AMH vs AFC as a means of hyper responders

 

Q. 1: Which follicles represent ovarian reserve? Ans:-Go to:

AIM:

This study aims to compare the efficacy of AFC and AMH, as markers for ovarian reserve.

MATERIALS AND METHODS:

75 patients with PCO (polycystic ovaries) undergoing IVF were randomized with 75 non-PCO patients. On day 3, volume of ovary was acquired, ovarian volume was defined by VOCAL, and Sono AVC was used to count the number of antral follicles. Sum total of antral follicles in both ovaries was taken as total antral follicle count (AFC). AMH was measured on the same day. Long agonist protocol with recombinant FSH (rFSH) was used for IVF stimulation till at least two follicles of 18 mm were seen. hCG 10,000 iu was given and ovum pick up was done after 34-35 h. Primary end point was number of follicles >12 mm seen on day of hCG. Final end point was number of ova retrieved on ovum pick up. Correlation of AFC and AMH was checked for both end points and with each other.

RESULTS:

Correlation of AFC and follicles >12 mm on day of hCG in PCO group is 0.56 and non-PCO group is 0.63,¹ and for AMH and follicles >12 mm on day of hCG in PCO group is 0.42 and non-PCO group is 0.47. Correlation of AFC with number of ova retrieved on OPU in PCO group is 0.44 and for non-PCO group is 0.50. The value for AMH is 0.39 in PCO and 0.43 for non-PCO group. Comparing correlation of AFC and AMH for primary end point in PCO group has ‘z’ value 1.11(onetailed significance 0.1335, twotailed significance 0.267) and in non-PCO group comparison shows a ‘z’ value of 1.39 (one tailed significance 0.0823, two-tailed significance 0.1645). Therefore in both groups, AFC and AMH correlates with total number of follicles >12 mm on day of hCG, but both AFC and AMH have independent significance. Comparing correlation of AFC and AMH with number of ova retrieved on OPU, in non-PCO group has ‘z’ value of 0.54(one tailed 0.2946, two-tailed 0. 5892). In PCO group, this comparison shows, ‘z’ value of 0.36(one tailed 0.3594, two tailed 0.7188).

CONCLUSION:

AFC and AMH correlate with each other but have independent significance for estimating follicles >12 mm on day of hCG. For ova retrieved on OPU, in PCO group, AMH and AFC have similar significance. In non-PCO, AMH may increase accuracy of estimation of number of ova retrieved on OPU over AFC, but difference is not significant. AFC only may suffice for estimation of number of ova retrieved on OPU for all practical purposes.

KEY WORDS: Anti-mullerian hormone, antral follicle count, ovarian reserve

Which Ovarian reserve relates to secondary, pre antral and antral ovarian follicle pool.

 

Q.2: Which serum level more specifically reflects ovarian reserve?  A) Earlier, ovarian reserve was assessed by serum FSH. B) Later AMH (Anti-mullerian hormone) was considered as to be a very reliable and more accurate than S.FSH, for assessment of ovarian reserve. C) Currently scientists are claiming that AFC is more relevant than AMH in forecasting Ov reserve whether AMH represent the kind of response in Ovulation induction,

 

 Q. 3: Which kind of follicles synthesizes AMH? Ans: Anti-mullerian hormone is produced by pre-antral follicles. The highest level of AMH expression is present in granulosa cells of 1) secondary, 2) pre-antral and 3) small antral follicles up to 6 mm in diameter.(Ref:  Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, et al. Antimullerian hormone expression pattern in human ovary: Potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod. 2004;10:77–83. [PubMed] [Google Scholar]  .As such,  level of AMH may represent the population of these follicles(1) secondary, 2) pre-antral and 3) small antral follicles up to 6 mm ). Antral follicles are the follicles between 2 and 9 mm on day 3 of menstrual cycle. . It has been shown that the number of antral follicles in the ovaries is proportionally related to the size of primordial follicle stock from which they were recruited. (Ref : Gougeon A, Echochard R, Thalabard JC. Age-related changes of the population of human ovarian follicles: Increase in the disappearance rate of nongrowing and early-growing follicles in aging women. Biol Reprod. 1994;50:653–63. [PubMed] [Google Scholar]

 

 

 

Q.4: What then represents biological clock or ovarian ageing? Ans: The antral follicle count (AFC) is believed to represent the quantitative aspect of ovarian aging.[Ref: Broekmans FJ, Kwee J, Hendriks DJ, Mol BW, Lambalk CB. A systematic review of tests of predicting ovarian reserve and IVF outcome. Hum Reprod Update. 2006;12:685–718. [PubMed] [Google Scholar]

Q.5: Who are expected to be normal responders? Ans: Ovarian diameter between 2 and 3 cm, ovarian volume between 3 and 6.6 cc, AFC 5-12), with regular menstrual cycles and no biochemical or clinical signs of hyperandrogenemia.

Q.6 : What about FSH?  Ans: FSH don’t represent kind of response to gonadotrophins. FSH did show high values for low reserve ovaries but its values are not found to be different for normal and hyper-responding – PCO groups. But there is still ongoing debate about correlation between AFC and AMH and to analyze which of the two is more reliable about type of response.

 

 

 

 

 

 Q.7: What advancement has been made in last 2 decades in assessing the AFC accurately?  Ans: With advancement in ultrasound technology it is now possible to count antral follicles.. Comparison of AMH and AFC has been done in two groups: Polycystic ovaries PCOs and non-PCOs (normal ovaries) by many researchers

. S. FSH did show high values for low reserve ovaries but its values are not found to be different for normal and hyper-responding – PCO groups.

Q. 10 . What is new methodology of estimating AFC to count with precision?  Ans: Methodology of VOCAL:--Baseline scan is  done on day 3 of the menstrual cycle using 3D US (ultrasound). After acquiring a 3D volume of the ovary, VOCAL (Volume calculation software) is to be used to define the ovarian volume. Angle of rotation for VOCAL will be  15°. Then Sono AVC (Automated volume calculation) was used to count the number of antral follicles in each ovary. Antral follicles are the follicles between 2 and 9 mm on day 3 of menstrual cycle. Sono AVC is based on inversion mode and color codes each follicle along with its diameter in all three orthogonal planes (x, y, z), mean diameter and follicular volume. Post-processing of Sono AVC was done in all patients to count the number of antral follicles more accurately.

Post-processing includes manually adding the follicles that were missed on automatic counting, removing the areas that were erroneously counted as antral follicles on automatic counting, cutting the area that was over-measured on automatic calculation and merging the areas that were part of the same follicle but was counted as separate follicles.The sum total of antral follicles in both ovaries was taken as total AFC.