Donna M. Fedorkow

The routine use of gonadotropin-releasing hormone agonists prior to in vitro fertilization and gamete intrafallopian transfer: a meta-analysis of randomized controlled trials*

OBJECTIVE To assess the efficacy of gonadotropin-releasing hormone agonists (GnRH-a) used in ovulation induction for in vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT). DESIGN Meta-analysis of 10 trials comparing treatment cycle outcomes after GnRH-a (n = 914) with other ovulation induction protocols (n = 722) and 7 trials comparing outcomes after short flare-up (n = 368) with longer suppression (n = 476) GnRH-a protocols. MAIN OUTCOME MEASURES The outcome of primary interest was clinical pregnancy rate (PR) per treatment cycle commenced. Data describing the amount of gonadotropin used, cycle cancellation rate, clinical pregnancy per ET, and multiple pregnancy and abortion rates were also analyzed. RESULTS Clinical PR per cycle commenced was significantly improved after GnRH-a use for IVF (common odds ratio [OR] 1.80, 95% confidence interval [CI] 1.33 to 2.44) and GIFT (common OR 2.37, 95% CI 1.24 to 4.51). Clinical PR per embryo transfer was also significantly improved with GnRH-a use (common OR 1.40, 95% CI 1.01 to 1.95). Cycle cancellation was decreased (common OR 0.33, 95% CI 0.25 to 0.44), whereas spontaneous abortion rate was similar with and without GnRH-a use. Cycle cancellation and PRs after short flare-up and longer suppression protocols were similar between groups. CONCLUSIONS This meta-analysis supports the routine use of GnRH-a for IVF and GIFT. Further research is needed, however, to assess the potential for increased rates of multiple pregnancy and ovarian hyperstimulation syndrome, which may be associated with this treatment.

A quantitative overview of controlled trials in endometriosis-associated infertility*

OBJECTIVE To undertake quantitative overviews of the following commonly used treatments for endometriosis-associated infertility: ovulation suppression, laparoscopic ablation, and conservative laparotomy. DESIGN A protocol was prospectively defined detailing the research question, mode of study identification, inclusion and exclusion, data extraction, and pooling methods. Studies were assessed for relevance and validity by independent reviewers and their findings compared. Data were extracted in a similar fashion. PATIENTS Women with visually diagnosed endometriosis, complaining of infertility. MAIN OUTCOME MEASURE Pregnancy as defined by positive pregnancy test. RESULTS Twenty-five relevant randomized controlled trials and cohort studies were identified with a total of 37 treatment comparisons. The common odds ratio (OR) from seven studies comparing ovulation suppression (danazol, medroxyprogesterone acetate [MPA], or gestrinone) versus placebo or no treatment was 0.85, suggesting no treatment benefit. The common OR for pregnancy after ovulation suppression (MPA, gestrinone, or GnRH agonist) versus danazol was also nonsignificant: 1.07. Although pooled data from trials of laparoscopic surgery suggested a treatment benefit, significant heterogeneity between studies undermines this conclusion. Laparoscopic data were similar to those from conservative laparotomy studies. Studies assessing conservative surgery plus danazol versus danazol alone showed no significant benefit from this adjunct. CONCLUSION Ovulation suppression is an ineffective treatment for endometriosis-associated infertility. Well-designed trials of laparoscopic ablation deserve a high priority.

The SOGC Statement on the WHI Report On Estrogen and Progestin Use in Postmenopausal Women

The recent Womens Health Initiative study report evaluated the long-term benefits and risks of hormone replacement therapy among healthy postmenopausal women. The report showed that the risk-benefit profile of continuous combined hormone replacement therapy was not consistent with the primary prevention of coronary heart disease. The Womens Health Initiative study of continuous combined hormone replacement therapy is a landmark study and the results provide valuable information for patients and clinicians. However, the most common indication for hormone replacement therapy is menopausal symptoms, for which it is effective, not prevention of disease, and the most common use is for less than three years. Nevertheless, even short-term use has small effects on some outcomes. This statement discusses how the findings of the Womens Health Initiative study can be applied to reach appropriate clinical decisions.

The use of an ultrasound bladder scanning device in women undergoing urogynaecologic surgery.

OBJECTIVE To compare the accuracy of using a bladder scanner to measure post-voiding residual urine volume with measurement by intermittent catheterization in a postoperative urogynaecology population. METHODS Prior to implementation of the study, nurses were trained in the use of a bladder ultrasound scanner. Post-void residual urine volume in postoperative patients was assessed by a nurse with the scanner; a second nurse, blinded to the scanner result, then catheterized the patients bladder. Each patient rated the pain experienced with bladder scanning and with catheterization. A prospective comparison of the volumes assessed by ultrasound and measured by catheterization used 127 pairs of data; each woman served as her own control. The correlation of urine volumes was determined, and the difference in pain score was calculated using the Student t test. RESULTS The mean age of patients was 56.5 years (range 40-79). All four bladder quadrants were visualized in 34.4% of scans. The correlation coefficient for volumes measured by scanning and catheterization was 0.70 (P < 0.001; range -349 mL to +692 mL). Consistently, using the scanner resulted in underestimation of the urine volume. The sensitivity of the bladder scanner (0.58 for residual volumes > 200 mL) therefore makes it a poor tool for assessing postoperative urinary retention in women undergoing urogynaecologic surgery. Pain scores recorded with catheterization (2.9/10) were significantly less than those recorded with bladder scanning (4.2/10) (P < 0.001). CONCLUSIONS Bladder scanning by staff nurses had limited value in assessing postoperative residual urine volumes. The accuracy of assessment might increase with greater experience with the procedure. The greater discomfort reported by patients with use of the scanner supports continued use of catheterization to assess residual urine volume.

Characteristics of patients with postpartum urinary retention

Between 1982 and 1987, 76 patients were identified retrospectively as having had a parturition complicated by postpartum urinary retention among 22 176 deliveries at the Mount Sinai Hospital, Toronto, giving an overall incidence of 3.4 per 1000 total deliveries and 4.4 per 1000 vaginal deliveries. Predisposing influences include first delivery, operative vaginal delivery, epidural anesthesia, and episiotomy. The potential for recurrence was noted in 4 of the 21 multiparous patients. A delay in diagnosis of up to 48 hours emphasizes the need for a high index of suspicion for this condition. Bacteriuria, while present in one-third of patients was not a universal finding. No optimal management plan was identified; however, bladder drainage remains the cornerstone of management.

Prevalence of Urinary Incontinence, Pelvic Organ Prolapse and Anal Incontinence in Women

Typically defined, burden of illness involves the determination of levels of mortality and morbidity. Urogynecologic and related disorders rarely pose a life-threatening illness. However, they often result in significant morbidities. The relevant morbidities have been characterized by Fletcher et al. as the five D’s [1]. These are disease (frequency), discomfort, disability, dissatisfaction and destitution (the financial cost of illness). Measures of morbidity must therefore include the full range of manifestations of disease that would be considered important.

Review: In peri- or postmenopausal women, DHEA does not improve symptoms and increases androgenic side effects

Question In women with peri- or postmenopausal symptoms, is dehydroepiandrosterone (DHEA) effective and safe for improving symptoms? Review scope Included studies compared DHEA, administered for 1 week, with placebo, no intervention, or hormone therapy (HT) in menopausal women. Outcomes included quality of life (QoL), adverse effects, change in menopausal symptoms, and sexual function. Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials, Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, PsycINFO, CINAHL, and LILACS (Jun 2014); Database of Abstracts of Reviews of Effects, Web of Knowledge, OpenGrey, Google, trial Web sites (www.clinicaltrials.gov and www.who.int/trialsearch/Default.aspx); and reference lists and conference abstracts were searched for randomized controlled trials (RCTs). 28 RCTs (n =1273, 1207 postmenopausal women, 66 perimenopausal women, age range 36 to 80 y) met the selection criteria. DHEA was administered orally (23 trials), by skin (3 RCTs), or intravaginally (2 RCTs). Control groups received placebo (23 RCTs), HT (6 RCTs), tibolone (3 RCTs), and no treatment (1 RCT). 17 RCTs reported random-sequence generation, 9 reported allocation concealment, and 14 used blinding. Main results Meta-analysis showed that DHEA did not improve QoL, change in menopausal symptoms, or sexual function compared with placebo or no treatment (Table); DHEA increased androgenic side effects (acne, greasy skin, and hirsutism) (1 RCT, odds ratio 6.57, 95% CI 1.37 to 31.59) but not acne or hirsutism, individually. DHEA did not improve sexual function (2 RCTs, standard mean difference 1.26, 95% CI 0.21 to 2.73) compared with HT; data were insufficient for QoL, menopausal symptoms, and adverse effects. Conclusion In symptomatic women with peri- or postmenopausal symptoms, dehydroepiandrosterone did not improve menopausal symptoms and resulted in increased androgenic side effects compared with placebo or no treatment. DHEA vs placebo or no treatment in peri- or postmenopausal women* Outcomes Number of trials (n) Standard mean difference (95% CI) Quality of life or well-being 9 (402) 0.04 (0.20 to 0.13) Change in menopausal symptoms 1 (66) 0.07 (0.42 to 0.55) Sexual function 6 (376) 0.19 (0.01 to 0.40) *CI defined in Glossary. Difference favors control. Difference favors DHEA. Commentary Vasomotor and sexual symptoms plague women during the menopausal transition, but the results of the WHI trial (1) scared many women and practitioners away from HT. In attempting to relieve symptoms, many women have turned to other supplements, including DHEA, that have been advocated with little or no scientific support regarding effects or comprehensive assessments of risks. That DHEA is a steroid precursor for testosterone and estradiol provides biologic plausibility that use may confer benefit. The effects of exogenous use of DHEA with normal adrenal function are not well-understood (2). The well-executed meta-analysis by Scheffers and colleagues highlights the difficulties of combining data from small studies with heterogeneous interventions, outcomes, and measurement tools. The quality of evidence was rated as low to moderate, with acknowledgment that the effects and estimates of even moderate-level evidence may change with further research. RCTs that assessed androgen side effects, including acne and hirsutism, found increases with DHEA compared with placebo or no treatment, but trials that assessed acne and hirsutism separately, using similar controls, did not find increases with DHEA use. RCTs that compared DHEA with HT were small and failed to show any advantage of DHEA for sexual function or control of vasomotor symptoms. The meta-analysis by Scheffers and colleagues suggests that DHEA does not perform better than HT, only mildly better than placebo, and no better than no treatment for QoL, vasomotor symptoms, and sexual function. The increase in androgenic side effects suggests that DHEA may do more harm than good.

Hormone therapy increased risk for kidney stones in healthy postmenopausal women

Source Citation Maalouf NM, Sato AH, Welch BJ, et al. Postmenopausal hormone use and the risk of nephrolithiasis: results from the Women’s Health Initiative hormone therapy trials. Arch Intern Med....

Annual screening with CA-125 and transvaginal ultrasonography did not reduce ovarian cancer incidence or mortality

Source Citation Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening randomized controlled trial...

A Review of the Evidence Regarding the Safety and Efficacy of Acupuncture during Parturition

Abstract a review of the literature regarding the use of acupuncture during labour and delivery was undertaken to address three questions: is acupuncture efficacious in reducing pain during labour, is acupuncture safe during labour, does acupuncture alter the progress of labour? The evidence for all three questions was found to be inconclusive due to the paucity of research and the absence of any clinical trials. Current clinical experience and the potential place for acupuncture as a treatment modality during parturition are forwarded but research is required before conclusions may be drawn.