatments.
Ovary without small antral follicles (reduced reserve)
Ovary without small antral follicles (reduced reserve)
On occasion a dynamic hormonal test known as clomiphene challenge may be helpful. In this test cycle day 2, 3 or 4 FSH/Estradiol are followed by oral clomiphene 100 mg daily on days 5-9 and the FSH/Estradiol tests are repeated seven days after the initial test. Under the stress of clomiphene (which is an anti-estrogen binding to estradiol receptors) the pituitary gland releases extra FSH hormone which in turn should hyper-stimulate ovaries possessing normal reserve to initiate production of several follicles each of which releases estradiol thus ultimately lowering the FSH level by cycle day 10. A significant percentage of women with diminished ovarian reserve exhibit normal day 3 FSH but markedly elevated day 10 FSH – a finding which carries similar prognostic implication to elevated baseline day 3 hormones, i.e. a much lower live birth rate regardless of the treatment.
The main reason for ovarian reserve testing is to define the exact likelihood of successful conception for each infertile couple so that they have best information in order to make an informed decision about different treatment options. In addition, the information may be of value in selecting ovarian stimulation regimen best suited for an individual patient. Women with severely reduced ovarian reserved, especially if it is associated with advanced age, are much more likely to achieve a successful birth using donor eggs (Donor Egg Program).