Sherif A. El-Nashar

Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis.

OBJECTIVE To determine whether gonadotropin-releasing hormone (GnRH) analog cotreatment with chemotherapy provides better reproductive outcomes for women at risk of premature ovarian failure (POF) as a side-effect of gonadotoxic chemotherapy. DESIGN Systematic review and meta-analysis. SETTING University-affiliated research centers. PATIENT(S) None. INTERVENTION(S) Electronic and manual searches (e.g., MEDLINE, EMBASE, CENTRAL) up to January 2010 were performed to identify randomized controlled trials (RCTs) comparing GnRH cotreatment with chemotherapy alone in premenopausal women. MAIN OUTCOME MEASURE(S) Incidence of POF after treatment, incidence of women with resumption of ovulation, POF after an initial normal cycle, normal cycles but abnormal markers of ovarian reserve, spontaneous occurrence of pregnancy after treatment, and time to reestablishment of menstruation; data also extracted to allow for an intention-to-treat analysis. RESULT(S) Twenty-eight RCTs were identified, but only six met the inclusion criteria. Data were only available for the incidence of women with new onset of POF, resumption of ovulation, and occurrence of pregnancy. The incidence of POF or resumption of ovulation both demonstrated a statistically significant difference in favor of the GnRH cotreatment. The occurrence of spontaneous pregnancy showed no statistically significant difference between GnRH cotreatment and the control groups. CONCLUSION(S) Evidence from RCTs suggests a potential benefit of GnRH cotreatment with chemotherapy in premenopausal women, with higher rates of spontaneous resumption of menses and ovulation but not improvement in pregnancy rates. Data relating to study quality and possible bias for the majority of the outcomes in this review were not available, denoting possible selective reporting of trial data.

Sling surgery for stress urinary incontinence in women: a systematic review and metaanalysis.

OBJECTIVE Understanding the long-term comparative effectiveness of competing surgical repairs is essential as failures after primary interventions for stress urinary incontinence (SUI) may result in a third of women requiring repeat surgery. STUDY DESIGN We conducted a systematic review including English-language randomized controlled trials from 1990 through April 2013 with a minimum 12 months of follow-up comparing a sling procedure for SUI to another sling or Burch urethropexy. When at least 3 randomized controlled trials compared the same surgeries for the same outcome, we performed random effects model metaanalyses to estimate pooled odds ratios (ORs). RESULTS For midurethral slings (MUS) vs Burch, metaanalysis of objective cure showed no significant difference (OR, 1.18; 95% confidence interval [CI], 0.73-1.89). Therefore, we suggest either intervention; the decision should balance potential adverse events (AEs) and concomitant surgeries. For women considering pubovaginal sling vs Burch, the evidence favored slings for both subjective and objective cure. We recommend pubovaginal sling to maximize cure outcomes. For pubovaginal slings vs MUS, metaanalysis of subjective cure favored MUS (OR, 0.40; 95% CI, 0.18-0.85). Therefore, we recommend MUS. For obturator slings vs retropubic MUS, metaanalyses for both objective (OR, 1.16; 95% CI, 0.93-1.45) and subjective cure (OR, 1.17; 95% CI, 0.91-1.51) favored retropubic slings but were not significant. Metaanalysis of satisfaction outcomes favored obturator slings but was not significant (OR, 0.77; 95% CI, 0.52-1.13). AEs were variable between slings; metaanalysis showed overactive bladder symptoms were more common following retropubic slings (OR, 1.413; 95% CI, 1.01-1.98, P = .046). We recommend either retropubic or obturator slings for cure outcomes; the decision should balance AEs. For minislings vs full-length MUS, metaanalyses of objective (OR, 4.16; 95% CI, 2.15-8.05) and subjective (OR, 2.65; 95% CI, 1.36-5.17) cure both significantly favored full-length slings. Therefore, we recommend a full-length MUS. CONCLUSION Surgical procedures for SUI differ for success rates and complications, and both should be incorporated into surgical decision-making. Low- to high-quality evidence permitted mostly level-1 recommendations when guidelines were possible.

Prediction of Treatment Outcomes After Global Endometrial Ablation

OBJECTIVE: To report rates of amenorrhea and treatment failure after global endometrial ablation and to estimate the association between patient factors and these outcomes by developing and validating prediction models. METHODS: From January 1998 through December 2005, 816 women underwent global endometrial ablation with either a thermal balloon ablation or radio frequency ablation device; 455 were included in a population-derived cohort (for model development), and 361 were included in a referral-derived cohort (for model validation). Amenorrhea was defined as cessation of bleeding from immediately after ablation through at least 12 months after the procedure. Treatment failure was defined as hysterectomy or reablation for patients with bleeding or pain. Logistic and Cox proportional hazard regression models were used in model development and validation of potential predictors of outcomes. RESULTS: The amenorrhea rate was 23% (95% confidence interval [CI] 19–28%) and the 5-year cumulative failure rate was 16% (95% CI 10–20%). Predictors of amenorrhea were age 45 years or older (adjusted odds ratio [aOR] 2.6, 95% CI 1.6–4.3); uterine length less than 9 cm (aOR 1.8, 95% CI 1.1–3.1); endometrial thickness less than 4 mm (aOR 2.7, 95% CI 1.2–6.3); and use of radio-frequency ablation instead of thermal balloon ablation (aOR 2.8, 95% CI 1.7–4.9). Predictors of treatment failure included age younger than 45 years (adjusted hazard ratio [aHR] 2.6, 95% CI 1.3–5.1); parity of 5 or greater (aHR 6.0, 95% CI 2.5–14.8); prior tubal ligation (aHR 2.2, 95% CI 1.2–4.0); and history of dysmenorrhea (aHR 3.7, 95% CI 1.6–8.5). After global endometrial ablation, 23 women (5.1%, 95% CI 3.2–7.5%) had pelvic pain, three (0.7%, 95% CI 0.1–1.9%) were pregnant, and none (95% CI 0–0.8%) had endometrial cancer. CONCLUSION: Population-derived rates and predictors of treatment outcomes after global endometrial ablation may help physicians offer optimal preprocedural patient counseling. LEVEL OF EVIDENCE: II

A randomized clinical trial of a levonorgestrel-releasing intrauterine system and a low-dose combined oral contraceptive for fibroid-related menorrhagia.

To compare the efficacy of a levonorgestrel‐releasing intrauterine system (LNG‐IUS) with that of a low‐dose combined oral contraceptive (COC) in reducing fibroid‐related menorrhagia.

Levonorgestrel-releasing intrauterine system compared to low dose combined oral contraceptive pills for idiopathic menorrhagia: a randomized clinical trial

BACKGROUND This study compared the efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS) to low dose combined oral contraceptive pills (COC) in the management of idiopathic menorrhagia. STUDY DESIGN A single-center, open, randomized clinical trial. One hundred twelve women complaining of excessive menstruation who desired contraception were randomized to receive LNG-IUS or COC. Treatment failure was defined as the need for medical or surgical treatment during the follow-up. Other outcomes included: menstrual blood loss (MBL) by alkaline hematin and by pictorial blood assessment chart (PBLAC), hemoglobin levels and assessment of lost days in which physical or mental health prevented participating women from performing usual activities. RESULTS At baseline, LNG-IUS (n=56) and COC (n=56) groups were comparable in age (mean ± S.D.) (39.3 ± 6.7 vs. 38.7 ± 5.2 years, p=.637), parity (median and range) [3(1-6.4) vs.3(2-6), p=.802] and BMI (mean ± S.D.) (29.6 ± 5.9 vs. 31.1 ± 5.7 kg/m(2), p=.175). Time to treatment failure was longer in LNG compared to COC group with a total of 6 (11%) patients who had treatment failure in the LNG-IUS compared to 18 (32%) in COC group with a hazard ratio of 0.30 (95% CI, 0.15-0.73, p=.007). Using alkaline hematin, the reduction in MBL (mean ± S.D.) was significantly more in the LNG-IUS group (87.4 ± 11.3%) compared to the COC group (34.9 ± 76.9%) (p=.013). Utilizing PBLAC scores, the reduction in the LNG-IUS (86.6 ± 17.0%) group was significantly more compared to the COC group (2.5 ± 93.2%) (p<.001). In the LNG-IUS group, increase in the hemoglobin and ferritin levels (mean ± S.D.) were noted (from 10.2 ± 1.3 to 11.4 ± 1.0 g/dL; p<.001; with reduction of the number of lost days (from 6.8 ± 2.6 to 1.6 ± 2.4 days, p=.003). CONCLUSION The LNG-IUS is a more effective therapy for idiopathic menorrhagia compared to COC.

Reproductive outcome after transplantation of ovarian tissue: a systematic review

BACKGROUND Despite interest in ovarian tissue transplantation (OTT) as a promising procedure for fertility preservation, to date, no precise data are available about its effectiveness. We systematically reviewed reproductive function after OTT for fertility preservation in women at high risk of premature ovarian failure (POF). METHODS We searched the MEDLINE, EMBASE, Cochrane Systematic Reviews, CENTRAL, Web of Science and Scopus databases for studies on the reproductive outcomes after OTT in humans up to June 2007. Women with follicle-stimulating hormone (FSH) >30 IU/l at the time of OTT were included in a meta-analysis of individual-patient data to evaluate the time to re-establishment of ovarian function (ROF). Secondary outcomes included short-term (<12 months) and long-term (>12 months) ovarian function (OVF) and pregnancy after OTT. RESULTS We identified 25 reports including 46 unique cases. OTT was performed to treat POF in 27 women, to prevent POF in 15, to treat infertility in 2 and accidentally in 1. In 23 women with FSH >30 at the time of OTT, OVF was re-established with a median time to ROF of 120 days (range 60-244). Within 6 months after ROF, four women had recurrent ovarian failure. There are insufficient data to evaluate the long-term OVF (>12 months). Fresh grafts had an increased likelihood of return of OVF and a decreased likelihood for recurrent ovarian failure compared with cryopreserved grafts [HR of 2.44 (95% CI 0.92, 6.49) and 0.47 (95% CI 0.18, 1.12), respectively]. In 25 women who sought pregnancy, eight women had nine pregnancies at 12 months, giving a cumulative pregnancy rate of 37% (95% CI 19, 60). CONCLUSIONS Transplantation of ovarian tissue can re-establish OVF after POF; however, the efficacy of OTT using cryopreserved tissues is not yet equivalent to that of fresh grafts. A controlled multicenter trial with sufficient follow-up would provide valid evidence of the potential benefit of this procedure.

Pictorial blood loss assessment chart in the evaluation of heavy menstrual bleeding: diagnostic accuracy compared to alkaline hematin.

Background/Aims: The pictorial blood assessment chart (PBAC) is a method for evaluation of menstrual blood loss (MBL). This study was conducted to evaluate the accuracy of the PBAC score in diagnosing MBL compared to alkaline hematin as a gold standard. Methods: Two cohorts were constructed: 30 women who reported ‘normal’ menses and 170 who reported ‘heavy’ menses. Evaluation of menstruation was performed using the PBAC score and by alkaline hematin. Results: Women who reported normal menses were younger (p = 0.071), had lower parity [median parity of 3 (range 1–6) vs. 4 (range 1–12), p < 0.001] and higher hemoglobin levels (11.1 ± 1.1 vs. 10.1 ± 1.6 g/dl, p < 0.001). PBAC scores and MBL by alkaline hematin were significantly correlated (Spearman r = 0.600, p < 0.001). The PBAC score of 150 had a ĸ of 0.593 (95% CI 0.480–0.687) and an area under the curve of 0.796 (95% CI 0.770–0.821). In a multivariable regression PBAC score >150, presence of blood clots and period duration >7 days were independent predicators of heavy menstrual bleeding with an overall area under the curve of 0.858 (95% CI 0.835–0.879). Conclusions: The PBAC score is a simple and accurate tool for semiobjective of MBL that can be used in clinical practice to aid the decision about treatment and follow-up.

Techniques for cryopreservation of individual or small numbers of human spermatozoa: a systematic review

BACKGROUND Despite interest in cryopreservation of individual or small number of human spermatozoa, to date, little data is available as regards its effectiveness. We systematically reviewed the outcome after cryopreservation of individual or small numbers of human spermatozoa in patients with severe male factor of infertility. METHODS We searched the MEDLINE, EMBASE, Cochrane Systematic Reviews, CENTRAL, Web of Science, Scopus databases for relevant studies up to June of 2008. The search used terms referring to cryopreservation of small amount of sperm. Included studies were limited to human studies with no language restrictions. RESULTS We identified 30 reports including 9 carriers used for cryopreservation of small quantities/numbers of human spermatozoa (7 non-biological and 2 biological carriers). A wide variety of cryopreservation vehicles were reported. The recovery rate of spermatozoa cryopreserved in a known small number varied widely from 59 to 100%. Fertilization rates were in the range of 18-67%. Frozen-thawed spermatozoa, using this method, were subsequently used for intracytoplasmic sperm injection in only five studies, with few pregnancies reported so far. To date, there remains no consensus as to the ideal carrier for cryopreservation of small number of spermatozoa for clinical purposes. CONCLUSIONS Cryopreservation of individual or small numbers of human spermatozoa may replace the need for repeated surgical sperm retrieval. A controlled multicenter trial with sufficient follow-up would provide valid evidence of the potential benefit of this approach.

Global endometrial ablation for menorrhagia in women with bleeding disorders

OBJECTIVE: To evaluate the efficacy of global endometrial ablation in women with bleeding disorders who presented with menorrhagia. METHODS: A records-linkage system was used to construct a retrospective cohort of 41 women with bleeding disorders (coagulopathy) and a reference group of 111 randomly selected women without bleeding disorders from a pool of 943 women who underwent global endometrial ablation (with thermal balloon ablation technology or bipolar radiofrequency ablation technology) for menorrhagia at Mayo Clinic (Rochester, Minnesota) from January 1995 through December 2005. Demographic data, type of global endometrial ablation therapy and reablation, and hysterectomy data were extracted from the database. RESULTS: There was no significant difference in baseline age, parity, body mass index, uterine size, type of global endometrial ablation therapy, or duration of follow-up between the groups. Two women (5%) in the coagulopathy group had hysterectomy or reablation, compared with 8 (7%) in the reference group (Fisher exact test, P=.728). A Kaplan-Meier plot showed no difference in the time to treatment failure between the groups (log-rank test, P=.534). Procedural-related complications were generally minor and infrequent (9 of 152 [6%]). Complications were equally distributed in the coagulopathy (4 of 41) and reference groups (6 of 111) (Fisher exact test, P=.267). CONCLUSION: Global endometrial ablation is an effective treatment choice for women with coagulopathy presenting with menorrhagia. LEVEL OF EVIDENCE: II

Pathologic Characteristics of Hysterectomy Specimens in Women Undergoing Hysterectomy after Global Endometrial Ablation

STUDY OBJECTIVE To describe uterine pathologic features in women who underwent hysterectomy because of failed global endometrial ablation (GEA). DESIGN Retrospective cohort study from 1998 through 2005 (Canadian Task Force classification III). SETTING Tertiary referral center. PATIENTS Sixty-nine women who underwent hysterectomy because of GEA failure. INTERVENTIONS Pathology reports were available for 67 patients. Descriptions of hysterectomy specimens after GEA were reviewed. MEASUREMENTS AND MAIN RESULTS Rates of pathologic findings in hysterectomy specimens after failed GEA were determined. Reasons for hysterectomy in the 67 patients with available pathology reports were bleeding in 34 (51%), pain in 19 (28%), and bleeding and pain in 14 (21%). The pathology reports of these specimens showed leiomyomas in 33 specimens (49%); intramural myomas were present in 15 women (44%) who underwent hysterectomy because of bleeding and 8 women (42%) who underwent hysterectomy because of pain. Hematometra was identified in 7 pathologic specimens (10%). Specifically, hematometra was identified in specimens from 5 of 19 women who underwent hysterectomy because of pain (26%). CONCLUSION Hematometra was a significant finding in women who underwent hysterectomy because of persistent pain after GEA. A possible pathologic predictor of GEA failure may be intramural leiomyomas.