Diminished ovarian reserve Flashcards
Bologna classification
2 of the following characteristics to be considered a poor responder:
-Maternal age 40+ or other RFs for poor response e.g. excision of bilateral endometriomas
-Poor response in previous cycles with retrieval of 3 or less oocytes in a conventional stimulation protocol (or a cancelled cycle for poor response)
-Low AFC <5-7 follicles or low AMH (<3.5-8pmol/L)
OR two previous episodes of poor ovarian response after maximal stimulation.
Poseidon criteria
Patient orientated strategies encompassing individualised oocyte number
Newer classification system
Moves from a concept of poor ovarian response to poor prognosis patients
Aims to stratify low prognosis patients on the combination of quantitative and qualitative parameters
Female age and egg quality, rates of aneuploidy etc make these groups more homogenous rather than the Bologna which is a heterogenous population of ‘poor responders”
Group 1 Poseidon
“Good reserve, good quality”
<35 years, AMH >8.6pmol/L or AFC >5
Type a) <4 eggs at previous OPU
Type b) 4-9 eggs at previous OPU
Possible reasons:
Insufficient gonadotrophin dose
Asynchronous development
Genetic polymorphism of FSH-R, LH-R
Trigger and/or oocyte pick up issues
Treatment suggestions:
GnRH antagonist max stim, consider priming (E2, testosterone - though no strong evidence)
consider LH supplementation
Number of oocytes needed to obtain one euploid blastocyst = 5
Group 2 Poseidon
“Good reserve, poor quality”
>/= 35 yrs, AMH >8.6pmol/L or AFC >5
Type a) <4 oocytes at previous OPU
Type b) 4-9 oocytes at OPU
Possible reasons:
Insufficient gonadotrophin dose
Asynchronous development
Genet polymorphism of FSH-R, LH-R
Trigger and/or oocyte pick up issues
Treatment suggestions:
GnRH antagonist max stim, consider priming (E2, testosterone, OCP - though no strong evidence)
consider LH supplementation
Number of oocytes needed to obtain one euploid blastocyst = 10-12
Group 3 Poseidon
“Poor reserve, good quality”
<35 years, AMH <8.6pmol/L or AFC </=5
Reasons for poor response:
Poor ovarian reserve
Asynchronous development
Management:
Max stimulation Consider long GnRHa protocol if doesn’t respond to antagonist, consider E2/androgen priming.
Need 5 oocytes to obtain one euploid embryo
Group 4 Poseidon
“Poor reserve, poor quality”
>/= 35 years, AMH <8.6pmol/L or AFC </= 5
Reasons:
Poor ovarian response
Asychronous development
High aneuploidy rate
Management: Max stimulation Consider long GnRHa protocol if doesn’t respond to antagonist, consider E2/androgen priming. LH supplementation.
Need 10-12 oocytes to obtain one euploid embryo
Definitions:
Ovarian reserve
Oocyte quality
Ovarian response
Ovarian reserve - the number of oocytes remaining in the ovary
Oocyre quality - potential of an oocyte to result in a live-born infant
Ovarian response - actual oocyte yield with ovarian stimulation
Ovarian reserve tests
Anit-mullerian hormone (AMH) - glycoprotein of the TGF-B (transforming growth factor B) family, produced by the primary, preantral and early antral follicles.
Antral follicle count (AFC) - total number of follicles across both ovaries between 2-10mm in size in early follicular phase
Early follicular FSH (with oestradiol)
Early follicular Inhibin B - glycoprotein secreted primarily by preantral follicles.
Clomiphene citrate challenge test (CCCT) - provocative test - now obsolete as AMH and AFC much more reliable.
Inhibin B as a marker of ovarian reserve
Ovarian reserve decreases –> inhibin B early follicular levels fall –> lower central negative feedback to pituitary –> inc FSH production –> results in high early follicular FSH –> earlier onset of new follicular growth –> inc in E2 concentrations –> decreases follicular phase length and therefore overall cycle
Basal serum FSH and E2
Elevated levels on day 2-3-4 in women with DOR.
Specific but not sensitive test for DOR (if normal reassuring, if elevated = non-specific)
Significant intra and intercycle variability - limits realiability.
E2 useful only as an aid to the correct interpretation of a normal basal serum FSH value.
If basal FSH if normal but E2 elevated in early follicular phase this can also indicate DOR.
Clomiphene citrate challenge test
measurement of serum FSH prior to (day 3) and after (D10), administration of 100mg of CC on cycle days 5-9.
Lower levels of Inhibin B and E2 –> neg feedback decreased on pituitary –> higher FSH. So after CCCT would see higher FSH levels and indicate DOR. It is not superior to non-dynamic tests for predicting POR or pregnancy after IVF and so has been abandoned.
AMH
Produced from granulosa cells of primary, preantral and early antral follicles.
Gonadotrophin independent and so stays constant throughout menstrual cycle.
Can be decreased by COCP (particularly those with lower levels of AMH).
More sensitive than basal serum FSH, tends to decline before FSH rises.
Ovarian volume
Reduces as women age.
Uncommonly used for clinical prediction given high inter and intracycle variability and general lack of sensitivity.
AFC
The sum of the number of antral follicles (2-10mm) in both ovaries, observed by TVUSS in the early follicular phase.
AFC has low intercycle variability and high interobserver reliability in experienced centres.
Which marker is the best?
AMH and AFC have been shown to be equivalent in multiple studies.
AMH testing is simpler and can be done at any time of the menstrual cycle.
AFC is a reasonable alternative.
No benefit in combined ORTs - no more useful than AMH or AFC alone.
