High Antral Follicle Count Research Articles

MALDI-MS lipid profiles of oocytes recovered by ovum pickup from Bos indicus and 1/2 indicus × taurus with high vs low oocyte yields.

The aim of the present study was to compare the lipid profile in oocytes of indicus and 1/2 indicus × taurus cows with high and low antral follicle count (AFC)/oocyte yields. After an OPU procedure (D0), antral follicles ≥3mm were counted by ultrasonography (D4, 19, 34, 49, 64), and cows were assigned to groups with either high AFC (≥30 follicles; indicus, NH group; 1/2 indicus × taurus, AH group) or low AFC (≤15 antral follicles; indicus, NL group; 1/2 indicus × taurus, AL group). The lipid profiles of the oocytes were determined by MALDI-MS. For GI, GII and GIII oocytes, the indicus samples tend to cluster separately from the 1/2 indicus × taurus samples. The lipid species [PC (P-38:5)+H](+) and/or [PC (P-36:2)+Na](+) , [PC (38:2)+H](+) , [PC (38:5)+Na](+) and [TAG (60:8)+NH(4) ](+) were more abundant in indicus (NH and NL groups) than 1/2 indicus × taurus. The higher lipid content in the indicus oocytes likely reflects differences in the rate of lipid metabolism and may contribute to oocyte competence and embryo development.

Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol.

STUDY QUESTIONCan predictors of low and high ovarian responses be identified in patients undergoing controlled ovarian stimulation (COS) in a GnRH antagonist protocol?SUMMARY ANSWERCommon prognostic factors for high and low ovarian responses were female age, antral follicle count (AFC) and basal serum FSH and LH.WHAT IS KNOWN ALREADYPredictors of ovarian response have been identified in GnRH agonist protocols. With the introduction of GnRH antagonists to prevent premature LH rises during COS, and the gradual shift in use of long GnRH agonist to short GnRH antagonist protocols, there is a need for data on the predictability of ovarian response in GnRH antagonist cycles.STUDY DESIGN, SIZE, DURATIONA retrospective analysis of data from the Engage trial and validation with the Xpect trial. Prognostic models were constructed for high (>18 oocytes retrieved) and low (<6 oocytes retrieved) ovarian response. Model building was based on the recombinant FSH (rFSH) arm (n = 747) of the Engage trial. Multivariable logistic regression models were constructed in a stepwise fashion (P < 0.15 for entry). Validation based on calibration was performed in patients with equivalent treatment (n = 199) in the Xpect trial.PARTICIPANTS/MATERIALS, SETTING, METHODSInfertile women with an indication for COS prior to IVF. The Engage and Xpect trials included patients of similar ethnic origins from North America and Europe who had regular menstrual cycles. The main causes of infertility were male factor, tubal factor and endometriosis.MAIN RESULTS AND THE ROLE OF CHANCEIn the Engage trial, 18.3% of patients had a high and 12.7% had a low ovarian response. Age, AFC, serum FSH and serum LH at stimulation Day 1 were prognostic for both high and low ovarian responses. Higher AFC and LH were associated with an increased chance of high ovarian response. Older age and higher FSH correlated with an increased chance of low ovarian response. Region (North America/Europe) and BMI were prognostic for high ovarian response, and serum estradiol at stimulation Day 1 was associated with low ovarian response. The area under the receiver operating characteristic (ROC) curve (AUC) for the model for a high ovarian response was 0.82. Sensitivity and specificity were 0.82 and 0.73; positive and negative predictive values were 0.40 and 0.95, respectively. The AUC for the model for a low ovarian response was 0.80. Sensitivity and specificity were 0.77 and 0.73, respectively; positive and negative predictive values were 0.29 and 0.96, respectively. In Xpect, 19.1% of patients were high ovarian responders and 16.1% were low ovarian responders. The slope of the calibration line was 0.81 and 1.35 for high and low ovarian responses, respectively, both not statistically different from 1.0. In summary, common prognostic factors for high and low ovarian responses were female age, AFC and basal serum FSH and LH. Simple multivariable models are presented that are able to predict both a too low or too high ovarian response in patients treated with a GnRH antagonist protocol and daily rFSH.LIMITATIONS, REASONS FOR CAUTIONAnti-Müllerian hormone was not included in the prediction modelling.WIDER IMPLICATIONS OF THE FINDINGSThe findings will help with the identification of patients at risk of a too high or too low ovarian response and individualization of COS treatment.STUDY FUNDING/COMPETING INTERESTSFinancial support for this study and the editorial work was provided by Merck, Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ, USA. F.J.B. received a grant from CVZ to his institution; P.J.M.V. and H.W. are employees of MSD, and B.M.J.L.M. was an employee of MSD at the time of development of this manuscript.TRIAL REGISTRATION NUMBERSNCT 00696800 and NCT00778999.

Can Ultrasensitive Anti-Müllerian Hormone Testing Predict Failed Response to Ovarian Stimulation?

Can Ultrasensitive Anti-Müllerian Hormone Testing Predict Failed Response to Ovarian Stimulation?

Unilateral oophorectomy results in compensatory follicular recruitment in the remaining ovary at time of ovarian stimulation for in vitro fertilization

To assess the effect of unilateral oophorectomy (UO) by assessing ovarian reserve (OVR) and the response to gonadotropin stimulation in women with UO undergoing in vitro fertilization (IVF) compared with the response of the ipsilateral ovary of women without UO. Historical cohort study. Academic fertility clinic. Fifty-one women with single ovary compared with a referent group with both ovaries in a 1:2 fashion. None. Day-3 follicle-stimulating hormone (FSH), estradiol, and antral follicle counts as measures of OVR, and IVF outcomes including number of follicles aspirated and oocytes retrieved. The baseline demographics and serum markers of OVR were not different. Referent women had greater follicular yield and oocyte numbers when compared with women with UO; however, when compared with the ipsilateral ovary of the referents, women with UO had a higher antral follicle count and greater follicle and oocyte numbers. In multivariate analyses, the ovary from women with UO was more likely to yield more than the median number of follicles and oocytes than the ipsilateral ovary in referent women. Live-birth rates in both groups were similar. Our results suggest that the remaining ovary appears to compensate in follicular yield after UO in women, confirming the animal data. Women with UO can be reassured and appropriately counseled regarding IVF.

142 EFFECT OF HIGH AND LOW ANTRAL FOLLICLE COUNT IN PUBERTAL BEEF HEIFERS ON IVF

Pubertal heifers can be classified between those with high (n = 25) or low (n = 15) antral follicle counts (AFC). The objective of this study was to determine oocyte development and maturation (e.g. fertility) in an IVF system for high- and low-AFC heifers. From a pool of 120 heifers, 10 high- and 10 low-AFC heifers were determined by transrectal ultrasonography; all heifers with evidence of oestrous cyclicity (i.e. pubertal) were synchronized with two 5-mL injections of prostaglandin F2α 11 days apart. Heifers were euthanized over 4 days on Days 15 to 16 of the synchronized oestrous cycle. A total of 15 heifers (n = 7 high and n = 8 low AFC) were at the appropriate stage of the oestrous cycle. Ovaries were collected and transported to the laboratory. Follicles less than 8 mm in diameter were aspirated. The IVF procedures and media were as previously described (Miles et al. 2004. Biol. Reprod. 71, 1919–1926). Cumulus-oocyte complexes (COC) were identified and washed in oocyte collection medium and then in maturation medium and were cultured (5% CO2; 38.5°C) for 24 h. Following maturation, COC were transferred and washed in fertilization medium. Thawed frozen semen from a crossbred bull was subjected to the swim-up procedure. Motile spermatozoa were collected and added to COC to yield a final concentration of spermatozoa per milliliter of fertilization medium. About 24 h later, presumptive zygotes were washed in development medium, placed in microdrops of development medium, and cultured for 8 days. On Days 3 and 8 after fertilization, cleavage and blastocyst development, respectively, were assessed. Data were analysed using the Proc Mixed procedure of SAS (SAS Institute Inc., Cary, NC, USA) and the model included the effects of day of collection (n = 4), group (n = 7 high- or n = 8 low-AFC heifers), and the interaction. The interaction did not differ (P = 0.10). Day of collection influenced (P &lt; 0.05) the number of COC and the number of oocytes cleaved. High- compared to low-AFC heifers had the greater (P &lt; 0.05) numbers of COC (42.7 ± 4.66 v. 22.1 ± 4.59), oocytes that cleaved (28.1 ± 3.60 v. 15.9 ± 3.55), and developed to blastocysts (13.2 ± 1.71 v. 6.2 ± 1.69). However, there was no difference (P &gt; 0.10) in the percentage of COC that cleaved (65.3 ± 5.58 v. 66.2 ± 5.50%, high v. low, respectively) or that developed to blastocysts (46.7 ± 6.75 v. 42.2 ± 6.65%). In conclusion, AFC did not appear to affect oocyte maturation and development through the blastocyst stage.

Predictive value of antral follicle count and anti-Müllerian hormone for follicle and oocyte developmental competence during the early prepubertal period in a sheep model

Circulating anti-Müllerian hormone (AMH) and antral follicle count (AFC) are addressed as suitable markers of oocyte quantity and quality during adulthood. To investigate whether AFC and circulating AMH could predict follicle development and oocyte quality during the prepubertal period we used 40-day-old ewe lambs with high, intermediate and low AFC (≥30, 16-29 and≤15 follicles respectively). The analysis of the response to the exogenous FSH ovarian reserve test showed a positive correlation between AFC, AMH plasma levels, total follicle number and the number of large follicles (≥3mm) grown after exogenous FSH administration. The incorporation of abattoir-derived oocytes collected from ovaries with different AFC in an in vitro embryo production system showed that a high AFC can predict oocyte quality in prepubertal ovaries, reflecting an ovarian status suitable for follicular development. The histological quantification of the ovarian reserve evidenced that AFC was not predictive of differences in either the number of healthy follicles or the size of the primordial follicle pool in prepubertal ovaries. Further studies are needed to investigate the implication on the reproductive performance of the significant inter-individual differences found in the present study in AFC and circulating AMH in the early prepubertal period.

Withdrawal of GnRH agonist decreases oestradiol and VEGF concentrations in high responders

This study evaluated whether the withdrawal of a gonadotrophin-releasing hormone (GnRH) agonist before triggering ovulation reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in high-risk infertility patients who were treated with gonadotrophins. GnRH agonist was withdrawn for 2 or 3 days when dominant follicles were ⩾14mm in diameter, according to the GnRH agonist long protocol. Non-withdrawal of GnRH agonist was used as control. The serum concentration of oestradiol on the ovulation trigger day was significantly decreased in the GnRH agonist withdrawal group compared with the control group (5750.78±2344.77pg/ml versus 8076.43±1981.67pg/ml); however, the number of retrieved oocytes and the fertilization rate were similar between the groups. In addition, the concentrations of vascular endothelial growth factor in plasma on day of human chorionic gonadotrophin administration and follicular fluid on the oocyte retrieval day were decreased following GnRH agonist withdrawal. In fresh embryo transfer cycles, rates of clinical pregnancy, implantation and OHSS were not different between the groups. When GnRH agonist withdrawal was followed by total embryos cryopreserved, the rate of OHSS was decreased compared with the control group (0% versus 8.70%). Clinical pregnancy rates in cryopreserved embryo transfer cycles were comparable between the two groups.This study was a prospective, clinical and laboratory study of 96 patients (corresponding to 96 cycles) with high antral follicle counts, who were at high risk for ovarian hyperstimulation. The study was carried out between May and September 2012. Gonadotrophin-releasing hormone (GnRH) agonist was withdrawn in 47 cycles for 2 or 3 days when the dominant follicles were ⩾14mm in diameter, according to the GnRH agonist long protocol. The non-withdrawal of GnRH agonist in 49 cycles was used as the control. The serum concentrations of oestradiol on the ovulation trigger day were significantly decreased in the GnRH agonist withdrawal group compared with the control group (5750.78±2344.77pg/ml versus 8076.43±1981.67pg/ml; P<0.001); however, the numbers of retrieved oocytes and fertilization rates were similar between the two groups. In addition, the concentrations of VEGF in plasma on the day of human chorionic gonadotrophin administration and follicular fluid on the oocyte retrieval day were decreased following GnRH agonist withdrawal. In fresh embryo transfer cycles, the rates of clinical pregnancy, implantation and ovarian hyperstimulation syndrome (OHSS) were not different between the two groups. When GnRH agonist withdrawal was followed by cryopreservation of all embryos, the rate of OHSS was decreased compared with the control group (0% versus 8.70%). Clinical pregnancy rates in vitrified–warmed embryo transfer cycles were comparable between the two groups. The appropriate withdrawal of GnRH agonist, before triggering ovulation, decreased the concentrations of oestradiol and VEGF in patients undergoing ovarian stimulation, which may reduce the incidence of ovarian hyperstimulation.

Venous thrombosis during assisted reproduction: Novel risk reduction strategies

Ovarian hyperstimulation syndrome (OHSS) affects 5% of IVF cycles and incurs a 100-fold increase in risk of venous thrombosis over natural conceptions. Identification of women at risk of OHSS can be achieved using antral follicle count (AFC) and anti-Müllerian hormone (AMH). For those women with a high AFC or AMH combining a GnRH antagonist with a conventional hCG trigger will reduce the risk of OHSS and still allow a fresh transfer to occur. Complete abolition of OHSS is however now a reality by avoiding exposure to exogenous hCG. This can be achieved by segmentation of the IVF cycle using a GnRH agonist for final oocyte maturation and then freezing all oocytes or embryos with subsequent replacement of a single embryo in the context of a frozen embryo transfer. This novel approach will ensure a VTE risk equivalent to natural conception and can be combined with conventional thromboprophylaxis strategies.

Granulosa cells are refractory to FSH action in individuals with a low antral follicle count

The reason ovarian function and fertility are diminished in women with a low antral follicle count (AFC), despite significant numbers of follicles remaining in ovaries, is unknown. The bovine model is unique to address this question because cattle and women with a low AFC exhibit similar phenotypic characteristics including a diminished ovarian reserve, reduced circulating concentrations of anti-Müllerian hormone (AMH) but heightened FSH secretion during reproductive cycles. Because women and cattle with a low AFC respond minimally to gonadotropin stimulation during IVF cycles or superovulation, granulosa cells in individuals with a low AFC are hypothesised to be refractory to FSH. The present study evaluates this hypothesis by testing whether capacity of granulosa cells to respond to FSH differs between cattle with a low and a high AFC. Granulosa cells from cattle with a low (≤15 follicles ≥3 mm in diameter) or a high (≥25 follicles) AFC were cultured with different doses of FSH. Treatments were evaluated by measurement of oestradiol (E), progesterone (P) and AMH in media and abundance of mRNAs for aromatase (CYP19A1), AMH, FSH receptor (FSHR) and oxytocin (OXT). Progesterone and OXT mRNA are well-established markers of granulosa cell luteinisation. Although high doses of FSH induced granulosa cell luteinisation, basal and FSH-induced increases in E and AMH production and expression of mRNAs for CYP19A1, FSHR and AMH in granulosa cells were much lower, while P production and OXT mRNA expression were higher in non-luteinised and luteinised granulosa cells from the low than the high AFC group. Granulosa cells in cattle with a low AFC are refractory to FSH action, which could explain why ovarian function, responsiveness to gonadotropin stimulation and fertility are diminished in individuals with a low versus a high AFC.

Ovarian Hyperstimulation Syndrome Prevention Strategies: Oral Contraceptive Pills-Dual Gonadotropin-Releasing Hormone Agonist Suppression with Step-Down Gonadotropin Protocols

The identification of patients at high risk for excessive responses to ovarian stimulation for in vitro fertilization and embryo transfer is essential in the tailoring of safe and effective treatment strategies. Known factors associated with increased sensitivity to gonadotropins include polycystic ovary syndrome, young age, prior ovarian hyperstimulation syndrome (OHSS), high baseline antral follicle count, and high baseline ovarian volume. Although several treatment strategies have been proposed for these patients, this report describes the experience using the dual suppression with gonadotropin step-down protocol. This protocol uses oral contraceptive pretreatment in combination with a long gonadotropin-releasing hormone agonist followed by a programmed step-down in gonadotropin dosing. Hormonal characteristics of dual suppression include an improved luteinizing hormone-to-follicle-stimulating hormone ratio and lower serum androgens, particularly dehydroepiandrosterone sulfate. Clinical characteristics of the protocol include a lower cancellation rate and favorable clinical and ongoing pregnancy rates per initiated cycle while mitigating the risk of OHSS.

The Correlation between Testosterone and Progesterone Levels on Day of HCG and IVF Outcome

Study Objective: To determine the relationship between testosterone and progesterone levels on day of HCG and IVF outcome. Design: Retrospective analysis. Setting: Weill Cornell Medical College- The Center for Reproductive Medicine and Infertility. Patients: Fifty consecutive patients who underwent IVF stimulation using Lupron or low dose Lupron (LDL) suppression protocols were included (25 Lupron, 25 LDL). Patients older than 35 were excluded. Intervention: Frozen serum samples from day 2/3 of the cycle, as well as day of HCG were pulled and re-analyzed for testosterone and progesterone levels . Statistical analysis was performed using the student t test, Mann-Whitney U test and chi-square test when appropriate. P<0.05 was considered statistically significant. Measurements and Main Results: There was no significant difference between the groups in age, BMI, days of stimulation, random day 3 FSH, LH levels, Day 2/3 Progesterone and Testosterone levels and the total dose of gonadotropins. Those undergoing stimulation with Lupron had a higher antral follicle count (13.5 vs. 11.6 p=0.02). We identified a trend towards a higher testosterone levels on day of HCG in the LDL protocol when compared with the Lupron protocol (56.7 29.8 Vs 45.0 26.3 P=0.12). No difference was seen in Progesterone levels on day of HCG (0.640.26 vs. 0.74 0.38 p=0.04). We found no difference between the 2 protocols in terms of number of oocytes retrieved, number of mature oocytes, fertilization rate, implantation rate and pregnancy rates.Tabled 1LupronLDLP valueAge31.332.2NSBMI23.122.5NSAFC13.511.60.02Random FSH MIU/ML7.07.6NSRandom LH MIU/ML4.94.5NSTotal Gonadotropins IU1503.61834.4NSDays of Stimulation8.89NSTestosterone on HCG day (ng/dl)45 ± 26.356.7 ± 29.80.15Progesterone on day of HCG (ng/ml)0.64 ± 0.260.74 ± 0.38NS Open table in a new tab Conclusion: There was no significant difference between the Lupron and LDL protocol in terms of IVF outcomes and testosterone and progesterone levels prior to and on the day of HCG injection. There may be a wide range of testosterone levels that can be tolerated without a detrimental effect on IVF outcomes.

Age-related normogram for antral follicle count: McGill reference guide

To produce age-related normograms for antral follicle count in an infertile population without polycystic ovaries. Retrospective cohort analysis. University teaching center. Eighteen hundred sixty-six infertile patients. Baseline transvaginal ultrasound examination between days 2 and 4 of the menstrual cycle. Correlation between age and different percentiles of antral follicle count. The age-related normogram for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentile of antral follicle count showed a biphasic mode of antral follicle count decline with two different rates of antral follicle count loss: a steep-slope phase (high rate of antral follicle count loss) and a moderate-slope phase (restrained rate of antral follicle count losses). In the low antral follicle count percentiles (3rd, 10th, 25th), the phase of high loss rate of follicles preceded the phase of slow loss rate, whereas in the high antral follicle count percentiles (75th, 90th, 97th) the opposite was found. Age-related normograms in infertile women without polycystic ovaries demonstrate a biphasic pattern of decreased antral follicles. These normograms could provide a reference guide for the clinician in consulting with women with infertility. However, future validation with longitudinal data is still needed.

Three‐dimensional ultrasound features of the polycystic ovary in Chinese women

To quantify the three-dimensional (3D) ultrasound characteristics of ovaries in Chinese women with polycystic ovarian syndrome (PCOS) and to compare these with previous data on a Caucasian cohort with PCOS. 3D pelvic ultrasound was performed in 40 Chinese women with PCOS and 40 controls. Ovarian volume, stromal volume and echogenicity, and antral follicle count (AFC) were measured and ovarian blood flow was quantified using both 3D power Doppler and two-dimensional (2D) pulsed wave Doppler. These data were compared with previously published data on a Caucasian cohort with PCOS. Compared with controls, women with PCOS had a higher AFC (median (range), 15 (11-30) vs. 5.5 (1-10) per ovary, P < 0.01), ovarian volume (12.32 (8.10-16.16) mL vs. 5.64 (2.62-8.81) mL, P < 0.01) and stromal volume (9.74 (6.44-13.56) mL vs. 4.07 (1.52-6.67) mL, P < 0.01) but were comparable in stromal echogenicity and ovarian blood flow as measured by 3D power Doppler or 2D pulsed wave Doppler indices. However, in comparison with a previously reported Caucasian cohort with PCOS, the ovaries of Chinese women with PCOS had a significantly smaller stromal volume (median (range), 9.74 (6.44-13.56) mL vs. 10.79 (5.65-17.12) mL, P < 0.05), were less echogenic as reflected in a lower mean gray value (22.43 (13.13-35.50) vs. 32.36 (19.35-53.71), P < 0.01), and had reduced ovarian blood flow as reflected in a lower flow index (30.19 (23.32-44.88) vs. 33.54 (21.88-51.65), P < 0.05). Based on 3D ultrasound measurements, Chinese women with PCOS have an increased stromal volume compared with controls. However, their stromal volume, echogenicity and vascularity is significantly lower than that in Caucasian women with PCOS. The possible etiology for these differences is discussed.

Evaluation of antral follicle count and ovarian morphology in crossbred beef cows: Investigation of influence of stage of the estrous cycle, age, and birth weight1,2

Depletion of the ovarian reserve is associated with reproductive senescence in mammalian females, and there is a positive relationship between the size of the ovarian reserve and the number of antral follicles on the surface of the ovary. Therefore, we conducted a series of experiments to investigate the influence of stage of the estrous cycle, age, and birth weight on antral follicle counts (AFC) in beef cows and heifers. Pairs of ovaries were collected from crossbred beef cows at slaughter (n = 72) or at necropsy (n = 333; 0 to 11 yr of age); all visible antral follicles were counted, the ovaries were weighed, and stage of the estrous cycle was estimated based on ovarian morphology. There was no influence of estimated stage of the estrous cycle on AFC (P = 0.36). There was a small but positive effect of birth weight on AFC [AFC = -1.7 + 0.31(birth weight); P = 0.007, r(2) = 0.05]. When antral follicle counts were regressed on age, there was a quadratic effect of age such that AFC increased until 5 yr of age and decreased thereafter [AFC = 12.9 + 9.0(yr) - 0.86(yr(2)); P < 0.001, r(2) = 0.22]. In a third experiment, crossbred beef heifers (n = 406; 353 to 463 d of age) at 3 locations were subjected to ovarian ultrasonography on unknown day of the estrous cycle. Heifers were classified as low AFC (<15 follicle, n = 84) or high AFC (>24 follicles, n = 178). Whereas estimated stage of the estrous cycle did not influence AFC (P = 0.62), heifers classified as low AFC had smaller ovaries (P = 0.001), decreased birth weight (P = 0.003), and a decreased heifer pregnancy rate (P = 0.05) compared with heifers in the high AFC group. From these results, we conclude that AFC in beef cows and heifers is influenced by birth weight and age but not by stage of the estrous cycle. In beef cows, the number of antral follicles increases to 5 yr of age and then begins to decline. This may indicate that a decrease in fertility due to decline of the ovarian reserve may begin earlier than previously thought in beef cows.

Evidence That High Variation in Ovarian Reserves of Healthy Young Adults Has a Negative Impact on the Corpus Luteum and Endometrium During Estrous Cycles in Cattle1

Low progesterone concentrations and diminished ovarian reserves (total number of healthy oocytes) during reproductive cycles are linked to infertility in single-ovulating species like cattle. However, the extent and mechanisms whereby the inherently high variation in ovarian reserves may negatively affect progesterone production are unknown. Cattle were chosen to address these questions because the size of their ovarian reserves can be predicted based on an antral follicle count (AFC) during follicular waves. The present study determined if progesterone concentrations, differentiation and function of the corpus luteum (CL), and endometrial thickness differed during reproductive cycles of age-matched healthy young adult cattle with low versus high AFC during follicular waves. The results showed that, despite enhanced LH secretion, progesterone concentrations were lower during estrous cycles for animals with low versus high AFC. Animals with low versus high AFC also had a decreased basal, LH-, and 25-hydroxycholesterol-induced capacity of luteal and granulosal cells to produce progesterone, reduced amounts of STAR and mRNAs for STAR and LH receptor in the CL, and no change in endometrial thickness during estrous cycles. Taken together, these results 1) supported the conclusion that high variation in ovarian reserves of young adults is associated with alterations in differentiation and function of the CL and 2) provided insight into the potential factors that may cause suboptimal luteal function (e.g., heightened LH secretion and desensitization of the LH receptor, diminished LH responsiveness, diminished STAR, inherent deficiency in capacity of granulosal cells to undergo luteinization) and infertility (e.g., low progesterone, poor endometrial growth) in individuals with diminished ovarian reserves.

Clinical predictors of human blastocyst formation and pregnancy after extended embryo culture and transfer

To determine the clinical factors associated with blastocyst development and pregnancy. Evaluation of a prospectively collected IVF database. An academic IVF practice. Couples (n = 529) undergoing their first IVF cycle who qualified for extended embryo culture (more than six zygotes) over the past 5 years. Seven or eight zygotes were cultured for 5 days, assessed for quality, and then transferred with excess zygotes cryopreserved at the pronuclear stage. Clinical predictors of blastocyst development and pregnancy. The mean blastocyst development rate was 49.8%, with a median number of total and good-quality blastocysts of 4 and 2, respectively. Clinical factors that were significantly associated with good-quality blastocyst formation were younger female age, increased parity, standard insemination, and lower doses of gonadotropins. Clinical factors that were significantly associated with successful pregnancy were younger female age, higher antral follicle counts, greater numbers of total and good-/excellent-quality blastocysts, and absence of male factor infertility. Several clinical factors are associated with the development of good-quality blastocysts after extended embryo culture and successful pregnancy outcome. These patient and cycle characteristics may be very useful in selecting the best candidates for extended embryo culture and single blastocyst transfers, thus optimizing outcomes while reducing the risks associated with multiple pregnancies.

Variation in the Ovarian Reserve Is Linked to Alterations in Intrafollicular Estradiol Production and Ovarian Biomarkers of Follicular Differentiation and Oocyte Quality in Cattle1

The mechanisms whereby the high variation in numbers of morphologically healthy oocytes and follicles in ovaries (ovarian reserve) may have an impact onovarian function, oocyte quality, and fertility are poorly understood. The objective was to determine whether previously validated biomarkers for follicular differentiation and function, as well as oocyte quality differed between cattle with low versus a high antral follicle count (AFC). Ovaries were removed (n = 5 per group) near the beginning of the nonovulatory follicular wave, before follicles could be identified via ultrasonography as being dominant, from heifers with high versus a low AFC. The F1, F2, and F3 follicles were dissected and diameters determined. Follicular fluid and thecal, granulosal, and cumulus cells and the oocyte were isolated and subjected to biomarker analyses. Although the size and numerous biomarkers of differentiation, such as mRNAs for the gonadotropin receptors, were similar, intrafollicular concentrations of estradiol and the abundance of mRNAs for CYP19A1 in granulosal cells and ESR1, ESR2, and CTSB in cumulus cells were greater, whereas mRNAs for AMH in granulosal cells and TBC1D1 in thecal cells were lower for animals with low versus a high AFC during follicle waves. Hence, variation in the ovarian reserve may have an impact on follicular function and oocyte quality via alterations in intrafollicular estradiol production and expression of key genes involved in follicle-stimulating hormone action (AMH) and estradiol (CYP19A1) production by granulosal cells, function and survival of thecal cells (TBC1D1), responsiveness of cumulus cells to estradiol (ESR1, ESR2), and cumulus cell determinants of oocyte quality (CTSB).

Antral Follicle Count Reliably Predicts Number of Morphologically Healthy Oocytes and Follicles in Ovaries of Young Adult Cattle1

Methods to predict numbers of healthy oocytes in the ovaries of young adults could have important diagnostic relevance in family planning and animal agriculture. We have observed that peak antral follicle count (AFC) determined by serial ovarian ultrasonography during follicular waves is very highly reproducible within individual young adult cattle, despite 7-fold variation among animals. Herein, we tested the hypothesis that AFC is positively associated with the number of morphologically healthy oocytes and follicles in ovaries and with serum concentrations of anti-Müllerian hormone (AMH), an indirect marker for number of healthy follicles and oocytes in ovaries. In the present study, age-matched young adult cattle (12-18 mo old) were subjected to serial ultrasonography to identify animals with a consistently high (> or =25 follicles that were > or =3 mm in diameter) or low (< or =15 follicles) AFC during follicular waves. Differences in serum AMH concentrations, ovary weight, and number of morphologically healthy and atretic follicles and oocytes were determined. The phenotypic classifications of cattle based on AFC during follicular waves or AMH concentrations both predict reliably the relative number of morphologically healthy follicles and oocytes in ovaries of age-matched young adult cattle.

Three-dimensional ultrasound features of the polycystic ovary and the effect of different phenotypic expressions on these parameters

The aim of this study was to quantify the three-dimensional (3D) ultrasound characteristics of ovaries in Caucasian women with polycystic ovarian syndrome (PCOS) and to examine if these values differed between different phenotypic forms. 3D pelvic ultrasound was performed in 40 women with PCOS and in 40 controls. Total ovarian volume, stromal volume and echogenicity and antral follicle count (AFC) were measured and ovarian blood flow was quantified using both 3D power Doppler and two-dimensional pulsed-wave Doppler. Women with PCOS had a higher AFC (median 16.3 versus 5.5 per ovary, P < 0.001) and ovarian volume (12.56 versus 5.66 ml, P < 0.001). Stromal volume (10.79 versus 4.69 ml, P < 0.001) and stromal vascularization (VI: 3.85 versus 2.79%, P < 0.001; VFI: 1.27 versus 0.85, P < 0.001) were also increased in women with PCOS. There were no significant differences in stromal echogenicity or pulsed-wave Doppler indices between women with PCOS and the controls. Among the women with PCOS, ovarian vascularity was significantly higher in 30 women who were hirsute compared with normoandrogenic women (FI: 33.94 versus 29.30, P < 0.05) and in 14 women with PCOS who were of normal weight compared with obese women (VI: 4.51 versus 3.25%, P < 0.05; VFI: 1.56 versus 1.22, P < 0.05). Based on 3D ultrasound, women with PCOS have an increased stromal volume and vascularity. Stromal vascularity is significantly higher in women with PCOS who are hirsute and of normal weight.

Evaluation of the relationship between follicular fluid oxidative stress, ovarian hormones, and response to gonadotropin stimulation

To investigate the relationship between oxidative stress and the underlying causes of infertility, preovulatory ovarian hormones, and ovarian response to gonadotropin stimulation in patients undergoing assisted reproductive techniques. Prospective, cross-sectional study. Assisted conception unit, university hospital. One hundred thirty women presenting with infertility, of the following types: male factor (n = 56), unexplained (n = 36), tubal factor (n = 16), polycystic ovary syndrome (n = 15), and endometriosis (n = 7). Follicular fluid (FF) and peripheral blood samples were collected at oocyte retrieval. Blood and FF samples were analyzed for inhibin A, inhibin B, activin A, anti-Müllerian hormone, and E(2) by using ELISA. Total antioxidant capacity (TAC) was measured in plasma and FF by using a calorimetric microplate assay. There was no significant relationship between plasma or FF TAC and the underlying etiology of infertility. There was a statistically significant positive association between FF E(2) levels and TAC (r = 0.26). Higher antral follicle count, delta E(2) (day 3 E(2) minus day 2 E(2)), preovulatory serum anti-Müllerian hormone, inhibin B, and E(2) were associated with good ovarian response, whereas higher FF E(2) was associated with a statistically significant poor response. No significant direct relationship was observed between TAC and ovarian response as well as between TAC or any of the parameters measured and pregnancy outcome. Oxidative stress has an impact on the production of granulosa cell steroid hormones, in particular E(2), which is an important predictor of ovarian response. The positive association between FF E(2) and total antioxidant capacity suggests that E(2) may play a role in the ovarian antioxidant-oxidant balance.