Decline In Antral Follicle Count Research Articles

The association of serum phthalate metabolites with biomarkers of ovarian reserve in women of childbearing age

Phthalates (PAEs) are widely used plasticizers drawing increasing concern due to reproductive toxicity. However, studies on serum PAEs metabolites (mPAEs) and their associations with human ovarian function remain very scarce. In this study, from April 2019 to August 2020, a total of 297 women of childbearing age were recruited in Tianjin, China. Eleven mPAEs were analyzed in serum samples and eight mPAEs were detected at frequencies > 65% with median concentrations of 0.43–15.3 ng/mL. In multinomial logistic analysis, an increase in serum mono (2-isobutyl) phthalate (miBP) was associated with decline in antral follicle count (AFC) (OR=1.26, 95% CI: 0.99, 1.61) and 5-mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP) was significantly associated with AFC increase (OR=1.43, 95% CI: 1.06, 1.92), which were aligned with the associations found between mPAEs and AMH through generalized linear regression. In multiple linear regression models, per 10% increase in serum mono (2-ethylhexyl) phthalate (mEHP), mono (2-ethyl-5-oxohexyl) phthalate (mEOHP) (oxo-mEHP), and principal component 1 featured for high concentrations of mono-n-butyl phthalate (mBP), miBP and mEHP were associated with 0.15 (95% CI: −0.29, −0.02), 0.01 (95% CI: −0.01, 0.00) and 0.01 (95% CI: −0.02, 0.00) ln-unit decrease in estradiol (E2) levels, respectively, while mono-[(2-carboxymethyl) hexyl] phthalate (mCMHP) (carboxymethyl-mEHP) was positively associated with 0.05 ln-unit increase of E2 (95% CI: 0.02, 0.08). The observed negative associations between mPAEs and the Anti-Müllerian hormone (AMH) also aligned with the change in AFC. Generalized linear regression also revealed nonlinear associations between mono-ethyl phthalate (mEP), mCMHP and follicle-stimulating hormone (FSH). Overall, serum mEHP and its metabolites were negatively associated with E2. miBP was negatively associated with AFC. The nonlinear associations between mPAEs and FSH, and AMH need further study.

Excerpts From the World Medical Literature.

Summary: This meta-analysis reviewed three cohort and three case-control studies that included a total of 353 women who underwent uterine artery embolization (UAE) where measurement of antimüllerian hormone (AMH) was used as the end point to determine impact on ovarian reserve. The primary outcome was change in AMH level after UAE; secondary outcomes were changes in follicle stimulating hormone (FSH) and antral follicle count (AFC). The studies included in this meta-analysis were evaluated for quality, risk of bias, and heterogeneity. Length of follow-up was between 3 and 6 months. Various embolization agents were used, but the UAE technique was quite consistent. Women over age 40 were included in several of these studies. Pooled analysis of all six studies showed no significant change in post-embolization AMH concentration (weighted mean difference [WMD] −0.60 ng/mL; 95% confidence interval [CI] −1.51 to 0.31). The results were the same for women aged <40 years. There was no statistically significant change in AMH concentration at 1 year of follow-up (WMD −0.09; 95% CI −0.32 to 0.14). In terms of secondary outcomes, there was no significant difference in FSH level post-UAE (WMD 4.32; 95% CI −0.53 to 9.17); two studies that included a total of 62 women and evaluated AFC at 3 months as an outcome measure showed a significant decline in AFC 3 months post-UAE (WMD −3.28; 95% CI −5.62 to −0.93).

Age related normogram for antral follicle count in general population and comparison with previous studies

ObjectiveTo construct antral follicle count (AFC) nomogram of general population for every age and to compare our data with previous studies to assess whether available AFC nomograms present any geographical inconsistency. Study designA prospective cross-sectional study was conducted to document AFC nomogram among women in 20–50 years with regular menstrual bleeding. Patients admitted with hirsutism, menstrual irregularity, diagnosis of current/history of endometrioma and hormonal drug use within the last 6 months were excluded. For the final analysis, a total of 381 eligible women were recruited in which all scanning was performed in the early follicular phase. The 25th, 50th and 75th percentiles were compared with previous nomogram. ResultsThe mean decrease of AFC in each year was 0.41. Among the age groups, there were no statistical significance between 20–24, 25–29 and 30–34, whereas decline in AFC was obvious after 35 years and beyond. The figures comparing our data and previous studies depicted similar steady decline at 25th, 50th and 75th percentiles. ConclusionThe current age related nomogram presented a steady decline in AFC that became significant after 35 years in otherwise healthy women with regular menstrual bleeding. Those percentiles might be used as a reference guide to point out the current status of ovarian reserve for a given woman. Additionally, producing nomogram might enforce using percentiles instead of constant thresholds to define various medical conditions such as polycystic ovarian morphology or diminished ovarian reserve. However, longitudinal data with larger sample size are still needed for the validation of those percentiles.

Excessive Age-Related Decline in Functional Ovarian Reserve in Infertile Women: Prospective Cohort of 15,500 Women.

Whether infertile women exhibit accelerated ovarian aging and whether a low ovarian reserve is overrepresented in infertility populations is not known. To compare the age-related decline in antral follicle count (AFC), a biomarker of the ovarian reserve, in fertile and infertile women. Cross-sectional data from a large prospective cohort study conducted from January 2013 to December 2014. Thirteen fertility centers across Spain. Consecutive women aged 18 to 45 years of age attending the fertility centers either seeking fertility treatment or as fertile women wishing to act as potential oocyte donors. Standardized AFC assessment on day 2 to 4 of the cycle. Age-related decline of AFC for both fertile and infertile women. A total of 15 500 women, of whom 5722 were potential donors and 9778 were patients seeking fertility treatment, participated in the study. Average AFC was greater in potential oocyte donors than in infertile women (20 [interquartile range, 16-24] vs 10 [interquartile range, 6-15], respectively; P < .001), a difference that was maintained after adjustment for age (P < .001) in a model predicting log(AFC) from donor vs infertility, adjusting for 2-year age bands. The age-related decline in AFC was much steeper in infertile women compared with that of potential oocyte donors, with an increased prevalence of a low ovarian reserve (AFC < 5) at all ages in infertile women. The age-related decline in AFC was substantially greater in infertility patients than potential oocyte donors. Overrepresentation in infertility populations of women with low ovarian reserve may be an additional functional cause of infertility.

Age-Related Normogram for Ovarian Antral Follicle Count in Women with Polycystic Ovary Syndrome and Comparison with Age Matched Controls Using Magnetic Resonance Imaging.

Antral Follicle count (AFC) is a reliable marker for ovarian reserve. Previous studies have used transvaginal ultrasound for estimation of AFC, however we used magnetic resonance imaging (MRI) for estimation of AFC and for creating an age-related normogram in patients with polycystic ovary syndrome (PCOS) and compared it with normal patients. The aim of this study is to create an age related normogram for AFC in women with PCOS and to compare that with women without polycystic ovarian syndrome using MRI. A total of 1500 women were examined, out of which 400 fitted the criteria for PCOS. They all underwent MRI study and similar age matched women without PCOS also underwent MRI examination. Normogram for AFC were obtained using LMS software and a percentile chart was obtained. Normogram for AFC in PCOS women showed decline in number of AFC as the age progresses and the decline was linear. The normogram for AFC was compared with equal number of patients without PCOS and they also showed decline in AFC as the age progresses, however the decline was exponential and faster. Age related normogram for AFC is widely used and considered as best clinical predictor for ovarian response in assisted reproductive technology. Knowledge of ovarian reserve is important in PCOS and non-PCOS females as PCOS patients are at risk for ovarian hyperstimulation syndrome during gonadotrophin theraphy. MRI is an equally effective and in some times better alternative to transvaginal ultrasound as it has got its own advantages.

Impact of pituitary suppression on antral follicle count and oocyte recovery after ovarian stimulation

To investigate the potential influence of short-term pituitary suppression on antral follicle count (AFC) and correlate the AFC with the number of oocytes retrieved after ovarian stimulation. Retrospective study. University fertility center. A total of 1,479 infertile patients. Patients had baseline AFC, when they were not on any medications known to cause pituitary suppression, and follow-up AFC (suppressed AFC) while on E2, GnRH agonist (GnRH-a), oral contraceptive (OC) pills, or OC pills/GnRH-a in preparation for ovarian stimulation, performed within 6 months of initial baseline AFC. The AFC at baseline, AFC during pituitary suppression, and the number of oocytes retrieved. Although there was an average unadjusted decline of 0.4, 0.9, 2.2, and 3.0 in AFC while patients were on E2, GnRH-a, OC pills, and OC pills/GnRH-a, respectively, this decline was driven by age, baseline AFC, and the hormones used. Although baseline and suppressed AFC were found to be good predictors of the number of oocytes retrieved after ovarian stimulation, statistically, suppressed AFC was found to be a marginally better predictor. Short-term pituitary suppression has a negative impact on AFC. This decline in AFC may influence the number of oocytes retrieved, suggesting the suppressive impact of exogenous hormones on the biological capacity of the ovary during stimulation.

Impact of endometriomas and their removal on ovarian reserve.

The effect of endometrioma on ovulatory function and ovarian reserve was unclear. Conflicting opinions exist regarding effect of endometrioma excision on ovarian reserve. Endometriomas do not seem to affect ovulatory function. Women with endometrioma have lower antral follicle count and serum anti-Müllerian hormone levels than age-matched healthy controls. There is high-quality evidence suggesting a significant decline in serum anti-Müllerian hormone levels following endometrioma excision. However, a similarly significant decline in antral follicle count is not demonstrated. Cauterization seems to be a contributing factor to ovarian damage and suturing the cyst bed could perhaps be a better alternative. It seems prudent to warn patients regarding loss of ovarian reserve following endometrioma excision. Surgeons should cautiously limit the use of cauterization following stripping of endometrioma. Well designed studies comparing effect of various haemostatic measures on ovarian reserve are needed.

Age-related normogram for antral follicle count in women with polycystic ovary syndrome

Antral follicle count (AFC) has been shown to be a reliable marker for ovarian reserve. The aims of this study were to create an age-related normogram for AFC in infertile women with polycystic ovary syndrome (PCOS) and to compare age-related decline in AFC between infertile women with and without PCOS. A retrospective cohort study was conducted. Of a total of 4956 women, 619 women fit criteria for PCOS. In those with PCOS, there were large variations in the AFC between the 10th and 90th percentiles in all age groups. The rate of decline in AFC among women with PCOS was linear, while in those with non-PCOS, it was exponential until 30 years of age, and then became similar to that of PCOS. The rate of follicle loss per year was significantly slower in PCOS women compared with that in non-PCOS women. In both groups, the fastest period of follicle loss was between the ages of 18 and 30. The average follicle loss was 0.8 follicles/year in PCOS women and 1.7 follicles/year in those without PCOS (P<0.001). This study concludes that age-related decline in AFC among women with PCOS is slower than in those without PCOS.Antral follicle count (AFC) has been shown to be a reliable marker for ovarian reserve. The aims of this study were to create an age-related normogram for AFC in women with polycystic ovary syndrome (PCOS), and to compare age-related decline in AFC between women with and without PCOS. A retrospective cohort study was conducted. All patients underwent a baseline transvaginal ultrasound that was performed on day 2–4 of the menstrual cycle. The total number of antral follicles of 2–9mm in diameter was recorded. Of total 4956 women, 619 women fit criteria for PCOS. In those with PCOS, there were large variations in the AFC between the 10th 90th percentiles in all age groups. The rate of decline in AFC among women with PCOS was linear; while in those with non-PCOS, it was exponential until 30 years of age, and then became similar to that of PCOS. The rate of follicle loss per year was significantly slower in PCOS women compared with that in non-PCOS women. In both groups, the fastest period of follicle loss was between the ages 18–30 years. The average follicle loss was 0.8 follicles/year in PCOS women and 1.7 follicles/year in those without PCOS (P<0.001). We have concluded that age-related decline in AFC among women with PCOS is slower than in those without PCOS. Further studies are needed to determine if the AFC normogram in women with PCOS could be clinically relevant to select the optimal gonadotrophin dose for ovulation induction.

Correlação entre a idade e a contagem dos folículos antrais em mulheres inférteis

To produce age-related nomograms for ovarian antral follicle count (AFC) in infertile women. It was done a cross-sectional study of patients attended in the center of assisted reproduction Fêmina, from March 2010 to October 2011. The patients were submitted to transvaginal ultrasonography from day 2 to day 4 of their menstrual period. Patients included were between 21 to 45 years old, with regular menses, two healthy ovaries, without any evidence of endocrinopathies and who gave written informed consent. Patients excluded were smokers, with galactosemia or ovarian cysts, with antecedents of liver disease, ovarian surgeries or who were treated with chemotherapy or radiotherapy. In order to check the evolution of the AFC in relation to patient age, we used the 5th, 25th, 50th, 75th and 95th percentiles. Linear regression was carried out using these percentiles, permitting us to determine the effect of age on the CFA. A total of 172 patients with a mean age of 32.7 years were included in the trial. The male and tubal factors were the main causes of infertility, accounting for 65% of cases. The age-related nomogram for the 5th, 25th, 50th, 75th and 95th percentiles of AFC revealed that changes were best fitted by a linear function. The percentiles that showed the highest correlations were 25 (r=-0.9; p<0.001), 50 (r=-0.9; p<0.001) and 75 (r=-0.9; p<0.001). A nomogram was constructed correlating age with the different AFC percentiles in infertile women without endocrinopathies. This showed a linear pattern of decline in AFC with age in all percentiles. These nomograms could provide a reference guide for the clinician. However, future validation, with longitudinal data, still is needed.

Age-specific nomogram for the decline in antral follicle count throughout the reproductive period

To investigate the relationship between antral follicle count (AFC) and chronological age and to establish normal values for AFC in women with regular menstrual cycles. Cross-sectional study. University hospital. Four hundred fifteen premenopausal women were recruited for the study. Data from 362 patients were available for the statistical analysis. AFC was measured by transvaginal ultrasound examination. Estimating the relationship between AFC and age and developing the AFC nomogram. The analysis showed a linear decline in AFC with age; for every year increase in age, the median AFC decreases by 0.4. The AFC corresponding to the 5th, 25th, 50th, 75th, and 95th centiles for each age have been calculated. A linear relationship of AFC to age was found. For the first time, a nomogram reporting normal and interquartile values for AFC, age by age, throughout the reproductive period has been provided. Until now, the interpretation of the measurement was mainly based on the individual experience of the operator, because no normative data were present. Therefore, the establishment of a nomogram of AFC values is the first step to counsel patients on a scientific basis.

X-chromosome inactivation and ovarian age during the reproductive years

To explore whether skewed X-chromosome inactivation (XCI) is related to indicators of ovarian age. The XCI skewing percent and indicators of ovarian age were measured in women with recent pregnancy losses and women with recent livebirths. All analyses adjust for chronologic age and pregnancy outcome. Hospital in eastern central New York. One hundred thirty-six women with informative XCI assays: 83 with index pregnancy losses and 53 with livebirths. None. The primary indicators of ovarian age were antral follicle count, levels of FSH and inhibin B. A secondary indicator was level of estradiol (E2). The XCI skewing percent, defined either continuously or categorically (> or =90%), was unrelated to the indicators of ovarian age. The sample was large enough to rule out as unlikely a modest decline in antral follicle count or a modest increase in FSH in relation to skewed XCI. X-chromosome anomalies are associated with skewed XCI and with premature ovarian failure. Our data raise the possibility that X-chromosome anomalies may not be an important influence on ovarian aging in menstruating women.