A clinical predictive model for live birth in women of advanced age undergoing PGT cycles.

PURPOSE: The trend of delaying childbirth has resulted in a growing number of advanced-aged women who are opting for preimplantation genetic testing (PGT) to screen for monogenic diseases or structural chromosomal rearrangements (PGT-M and PGT-SR). This increase in demand necessitates the development of a clinical predictive model for live birth outcomes in these women. Therefore, the objective of this study is to construct a comprehensive predictive model that assesses the likelihood of achieving a successful live birth in advanced-aged women undergoing PGT-M and PGT-SR treatments. METHODS: A retrospective cohort study of 37-45-year-old women undergoing preimplantation genetic testing for monogenic disease or structural chromosomal rearrangement cycles from 2010 to 2021 was conducted at a university hospital reproductive centre. The purpose was to develop a clinical predictive model for live birth in these women. The main outcome studied was the cumulative live birth rate in the first or subsequent cycles. Developing a decision tree enabled a comprehensive study of clinical parameters and expected outcomes. RESULTS: The analysis included 158 women undergoing 753 preimplantation genetic testing cycles. The cumulative live birth rate was 37.342% (59/158). Decision tree analysis revealed that women aged ≤ 40.1 or women > 40.1 with one or more top-quality transferable embryos in their first cycle had the best chance for a live baby (56% and 41%, respectively). Those older than 40.1 without top-quality embryos and seven or fewer dominant follicles had no live births. A Kaplan-Meier curve showed that for autosomal dominant diseases, there was a negligible increase in live birth rate after three cycles, compared to six cycles in autosomal recessive inheritance. CONCLUSION: In older women, the chance of delivering after repeated cycles is higher in those with at least one top-quality unaffected embryo in their first preimplantation genetic testing cycle. Additional preimplantation genetic testing cycles after three in carriers of an autosomal dominant disorder and six in those with an autosomal recessive disorder should be considered prudently.

The impact of fragile X premutation carrier status on embryo morphokinetic development.

RESEARCH QUESTION: Does inheritance of the fragile X mental retardation 1 (FMR1) premutation allele affect embryo morphokinetic development? DESIGN: A retrospective cohort analysis of 529 embryos from 126 IVF cycles of 39 FMR1 premutation female carriers undergoing preimplantation genetic testing for monogenic/single gene defects (PGT-M). Morphological and morphokinetic parameters obtained using a time-lapse monitoring system were compared between embryos that inherited the FMR1 premutation allele (FMR1 group, n = 271) and those who received the normal allele (normal group, n = 258). The following embryo outcome measures were compared: morphokinetic parameters up to day 3, start of blastulation time (tSB) for day 5 embryos and the rate of top-quality embryos on days 3 and 5. RESULTS: No differences were found in morphokinetic parameters between the groups from the time of intracytoplasmic sperm injection (ICSI) until a biopsy on day 3. The blastulation rate in the two groups was comparable. However, the start of blastulation was delayed in FMR1 embryos compared to that in the genetically normal embryos (median tSB: 104.2 h [99.3-110.3] versus 101.6 h [94.5-106.7], P = 0.01). In addition, the rate of top-quality FMR1 embryos was lower than that of genetically normal embryos (25.6% versus 38.8%, P = 0.04). CONCLUSION: Embryos that inherit the FMR1 premutation allele are of lower quality at the blastocyst stage compared with those that do not inherit the mutated allele.

A decision tree analysis applied to women aged 43-45: who should be referred for ovum donation?

RESEARCH QUESTION: In women at the advanced age of 43-45 years undergoing repeated IVF cycles with autologous oocytes, who has the highest chance for birth and who should be referred early to receive donor oocytes? DESIGN: A retrospective cohort study was conducted at a university hospital reproductive centre. The computerized database of 394 women aged 43-45 years undergoing 1528 non-donor IVF or intracytoplasmic sperm injection cycles between 2010 and 2019 was analysed. A decision tree was developed, enabling a comprehensive study of a set of clinical parameters and the expected outcomes. RESULTS: The cumulative clinical pregnancy rate was 15.0% (59/394) and the cumulative live birth rate was 8.4% (33/394). The decision tree developed to predict women who should be offered egg donation included age, poor ovarian response to stimulation, the number of top-quality embryos, dominant follicles, previous pregnancy or live birth, fertilized oocytes and body mass index. The model showed that a good ovarian response in the first cycle was the best predictor for live birth (13.3% gave birth). However, among women with poor responses, 7.1% of those who were younger than 43.5 years gave birth, and none of the women who were older than 43.5 years did. CONCLUSIONS: Women over 43.5 years old with fewer than four oocytes collected in their first IVF cycle should be offered ovum donation, since their live birth rate in subsequent cycles is negligible.

A decision tree model for predicting live birth in FMR1 premutation carriers undergoing preimplantation genetic testing for monogenic/single gene defects.

RESEARCH QUESTION: Can patient selection for successful preimplantation genetic testing for women who are fragile X (FMR1) premutation carriers be optimized using a decision tree analysis? This decision support tool enables a comprehensive study of a set of clinical parameters and the expected outcomes. DESIGN: A retrospective case-control study analysing the results of 264 fresh and 21 frozen preimplantation genetic testing for monogenic disorders/single gene defects (PGT-M) cycles in 64 FMR1 premutation carriers. Primary outcome was live birth per cycle start. Live birth rate was calculated for the start of the ovarian stimulation cycle. Fresh and frozen embryo transfers from the same cycle were included. RESULTS: The decision tree model showed that the number of cytosine guanine (CGG) repeats was only a moderate predictor for live birth, whereas an age younger than 36 years was the best predictor for live birth, followed by a collection of 14 or more oocytes. These findings were supported by the results of the logistic regression, which found that only age and oocyte number were significantly associated with live birth (P = 0.005 and 0.017, respectively). CONCLUSIONS: The number of CGG repeats is a relatively poor predictor for live birth in PGT-M cycles. FMR1 premutation carriers are no different from non-carriers. Age is the best identifier of live birth, followed by the number of retrieved oocytes.

Effects of letrozole or tamoxifen coadministered with a standard stimulation protocol on fertility preservation among breast cancer patients.

PURPOSE: To assess the effects of letrozole or tamoxifen coadministration on fertility preservation treatment outcomes. METHODS: Retrospective cohort study of 118 breast cancer patients undergoing fertility preservation treatment between 2008 and 2018. Patients who received letrozole (n = 36) or tamoxifen (n = 30) were compared to controls (n = 52) who underwent standard ovarian stimulation protocols. The primary outcome measures included the number of retrieved oocytes, mature oocytes (MII), fertilization, and top-quality embryo rates. The secondary outcome measures included duration of stimulation, gonadotropin dose and peak estradiol level. RESULTS: The number of oocytes retrieved, MII oocytes, fertilization rate, duration of stimulation, or gonadotropin dose were similar in the letrozole and tamoxifen groups, compared to controls. Top-quality embryo rate was lower in the tamoxifen group compared to controls (25% vs 39.4%, respectively, P = 0.034). The abnormal fertilization rate was higher in the letrozole group compared to controls (7.8% vs 3.60%, respectively, P = 0.015). A stepwise logistic regression analysis revealed that letrozole and peak estradiol were significantly associated with abnormal fertilization (OR 11.94; 95% CI 2.35-60.4, P = 0.003 for letrozole and OR 1.075; 95% CI 1.024-1.12, P = 0.004 per 100 unit change in estradiol). CONCLUSIONS: There may be a negative effect of letrozole or tamoxifen on fertilization and embryo quality, in fertility preservation cycles. Further studies are needed to confirm these findings.

Morphokinetic characteristics of embryos originating from extremely small follicles: A prospective study.

OBJECTIVE: To investigate the developmental potential of oocytes and embryos derived from extremely small follicles (<10 mm) in comparison to those originated in larger follicles. STUDY DESIGN: A prospective study, undertaken in a university affiliated single center tertiary hospital. The study included 98 patients undergoing infertility treatments. On the day of ovum pickup (OPU) follicles were counted and measured. Aspiration of follicles larger and smaller than 10 mm was undertaken separately and the development of embryos originating from oocytes from these follicles was followed up using different wells for each embryo. There was no low limit of size for aspiration. Each oocyte retrieved was marked for its origin and numbered for further follow up. We recorded: Oocytes retrieved, maturation stage, fertilization rate, cleavage rate, morphokinetic parameters, embryo transfers, embryo freezing, oocyte freezing and biopsy rate for preimplantation genetic diagnosis (PGD). Quality was evaluated by the morphokinetic parameters of the embryos developed using time-lapse imaging technology. Day 3 KIDScore was calculated to all embryos. RESULTS: Small follicles compared to large follicles displayed lower recovery rate (45% vs. 74%, P < 0.0001), fewer matured oocytes (37.5% vs. 61.7%, P < 0.0001), higher rates of GV oocytes (20.7% vs., 3.7%, P < 0.0001), and lower fertilization rate (43.7% vs. 63.3%, P < 0.0001. However, morphokinetic variables were similar between embryos that originated from either small or large follicles. Median KIDscores were identical for embryos from small or large follicle origin. CONCLUSIONS: Embryos originated from small follicles were not different than embryos from larger follicles, as assessed by morphokinetic parameters in time lapse system. In view of our findings, physicians should bear in mind that small follicle aspiration might yield good quality embryos.

Complicated Clinical Course and Poor Reproductive Outcomes of Women with Tubo-Ovarian Abscess after Fertility Treatments.

STUDY OBJECTIVE: To assess the clinical course and surgical and fertility outcomes of patients diagnosed with tubo-ovarian abscess (TOA) after fertility treatment. DESIGN: Parallel case series over 10 consecutive years (Canadian Task Force classification II-2). SETTING: Tel Aviv Sourasky Medical Center, a tertiary university-affiliated hospital. PATIENTS: Thirty-seven women who were diagnosed with TOA after fertility treatments (in vitro fertilization and intrauterine insemination) were compared with 313 women who were diagnosed with TOA not associated with fertility treatments during the same time period. INTERVENTION: Medical records search, chart review, and phone survey were used to assess clinical course and surgical and reproductive outcomes. MEASUREMENTS AND MAIN RESULTS: Women with TOA after fertility treatments had significantly higher inflammatory markers upon admission compared with the nonfertility treatment group (mean white blood cell count, 16.1 × 1000/mm3 [standard deviation [SD], ±4.3] vs 13.8 × 1000/mm3 [SD, ±6.3], p = .001, respectively; and mean C-reactive protein, 149 mg/L [SD, ±78.3] vs 78.2 mg/L [SD, ±68.5], p = .001, respectively). In addition, TOA after fertility treatments was associated with a significantly higher surgical intervention rate and a more complicated clinical course, as evidenced by a shorter time interval from admission to surgery (2.1 days vs 3.2 days, p = .01), higher rates of antibiotic failure, higher conversion rate from laparoscopy to laparotomy (14.2% vs 3.2%, p = .005), increased perioperative complications rate (25.0% vs 3.8%, p = .0001), and a longer hospitalization stay (7.2 days vs 4.8 days, p = .01). Clinical pregnancy rate per cycle in women with TOA after fertility treatments was 9%, and 1 case of live birth was recorded. CONCLUSIONS: Our data indicate that TOA after fertility treatment has a substantial effect on the clinical course and surgical outcome. Prophylactic antibiotic treatment before ovum retrieval and deferral of embryo transfer should be considered in patients at risk of infection.

Surgical Intervention in Patients with Tubo-Ovarian Abscess: Clinical Predictors and a Simple Risk Score.

STUDY OBJECTIVE: To identify the clinical characteristics associated with surgical intervention in patients with tubo-ovarian abscess (TOA). DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Tertiary university-affiliated hospital. PATIENTS: Three hundred thirty-five patients were diagnosed with TOA based on sonographic and clinical criteria. Patients who underwent surgical intervention were compared with patients managed conservatively. INTERVENTION: Electronic medical records were used to identify patients who were diagnosed with TOA between 2007 and 2015. All patients received the same antibiotic regimen upon admission. The data extracted included microbial and pathologic reports. Clinical characteristics such as disease severity and outcomes were compared. The clinical predictors available on patient admission for surgical intervention were identified retrospectively. A logistic regression was used to determine the independent predictors of treatment failure. A risk score was created by giving a nominal weight to each predictor. The score was validated by a random bootstrap analysis. An additional validation cohort that consisted of patients diagnosed with TOA during the 2 years after the original study period was applied to the final score. MEASUREMENTS AND MAIN RESULTS: The following variables of patients who underwent surgical intervention in comparison with those successfully treated and were enrolled into the score analysis differed significantly: age at admission (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3-3.5), mean leukocytosis at admission (OR, 2.2; 95% CI, 1.3-3.6), ultrasonographic measurement of abscess diameter (OR, 3.6 95% CI, 2.0-6.3), and the presence of bilateral abscess (OR, 2.2; 95% CI, 1.3-3.9). Risk groups A, B, C, and D were positively correlated with the need for surgical intervention. Those in the highest risk group D had an antibiotic failure rate of 92%, as compared with those with the lowest risk group, in which there was a 20% risk of antibiotic failure. CONCLUSIONS: Antibiotic treatment failure for TOA can be predicted on patient admission using a novel risk assessment score.

Hydrosalpinx Sclerotherapy Before In Vitro Fertilization: Systematic Review and Meta-analysis.

The presence of a hydrosalpinx has been shown to impair the outcome of in vitro fertilization (IVF) treatment. This outcome can be improved by removing the hydrosalpinx; however, there are some concerns regarding its feasibility and safety, especially in women with previous surgeries and dense adhesions. The purpose of our meta-analysis was to evaluate the efficacy of hydrosalpinx aspiration with or without sclerotherapy on the risk of recurrence and the IVF outcome compared with salpingectomy or no intervention. We performed an electronic-based search using PubMed, Embase, Ovid MEDLINE, Google Scholar, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials. Our main outcome measures were the recurrence rate, fertility outcome, and adverse events. Ten studies were included in our review. The overall recurrence rates of hydrosalpinx aspiration with or without sclerotherapy were 21.7% to 30.5% and 21.8% to 32.5%, respectively. There was no difference in the clinical pregnancy or miscarriage rate between hydrosalpinx sclerotherapy and salpingectomy. When compared with salpingectomy, hydrosalpinx aspiration only was associated with a significantly lower clinical pregnancy rate and higher miscarriage rate. Compared with no intervention, hydrosalpinx aspiration resulted in significantly higher clinical pregnancies rates but a similar miscarriage rate. We conclude that hydrosalpinx sclerotherapy before IVF improves the fertility outcome and can be used as an alternative to salpingectomy.

Prolonged activation of the coagulation system during in vitro fertilization cycles.

OBJECTIVE: To investigate coagulation system changes during an in-vitro fertilization (IVF) cycle using Thromboelastogram (TEG) that enables analysis of the elastic properties of whole blood samples and provides a global assessment of the hemostatic function. STUDY DESIGN: A prospective study. TEG indices were evaluated in 23 women who underwent controlled ovarian stimulation for IVF at four points in time: 1. At the beginning of the cycle (corresponding to the lowest levels of E2), 2. On the day of hCG administration (maximal stimulation with highest E2 levels), 3. On the day of ovum pickup and 4. At the first pregnancy test (approximately 14days after ovum pickup). The main outcome measures were TEG indices including R-time (time until initial fibrin formation), K-time (time until a 20mm amplitude is achieved), α angle (the rate of clot formation), Maximum Amplitude (MA, strength of the fibrin clot), Coagulation Index (CI, calculated overall indicator of coagulation) and LY30 (the decrease in graph amplitude). RESULTS: R, K, α angle, MA and CI before hCG administration and at the time of the first pregnancy test were significantly higher compared to the baseline measurement before gonadotropins administration. No correlation was found between E2 and TEG indices. CONCLUSION: Ovarian stimulation is associated with prolonged increased coagulability that extends after the time of maximal ovarian stimulation. The lack of association between E2 levels and TEG indices suggest that additional factors may play a role in the pathogenesis of increased coagulability in women with ovarian stimulation.

Sclerotherapy in the management of ovarian endometrioma: systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of sclerotherapy for ovarian endometrioma on the risk of recurrence, clinical symptoms, and reproductive function. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Patients who underwent sclerotherapy of ovarian endometrioma. INTERVENTION(S): An electronic-based search with the use of Pubmed, Embase, Ovid Medline, Google Scholar, Clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials. MAIN OUTCOME MEASURE(S): Recurrence rate, symptoms relief, fertility outcome, and adverse events. RESULT(S): Eighteen studies were included in our review. The overall recurrence rates of endometrioma after sclerotherapy ranged from 0 to 62.5%. The risk of recurrence was significantly higher in women who were treated by means of ethanol washing than by means of ethanol retention. The number of oocytes retrieved was higher after endometrioma sclerotherapy compared with laparoscopic cystectomy, but clinical pregnancy rates were similar. There was no difference in the number of oocytes retrieved and the clinical pregnancy rates between the sclerotherapy-treated group with and the untreated group. CONCLUSION(S): Sclerotherapy for ovarian endometrioma may be considered in symptomatic women who plan to conceive.

The ovarian response in fragile X patients and premutation carriers undergoing IVF-PGD: reappraisal.

STUDY QUESTION: What is the association between the ovarian response and the number of CGG repeats among full mutation and premutation carriers of fragile X (FMR1), undergoing controlled ovarian hyperstimulation (COH) for PGD? SUMMARY ANSWER: Ovarian response was normal in full mutation patients but decreased in premutation carriers, although the number of repeats was not statistically significantly associated with the number of oocytes retrieved. WHAT IS KNOWN ALREADY: There is inconsistent data in the literature regarding ovarian response in FMR1 carriers. Studies exploring the ovarian response of full mutation patients are lacking. STUDY DESIGN, SIZE, DURATION: Retrospective study, a university affiliated tertiary hospital, IVF unit, PGD referral center. PARTICIPANTS/MATERIALS, SETTING, METHODS: We examined the medical records of all women undergoing fresh IVF-PGD cycles due to fragile X. Data recorded included demography, duration of stimulation, amount of gonadotropins administered, number of dominant follicles, maximal E2 levels and number of oocytes retrieved. Data were analyzed using univariate and multivariate mixed models. P-values <0.05 were considered significant. Data were collected from the medical records of 21 patients with a full mutation on the FMR1 gene and 51 premutation carriers. Overall 309 fresh cycles were analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: Premutation carriers displayed reduced ovarian response, as demonstrated by fewer oocytes retrieved. In contrast, full mutation patients had a normal response. Comparison of premutation carriers and full mutation patients showed: mean oocytes retrieved per cycle (8.4 ± 1.1 versus 14.1 ± 1.7, P = 0.005), lower levels of estradiol (E2; 1756 ± 177, versus 2928 ± 263, P = 0.0004), respectively. There was no significant difference between premutation carriers and full mutation patients in regard to fertilization rate, cleavage rate or biopsy rate. No correlation was found between the number of repeats in the premutation carriers and the number of oocytes retrieved or E2 levels. Age and the type of protocol were the only factors found to be in correlation with the number of the oocyte retrieved (P = 0.037, and P = 0.003, respectively) among the premutation carriers. Similarly, no association was found between the number of repeats and the fertilization rate, cleavage rate or biopsy rate among premutation carriers. LIMITATIONS, REASONS FOR CAUTION: We had a relatively low number of premutation carriers with >100 repeats, which made it challenging to draw a firm conclusions from this group. WIDER IMPLICATIONS OF THE FINDINGS: Physicians must address the increased risk for reduced ovarian response and  primary ovarian insufficiency (POI) among carriers and consider surveillance of ovarian reserve markers. The last, might expedite family plans completion or fertility preservation. STUDY FUNDING/COMPETING INTEREST(S): None.

The effect of endometrial injury on implantation and clinical pregnancy rates.

AIM: To assess the effect of endometrial scratching (ES) on in vitro fertilization-embryo transfer outcome (IVF-ET) Materials and methods: Retrospective matched case control study including all fresh IVF cycles performed between January 2006 and December 2012 at an academic IVF center. ES with an endometrial biopsy catheter was performed in the cycle preceding the index IVF cycle. Patients (n = 238) were pair matched with controls according to age, number of previous failed IVF cycles and number of embryos transferred. RESULTS: Demographic and cycle characteristics were comparable in all of the following: age, number of previous cycles, number of collected oocyte, number of embryos transferred and quality of transferred embryos. Implantation, clinical and ongoing pregnancy rates were comparable in both groups (28%, 34% and 18.4% vs 30%, 40.3% and 29%, in ES group and controls, respectively). Logistic regression analysis found no significant association between ES and pregnancy rate. CONCLUSIONS: Mechanical endometrial stimulation did not improve implantation and pregnancy rates. Furthermore, no factors that may predict which patients could benefit from ES were identified. Further prospective studies are warranted to evaluate possible benefits in different subsets of patients such as patients with recurrent implantation failures.

A New Perspective on the Risk of Hypercoagulopathy in Ovarian Hyperstimulation Syndrome Using Thromboelastography.

Thromboelastography (TEG) provides real-time assessment of hemostasis by measuring the viscoelastic properties, coagulation factor, and platelet activity in whole blood samples. In this prospective case-control study, we wanted to investigate whether blood clot formation assessment, using TEG, can identify a hypercoagulable state in women with severe ovarian hyperstimulation syndrome (OHSS). Thirty-six women who were hospitalized with severe OHSS were allocated to the OHSS group and 32 women undergoing controlled ovarian hyperstimulation but who did not develop OHSS were allocated to the control group. The TEG indices were compared between women with severe OHSS and controls. All the coagulation indices assessed by TEG were significantly different in the OHSS group compared to the controls, depicting a hypercoagulable state. Median coagulation index was 3.6 (interquartile range: 2.80-4.15) and 1.45 (interquartile range: 0.20-2.30) in study group and controls, respectively ( P < .001). Our results show that TEG can be used to depict a hypercoagulable state in women with severe OHSS.

The role of HCG increment in the 48h prior to methotrexate treatment as a predictor for treatment success.

OBJECTIVE: To evaluate the role HCG change in the 48h prior to methotrexate treatment as a predictor for treatment success. STUDY DESIGN: Medical records of all women who were diagnosed with ectopic pregnancy between January 2001 and June 2013 were reviewed. Four hundred and nine patients received methotrexate due to ectopic pregnancy. The "single dose" methotrexate protocol with 50mg/m2 was administered to patients with progressing ectopic pregnancy. HCG levels in days 1, 4 and 7 were used to evaluate methotrexate treatment success. The percentage of HCG change in the 48h prior to methotrexate treatment was compared between patients who were successfully treated and those who failed treatment with methotrexate. RESULTS: Single dose methotrexate was successful in 309 patients (75.4%, success group). The medians of HCG change in the 48h prior to methotrexate administration were significantly higher in the "failure group" (21% vs. 4%, p<0.01). In a logistic regression analysis, the of HCG percent increment prior to methotrexate administration was shown to be an independent predictor for treatment outcome. Receiver operator characteristic curve for HCG percent change was 0.751, at a cutoff value of HCG increment <12% the positive predictive value for treatment success reached 86%. CONCLUSIONS: Percentage of HCG increment in the 48h prior to methotrexate administration is an independent predictor for methotrexate treatment success. HCG increment <12% prior to methotrexate treatment is a good predictor for treatment success.

Adnexal Torsion in Postmenopausal Women: Clinical Presentation and Risk of Ovarian Malignancy.

STUDY OBJECTIVE: To investigate the clinical presentation, operative outcome, and incidence of malignancy in postmenopausal women who were diagnosed with adnexal torsion. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Tertiary university-affiliated hospital. PATIENTS: Postmenopausal women diagnosed with adnexal torsion between 1995 and 2014 (study group) were reviewed and compared with 220 premenopausal patients diagnosed with adnexal torsion during the same time period. INTERVENTION: Demographic data, clinical signs and symptoms, and intra- and postoperative characteristics were compared between the 2 groups. MEASUREMENTS AND MAIN RESULTS: During the study period 44 postmenopausal women were diagnosed with adnexal torsion. Continuous dull pain was the most common presenting symptom in the postmenopausal group (57%), whereas acute-onset sharp pain was the predominant symptom in the premenopausal group (86%). The time interval from admission to surgery was significantly longer in the postmenopausal group (24 vs 6 hours, p < .001). Laparoscopic surgery was performed in 84.5% of the cases in the premenopausal group, whereas it was carried out in only 50% of cases in the postmenopausal group (p < .001). Four women in the postmenopausal group were diagnosed with malignancy, whereas only 1 case of malignancy was found in the premenopausal group (9% vs .4%, respectively; p = .003). CONCLUSIONS: Adnexal torsion in postmenopausal women is an uncommon event with a unique presentation. Because ovarian malignancy is not an uncommon finding in this group of patients, preparation for more extensive surgery should be contemplated.

Effects of Fatigue on Residents' Performance in Laparoscopy.

BACKGROUND: The influence of fatigue on residents' performance in laparoscopy was prospectively assessed through a computer-based virtual reality simulation (VRS) model. STUDY DESIGN: Twenty-six residents (14 novices, 12 experienced) were recruited. In the first stage, each participant was initially tested on 8 VRS-based tasks. In the second, run-in stage, each resident had 8 hours of hands-on practice of the specific tasks chosen. Finally, participants were evaluated before and after 24 hours on call. For each task, a set of parameters reflecting proficiency, efficacy, and safety were documented. RESULTS: In most of the tasks assessed, sleep deprivation had a significant deleterious effect on the performance of residents, both in terms of efficiency (time to complete the task), and safety (errors). These observations were more pronounced among novices. For example, in camera manipulation at a 30-degree angle, the total time to complete the task was slower after sleep deprivation (novices: sleep deprivation = 136 seconds, control = 119 seconds; experienced: sleep deprivation = 112 seconds, control = 103 seconds; p = 0.03). Moreover, accuracy rates were lower after sleep deprivation: in the "grasping and clipping" task, a lower accuracy rate after sleep deprivation was noted (novices: sleep deprivation = 82.8%, control = 87.9%; experienced: sleep deprivation = 87.6%, control = 90.8%; p = 0.05). CONCLUSIONS: In this prospectively controlled study we observed reduced efficiency and safety in the performance of residents after sleep deprivation. Using an innovative study design, we eliminated the learning curve bias. Compared with novices, experienced residents performed relatively better after a night shift, and this may be attributed to better adaptation to sleep deprivation.

Second-dose methotrexate in ectopic pregnancies: the role of beta human chorionic gonadotropin.

OBJECTIVE: To evaluate the role of ß-hCG levels on days 1, 4, and 7 after methotrexate as predictors for second-dose requirement and success. DESIGN: Retrospective cohort study. SETTING: Tertiary university-affiliated hospital. PATIENT(S): A total of 1,703 patients were admitted because of ectopic pregnancy. Four hundred nine received methotrexate, of whom 73 women required a second dose. INTERVENTION(S): The "single-dose" methotrexate protocol with 50 mg/m(2) was administered to patients with progressing ectopic pregnancy. Surgical intervention was performed in cases of methotrexate second-dose treatment failure. MAIN OUTCOME MEASURE(S): Methotrexate second-dose requirement and success according to ß-hCG levels on days 1, 4 and 7. RESULT(S): Second-dose methotrexate was successful in 58 patients (79.4%, success group), whereas 15 patients (20.6%) failed treatment and required surgical intervention (failure group). The medians of ß-hCG levels on days 1, 4, and 7 were significantly higher in the "failure group" (1,601 vs. 2,844, 2,164 vs. 3,225, and 1,915 vs. 3,745 mIU/mL, respectively). Logistic regression analysis demonstrated that day-1 ß-hCG levels were the only significant independent variable for second-dose treatment outcome. The receiver operating characteristic curve for ß-hCG levels on day 1 was 0.727, and at a cutoff value of 2,234 mIU/mL the sensitivity and specificity reached the optimum for treatment success (77.5% and 73.3%, respectively). CONCLUSION(S): Day-1 ß-hCG levels were the only predictors for methotrexate second-dose requirement and treatment success. The cutoff value of ß-hCG on day 1 with the optimal treatment results was found to be 2,234 mIU/mL.