The Impact of High Circulating Anti-Müllerian Hormone on Endometrial Thickness and Outcome of Assisted Reproductive Technology in Women with Polycystic Ovarian Syndrome: A Cohort Study.

Background: Elevated circulating anti-Müllerian hormone (AMH) in women with the polycystic ovarian syndrome (PCOS) has been found to have a detrimental effect on endometrial function. This may adversely affect the outcome of in vitro fertilisation (IVF) in PCOS women. Aims: To investigate the impact of high serum AMH concentrations on endometrial thickness (ET) and the outcome of IVF in women with PCOS. Settings and Design: This retrospective cohort study included all PCOS women who underwent fresh IVF\intracytoplasmic sperm injection cycles between January 2016 and December 2021 in one major IVF centre. Materials and Methods: PCOS diagnosis was based on Rotterdam criteria, and participants were identified from centre database. All women received antagonist protocol. Primary outcomes were trigger-day ET and live birth rate (LBR). Circulating AMH was correlated with ET and ovarian response. Statistical Analysis Used: AMH levels were compared between women with and without live birth. ET and LBRs were compared between women with AMH <7.0 ng/ml versus those with AMH ≥7.0 ng/ml. Results: The study included 102 PCOS women, of which six were excluded due to poor response (n = 4), hyperresponse (n = 1) or fertilisation failure (n = 1). Of the remaining 96 women, 42 (43.8%) achieved a live birth. There was no statistically significant (P > 0.05) correlation between AMH and ET. Mean ± standard deviation AMH concentration was not significantly (P > 0.05) different between women with live birth (6.5 ± 3.4 ng/ml) and those without (6.5 ± 2.4 ng/ml). High AMH positively correlated with the number of oocytes retrieved, metaphase II oocytes and embryos (P = 0.003, 0.006 and 0.006, respectively). There was no statistically significant (P > 0.05) difference in ET or LBR between women with AMH <7.0 ng/ml (n = 72; ET, 10.7 ± 1.8 mm; LBR, 45.8% [33/72] versus those with AMH ≥7.0 ng/ml (n = 24; ET, 10.8 ± 1.7 mm; LBR, 37.5% [9/24]). Conclusions: High circulating AMH in PCOS women does not seem to negatively affect ET or LBRs during assisted reproductive technology.

Assessment of Circulating Anti-Müllerian Hormone in Women Using Hormonal Contraception: A Systematic Review.

Background: The status of ovarian reserve markers during hormonal contraception (HC) remains uncertain with conflicting literature data. The purpose of this study was to assess the impact of HC on circulating anti-Müllerian hormone (AMH) and other ovarian reserve markers. Materials and Methods: A systematic review was conducted, including all cohort, cross-sectional, and randomized controlled studies assessing serum anti Müllerian hormone concentration in women using HC. Data sources included MEDLINE, EMBASE, DynaMed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov, and the Cochrane Library from January 2000 to October 2018. Results: A total of 366 studies were identified, of which 15 were eligible, including 3280 women, mostly using combined HC (CHC). Articles were divided according to duration of HC into short- (2-3 weeks), medium- (2-6 months), long- (>1 year), and varied-term studies. Two study designs were identified, including studies comparing AMH before and during/after CHC and studies comparing CHC users versus nonusers. Short- and medium-term studies (n = 284) reported no change in circulating AMH in women using cyclical CHC for one to six cycles. Apart from one study, all long- and varied-term studies (six studies, n = 1601) consistently showed a marked decline in AMH, antral follicle count, and ovarian volume. Three long-term studies (n = 1324) provided evidence of AMH recovery after discontinuation of HC. Conclusion: Circulating AMH seems to remain unchanged in women using cyclical CHC for up to 6 months, but appears to markedly decline in long-term users with recovery after discontinuation.

The impact of uterine artery embolization on ovarian reserve: A systematic review and meta-analysis.

INTRODUCTION: Uterine artery embolization (UAE) has been gaining increasing popularity as an effective and minimally invasive treatment for uterine fibroids. However, there has been growing concern over the risk of unintended embolization of the utero-ovarian circulation, leading to reduction of ovarian blood supply with subsequent impairment of ovarian reserve. The purpose of this study was to investigate the impact of UAE on circulating anti-Müllerian hormone (AMH) and other markers of ovarian reserve. MATERIAL AND METHODS: This meta-analysis included all published cohort, cross-sectional and case-control studies, as well as randomized trials that investigated the impact of UAE on circulating AMH. Data sources included MEDLINE, EMBASE, Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and the Cochrane Library from January 2000 to June 2019. All identified articles were screened, and articles were selected based on the inclusion and exclusion criteria. AMH and other data were extracted from the eligible articles and entered into RevMan software to calculate the weighted mean difference between pre- and post-embolization values. PROSPERO registration number: CRD42017082615. RESULTS: This review included 3 cohort and 3 case-control studies (n = 353). The duration of follow up after UAE ranged between 3 and 12 months. Overall pooled analysis of all studies showed no significant effect of UAE on serum AMH levels (weighted mean difference -0.58 ng/mL; 95% CI -1.5 to 0.36, I2  = 95%). Subgroup analysis according to age of participants (under and over 40 years) and according to follow-up duration (3, 6 and 12 months) showed no significant change in post-embolization circulating AMH. Pooled analysis of serum follicle-stimulating hormone (FSH) concentrations (4 studies, n = 248) revealed no statistically significant change after UAE (weighted mean difference 4.32; 95% CI -0.53 to 9.17; I2  = 95%). Analysis of 2 studies (n = 62) measuring antral follicle count showed a significant decline at 3-month follow up (weighted mean difference -3.28; 95% CI -5.62 to -0.93; I2  = 94%). CONCLUSIONS: Uterine artery embolization for uterine fibroids does not seem to affect ovarian reserve as measured by serum concentrations of AMH and FSH.

First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine. OBJECTIVE AND RATIONALE: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. SEARCH METHODS: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. OUTCOMES: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06). WIDER IMPLICATIONS: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.

The role of oxidative stress in ovarian toxicity induced by haloperidol and clozapine-a histological and biochemical study in albino rats.

Oxidative stress has been implicated in reproductive toxicity induced by antipsychotics (APs). This study aims to further investigate the role of AP-induced oxidative stress in reproductive dysfunction. Thirty adult female albino rats were divided into three groups including a control group (n = 10) receiving distilled water, HAL group (n = 10) receiving haloperidol (HAL) (2 mg/kg/day), and CLZ group (n = 10) receiving clozapine (CLZ) (20 mg/kg/day). After 28 days, the rats were anesthetized, blood was withdrawn from their hearts, and ovaries were removed before they were sacrificed. Serum prolactin concentrations were measured. For each rat, one ovary was used for biochemical studies including mitochondrial complexes I and III activities and oxidative stress markers (lipid peroxidation, super oxide dismutase [SOD], catalase [CAT], and reduced glutathione [GSH]). The other ovary was used for histopathological examination and immunohistochemistry staining for p53 and Ki-67. HAL-treated rats showed significantly (p < 0.001) higher serum prolactin concentrations compared with other groups. HAL significantly inhibited complexes I (p < 0.001) and III activities (p < 0.05), while CLZ inhibited only complex I (p < 0.001). Lipid peroxidation was increased by HAL (p < 0.001) and CLZ (p < 0.01). HAL caused significant (p < 0.001) reductions in SOD, CAT, and GSH. CLZ caused a significant decrease in SOD (p < 0.001) and GSH (p < 0.01) with no effect on CAT. Histopathological studies of CLZ- and HAL-treated ovaries showed features suggestive of hyperprolactinemia and oxidative stress. Ki-67- and P53-immunostained sections were suggestive of disruption of cellular proliferation. These findings support the hypothesis that HAL and CLZ induce reproductive dysfunction through mechanisms involving ovarian mitochondrial dysfunction and oxidative stress.

The impact of laparoscopic ovarian drilling on AMH and ovarian reserve: a meta-analysis.

Laparoscopic ovarian drilling (LOD) has been widely used as an effective treatment of anovulatory women with polycystic ovarian syndrome (PCOS). However, there has been a growing concern over a possible damaging effect of this procedure on ovarian reserve. The objective of this study was to investigate the hypothesis that LOD compromises ovarian reserve as measured by post-operative changes in circulating anti-Müllerian hormone (AMH). This meta-analysis included all cohort studies as well as randomised controlled trials (RCTs) investigating serum AMH concentrations and other ovarian reserve markers in women with PCOS undergoing LOD. Various databases were searched including MEDLINE, EMBASE, Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and Cochrane Library from January 2000 to December 2016. Sixty studies were identified, of which seven were deemed eligible for this review. AMH data were extracted from each study and entered into the RevMan software to calculate the weighted mean difference (WMD) between pre- and post-operative values. Pooled analysis of all studies (n = 442) revealed a statistically significant decline in serum AMH concentration after LOD (WMD -2.13 ng/mL; 95% confidence interval (CI) -2.97 to -1.30). Subgroup analysis based on duration of follow-up, AMH kit, laterality of surgery and amount of energy applied during LOD consistently showed a statistically significant fall in serum AMH concentration. In conclusion, although LOD seems to markedly reduce circulating AMH, it remains uncertain whether this reflects a real damage to ovarian reserve or normalisation of the high pre-operative serum AMH levels. Further long-term studies on ovarian reserve after LOD are required to address this uncertainty.

The impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve: a systematic review.

BACKGROUND: Benign nonendometriotic ovarian cysts are very common and often require surgical excision. However, there has been a growing concern over the possible damaging effect of this surgery on ovarian reserve. OBJECTIVE: The aim of this metaanalysis was to investigate the impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve as determined by serum anti-Müllerian hormone level. DATA SOURCES: MEDLINE, Scopus, ScienceDirect, and Embase were searched electronically. STUDY DESIGN: All prospective and retrospective cohort studies as well as randomized trials that analyzed changes of serum anti-Müllerian hormone concentrations after excision of benign nonendometriotic cysts were eligible. Twenty-five studies were identified, of which 10 were included in this analysis. DATA EXTRACTION: Two reviewers performed the data extraction independently. RESULTS: A pooled analysis of 367 patients showed a statistically significant decline in serum anti-Müllerian hormone concentration after ovarian cystectomy (weighted mean difference, -1.14 ng/mL; 95% confidence interval, -1.36 to -0.92; I(2) = 43%). Subgroup analysis including studies with a 3-month follow-up, studies using Gen II anti-Müllerian hormone assay and studies using IOT anti-Müllerian hormone assay improved heterogeneity and still showed significant postoperative decline of circulating anti-Müllerian hormone (weighted mean difference, -1.44 [95% confidence interval, -1.71 to -1.1; I(2) = 0%], -0.88 [95% confidence interval, -1.71 to -0.04; I(2) = 0%], and -1.56 [95% confidence interval, -2.44 to -0.69; I(2) = 22%], respectively). Sensitivity analysis including studies with low risk of bias and excluding studies with possible confounding factors still showed a significant decline in circulating anti-Müllerian hormone. CONCLUSION: Excision of benign nonendometriotic ovarian cyst(s) seems to result in a marked reduction of circulating anti-Müllerian hormone. It remains to be established whether this reflects a real compromise to ovarian reserve.

Long-term reproductive performance after surgery for ovarian endometrioma.

OBJECTIVE: To determine the long-term impact of different types of endometrioma surgery on reproductive performance and on age of menopause. STUDY DESIGN: This was a longitudinal observational cohort study of 68 women with previous endometrioma surgery and 68 age- and weight-matched healthy controls. All participants' hospital records were reviewed and each woman completed a questionnaire and attended an interview. Pregnancy rates were compared between the study and control groups. In the study group, pregnancy rates were compared before and after surgery. RESULTS: Amongst the 38 women desiring pregnancy after endometrioma surgery, 19 (50%) achieved a spontaneous pregnancy during the follow-up period. This was not significantly different from a pre-operative pregnancy rate of 48% (22/46). Of these 19 patients, four achieved another pregnancy with fertility treatment. An additional eight patients conceived only with the help of fertility treatment, giving an overall long-term post-operative pregnancy rate of 71% (27/38). These results were significantly lower (p=0.0001) than the 98% (57/58) long-term natural pregnancy rate in the control group. Pregnancy rates in patients receiving fertility treatment significantly (p=0.001) increased from 7% (1/15) before surgery to 63% (12/19) post-operatively. In post-menopausal women, the median (quartile) age at menopause was similar in the study (n=9) and control groups (n=6) [48 (45-52) versus 49 (44-52) years, respectively]. CONCLUSION: Endometriomas per se appear to be the main cause of the reduced long-term reproductive performance of the affected patients, with little or no contribution from surgery. Furthermore, endometrioma surgery seems to improve the success rates of fertility treatment.

The influence of circulating anti-Müllerian hormone on ovarian responsiveness to ovulation induction with gonadotrophins in women with polycystic ovarian syndrome: a pilot study.

BACKGROUND: Women with polycystic ovarian syndrome (PCOS) are known to have elevated circulating Anti-Müllerian hormone (AMH), which has been found to desensitize ovarian follicles to follicle stimulating hormone (FSH). The purpose of this study was to investigate the impact of high circulating AMH on ovarian responsiveness to ovulation induction with gonadotrophins in PCOS women. METHODS: This prospective observational pilot study was conducted in two collaborating Fertility Centres in the UK and Egypt. The study included 20 consecutive anovulatory women with PCOS who underwent 34 cycles of human menopausal gonadotrophin (hMG) ovarian stimulation using chronic low-dose step up protocol. Blood samples were collected for the measurement of serum AMH concentrations in the early follicular (day 2-3) phase in all cycles of hMG treatment. The serum levels of AMH were compared between cycles with good vs. poor response. The good response rates and the total dose and duration of hMG treatment were compared between cycles with high vs. low serum AMH concentrations. RESULTS: Cycles with poor response (no or delayed ovulation requiring >20 days of hMG treatment) had significantly (p = .007) higher median{range} serum AMH concentration (6.5{3.2-13.4}ng/ml) compared to that (4.0{2.2-10.2}ng/ml) of cycles with good response (ovulation within 20 days of hMG treatment). ROC curve showed AMH to be a useful predictor of poor response to hMG stimulation (AUC, 0.772; P = 0.007). Using a cut-off level of 4.7 ng/ml, AMH had a sensitivity of 100% and specificity of 58% in predicting poor response. The good response rate was significantly (p < .001) greater in cycles with lower AMH (<4.7 ng/ml) compared to that in those with AMH > = 4.7 ng/ml (100% vs. 35%, respectively). All cycles with markedly raised serum AMH levels (> 10.2 ng/ml) were associated with poor response. Cycles with high AMH (> = 4.7 ng/ml) required significantly (p < .001) greater amounts (median {range}, 1087{450-1650}IU) and longer duration (20 {12-30}days) of hMG stimulation than cycles with lower AMH (525 {225-900}IU and 8{6-14}days). CONCLUSIONS: PCOS women with markedly raised circulating AMH seem to be resistant to hMG ovulation induction and may require a higher starting dose.

The predictive value of circulating anti-Müllerian hormone in women with polycystic ovarian syndrome receiving clomiphene citrate: a prospective observational study.

CONTEXT: Elevated serum anti-Müllerian hormone (AMH) concentration in women with polycystic ovarian syndrome (PCOS) is known to lower sensitivity of ovarian follicles to circulating FSH. This effect may compromise the outcome of clomiphene citrate (CC) ovulation induction. OBJECTIVE: The objective of the study was to investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS. DESIGN: This was a prospective cohort observational study. SETTING: The study was conducted at the Fertility Unit, Derby, United Kingdom. PATIENTS: Sixty anovulatory women with PCOS participated in the study. INTERVENTIONS: Serum AMH concentrations were measured on cycle day 2 during 187 CC cycles. These concentrations were compared between responders and nonresponders. The receiver-operating characteristic curve was used to evaluate the prognostic value of circulating AMH. The success rates of CC were compared between patients with high vs low AMH levels. The dose of CC required to achieve ovulation was correlated with serum AMH concentrations. MAIN OUTCOME MEASURES: Ovulation and pregnancy rates were measured. RESULTS: Serum AMH concentrations were significantly (P < .001) lower in responders (achieving ovulation) vs nonresponders (mean ± SEM, 2.5 ± 0.1 vs 5.8 ± 0.7 ng/mL, respectively). Similarly, serum AMH concentrations were significantly (P = .046) lower in pregnant (3.0 ± 0.4 ng/mL) vs nonpregnant patients (4.4 ± 0.5 ng/mL). There was a significant (P = .02) gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation. The receiver-operating characteristic curve showed AMH to be a useful predictor of no ovulation (area under the curve, 0.809; P < .001) with a useful cutoff level of 3.4 ng/mL. Ovulation and pregnancy rates were significantly higher (97%, P < .001, and 46%, P = .034) in patients with low AMH (<3.4 ng/mL) vs women with AMH 3.4 ng/mL or greater (48% and 19%). CONCLUSION: PCOS women with high circulating AMH (≥ 3.4 ng/mL) seem to be resistant to CC and may require a higher starting dose.

Impact of obesity on reproductive outcomes after ovarian ablative therapy in PCOS: a collaborative meta-analysis.

Obesity is known to interfere with reproductive outcomes in polycystic ovary syndrome. There is no consensus regarding the impact of obesity on reproductive outcomes after ovarian ablative therapy (OAT) and there is no level I evidence to answer this question. This systematic review and meta-analysis assessed the strength of the association between obesity and ovulation or pregnancy rates after OAT. MEDLINE and several other databases were searched from 2000 to September 2011 for studies reporting on OAT and reproductive outcomes. Data were synthesized to determine the relative risk of reproductive outcomes (ovulation and pregnancy) in lean (body mass index <25 kg/m(2)) compared with overweight or obese women. The study obtained 15 data sets (14 articles) for analysis, which included 905 subjects in the obese group and 879 subjects in the lean group. Lean women had increased ovulation rates (RR 1.43, 95% CI 1.22-1.66) compared with obese women. Pregnancy rates also showed a similar trend (RR 1.73, 95% CI 1.39-2.17). Reproductive outcomes were generally better in younger women, more recent studies and randomized controlled trials. It is concluded that lean women respond better to OAT than their obese counterparts. These epidemiological observations indicate that obesity alters reproductive outcomes after OAT negatively. Obesity is known to interfere with reproductive outcomes in polycystic ovary syndrome. There is no consensus regarding the impact of obesity on ovarian ablative therapy (OAT) and there is no level I evidence to answer this question. We therefore undertook a systematic review and meta-analysis to assess the strength of the association between obesity and ovulation or pregnancy rates after OAT. We searched MEDLINE and several other databases from 2000 to September 2011 for studies reporting on OAT and reproductive outcomes. Data were synthesized to determine the risk ratio of reproductive outcomes (ovulation and pregnancy) in lean (BMI <25 kg/m(2)) as opposed to overweight or obese women. We obtained 15 datasets (14 articles) for analysis, which included 905 subjects in the obese group and 879 subjects in the lean group. Lean women had increased ovulation rates (RR 1.43, 95% CI 1.22-1.66) as compared to obese women. Pregnancy rates also showed a similar trend (RR 1.73, 95% CI 1.39-2.17). Reproductive outcomes were generally better in younger women, more recent studies and randomized controlled trials. We conclude that lean women respond better to OAT than their obese counterparts. These epidemiological observations indicate that obesity alters reproductive outcomes after OAT negatively.

The validity of transvaginal ultrasound measurement of endometrial thickness: a comparison of ultrasound measurement with direct anatomical measurement.

OBJECTIVES: To compare transvaginal ultrasound measurements of endometrial thickness with direct anatomical measurements and consider the implications of these findings on clinical practice. DESIGN: Prospective observational study using two modalities blinded to each other's findings. SETTING: Singleton Hospital, Swansea, a medium-sized District General Hospital. SAMPLE: Forty-seven women admitted for hysterectomy. METHODS: All women underwent transvaginal ultrasound scan to measure the endometrial thickness within 16 hours of surgery. Anatomical measurement of the fresh specimen was carried out immediately after surgery. MAIN OUTCOME MEASURES: Agreement between ultrasound and anatomical measurements of the endometrial thickness. RESULTS: No ultrasound measurement was possible in 15% of patients. When both values were obtained, transvaginal ultrasound measurements were > 2 mm different from the ruler measurement in 13/40 (33%) with an obvious tendency of the ultrasound scan to over-estimate the endometrial thickness. The mean difference between the two measurements was -0.8 mm (limits of agreement -7.1 to +5.5 mm). The discrepancy was greater in women with endometrial thickness < or = 5 mm (-1.6 mm, limits of agreement -5.7 to +2.6 mm) compared with that in women with endometrial thickness > 5 mm (-0.2 mm, limits of agreement -7.6 to +7.2 mm). Kappa statistics showed good agreement between the two measurements in discriminating between thin and thick endometrium in 77% (kappa = 0.55). Transvaginal ultrasound misdiagnosed a thick endometrium as thin in 3/40 (8%) and misdiagnosed a thin endometrium as thick in 6/40 (15%). CONCLUSIONS: Transvaginal ultrasonography is of limited value as a screening test for abnormal endometrium in patients with postmenopausal bleeding if the only parameter of normality is an endometrial thickness of 5 mm or less.