Comparison of antral follicle count and serum anti‐Müllerian hormone level for determination of gonadotropin dosing in in‐vitro fertilization: randomized trial

Abstract

Objective To compare the proportion of women achieving a desired ovarian response following ovarian stimulation when gonadotropin dosing was determined based on antral follicle count (AFC) vs serum anti‐Müllerian hormone (AMH) level, in women undergoing in‐vitro fertilization (IVF) using the gonadotropin‐releasing hormone (GnRH) antagonist protocol. Methods This was a randomized double‐blind trial carried out in a university‐affiliated assisted reproduction unit. A total of 200 women undergoing their first IVF cycle using the GnRH‐antagonist protocol between April 2016 and February 2018 were randomized to determination of gonadotropin dosing based on either AFC or serum AMH level measured in the pretreatment cycle 1 month before the IVF cycle. Patients underwent IVF as per our center's standard protocol. The proportion of subjects achieving a desired ovarian response, defined as retrieval of six to 14 oocytes, was compared between the two study arms. Subgroup analysis of patients with baseline AFC > 5 and those with baseline AFC ≤ 5 was performed. Concordance in AFC and AMH categorization between the pretreatment cycle and the ovarian‐stimulation cycle was assessed using Cohen's kappa (κ). Results There was no significant difference in the proportion of patients achieving a desired ovarian response between the AFC (54%) and AMH (49%) groups (P = 0.479). The median number of oocytes retrieved was nine vs seven (P = 0.070), and the median follicular output rate was 0.54 vs 0.55 (P = 0.764) in the AFC and AMH groups, respectively. Similar findings were observed on subgroup analysis of subjects with AFC ≤ 5 and AFC > 5 at the start of ovarian stimulation (P > 0.05 for all comparisons). There was moderate concordance between AFC and AMH measured in the pretreatment cycle and the stimulation cycle (κ = 0.478 and 0.587, respectively). Conclusion The proportion of women achieving a desired ovarian response following ovarian stimulation using the GnRH‐antagonist protocol is similar when the gonadotropin‐dosing algorithm used is based on AFC or serum AMH level. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Clinical Application of AMH Measurement in Assisted Reproduction

“…Simple categorization may however over emphasize apparent milder discordances, for example in the above study an AMH of 1.3 ng/ml and an AFC of 7 would be recorded as discordant, but clinically many would perceive as equivalent with a similar response anticipated. In the trial by Li et al (51), among the 200 enrolled women, 26.5% showed discordance between categorization based on AMH or AFC in the pre-treatment cycle (k=0.560), with an overall discordance rate of around 30%. In women who were discordant in AMH and AFC categories, those having higher AMH within the same AFC quartile had significantly higher oocyte yield and cumulative live birth rate, and the ovarian responsiveness was intermediate between those where AMH and AFC were concordant on either the high or low end (52).…”

“…Although differences in performance characteristics of AMH and AFC have been reported in several multi-center RCTs ( 18 ), direct head-to-head performance comparison of AMH- or AFC-based dosing algorithms has been more limited. Specifically, two RCTs have compared the performance of a serum AMH or AFC algorithm in predicting ovarian response in an IVF program, with both concluding that there were no significant differences in the proportion of cycles attaining desired ovarian response when the gonadotropin dosing algorithm was determined based on either AMH or AFC ( 50 , 51 ). In the first study, 348 Vietnamese women were treated with a long GnRH agonist protocol, and 35.2% versus 28.4% of cycles attained the desired response when the AMH-based and AFC-based algorithms were adopted respectively (p>0.05), although the incidence of hyper-response was significantly lower in the AMH group (8.6%) compared to the AFC group (17.4%) ( 50 ).…”

“…In the first study, 348 Vietnamese women were treated with a long GnRH agonist protocol, and 35.2% versus 28.4% of cycles attained the desired response when the AMH-based and AFC-based algorithms were adopted respectively (p>0.05), although the incidence of hyper-response was significantly lower in the AMH group (8.6%) compared to the AFC group (17.4%) ( 50 ). In the second study, 200 participants from Hong Kong were treated on a GnRH antagonist protocol ( 51 ). There were no significant differences in the proportion of cycles with desired response between the AMH-based and AFC-based groups (49.0% versus 54.0%, p>0.05), or the number of oocytes retrieved or the follicular output rate.…”

Age‐specific reference ranges of serum anti‐müllerian hormone in healthy women and its application in diagnosis of polycystic ovary syndrome: a population study

“…Adult Chinese women were recruited when they were attending the following institutions for health check‐ups, family planning services or participation in other research projects: Queen Mary Hospital, Hong Kong; School of Public Health, The University of Hong Kong; The Family Planning Association of Hong Kong, Hong Kong; The University of Hong Kong—Shenzhen Hospital, Shenzhen; Peking University Third Hospital, Beijing.…”

“…Adult Chinese women were recruited when they were attending the following institutions for health check-ups, family planning services or participation in other research projects [17][18][19] Only those women fulfilling the following criteria were recruited: (1) ethnically Chinese, (2) aged between 20 and 44 years inclusive, (3) not having a known history of irregular menstrual cycles of shorter than 21 days or longer than 35 days for subjects aged below 40 years, but not mandatory for subjects aged ≥40 years considering the possibility of physiological ovarian ageing even in the normal population, (4) not having hormonal treatment (including regular hormonal contraceptives) in the past 3 months, (5) not pregnant or breastfeeding in the past 3 months, and (6) no history of infertility, radiotherapy, chemotherapy, ovarian surgery, hysterectomy or any endocrine disease (including pituitary and adrenal problems and other conditions with androgen excess) which might affect ovarian function. Written consent was obtained from the subjects before recruitment.…”