Dominant follicle growth patterns and associated endocrine dynamics in anovulatory and ovulatory waves in women.

Growth patterns and associated endocrine profiles were compared between dominant anovulatory (ADF) and ovulatory follicles (OvF) developing from different waves within and between menstrual cycles in women. Follicular mapping profiles of 49 healthy women of reproductive age and blood samples were obtained every 1-3 days. Sixty-three dominant follicles were classified into wave 1 (W1ADF; n = 8) and wave 2 (W2ADF; n = 6) anovulatory follicles and wave 2 (W2OvF; n = 33) and wave 3 (W3OvF; n = 16) ovulatory follicles. Comparisons were made between W1ADF and W2ADF, W2ADF and W2OvF, and W2OvF and W3OvF. The waves were numbered 1, 2, or 3 based on when the waves emerged relative to the preceding ovulation. W1ADF emerged closer to the preceding ovulation, and W2ADF emerged in the late luteal or early follicular phase. The interval from emergence to maximum diameter was shorter for W2ADF than W1ADF and for W3OvF than W2OvF. Selection of W3OvF occurred at a smaller diameter compared to W2OvF. W1ADF regressed at a faster rate than W2ADF. Also, W1ADF were associated with lower mean FSH and higher mean estradiol than W2ADF. In contrast, W3OvF were associated with higher FSH and LH compared to W2OvF. However, W2OvF were associated with higher progesterone than W3OvF. This study contributes to the understanding of the physiologic mechanisms underlying selection of the dominant follicle, ovulation, and pathophysiology of anovulation in women, as well as optimization of ovarian stimulation protocols for assisted reproduction.

Benefits of a plant-based diet and considerations for the athlete.

Individuals may opt to follow a plant-based diet for a variety of reasons, such as religious practices, health benefits or concerns for animal or environmental welfare. Such diets offer a broad spectrum of health benefits including aiding in the prevention and management of chronic diseases. In addition to health benefits, a plant-based diet may provide performance-enhancing effects for various types of exercise due to high carbohydrate levels and the high concentration of antioxidants and phytochemicals found in a plant-based diet. However, some plant-based foods also contain anti-nutrional factors, such as phytate and tannins, which decrease the bioavailability of key nutrients, such as iron, zinc, and protein. Thus, plant-based diets must be carefully planned to ensure adequate intake and absorption of energy and all essential nutrients. The current narrative review summarizes the current state of the research concerning the implications of a plant-based diet for health and exercise performance. It also outlines strategies to enhance the bioavailability of nutrients, sources of hard-to-get nutrients, and sport supplements that could interest plant-based athletes.

Interactions between serum FSH, inhibin B and antral follicle count in the decline of serum AMH during the menstrual cycle in late reproductive age.

Objective: To investigate the hormonal interrelationships during the menstrual cycle in women of late reproductive age with suppressed serum AMH and antral follicle count (AFC). Methods: Serum hormones (AMH, FSH, LH, estradiol, progesterone, inhibin A, inhibin B), AFC (2-10 mm) and AMH/AFC ratio (an estimate of AMH/follicle) were assessed every 2-3 days across the menstrual cycle in 26 healthy ovulatory women aged 18-50 years. Results: An 11-fold fall in AMH/AFC was observed in women aged ≥45 years compared to those 18-45 years (P < .001). Although women ≥45 years exhibited normal menstrual cycle patterns of serum estradiol, progesterone, LH and inhibin A, FSH was elevated (P < .001) and inhibin B suppressed (P < .001) compared to the younger group. Overall FSH was inversely correlated (r = .55, P < .05) and AMH directly correlated (r = .88, P < .01) with AFC; however, these relationships were curvilinear and more pronounced when AFC was low. Inhibin B was directly linearly correlated (r = .70, P < .01) with AFC across both high and low AMH/follicle groups. Conclusions: It is hypothesized that the marked fall in AMH/follicle in late reproductive age is attributed to the change in the hormonal interplay between the pituitary and ovary. The fall in AFC leads to a decrease in inhibin B and a concomitant increase in FSH by a recognized feedback mechanism. It is postulated the elevated FSH suppresses AMH either directly or indirectly through oocyte-specific growth factors leading to a marked fall in AMH/follicle. We propose that pituitary-ovarian and intra-ovarian regulatory systems underpin the accelerated fall in AMH/follicle during the transition to menopause.

Exploratory analysis of serum concentrations of oocyte biomarkers growth differentiation factor 9 and bone morphogenetic protein 15 in ovulatory women across the menstrual cycle.

OBJECTIVE: To characterize and evaluate the variation in serum concentrations of oocyte-secreted growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) throughout the menstrual cycle in women from young to advanced reproductive ages. DESIGN: Cross-sectional, observational, and exploratory study. SETTING: Multicenter university-based clinical practices and laboratories. PATIENT(S): Serum was collected every 1-3 days throughout the menstrual cycle from 3 cohorts of healthy, ovulatory women: menses to late luteal phase (21-29 years of age; n = 16; University of Otago) and across one interovulatory interval (18-35 years of age; n = 10; and 45-50 years of age; n = 15; University of Saskatchewan). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): To detect the changes in serum GDF9 and BMP15 across the cycle, mean concentration and variance were statistically modeled using a generalized additive model of location, shape and scale (GAMLSS). Follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, and anti-Müllerian hormone were also assessed. RESULT(S): GDF9 and BMP15 were detectable in 54% and 73% of women and varied 236-fold and 52-fold between women, respectively. Across the menstrual cycle, there were minimal changes in GDF9 or BMP15 within a woman for all cohorts, with no significant differences detected in the modeled mean concentrations. However, modeled variances were highest in the luteal phases of all women for BMP15 immediately after ovulation, regardless of age. CONCLUSION(S): Serial changes in GDF9 or BMP15 concentrations across the cycle were not statistically detected and are likewise similar across the reproductive lifespan. Further research is required to fully elucidate the utility of these oocyte biomarkers at diagnosing fertility potential and/or disease.

Ovarian follicular waves during the menstrual cycle: physiologic insights into novel approaches for ovarian stimulation.

Elucidation of multiple waves of antral ovarian follicular development during the menstrual cycle has challenged traditional concepts of female reproductive physiology and foundations of assisted reproductive therapies. Approximately two-thirds of women develop two follicle waves throughout an interovulatory interval and the remainder exhibit three waves of follicle development. Major and minor waves of follicle development have been observed. Major waves are those in which a dominant follicle develops; dominant follicles either regress or ovulate. In minor waves, physiologic selection of a dominant follicle is not manifest. Knowledge of waves of antral follicular development has led to the global adoption of novel ovarian stimulation strategies in which stimulation can be initiated at various times throughout the cycle. Random-start and luteal-phase ovarian stimulation regimens have had important clinical applications for women requiring urgent oocyte or embryo cryopreservation for fertility preservation prior to chemotherapy. Ovarian stimulation twice in the same cycle, referred to as double stimulation, may be used to optimize clinical outcomes in women with a poor ovarian response to stimulation as well as in those requiring fertility preservation before chemotherapy.

Age-related changes in luteal dynamics: preliminary associations with antral follicular dynamics and hormone production during the human menstrual cycle.

OBJECTIVE: The aim of the study was to test the hypothesis that the development of luteal phase dominant follicles (LPDFs) as women age is associated with abnormal luteal function. METHODS: Luteal and antral follicle diameter were quantified in ovulatory women of midreproductive age (MRA; 18-35 y; n = 9) and advanced reproductive age (ARA; 45-55 y; n = 16) every 1 to 3 days during one complete interovulatory interval. Blood was drawn at each visit and assayed for progesterone, estradiol, inhibin A, follicle-stimulating hormone, and luteinizing hormone. Luteal diameter and hormone profiles were compared within MRA and ARA women with versus without LPDFs. RESULTS: Luteal growth and regression profiles were similar in MRA women with typical versus no LPDFs (13.9, 14.8 mm; P > 0.1); however, luteal phase estradiol and progesterone were greater in MRA women with typical (91.1 ng/L, 8.81 µg/L) versus no (48.8 ng/L, 7.32 µg/L) LPDFs, respectively (LPDF effect, P < 0.1). In the ARA group, mean luteal diameter was lowest in women with atypical LPDFs (12.3 mm), greatest in those with typical LPDFs (16.0 mm), and moderate in those with no LPDFs (13.6 mm), (P < 0.1). Reduced luteal growth in ARA women with atypical versus typical and/or no LPDFs occurred simultaneously to greater luteal phase estradiol (199 vs 69.0, 78.4 ng/L) lower progesterone (7.38 vs 10.7, 13.8 ug/L), and lower inhibin A (36.3, 35.6, 51.2) (P < 0.1). CONCLUSIONS: The development of LPDFs as women age was associated with reduced luteal growth, greater estradiol, lower progesterone, and lower inhibin A. These findings provide preliminary evidence that variations in antral folliculogenesis contribute to luteal insufficiency during the menopausal transition.

Interrelationships among reproductive hormones and antral follicle count in human menstrual cycles.

It is recognised that ovarian factors, including steroid and protein hormones, are critical in the feedback regulation of pituitary gonadotropins; however, their individual contributions are less defined. The aim of this study was to explore the reciprocal relationships between ovarian and pituitary hormones across the normal ovulatory menstrual cycle as women age. FSH, LH, oestradiol, progesterone, inhibin A, inhibin B and anti-mullerian hormone (AMH) were measured in serum collected every 1-3 days across one interovulatory interval (IOI) from 26 healthy women aged 18-50 years. The antral follicle count (AFC) for follicles 2-5 mm, >6 mm and 2-10 mm were tabulated across the IOI. Independent associations between ovarian hormones/AFC vs pituitary follicle-stimulating hormone (FSH) and luteinising hormone (LH) were investigated using multivariate regression analysis. The data were sub-grouped based on the presence or absence luteal phase-dominant follicles (LPDF). Serum oestradiol and AMH were inversely correlated with FSH in both follicular and luteal phases. Inhibin B correlated inversely with FSH and LH in the late follicular phase and directly in the luteal phase. AFC, inhibin A and progesterone were not key predictors of either FSH or LH. The strong association between AMH and FSH with age implies that AMH, as well as oestradiol and inhibin B are important regulators of FSH. The change in feedback response of inhibin B with both FSH and LH across the cycle suggests two phases of the negative feedback.

Random start or emergency IVF/in vitro maturation: a new rapid approach to fertility preservation.

There is a need to develop rapid protocols for ovarian stimulation for women who wish to preserve their fertility following diagnosis of cancer. Conventional gonadotropin stimulation protocols are lengthy and are delayed until the start of the next menstrual period, potentially compromising cancer treatments. The development of random start IVF/in vitro maturation has made significant strides for enabling couples undergoing cancer therapy to achieve a family. However, several unanswered questions still remain. What do we know about the endocrinology of stimulating ovarian follicular activity outside the established protocols of stimulation during the follicular phase? This article explores what is known about antral follicle development during the menstrual cycle, novel ovarian stimulation proposals for optimizing assisted reproductive therapies in women, and direction.

Cycle-phase dependent associations between CRP, leptin, and reproductive hormones in an urban, Canadian sample.

OBJECTIVES: To assess the relationships among reproductive hormones, follicular development, inflammation, and adiposity in a sample of urban, Canadian women. MATERIALS AND METHODS: Participants (n = 41) had blood collected every 3 days through one interovulatory interval (IOI) to measure estradiol, progesterone, LH, FSH, leptin, and C-reactive protein (CRP). Participants underwent daily transvaginal ultrasound examinations during the IOI to quantify all follicles > 2 mm. CRP and leptin tertiles were used to compare conditions of high and low inflammatory processes and adiposity, respectively. RESULTS: Luteal phase estradiol, luteal phase LH, and follicular phase progesterone were lower among individuals in the highest CRP tertile (adjusted r(2) = 0.63, 0.70, 0.76, respectively). Luteal and follicular phase follicle diameter was greatest in the high CRP tertile (adjusted r(2) = 0.68, 0.71). Follicular phase progesterone was lowest among individuals in the highest leptin tertile, and follicular phase FSH was lowest among individuals in the lowest leptin tertile (adjusted r(2) = 0.54, 0.45). Luteal phase follicle diameter was highest among those in the moderate leptin tertile (adjusted r(2) = 0.49). DISCUSSION: This study is a first comprehensive assessment of the relationship between multiple ovarian function components and inflammatory biomarkers. The results are interpreted to mean that inflammatory and energetic stressors produce differential effects depending on population, adiposity, and cycle phase. Am J Phys Anthropol 160:389-396, 2016. © 2016 Wiley Periodicals, Inc.

Associations Between Antral Ovarian Follicle Dynamics and Hormone Production Throughout the Menstrual Cycle as Women Age.

BACKGROUND: The physiological origins of age-related changes in hormone production during the menstrual cycle are uncertain. OBJECTIVE: The objective of the study was to test the hypothesis that changes in antral follicle dynamics are associated with changes in hormone production as women age. METHODS: A prospective, observational study was conducted in ovulatory women of midreproductive age (MRA; 18-35 y; n = 10) and advanced reproductive age (ARA; 45-55 y; n = 20). The numbers and diameters of all follicles of 2 mm or greater were quantified ultrasonographically every 1-3 days for one interovulatory interval; the growth profiles of individually identified follicles of 4 mm or greater were tabulated. Blood samples were assayed for FSH, LH, estradiol, progesterone, inhibin A and B, and anti-Mullerian hormone. RESULTS: Fifty percent of women in both the MRA and ARA groups developed one to two luteal-phase dominant follicles (LPDFs). MRA women with typical LPDFs had greater luteal-phase inhibin B (44.2 vs 17.0 ng/L) and estradiol (91.3 vs 51.7 ng/L) compared with those without LPDFs (P < .05). Luteal-phase estradiol was greater (184 vs 79 ng/L), inhibin B was greater (25.3 vs 12.7 ng/L), and progesterone was lower (6.98 vs 13.8 µg/L) in ARA women with atypical vs no LPDFs (P < .01). CONCLUSION: Changes in antral follicle dynamics are associated with changes in hormone production as women age. The development of LPDFs in women of MRA was associated with elevated luteal-phase estradiol. A similar but exaggerated elevation in late luteal-early follicular-phase estradiol, accompanied by lower progesterone, was observed in ARA women with atypically large and persistent LPDFs.

Detection of serum antimüllerian hormone in women approaching menopause using sensitive antimüllerian hormone enzyme-linked immunosorbent assays.

OBJECTIVE: Current antimüllerian hormone (AMH) immunoassays are insufficiently sensitive to detect circulating AMH levels in ovulatory women approaching menopause. The aim of this study was to detect serum AMH levels across the menstrual cycle with age, using two new AMH enzyme-linked immunosorbent assay (ELISA) kits with increased sensitivity and differing specificity. METHODS: Serum AMH levels were determined every 2 to 3 days across the interovulatory interval of menstrual cycles among women of early-mid reproductive age (18-35 y; n = 10) and late reproductive age (45-55 y; n = 17). Two highly sensitive AMH ELISAs (designated 24/32 and 24/37) with differing sensitivities were developed and applied to sera using a recombinant human pro-mature AMH preparation as reference. A third AMH ELISA (Gen II AMH ELISA kit; Beckman Coulter, Brea, CA) used was directed on mature-pro regions of AMH. RESULTS: AMH levels in all cycles were detectable with the 24/32 and 24/37 AMH ELISAs. AMH levels across the menstrual cycle were highly correlated (r = 0.98) between the 24/32 and 24/37 AMH ELISAs and the Gen II AMH ELISA (r = 0.94), but with large intracycle variations observed in older women. In late reproductive age, more than 95% of AMH values were detectable with the 24/32 and 24/37 AMH ELISAs, whereas only 36% of AMH values were detectable with the Gen II AMH ELISA. AMH levels were detected in cycles with lower antral follicle count and at a later age using the 24/32 and 24/37 AMH ELISAs compared with the Gen II AMH ELISA. AMH level correlated with antral follicle count in younger women, but not in older women. CONCLUSIONS: The new 24/32 and 24/37 AMH ELISAs have the sensitivity to monitor ovarian follicle profiles in late reproductive age.

Diffraction-enhanced Synchrotron Imaging of Bovine Ovaries Ex Vivo.

OBJECTIVES: The objective of this study was to test the hypothesis that diffraction-enhanced imaging (DEI), a synchrotron x-ray imaging technique, would provide greater contrast for evaluating bovine ovaries compared with conventional diagnostic ultrasonography. MATERIALS AND METHODS: Bovine ovaries were evaluated ex vivo as follows: fresh without radiographic arterial contrast (n = 2), fresh with contrast (n = 1), preserved in 10% formalin without contrast (n = 2), and preserved with contrast (n = 1). Each ovary was imaged with DEI and subsequently with ultrasonography and histology. The ability to visualize and differentiate preantral and antral follicles, corpora lutea (CL), and cumulus oocyte complexes (COCs) were compared using DEI, ultrasonography, and histology. The diameter of follicles and CL were measured and compared using ultrasonography, DEI, and histology. The diameter of the smallest follicle detected was reported using each of the three imaging methods. The number of antral follicles (antral follicle count ≥2 mm) was compared between ultrasonography and DEI. RESULTS: DEI enabled the detection of 71% of follicles and 67% of CL that were detected ultrasonographically. However, DEI did not allow the detection of COCs and cell layers of the follicle wall that were visualized histologically. Luteal tissues were not easily distinguished using DEI, and DEI was inferior for differentiating follicles and CL compared with ultrasonography. The mean follicle diameter was similar between DEI (4.00 ± 0.35 mm, fresh with contrast; 9.62 ± 2.43 mm, fresh without contrast) and ultrasonography (3.85 ± 0.28 mm, fresh with contrast; 8.97 ± 2.60 mm, fresh without contrast) (P > .05). However, the mean follicle diameter was greater using both DEI (4.00 ± 0.35 mm) and ultrasonography (3.85 ± 0.28 mm) compared with histology (2.21 ± 0.38 mm; P = .01, fresh ovaries with contrast). The mean CL diameter was similar between DEI (11.64 ± 1.67 mm), ultrasonography (9.34 ± 0.35 mm), and histology (9.59 ± 0.36 mm) (P > .05). The mean diameter of the smallest follicle detected was similar between DEI (3.06 ± 0.45 mm) and ultrasonography (2.95 ± 0.74 mm); both DEI and ultrasonographic measurements were greater than histology (0.39 ± 0.04 mm, P < .0001). The mean antral follicle count was similar between ultrasonography (6.50 ± 0.71 mm, fresh with no contrast; 6.50 ± 2.50 mm, preserved with no contrast) and DEI (4.50 ± 0.50 mm, fresh with no contrast; 6.50 ± 0.50 mm, preserved with no contrast) (P > .05). CONCLUSIONS: The contrast resolution of antral follicles, CL, and COCs in bovine ovaries was inferior using DEI compared with ultrasonography and histology. Alternative synchrotron techniques, such as phase-contrast computed tomography and DEI computed tomography, may prove more effective than DEI for imaging ovaries ex vivo.

Systemic inflammation is associated with ovarian follicular dynamics during the human menstrual cycle.

BACKGROUND: Ovarian processes and the timing of ovulation are important predictors of both female fertility and reproductive pathology. Multiple waves of antral follicular development have been documented during the menstrual cycle in women. However, the mechanisms underlying the development of follicular waves and their clinical significance are not fully understood. The objective of this study was to examine the relationship between C-reactive protein (CRP) and follicular waves in healthy women. We wanted to determine whether follicular wave dynamics influence systemic inflammation, as ovarian activity increases local inflammatory processes and blood flow. We tested the hypothesis that women with 3 follicular waves would have higher CRP concentrations than those with 2 waves. We further hypothesized that a greater number of major waves (those with a dominant follicle) would be positively associated with CRP. METHODS/PRINCIPAL FINDINGS: Thirty-nine healthy women underwent daily transvaginal ultrasound examinations for one interovulatory interval, as part of an earlier study. Serum was collected every 3 days during the interovulatory interval (IOI). Enzyme-linked immunosorbent assays were conducted to quantify serum CRP concentrations. Women with 3 waves had higher average log CRP concentrations (n = 14, -0.43±0.35) over the IOI than those with 2 waves (n = 25, -0.82±0.47, p = 02). Average log CRP concentrations were greater in women with 3 (0.30±0.31) versus 1 (-0.71±0.55) or 2 (-0.91±0.47) major waves (p = 0.03). Greater average CRP over the IOI was attributed to greater CRP in the follicular, but not the luteal phase, of the IOI. CONCLUSIONS/SIGNIFICANCE: A greater number of total antral follicular waves, in particular major waves, corresponded to greater serum concentrations of CRP. These findings suggest that women with a greater number of follicular waves exhibit greater tissue remodeling and therefore greater local and systemic inflammation.

Age-related changes in major ovarian follicular wave dynamics during the human menstrual cycle.

OBJECTIVE: Changes in antral follicle count, hormone production, and menstrual cyclicity as women age are well documented. However, age-related changes in ovarian follicular wave dynamics in women are not understood. The objective of this study was to test the hypothesis that major follicular wave dynamics (ie, those in which a dominant follicle develops) differ in women with age. METHODS: A prospective, cross-sectional, observational study was conducted in 58 women of mid-reproductive age (MRA; 18-35 y; n = 27), late reproductive age (LRA; 36-44 y; n = 10), and advanced reproductive age (ARA; 45-55 y; n = 21). The number and diameters of all follicles ≥ 2 mm were quantified ultrasonographically every 2 to 3 days for one complete interovulatory interval (IOI). Only ovulatory cycles were evaluated. Antral follicle count and major follicular wave dynamics during the IOI were compared among age groups using SPSS version 19.0 (α = 0.05). RESULTS: One (36/58, 62%) or two (22/58, 38%) major follicular waves were observed during the IOI in all women evaluated. The prevalence of follicular-phase dominant follicles (FPDFs) and luteal-phase dominant follicles (LPDFs) was not different among the MRA, LRA, and ARA groups (FPDFs: 27/27 [100%], 10/10 [100%], and 20/21 [95%], respectively; LPDFs: 10/17 [37%], 3/10 [30%], and 10/21 [48%], respectively; P > 0.050). All FPDFs were ovulatory. One LPDF ovulated during menses in the ARA group; all other LPDFs in the MRA, LRA, and ARA groups were anovulatory. On average, LPDFs emerged earlier relative to ovulation (days -6, -2, and -2; P = 0.049), grew longer (11, 3, and 6 d; P = 0.005), and developed to a larger diameter (24, 11, and 11 mm; P = 0.032) in the ARA group versus the MRA and LRA groups. In follicular-phase major waves, there was a tendency for a greater prevalence of polyovulation as women aged (ARA 3/21 [14%] vs MRA 0/27 [0%]; P = 0.070). CONCLUSIONS: One or two major follicular waves develop during the IOI, irrespective of age. The prevalence of LPDFs (range, 30%-50%) and FPDFs (range, 95%-100%) during the IOI does not differ with age. However, the growth dynamics of major waves change as women age. On average, LPDFs emerge earlier, grow for a longer period, and grow to a larger diameter in ovulatory women of advanced versus mid or late reproductive age. There is a greater tendency for polyovulation in the follicular-phase major wave as women age.

Synchronization of ovarian stimulation with follicle wave emergence in patients undergoing in vitro fertilization with a prior suboptimal response: a randomized, controlled trial.

OBJECTIVE: To test the hypothesis that synchronizing initiation of ovarian stimulation with follicle wave emergence would optimize IVF/intracytoplasmic sperm injection (ICSI) outcomes in patients with a prior suboptimal response. DESIGN: Prospective, randomized, controlled trial. SETTING: Academic and private reproductive endocrinology and infertility centers. PATIENT(S): Eighty women ≤ 43 years of age with a history of a suboptimal response. INTERVENTION(S): Initiation of recombinant FSH/GnRH antagonist/recombinant LH/hCG on day 1 (n = 39) or day 4 (n = 41). MAIN OUTCOME MEASURE(S): Numbers of clinical and biochemical pregnancies, follicles ≥ 10 and ≥ 15 mm, oocytes collected, fertilized oocytes, cleavage stage embryos, and blastocysts; serum E(2) concentrations. Outcomes were compared between treatment groups. RESULT(S): The numbers of follicles that developed to ≥ 10 and ≥ 15 mm and serum E(2) were greater when recombinant FSH was initiated on day 1 (5.4, 4.3, 5,827.2 pmol/L) versus day 4 (3.6, 2.5, 4,230.1 pmol/L). The numbers of collected, metaphase II, and fertilized oocytes; cleavage stage embryos; and blastocysts were not different between groups. When we evaluated only those cycles that proceeded to oocyte pick-up, a lower implantation rate (16.1%, 56.0%), biochemical pregnancy rate (PR) (16.1%, 48.0%), and clinical PR (12.9% vs. 36.0%) were detected in the day 1 group versus day 4 group. CONCLUSION(S): Synchronizing initiation of ovarian stimulation with follicle wave emergence in patients with a prior suboptimal response resulted in an increase in the number of dominant follicles and serum E(2) concentrations; however, improvements in oocyte, embryo, or pregnancy outcomes did not occur. CLINICAL TRIAL REGISTRATION NUMBER: NCT00439829.

A practical method for ultrasonographically monitoring the day-to-day growth of individual ovarian follicles in women undergoing assisted reproduction.

The objective of this study was to validate the use of the nonidentity (NonID) method compared with the identity (ID) method for tracking the day-to-day growth of individual follicles in women undergoing ovarian stimulation for assisted reproduction. A retrospective observational study was conducted in 20 women during ovarian stimulation. Conventional 2-D transvaginal ultrasonography was used to monitor follicle growth every 2-3 days throughout stimulation. Video clips of both ovaries were obtained in sagittal and coronal planes at each visit. Standardized diameter measurements of all follicles ≥4 mm were made retrospectively from video clips. The growth profiles of all follicles that developed to ≥10 mm were determined using the ID and NonID methods. Using Lin's concordance statistics, we documented that agreement between methods was 91% for follicles <10 mm, 96% for follicles 10-15 mm and 99% for follicles >15 mm. Lin's concordance correlation coefficient between the two methods was 0.96 (standard error = 0.003). We concluded that the NonID method is a practical, effective tool for monitoring the day-to-day growth of individual ovarian follicles in women undergoing assisted reproduction.

Ovarian antral folliculogenesis during the human menstrual cycle: a review.

BACKGROUND Ovarian follicles undergo dynamic morphologic and endocrinologic changes during the human menstrual cycle. The physiologic mechanisms underlying recruitment and selection of antral follicles in women are not fully elucidated. METHODS A comprehensive review of >200 studies was conducted using PubMed. The objective was to compare and contrast different perspectives on human antral folliculogenesis. RESULTS Antral folliculogenesis has been studied using histologic, endocrinologic and/or ultrasonographic techniques. Different theories of antral follicle recruitment include: (i) continuous recruitment throughout the menstrual cycle; (ii) recruitment of a 'cohort' of antral follicles once in the late-luteal phase or early-follicular phase of each cycle and (iii) recruitment of two or three 'cohorts' or 'waves'  during each cycle. Generally, a single dominant follicle is selected in the mid-follicular phase of each cycle and this follicle ovulates at mid-cycle. However, a dominant follicle may also be selected during anovulatory waves that precede the ovulatory wave in some women. CONCLUSIONS There is increasing evidence to indicate that multiple waves of antral follicles develop during the human menstrual cycle. Ovarian follicular waves in women are comparable with those documented in several animal species; however, species-specific differences exist. Enhancing our understanding of the endocrine and paracrine mechanisms underlying antral follicular wave dynamics has clinical implications for understanding age-related changes in reproductive function, optimizing hormonal contraceptive and ovarian stimulation regimens and identifying non-invasive markers of the physiologic status of follicles which are predictive of oocyte competence and assisted reproduction outcomes.

Does the Ovarian Stimulation Phase Length Predict In vitro Fertilization Outcomes?

BACKGROUND: Bi-directional communication between the follicle and oocyte is necessary to regulate follicle and oocyte development. Currently, it is not practical to monitor the serial growth of individual follicles during assisted reproduction. The ovarian stimulation phase length (SPL) is an indirect measure of mean follicular growth rate. The objective of this study was to test the hypothesis that a short or long SPL would be associated with suboptimal outcomes in women undergoing in vitro fertilization (IVF). MATERIALS AND METHODS: A retrospective cohort study was conducted in 140 women who underwent IVF. Follicle development was monitored every 2-3 days during ovarian stimulation using transvaginal ultrasonography. Once > 3 follicles reached ≥ 17 mm, human chorionic gonadotropin (hCG) was administered. Oocyte retrieval was performed approximately 35 hours after hCG. Oocytes underwent IVF on the day of collection and were evaluated daily thereafter. Embryos were transferred on days 3 or 5, depending on the number and quality of embryos available. Associations between SPL, age, follicle, oocyte, embryo and pregnancy outcomes were evaluated (SPSS version 17.0; SPSS Inc., Chicago, IL, USA). RESULTS: A SPL of 11 days was associated with an optimal number of follicles that developed to ≥ 6 mm, ≥ 10 mm and ≥ 15 mm; serum estradiol concentrations; and number of oocytes collected (p<0.05). Gradual reductions in the number of developing follicles, serum estradiol concentrations and number of oocytes collected occurred with SPL less than or greater than 11 days (p<0.05). The SPL did not influence endometrial, embryo or pregnancy outcomes (p>0.05). Associations between SPL and outcomes were not influenced by age (p>0.05). CONCLUSION: The ovarian SPL can be used to predict the number of follicles that develop, oocytes collected and serum estradiol concentrations, but not embryo or pregnancy outcomes.