Anti-Müllerian Hormone in Pathogenesis, Diagnostic and Treatment of PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. It is characterized by chronic anovulation, hyperandrogenism, and the presence of polycystic ovary in ultrasound examination. PCOS is specified by an increased number of follicles at all growing stages, mainly seen in the preantral and small antral follicles and an increased serum level of Anti-Müllerian Hormone (AMH). Because of the strong correlation between circulating AMH levels and antral follicle count on ultrasound, Anti-Müllerian Hormone has been proposed as an alternative marker of ovulatory dysfunction in PCOS. However, the results from the current literature are not homogeneous, and the specific threshold of AMH in PCOS and PCOM is, therefore, very challenging. This review aims to update the current knowledge about AMH, the pathophysiology of AMH in the pathogenesis of PCOS, and the role of Anti-Müllerian Hormone in the treatment of this syndrome.

Ultrasound Characterization of Disordered Antral Follicle Development in Women with Polycystic Ovary Syndrome.

CONTEXT: The mechanism of oligo-anovulation in polycystic ovary syndrome (PCOS) is unknown. OBJECTIVES: To evaluate follicular and endocrine characteristics of anovulatory and sporadic ovulatory cycles in women with PCOS. DESIGN: Prospective, longitudinal study. SETTING: Academic clinical research unit. PARTICIPANTS: 26 reproductive-aged women (18-38 years) with PCOS, observed during natural anovulatory (PCOS-Anov; n = 12) and sporadic ovulatory cycles (PCOS-Ov; n = 14), and 12 controls. INTERVENTIONS: Transvaginal ultrasonography and venipuncture were performed every other day for 4 to 6 weeks in women with PCOS or at 1 interovulatory interval in control subjects. MAIN OUTCOME MEASURES: Follicle number and diameter (ie, ≥2 mm) were quantified at each visit. Individual growth profiles were assessed for all follicles that grew to ≥7 mm. Blood samples were assayed for follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone. RESULTS: Follicular excess, or heightened follicle number versus controls, was observed across anovulatory and sporadic ovulatory cycles in PCOS. In PCOS-Anov, follicles emerged cyclically in some women (6/12; 50%) and continuously in others (6/12; 50%), then grew to a mean maximum diameter of 7.2 mm and regressed within 4.7 days. In PCOS-Ov, follicles mostly emerged cyclically as part of a cohort and dominant follicles showed normal growth to ovulation-albeit mean and maximum luteal progesterone concentrations were significantly lower versus controls. CONCLUSIONS: Follicle growth and regression were detected on ultrasonography amidst perpetual follicular excess in PCOS. Documentation of continuous follicle recruitment and turnover, the absence of persistence, and altered luteal progesterone following sporadic ovulation, provide formative data on antral follicle development in PCOS.

Comparison of uterine, endometrial and ovarian blood flow by transvaginal color Doppler ultrasound in ovulatory and anovulatory cycles.

OBJECTIVES: Blood flow to uterus and ovaries is demonstrated to be altered during mensturation. Studies has been published stating that blood flow differs also in ovulatory and anovulatory cycles. In this study, using color Doppler ultrasound, we aim to compare uterine, endometrial and ovarian blood flow during ovulatory and anovulatory cycles. MATERIAL AND METHODS: Women volunteers who are aged between 18-40 had no endocrinological problem and not recieving exogenous hormone therapy were included to study. Blood levels of FSH, LH, E2, prolactine, DHEAS, free T4 were collected in early follicular phase. Uterina, subendometrial and intraovarian artery blood flow pulsatility and resistance indexes were analysed using Doppler USG technique. Patients were called out to control on 21st of cycle and progesterone levels were analysed. Patients who has ovulation signs in USG and progesterone level above 5 ng/mL were included to ovulatory cycle group. Patient who has no signs of ovulation in ultrasound and has not enough progesterone level were included to anovulatory cycle group. RESULTS: LH and E2 levels were significantly higher in anovulatory patients. No correlation was found between endometrial blood flow resistance and basal E2, prolactine, testosterone levels. However, DHEAS levels were related to endometrial blood flow resistance in anovulatory cycles. No correlation was found between ovarian blood flow resistance/uterine blood flow resistance and basal E2, prolactine, testosterone, DHEAS levels. CONCLUSIONS: There is statistically significant difference between endometrial, ovarian, uterine artery blood flow resistance in ovulatory and anovulatory cycles. Blood flow resistance was found to be increased in anovulatory patients. Increased E2 levels in anovulatory cycles were related to endometrial linethickness and endometrial volume.

Phase IV, open-label, randomized study of low-dose recombinant human follicle-stimulating hormone protocols for ovulation induction.

BACKGROUND: This Phase IV, open-label, multicentre, randomized study (MEnTOR) compared two low-dose recombinant human follicle-stimulating hormone (r-hFSH) protocols for ovulation induction. METHODS: This study was conducted in six Middle Eastern countries between March 2009 and March 2011. Eligible women (18-37 years), with World Health Organization Group II anovulatory infertility, were randomized to receive r-hFSH (starting daily dose: 75 IU) as a chronic low-dose (CLD) (37.5 IU dose increase on Day 14) or low-dose (LD) (37.5 IU dose increase on Day 7) protocol if no follicles were ≥ 10 mm. The maximum r-hFSH daily dose permitted was 225 IU/day. The total length of ovarian stimulation could not exceed 35 days, unless ultrasound assessment suggested imminent follicular growth and maturation. Patients underwent only one treatment cycle. Primary endpoint: incidence of mono-follicular development. Secondary endpoints included: stimulation duration and rates of bi-follicular development; human chorionic gonadotrophin administration rate; clinical pregnancy; and cycle cancellation (owing to inadequate response). Adverse events (AEs) were recorded. The primary efficacy analysis was performed using data from all patients who received at least one dose of correct study medication, had at least one efficacy assessment, and no protocol violations at treatment start (CLD group, n=122; LD group, n=125). RESULTS: Mono-follicular development rates (primary endpoint) were similar in both groups (CLD: 56.6% [69/122] versus LD: 55.2% [69/125], p=0.93; primary efficacy analysis population). Similarly, there were no significant differences between groups in bi-follicular development, clinical pregnancy or cycle cancellation (inadequate response) rates. In patients who received human chorionic gonadotrophin injections, the mean duration of stimulation was 13.7 days in the CLD group and 12.9 days in the LD group. Clinical pregnancy rates for those patients who received an hCG injection were similar in both groups (CLD: 20.2% [19/94] versus LD: 19.8% [18/91], p=0.94; primary efficacy analysis population). Most AEs were mild in severity. Only one case of ovarian hyperstimulation syndrome was reported (mild; CLD group). CONCLUSIONS: Efficacy and safety outcomes were similar for the two protocols.

A five-day progesterone plus eCG-based fixed-time AI protocol improves fertility over spontaneous estrus in high-producing dairy cows under heat stress.

This study compared the efficiency of a five-day or standard (nine-day) progesterone-based regimen combined with equine chorionic gonadotrophin (eCG) in a fixed-time AI (FTAI) protocol for dairy cows. The data examined were derived from 3577 inseminations conducted in three dairy herds. Animals with no estrus signs detected over 21 days were randomly assigned to a PRID-9 or PRID-5 group. Cows in each group received a progesterone intravaginal device (PRID) for 9 or 5 days, respectively, PGF(2α) and eCG on PRID removal, and GnRH 48 h later. Fixed-time AI was performed 12 h after the GnRH dose. Cows artificially inseminated following spontaneous estrus during the study period were considered as controls. Based on the odds ratio, the likelihoods of animals in PRID-9 in the warm (conception rate [CR] of 22.3%) and cool (32% CR) periods, and control animals in the warm period (26.6% CR) becoming pregnant were reduced (by factors of 0.6, 0.3 and 0.4, respectively) compared with the control animals in the cool period (CR of 43.7%). The risk of a twin pregnancy was higher (51.4%) for cystic PRID-9 cows (by a factor of 3.6) and lower (9.9%) for cyclic PRID-5 animals (by a factor of 0.4) compared with the PRID-9 cyclic cows. These findings indicate that the proposed protocol achieves similar results during the cool or warm season to those obtained when AI is conducted at spontaneous estrus during the cool season. In addition, PRID-5 reduced twin pregnancy compared with PRID-9.

Endometrial thickness in women with ovulatory dysfunction.

This study is designed to evaluate the relationship between endometrial thickness and clinical/biochemical parameters in women with chronic anovulation. One hundred and twenty women with ovulatory dysfunction were prospective included, endometrial thickness and endocrine and metabolic parameters were measured. The interval between the examination day and the day of the most recent menstrual bleeding (the anovulatory interval) for the studied subject was an average of 145 ± 186 days. The endometrial thickness averaged 7.1 ± 3.2 mm. Correlation analyses revealed that the endometrial thickness was positively correlated with body mass index but was not correlated with age, serum androgens, or estradiol (E2) levels. We further classified the subjects into two groups based on endometrial thickness: Group A, endometrial thickness <7 mm and Group B, endometrial thickness ≥7 mm. The anovulatory interval, follicle-stimulating hormone, luteinizing hormone, E2 and androgen levels were not significantly different between Groups A and B. Group B had higher body weight and more risk for metabolic syndrome. We concluded that endometrial thickness in women with ovulatory dysfunction is positively correlated with body weight status but is not correlated with serum androgens or E2 levels.

Repeat transvaginal ultrasound-guided ovarian interstitial laser treatment improved the anovulatory status in women with polycystic ovarian syndrome.

OBJECTIVE: To assess the effectiveness of repeated transvaginal ultrasound-guided ovarian interstitial laser treatment in the management of anovulatory patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: A retrospective study was performed in our department on 27 anovulatory PCOS women who failed to respond to the first ultrasound-guided transvaginal ovarian interstitial laser treatment. Each woman received a repeat procedure and postoperative rates of ovulation and pregnancy were monitored. RESULTS: Of 27 patients, 18 (66.67%) ovulated spontaneously following the repeated ultrasound-guided transvaginal ovarian interstitial laser treatment Ten women became pregnant within six postoperative months and a cumulative pregnancy rate of 37.04% was achieved. There were no significant operative complications. CONCLUSION: Repeated ultrasound-guided transvaginal ovarian interstitial laser treatment is an effective and safe management in anovulatory PCOS patients who fail to respond or have a transient response to the first transvaginal ovarian interstitial laser treatment.

Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries.

BACKGROUND: Polycystic ovarian morphology (PCOM) at ultrasound is currently used in the diagnosis of polycystic ovary syndrome (PCOS). We hypothesized that the previously proposed threshold value of 12 as an excessive number of follicles per ovary (FN) is no longer appropriate because of current technological developments. In this study, we have revisited the thresholds for FN and for the serum Anti-Müllerian hormone (AMH) level (a possible surrogate for FN) for the definition of PCOM. METHODS: Clinical, hormonal and ultrasound data were consecutively recorded in 240 patients referred to our department between 2008 and 2010 for exploration of hyperandrogenism (HA), menstrual disorders and/or infertility. RESULTS: According to only their symptoms, patients were grouped as: non-PCOS without HA and with ovulatory cycles (group 1, n = 105), presumption of PCOS with only HA or only oligo-anovulation (group 2, n = 73) and PCOS with HA and oligo-anovulation (group 3, n = 62). By cluster analysis using androgens, LH, FSH, AMH, FN and ovarian volume, group 1 appeared to be constituted of two homogeneous clusters, most likely a non-PCOM non-PCOS subgroup (n = 66) and a PCOM, non-PCOS (i.e. asymptomatic) subgroup (n = 39). Receiver operating characteristic curve analysis was applied to distinguish the non-PCOM non-PCO members of group 1 and to group 3. For FN and serum AMH respectively, the areas under the curve were 0.949 and 0.973 and the best compromise between sensitivity (81 and 92%) and specificity (92 and 97%) was obtained with a threshold values of 19 follicles and 35 pmol/l (5 ng/ml). CONCLUSIONS: For the definition of PCOM, the former threshold of >12 for FN is no longer valid. A serum AMH >35 pmol/l (or >5 ng/ml) appears to be more sensitive and specific than a FN >19 and should be therefore included in the current diagnostic classifications for PCOS.

Transvaginal ultrasound-guided ovarian interstitial laser treatment in anovulatory women with polycystic ovary syndrome: a randomized clinical trial on the effect of laser dose used on the outcome.

OBJECTIVE: To explore an optimal laser dose of transvaginal ultrasound-guided ovarian interstitial laser coagulation in management of anovulation in patients with polycystic ovary syndrome (PCOS). DESIGN: Randomized, controlled trial. SETTING: A reproductive medical center. PATIENT(S): Eighty women with PCOS and clomiphene citrate-resistant infertility underwent ultrasound-guided transvaginal ovarian interstitial yttrium aluminum garnet laser treatment. All subjects were divided randomly into four groups of A, B, C, and D. INTERVENTION(S): Group A, one coagulation point per ovary; group B, two points; group C, three points; group D, four to five points. MAIN OUTCOME MEASURE(S): Postoperative ovulation rate, pregnancy rate, and some biochemical parameters. RESULT(S): The rates of ovulation in groups C (75.00%, 95% confidence interval [CI]: 51%-91%) and D (80.00%, 95% CI: 56%-94%) within 6 postoperative months were significantly higher than in groups A (5.00%, 95% CI: 0%-25%) and B (15.00%, 95% CI: 3%-38%). The pregnancy rates in groups C (45.00%, 95% CI: 23%-69%) and D (40.00%, 95% CI: 19%-64%) also were significantly higher than in groups A (5.00%, 95% CI: 0-25%) and B (10.00%, 95% CI: 1%-32%). The mean serum T levels were significantly lower in groups C (2.08 +/- 0.62 nmol/L) and D (2.07 +/- 0.42 nmol/L) compared with groups A (3.10 +/- 0.63 nmol/L) and B (2.95 +/- 0.63 nmol/L). CONCLUSION(S): One and two intraovarian laser coagulation points per ovary are associated with poor outcomes. Three points per ovary seem to represent the plateau of effective dose for the ovarian interstitial laser treatment in PCOS.

[Ultrasound-guided transvaginal ovarian interstitial laser treatment in patients with polycystic ovary syndrome: a laser dose-finding study].

OBJECTIVE: To evaluate the clinical and endocrine effectiveness of different laser doses for ultrasound-guided transvaginal ovarian interstitial laser treatment in patients with polycystic ovary syndrome (PCOS). METHODS: Between January 2005 and July 2007, 56 women with clomifene citrate-resistant PCOS selected from the patients who were referred to Shenzhen Maternity and Child Healthcare Hospital with a request for fertility underwent ultrasound-guided transvaginal ovarian interstitial laser treatment. All subjects were randomly divided into four groups of A, B, C and D. In group A, one coagulation point per ovary was done and group B, two points; group C, three points; group D, four to five points. The size of each point was about 10 mm in diameter (the electrical laser was projected persistently for 1-3 min with a power of 3 -5 W). The serum sexual hormone level, ovulation rate and pregnancy rate within six postoperative months were compared among the four groups. RESULTS: (1) The spontaneous ovulation rates of groups A (0) and B (21%) within six postoperative months were significantly lower than groups C (71% ,P <0. 05) and D (79%, P < 0.01). The accumulative pregnancy rates of group C(43%) and D(36%) for six postoperative months were significantly higher than group A (0; P < 0.01, P < 0.05). Although they were also higher than that of group B, no statistical significance was found (P > 0.05). (2) No statistically significant differences were found among four groups when various preoperative hormone values were compared (P > 0. 05). The mean serum luteinizing hormone (LH), testosterone level and LH/ follicle stimulating hormone (FSH) ratio was significantly lower postoperatively in groups C [(6.3 +/- 2.6) U/L, (2.2 +/- 0.7) nmol/L, 1.1 +/- 0.3] and D [(5.8 +/- 2.5) U/L, (2.1 +/- 0.4) nmol/L, 1.0 +/- 0.4] than in groupsA [(11.9 +/- 3.1) U/L, (3.9 +/- 1.6) nmol/L, 2.1 +/- 0.5] and B [(10.4 +/- 3.9) U/L, (3.3 +/- 1.1) nmol/L, 2.0 +/- 0.6], respectively (P < 0.05). The mean LH, testosterone level and LH/FSH ratio reduced more obviously in groups C (42%, 39% and 42%) and D (53%, 40% and 58%) than in groups A (4%, 9% and 16%) and B (11%, 6% and 5%; P < 0.05). All above-mentioned parameters between groups C and D had no statistical significant difference (P > 0.05). CONCLUSIONS: One and two intraovarian laser coagulation points per ovary are associated with poor results. Three points per ovary seem to represent the plateau of effective dose for the ovarian interstitial laser treatment. Increasing the dose above it does not improve the outcome.

Anti-mullerian hormone is associated with advanced glycosylated end products in lean women with polycystic ovary syndrome.

OBJECTIVE: Oocyte maturation process characterizes polycystic ovary syndrome (PCOS). The mechanisms of this abnormality leading to chronic anovulation are under investigation. Advanced glycosylated end products (AGEs), a marker of oxidative stress linked with oocyte maturation are localized in granulosa cells and are increased in sera, in women with PCOS. The aim of this study was to investigate the relationship, whether there is an association between the anti-mullerian hormone (AMH), a hormone produced by granulosa cells and AGEs in ovulatory and anovulatory PCOS (PCOS-Anov), as well as in non-PCOS anovulatory (Non-PCOS Anov) women. Design Cross-sectional study. METHODS: Data from sixty women with PCOS (37 anovulatory and 23 regularly ovulating) were compared with eleven Non-PCOS Anov women and 25 normal women. In each subject biochemical, hormonal, and ultrasonographic parameters were studied. RESULTS: AMH values were statistically significantly higher in PCOS-Anov (7.63+/-3.12) in comparison with ovulatory PCOS (PCOS-Ov; 4.92+/-2.50), Non-PCOS Anov (3.66+/-1.4), and controls (4.02+/-1.27 ng/ml). AGEs demonstrated a similar pattern: 8.70+/-1.65 in PCOS-Anov, 7.43+/-1.79, PCOS-Ov, 5.21+/-0.09, Non-PCOS Anov, and 5.85+/-0.89 U/ml in controls (P<0.005 for all comparison respectively). Follicle number was significantly higher in PCOS-Anov in comparison with other groups. A significant positive correlation between AMH and AGEs was observed (r: 0.326, P<0.01), and with the estimated AMH/AGEs ratio to follicle number (r: 0.42, P: 0.0001) and the presence of anovulation. CONCLUSIONS: These data suggest that an oxidative marker, AGEs, and AMH, may interact in the anovulatory mechanisms in women with PCOS.

Rosiglitazone as treatment for clomiphene citrate-resistant polycystic ovary syndrome: factors associated with clinical response.

PURPOSE: To identify the various clinical, biochemical, and ultrasonographic factors that determine clinical response to rosiglitazone as a first-line therapy in a series of women with newly diagnosed clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). METHODS: This retrospective analysis included 200 women with newly diagnosed CC-resistant PCOS who received rosiglitazone as a first-line therapy between 2001 and 2006. The effect of clinical and biochemical characteristics on the ovulation and pregnancy rates during rosiglitazone therapy was evaluated. Women were divided into three categories according to the severity of clinical and biochemical parameters of PCOS. The success rates were compared among the categories using contingency table analysis. Multiple regression analysis was used to identify independent predictors of success of rosiglitazone therapy. RESULTS: Body mass index (BMI) > or = 35 kg/m(2), serum testosterone concentration > or = 4.5 nmol/L, free androgen index (FAI) > or = 15, and with duration of infertility > 3 years were associated with poor response to rosiglitazone therapy. In rosiglitazone responders, women with lower pretreatment serum luteinizing hormone (LH) concentrations or a lower LH/follicle-stimulating hormone (FSH) ratio are more likely to have a sustained beneficial effect. CONCLUSIONS: Marked obesity, marked hyperandrogenism, and long duration of infertility in women with newly diagnosed CC-resistant PCOS were predictors of resistance to rosiglitazone therapy as a first-line treatment.

Detection of anovulation by heatmount detectors and transrectal ultrasonography before treatment with progesterone in a timed insemination protocol.

Our objective was to determine the accuracy of identifying noncycling lactating dairy cows before the application of a timed artificial insemination (AI) protocol [with or without progesterone supplementation via a controlled internal drug-release (CIDR) insert and 2 different timings of AI] by using heatmount detectors and a single ovarian ultrasound examination. At 6 locations in the Midwest, 1,072 cows were enrolled in a Presynch protocol (2 injections of PGF(2alpha) 14 d apart), with the second injection administered 14 d before initiating the Ovsynch protocol (injection of GnRH 7 d before and 48 h after PGF(2alpha) injection, with timed AI at 0 or 24 h after the second GnRH injection). Heatmount detectors were applied to cows just before the first Presynch injection, assessed 14 d later at the second Presynch injection (replaced when activated or missing), and reassessed at initiation of the Ovsynch protocol. Ovaries were examined for the presence of a corpus luteum (CL) by ultrasound before the initiation of treatment. Treatments were assigned to cows based on the presence or absence of a CL detected by ultrasound: 1) no CL + no CIDR; 2) no CL + CIDR insert for 7 d; and 3) CL present. Further, alternate cows within the 3 treatments were assigned to be inseminated concurrent with the second GnRH injection of Ovsynch (0 h) or 24 h later. Pregnancy was diagnosed at 33 and 61 d after the second GnRH injection. By using low (<1 ng/mL) concentrations of progesterone in serum as the standard for noncycling status, heatmount detectors were activated on a large percentage of noncycling cows (>60%), whereas the single ultrasound examination incorrectly classified noncycling cows only 21% of the time. Conversely, cycling cows (progesterone > or =1 ng/mL) were correctly identified 70 to 78% of the time by heatmount detectors, but 85 to 92% were correctly identified by ultrasound. Overall accuracy of heatmount detectors and ultrasound was 71 and 84%, respectively. Application of progesterone to cows without a CL at the time of the first injection of GnRH reduced the incidence of ovulation but increased the proportions of pregnancies per AI at d 33 or 61 compared with nontreated cows without a CL at the onset of the Ovsynch protocol. Percentages of cows pregnant and pregnancy survival did not differ for cows having a CL before treatment compared with those not having a CL and treated with progesterone. Compared with no response, when a follicle ovulated in response to the first GnRH injection, percentage of cows becoming pregnant after the timed AI increased from 33.3 to 41.6%. Timing of AI at 0 or 24 h after the second GnRH injection did not alter pregnancies per AI, but cows having luteal activity before treatment had improved pregnancies per AI compared with noncycling cows. We conclude that identifying noncycling cows by ultrasound was more accurate than by heatmount detectors. Subsequent progesterone treatment of previously cycling cows not having a CL at the onset of Ovsynch increased the proportion of pregnant cows, equal to that of cows having a CL but not treated with progesterone.

Assessment of a practical method for identifying anovular dairy cows synchronized for first postpartum timed artificial insemination.

Our objective was to determine whether a single examination of ovaries using transrectal ultrasonography at the first GnRH injection of a Presynch + Ovsynch protocol is a useful method for assessing cyclicity status and thereby enabling differential management of anovular vs. cyclic cows. Lactating Holstein cows (n = 842) receiving a Presynch + Ovsynch protocol to initiate first postpartum timed artificial insemination (TAI) were used to compare 2 methods for assessing cyclicity status before TAI. For the standard method (using RIA), blood samples were collected at the second PGF2alpha injection of Presynch and the first GnRH injection of Ovsynch, and cows with serum progesterone > or = 1.0 ng/mL in one or both samples were classified as cycling, whereas cows with serum progesterone < 1.0 ng/mL in both samples were classified as anovular. For the practical method, transrectal ultrasonography (U/S) was used to determine the presence or absence of a corpus luteum (CL) at the first GnRH injection of Ovsynch, and cows without CL were classified as anovular, whereas cows with CL were classified as cycling. Statistical agreement (kappa) between the RIA and U/S methods to identify cycling cows was 0.66. Sensitivity, specificity, positive predictive value, and negative predictive value of U/S to identify anovular status were 85.7, 87.7, 64.7, and 95.9%, respectively. We conclude that assessing the presence or absence of CL at the first GnRH injection of a Presynch + Ovsynch protocol using U/S is a reliable and practical method for identifying the cyclicity status of cows before first TAI, but may slightly overestimate the proportion of anovular cows compared with the RIA method.

[Features of morphometry of ultrasound and endometrial histology in the anovulatory polycystic ovary syndrome women].

OBJECTIVE: To investigate the relationship between ultrasonographic features of endometrium and the relation of histological staging of the endometrium and sexual hormone levels in anovulatory polycystic ovary syndrome (PCOS) women. METHODS: Seventy-six anovulatory PCOS patients and 32 women with normal ovulation were enrolled in this study. Ultrasonographic examination, and transmission electron microscope were used to observe endometrium. The expressions of nulear antigen associated with cell proliferation Ki-67 and calcitonin were analyzed by immunohistochemistry. The sexual hormone levels were measured by chemiluminescent microparticle immunoassay. RESULTS: In 11 patients the endometrium showed secretory change out of 76 anovulatory PCOS patients. The frequency of secretory change of the endometrium was not increased with the increase of menses-biopsy interval (P > 0.05). The frequency of abnormal stroma was significantly lower in tripleline endometria than those in non-tripleline endometria (9% vs 43%, P < 0.05). Compared with the control group, the anovulatory PCOS group showed a significant higher expression of Ki-67 in the glandular cell of the secretory phase endometrium (P < 0.05). In the proliferative endometrium, anovulatory PCOS group had more cell organelles than those of the control group. The endometrium showed insufficient secretory changes in the anovulatory PCOS patients. CONCLUSIONS: Proliferative and secretory stage of the endometrium in the anovulatory PCOS group show abnormal features. The abnormal stroma may contribute to the hyperechonic images of the endometrium in the anovulatory PCOS patients.

Causes, characteristics and consequences of anovulatory follicles in superovulated sheep.

Efficiency of superovulatory protocols is affected by the occurrence of reproductive abnormalities, such as the presence of anovulatory follicles. The objective of current study was to assess the incidence and possible causes of anovulatory follicles in superovulated sheep, in order to characterize the endocrine functionality of these follicles in terms of estradiol production and to evaluate their relationship with development of embryos from other follicles. The number and size of all follicles present in the ovaries of 12 sheep treated with a superovulatory FSH step-down treatment was assessed by ultrasonography. On Day 3 after subsequent estrus behaviour, the number of corpora lutea and anovulatory follicles were recorded and the fluid of anovulatory follicles >or=5mm in size was aspirated and assayed for estradiol. At once, embryos were recovered to evaluate their viability. In current study, anovulatory structures averaged 34.6% of the follicles developing to preovulatory sizes. The number of anovulatory follicles was determined by the existence of follicular dominance effects, since they increased with a higher difference in size between the largest and the second largest follicle at the beginning of the superovulatory treatment (P<0.05, r(2)=0.420). Most of the anovulatory follicles showed signs of functionality failures, indicated by a low mean estradiol concentration (9.9+/-1.1 ng/ml). However, a 22.4% of them were highly estrogenic (>200 ng/ml) and their permanence beyond the ovulation was related to a drop in the embryo viability rate (P<0.005), leading to decreased final superovulatory yields.

Müllerian-inhibiting substance reflects ovarian findings in women with polycystic ovary syndrome better than does inhibin B.

OBJECTIVE: To investigate Müllerian-inhibiting substance (MIS) levels in women with polycystic ovary syndrome (PCOS), as well as relationships to ovarian morphology, levels of inhibin B, and other reproductive hormones. DESIGN: Prospective clinical study. SETTING: Academic endocrinology centers in Palermo, Italy and New York. PATIENT(S): Forty-six women with PCOS, recruited on the basis of the classic criteria of chronic anovulation and hyperandrogenism, and 25 age-matched ovulatory controls. INTERVENTION(S): Fasting blood was obtained in all subjects in the early follicular phase (days 5-6) after spontaneous or induced menses (in PCOS), and transvaginal ultrasounds were performed. MAIN OUTCOME MEASURE(S): Assessment of values for luteinizing hormone (LH), testosterone (T), androstenedione (A), estradiol (E2), inhibin B, MIS, fasting insulin, and the calculated quantitative sensitivity check index (QUICKI), as well as assessments of ovarian volume and blood flow. RESULT(S): Women with PCOS had higher LH, T, and A; higher insulin and lower QUICKI; and higher ovarian volume and lower pulsatility index. Inhibin B concentrations were statistically significantly higher in PCOS patients (70 +/- 8.0 vs. 40 +/- 3.4 pg/mL), as was MIS (6.7 +/- 0.9 vs. 4.6 +/- 0.5 ng/mL). Inhibin B had a statistically significant direct correlation with levels of MIS (r = 0.351). However, MIS, but not inhibin B, had a statistically significant positive correlation with ovarian size (r = 0.350); the reproductive hormones LH, T, A, and E2; and insulin (r = 0.249), independent of body mass index. Women with PCOS with the highest levels of MIS had higher ovarian volumes and values of LH, T, A, and insulin. CONCLUSION(S): Measurements of MIS reflect ovarian findings in PCOS better than levels of inhibin B and are more frequently elevated. However, MIS lacks sensitivity for use as a diagnostic tool in PCOS.

Follicular size and response to Ovsynch versus detection of estrus in anovular and ovular lactating dairy cows.

In a commercial dairy herd, 316 lactating Holsteins were studied to determine the percentage of anovular cows, to examine follicular sizes in anovular cows, and to compare synchronized ovulation (Ovsynch) versus detection of estrus on fertility of ovular and anovular cows. Ultrasonography examinations at 47 to 53 d and at 54 to 60 d postpartum were used to measure follicles and to classify cows as ovular or anovular. Anovular cows were identified as those with no detectable luteal tissue by ultrasonography and by low progesterone in blood samples collected weekly. Anovular cows included 28% of 122 primiparous cows and 15% of 194 multiparous cows. Of 64 anovular cows, 20% had follicles > or = 25 mm that might be considered cystic (4% of total cows), 58% had 15- to 24-mm follicles, and 22% had 9- to 14-mm follicles. Cows identified as ovular and anovular were randomly assigned within cyclic status to one of two artificial insemination (AI) strategies: 1) AI after detected estrus during 21 d, or 2) timed AI after a 10-d Ovsynch protocol. Weekly ultrasonography continued for 21 d to detect ovulations. For the Ovsynch sub-groups, 97% of ovular and 94% of anovular cows ovulated after the second GnRH injection. Within 21 d, spontaneous ovulations for the detection of estrus sub-groups were 42% of anovular cows vs. 89% of ovular cows. Conception rates were greater for ovular cows regardless of treatment, but conception rates between respective Ovsynch and estrus detection groups for ovular (32%, 35%) or anovular (9%, 11%) cows were similar. Although 20% of lactating cows were not cyclic by about 60 d postpartum, nearly all ovulated following Ovsynch. However, anovular cows had lower conception than ovular cows whether inseminated after detected estrous or after Ovsynch.

A randomized clinical trial of treatment of clomiphene citrate-resistant anovulation with the use of oral contraceptive pill suppression and repeat clomiphene citrate treatment.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness and endocrine response of oral contraceptive ovarian suppression followed by clomiphene citrate in patients who previously were clomiphene citrate resistant. STUDY DESIGN: Forty-eight patients from a private tertiary infertility clinic were assigned randomly prospectively to either group 1 (oral contraceptive/clomiphene citrate), which received continuous oral contraceptives followed by clomiphene citrate, or to group 2 (control) received no treatment in the cycle before clomiphene citrate treatment. On day 3, 17 beta-estradiol, follicle-stimulating hormone, luteinizing hormone, and androgens were assayed before and after treatment. Follicle growth, ovulation, and pregnancy were evaluated. The Student t test and analysis of variance were used for statistical significance. RESULTS: The oral contraceptive/clomiphene citrate group had a significantly higher percentage of patients who ovulated and of ovulatory cycles and pregnancies. Significantly lower levels of 17 beta-estradiol, luteinizing hormone, and androgen levels were seen in the oral contraceptive/clomiphene citrate group, with no significant changes in group 2. CONCLUSION: Suppression of the ovary with oral contraceptives results in excellent rates of ovulation and pregnancy in patients who previously were resistant to clomiphene citrate. The decreases in ovarian androgens, luteinizing hormone, and 17 beta-estradiol may be responsible for the improved response.