Risk of foetal harm with letrozole use in fertility treatment: a systematic review and meta-analysis.

BACKGROUND: The aromatase inhibitor letrozole is increasingly recommended for ovulation induction, as it is more effective with fewer side-effects than other agents. But many clinicians are reluctant to use the drug for fertility treatment due to a strong-label warning against its use, which warns about congenital malformation risk to the foetus in women seeking pregnancy. OBJECTIVE AND RATIONALE: The aim of this study was to determine the risks of congenital malformations and pregnancy loss with letrozole compared with clomiphene primarily, and with other fertility drugs and natural conception. SEARCH METHODS: A systematic review and meta-analysis using PRISMA harms guidelines. We searched MEDLINE, EMBASE and other sources from inception until January 2020, with the MeSH words for 'letrozole' and pregnancy OR foetal/neonatal outcome. We included studies reported on congenital malformations in foetuses born to mothers conceived after fertility treatment, with letrozole versus clomiphene, placebo, gonadotrophins, metformin, natural conception or other agents, from randomised trials, comparative cohort studies and non-comparative observational cohorts. Quality of the studies was assessed using Cochrane risk of bias tool and Newcastle Ottawa Scale. The McMaster tool was used to assess the quality of reported harm for foetal congenital malformations in the studies. We compared the absolute risk of events using risk difference measures and pooled the findings using a fixed-effect model. We evaluated the statistical heterogeneity using forest plots and the I2 statistic and funnel plot to assess publication bias. We assessed the strength of evidence for congenital malformation and pregnancy loss as per the GRADE recommendations and with the Fragility index. OUTCOMES: We included 46 studies (18 randomised trials; 21 comparative cohorts; 7 non-comparative cohorts). Overall 2.15% (101/4697; 95% CI 1.7 to 2.5) of babies conceived on letrozole for fertility treatment had congenital foetal malformations. We did not observe a significant increase in congenital malformations with letrozole versus clomiphene in the randomised trials (risk difference (RD) 0.01, 95% CI -0.02, 0.03; I2 = 0%; 14 studies) and found a significant reduction in the cohort studies (RD -0.02, 95% CI -0.04, -0.01; I2 = 0%, 11 studies). The fragility index was 44% (7/16) (either an increase in the intervention arm or a decrease in control arm was needed to alter the results). The risks of pregnancy loss were not increased with letrozole versus clomiphene in the 14 randomised trials (RD -0.01, 95% CI -0.06, 0.04; I2 = 0%), and the risks were reduced in the six cohort studies (RD -0.09, 95% CI -0.17, -0.00; I2 = 68%). The GRADE quality of evidence was low to moderate for congenital malformations and pregnancy loss. We did not find any increased congenital malformation risk with letrozole versus gonadotrophins, natural conception or natural cycle ART, but the number of studies was small. WIDER IMPLICATIONS: There is no evidence that letrozole increases the risk of congenital foetal malformation or pregnancy loss compared with clomiphene, natural conception or other fertility agents, to warrant warning against its use. Given its therapeutic benefits and lack of evidence of harm to the foetus, clinicians should consider letrozole as first-line agent for ovulation induction.

The role of adjuvant systemic steroids in the management of periorbital cellulitis secondary to sinusitis: a systematic review and meta-analysis.

PURPOSE: The role of adjuvant systemic corticosteroids in the management of periorbital cellulitis and subperiosteal/orbital abscesses secondary to sinonasal infections is not well understood. Our objective was to systematically review the current evidence on the efficacy and side effects of systemic steroids when used in the management of periorbital cellulitis. METHODOLOGY: A systematic review of literature was conducted in accordance with PRISMA guidance. A systematic search of MEDLINE, Embase and Cochrane databases, MetaRegister and ISI conference proceedings was conducted. The outcomes of interest were duration of inpatient stay, requirement for surgical intervention, adverse effects and recurrent/residual symptoms. RESULTS: Four studies were identified involving 118 patients. Of these, 78 underwent treatment with systemic corticosteroids and 40 were controls. Meta-analysis demonstrated that the mean duration of inpatient stay was significantly shorter in the steroid group (WMD - 2.90 days; 95% CI - 3.07, - 2.73; p < 0.00001). There were no significant differences in requirement for surgical intervention (RR 0.93; 95% CI 0.50, 1.75; p = 0.83). Side effects were reported in 6/78 patients (7.7%), with 5 patients showing signs of hyperactivity and 1 patient with insomnia. These were mild except in one case, which required early cessation of corticosteroids. There was one case of recurrence of symptoms in each cohort (steroid vs. non-steroid) following discharge. CONCLUSIONS: The evidence suggests that systemic corticosteroids may offer some benefit in the management of periorbital cellulitis secondary to sinonasal infections. However, there is significant heterogeneity and risk of bias. A well-designed randomised controlled trial may provide a better insight into the efficacy of systemic steroids for this condition.

Peri-operative morbidity and fertility outcome after repeat abdominal myomectomy for large fibroid uterus.

This was a retrospective cohort study evaluating peri-operative morbidity of 66 women who underwent repeat abdominal myomectomy compared with 200 women who had primary myomectomy in the same period, matched for age and uterine size. We report the reproductive outcome of women seeking fertility after repeat myomectomy. More pre-operative GnRH analogues were used and midline abdominal skin incision performed in the repeat myomectomy group. The likelihood of major complication was three times higher in the repeat abdominal myomectomy group (OR 3.0, 95% CI 1.67-5.5, p < .001). There was a significantly longer mean hospital stay (p < .01), higher incidence of bleeding (p < .01) and urinary or wound infection (p < .01) in the repeat abdominal myomectomy group. Of the 47 women who had repeat myomectomy for fertility reasons, six women conceived and two live birth at term (4%). Our study highlights the significant peri-operative morbidity and poor subsequent live birth rate associated with repeat abdominal myomectomy.Impact statementWhat is already known on this subject? Repeat abdominal myomectomy is a major surgical procedure with significant morbidity. However, abdominal myomectomy for large fibroid uterus remains the preferred treatment method for women who wish to preserve fertility. Sufficient evidence related to the peri-operative morbidity and fertility outcome after repeat abdominal myomectomy is lacking.What do the results of this study add? This is the largest study reporting peri-operative morbidity and pregnancy outcome following repeat abdominal myomectomy. Our results highlight the three times increased risk of major complications associated with repeat abdominal myomectomy compared to primary myomectomy with the poor subsequent live birth rate.What are the implications of these findings for clinical practice and/or further research? Our study complements the sparse existing data on the outcome of repeat abdominal myomectomy and underscore the potentially significant peri-operative morbidity and poor subsequent live birth rate associated with the procedure. This information should be used in counselling women with fibroid recurrence after primary myomectomy before they embark on repeat surgery.

The effect of myo-inositol/di-chiro-inositol on markers of ovarian reserve in women with PCOS undergoing IVF/ICSI: A systematic review and meta-analysis.

INTRODUCTION: High levels of anti-Mullerian hormone and a high antral follicle count in women with polycystic ovary syndrome, reflecting increased ovarian antral follicles, predisposes them to have a high number of retrieved oocytes with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and an increased risk of ovarian hyperstimulation syndrome. Inositols, which act as insulin sensitizers, have the potential to alter folliculogenesis and the functional ovarian reserve, with subsequent benefits to reproductive outcomes following IVF/ICSI treatment. Published literature is, however, unable to provide definitive evidence of its efficacy. The objective of our review was to evaluate the effect of inositols on anti-Mullerian hormone, antral follicle count and reproductive outcomes in women with polycystic ovary syndrome undergoing IVF/ICSI. MATERIAL AND METHODS: We performed a literature search using standard methodology recommended by Cochrane. Randomized controlled trials and non-randomized studies comparing inositols with no treatment, placebo or other treatment were included in the review. Using standard methodology recommended by Cochrane we pooled results using the random effects model; our findings were reported as relative risk or mean differences. PROSPERO registration: CRD42017082275. RESULTS: We included 18 trials. The primary outcome was a change in anti-Mullerian hormone and antral follicle count before and after treatment, for which data were unsuitable for meta-analysis. A narrative review showed no consistent direction or size of effect. A meta-analysis for the secondary outcomes showed no evidence of a significant difference between inositol and control groups for any outcome: number of oocytes (mean difference -0.39, 95% confidence interval [CI] -1.11 to 0.33), number of metaphase II oocytes (mean difference 0.29, 95% CI -0.83 to 1.40), number of top grade embryos (risk ratio [RR] 1.02, 95% CI 0.93-1.12), clinical pregnancy rate (RR 1.16, 95% CI 0.87-1.53), and risk of ovarian hyperstimulation syndrome (RR 0.73, 95% CI 0.39-1.37). The quality of evidence was assessed as very low. CONCLUSIONS: There is insufficient evidence for an effect of inositols on ovarian reserve markers and to support their use as pretreatment before IVF/ICSI in women with polycystic ovary syndrome.

Overview of systematic reviews of non-pharmacological interventions in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a major contributor to subfertility, diabetes and cardiovascular disease in women. The role of non-pharmacological interventions to prevent these outcomes has been reported in many systematic reviews, but robust conclusions have not been made due to variations in the scope, quality and findings of these reviews. OBJECTIVE AND RATIONALE: Our aim was to provide an overview of existing evidence on the effects of non-pharmacological interventions in women with PCOS on fertility and non-fertility outcomes by a review of existing systematic reviews. SEARCH METHODS: We reviewed systematic reviews of randomized trials that have evaluated the effects of non-pharmacological interventions, such as lifestyle interventions, nutritional supplements or alternative medicine therapies in women with PCOS on fertility, endocrine, glycaemic and weight-related outcomes. We assessed the quality of systematic reviews with the AMSTAR tool, and reported the outcomes with regard to: fertility (live birth, clinical pregnancy, ovulation and menstrual cycle regularization); endocrine outcomes (Ferriman-Gallwey score, free androgen index, free testosterone and total testosterone levels); and glycaemic (fasting blood insulin, fasting blood glucose, homoeostatic model assessment) and weight-related (BMI) outcomes. We assessed the strength of evidence for significant outcomes as per the grading of recommendations assessment, development and evaluation (GRADE) system. OUTCOMES: We found twelve eligible systematic reviews which included between three (143 women) and 27 randomized trials (2093 women). Four reviews assessed the effects of lifestyle interventions (diet, physical activity and/or behavioural interventions); four evaluated nutritional supplements (one each on n-acetylcysteine, omega-3 fatty acids, inositol and vitamin D); and four studied alternative medical therapies (Chinese herbal medicine and acupuncture). All of the included reviews were of high quality and scored between 8 and 11 with the AMSTAR tool (with a maximum score of 11).Randomized evidence is lacking for live birth rate. N-acetylcysteine, inositol and the addition of alternative medicine to ovulation induction agents show preliminary potential to improve fertility (odds ratios (OR) for clinical pregnancy rate range from 1.99 to 4.83). Lifestyle interventions show benefits in improving hirsutism (mean difference (MD): -1.01 to -1.19). Lifestyle interventions (MD: -1.10 to -2.02), inositol (MD: -2.1) and acupuncture (MD: -1.90 to -3.43) all show some evidence of improvement in glycaemic outcomes and there is some evidence of reduced BMI with lifestyle interventions (MD: -0.15 to -1.12). All of these outcomes scored either low or very low quality of evidence on the GRADE score. WIDER IMPLICATIONS: Lifestyle interventions in women with PCOS appear to improve glycaemic results, androgenic symptoms and anthropometric outcomes. The role of inositol and N-acetylcysteine in women with PCOS needs further evaluation. Large primary trials on all interventions are needed for an agreed set of core outcomes.

Pharmacological and surgical treatment of nonreproductive outcomes in polycystic ovary syndrome: An overview of systematic reviews.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects up to 13% women and is associated with significant complications. The quality of evidence supporting the recommendations on treatment of nonreproductive outcomes in PCOS is unknown. OBJECTIVE: To summarize and appraise the methodological quality of systematic reviews and meta-analyses evaluating pharmacological and surgical treatments for nonreproductive outcomes in PCOS. METHODS: A literature search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed from inception until 15th of September 2017. Article selection, data extraction and quality appraisal of included reviews were performed in duplicate. A narrative synthesis of the findings was conducted. RESULTS: This overview included 31 reviews. The quality was low for 7 (23%), moderate for sixteen (52%) and high for 8 reviews (26%). Two reviews assessed psychological outcomes. Metformin improved anthropometric (7 of 10 reviews), metabolic (4 of 14 reviews) and endocrine outcomes (3 of twelve reviews). Thiazolidinediones improved metabolic (2 of 5 reviews) and endocrine outcomes (one of 5 reviews) but worsened weight gain (5 of 5 reviews). Combined oral contraceptive pill (COCP) improved clinical hyperandrogenism (2 of 2 reviews). Statins improved lipid profile (3 of 3 reviews) and testosterone level (2 of 3 reviews). There was no conclusive evidence from included systematic reviews regarding the use of other interventions. CONCLUSIONS: There is reliable evidence regarding the use of metformin for anthropometric outcomes and COCPs for hyperandrogenism in women with PCOS but not for other interventions. There is significant gap in knowledge regarding the management of psychological outcomes in women with PCOS which needs further evaluation.

Laparoscopic Excision Versus Ablation for Endometriosis-associated Pain: An Updated Systematic Review and Meta-analysis.

The aim of this study was to update the evidence on the surgical management of endometriosis-associated pain. Does laparoscopic excision offer any benefits over laparoscopic ablation? This is a systematic review and meta-analysis in which we searched MEDLINE, Embase, Institute for Scientific Information conference proceedings, the International Standard Randomised Controlled Trial Number registry, the Register and Meta-register for randomized controlled trials, the World Health Organization trials search portal, the Cochrane Library, and the British Library of electronic theses. Three randomized controlled trials were included, which enrolled 335 participants with a sample size per study ranging from 24 to 178 participants. Of these 3 studies, data from 2 could be pooled for meta-analysis. The primary outcome measure was the reduction in the visual analog scale score for dysmenorrhea. The secondary outcome measures included the reduction in the visual analog scale score for dyspareunia, dyschezia, and chronic pelvic pain and the reduction in Endometriosis Health Profile-30 core pain scores. The meta-analysis showed that the excision group had a significantly greater reduction in symptoms of dysmenorrhea (mean difference [MD] = 0.99; 95% confidence interval [CI], -0.02 to 2.00; p = .05) and dyschezia (MD = 1.31; 95% CI, 0.33-2.29; p = .009) compared with ablation. The symptoms of dyspareunia showed a nonsignificant benefit with excision (MD = 0.96; 95% CI, -0.07 to 1.99; p = .07). Data from 1 study showed a significant reduction in chronic pelvic pain (MD = 2.57; 95% CI, 1.27-3.87; p = .0001) and Endometriosis Health Profile-30 core pain scores (MD = 13.20; 95% CI, 3.70-22.70; p = .006) with the excision group compared with the ablation group. The limited available evidence shows that at 12 months postsurgery, symptoms of dysmenorrhea, dyschezia, and chronic pelvic pain secondary to endometriosis showed a significantly greater improvement with laparoscopic excision compared with ablation.

Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and summarize the existing evidence related to the efficacy and safety of transdermal T in postmenopausal women for the treatment of hypoactive sexual desire disorder (HSDD). DESIGN: Systematic reviews and meta-analysis. SETTING: Not applicable. PATIENT(S): Seven randomized controlled trials enrolled 3,035 participants; 1,350 women were randomized to treatment with T patch, and 1,379 women were randomized to placebo. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome: satisfying sexual episodes. SECONDARY OUTCOMES: sexual activity, orgasm, Profile of Female Sexual Function domains (desire), personal distress score, adverse events, acne, increased hair growth, facial hair, alopecia, voice deepening, urinary symptoms, breast pain, headache, site reaction, total adverse events, serious adverse events, withdrawal from study, and follow-up rate. RESULT(S): The T group had significantly more satisfying sexual episodes, sexual activity, orgasms, desire, significant change in Personal Distress Scale score, androgenic adverse events, acne, and hair growth compared with the placebo group. There was no significant difference between the two groups in increase in facial hair, alopecia, voice deepening, urinary symptoms, breast pain, headache, site reaction to the patch, total adverse events, serious adverse events, reasons for withdrawal from the study, and the number of women who completed the study. CONCLUSION(S): The short-term efficacy in terms of improvement of sexual function and safety of transdermal T in naturally and surgically menopausal women affected by HSDD either on or not on estrogen progestin hormone therapy is evident from this systematic review. The use of transdermal T is associated with increase in androgenic adverse events such as acne but is not associated with any serious adverse events.

Role of corticosteroids in Functional Endoscopic Sinus Surgery--a systematic review and meta-analysis.

BACKGROUND: The aim of our study is to systematically review the existing evidence on the role of corticosteroids in patients undergoing functional endoscopic sinus surgery (FESS). METHODOLOGY: Systematic search of MEDLINE (1950- 2014), EMBASE (1980-2014), metaRegister, Cochrane Library and ISI conference proceedings was carried out. RESULTS: Eighteen randomised controlled trials with 1309 patients were included. Use of local and/or systemic corticosteroids with FESS was reported in four categories; operative, anaesthesia related, post-operative outcomes and risk of recurrence. Meta-analysis for operative outcomes demonstrated that, mean operative time (MD -10.70 minutes; 95% CI -15.86, -5.55; P <0.0001) and mean estimated blood loss (MD -28.32 mls; 95% CI -40.93, -15.72; P <0.0001) was significantly lower; and surgical field quality (MD -0.81; 95% CI -1.32, -0.30; P = 0.002) was significantly better in corticosteroid group. Meta-analysis showed that post-operative endoscopic scores (SMD -0.39; 95% CI -0.60, -0.17; P = 0.0004) were significantly better in corticosteroid group compared to no corticosteroid group. There was no increase in risk of sinusitis (RR 0.64; 95% CI 0.32, 1.30; P = 0.22) between use of corticosteroids and no corticosteroids; There was no significant difference in recurrence risk of chronic rhinosinusitis (CRS) in mixed population studies (RR 0.77; 95% CI 0.35, 1.70; P = 0.52) between the two groups but analysis of studies reporting on chronic rhinosinusitis with nasal polyps (CRSwNP) (RR 0.64;95% CI 0.45,0.91;P=0.01) showed significant difference in favour of the corticosteroid group. CONCLUSION: Pre-operative use of local and/or systemic corticosteroids in FESS, results in significantly reduced blood loss, shorter operative time and improved surgical field quality. Studies are limited on the intra-operative use of corticosteroids to reduce postoperative pain. Postoperative corticosteroids improve postoperative endoscopic scores in CRS and recurrence rates in cases of CRSwNP.

Quality of life after total laparoscopic hysterectomy: a one-year follow-up study.

BACKGROUND: A small prospective observational cohort study with the aim to evaluate postoperative health-related quality of life (HRQOL) at one-year follow-up after total laparoscopic hysterectomy for benign gynecological conditions and to assess postoperative functions in terms of return to work, sexual activity and driving was conducted. METHODS: Sixty out of 65 women with a mean age of 45.7±5.4 responded to the questionnaire. Change in HRQOL was assessed by comparing the preoperative and postoperative QOL on scale of 1-5 grades. RESULTS: HRQOL improved significantly at 12 months postoperatively. Multiple logistic regression analysis showed that the presence of irregular periods (P=0.048) and dyspareunia (P=0.017) were significant predictors of overall postoperative improvement in QOL by 3 or more grades. Women with ovarian preservation were more likely to report overall improvement in HRQOL by 3 or more grades compared to those who had bilateral salpingo-oophrectomy (P=0.04). There was statistically significant improvement in QOL postoperatively as compared to preoperatively (P<0.0001). CONCLUSIONS: In our study we found that women presenting with dyspareunia were more likely to report higher improvement in postoperative QOL. This highlights that dyspareunia is a symptom which is a marker for chronic pelvic pain conditions like endometriosis, adenomyosis, fibroids and adhesions.

Hysteroscopy prior to the first IVF cycle: a systematic review and meta-analysis.

This systematic review and meta-analysis investigated the use of routine hysteroscopy prior to starting the first IVF cycle on treatment outcome in asymptomatic women. Searches were conducted on MEDLINE, EMBASE, Cochrane Library, National Research Register and ISI Conference Proceedings. The main outcome measures were clinical pregnancy and live birth rates achieved in the index IVF cycle. One randomized and five non-randomized controlled studies including a total of 3179 participants were included comparing hysteroscopy with no intervention in the cycle preceding the first IVF cycle. There was a significantly higher clinical pregnancy rate (relative risk, RR, 1.44, 95% CI 1.08-1.92, P=0.01) and LBR (RR 1.30, 95% CI 1.00-1.67, P=0.05) in the subsequent IVF cycle in the hysteroscopy group. The number needed to treat after hysteroscopy to achieve one additional clinical pregnancy was 10 (95% CI 7-14) and live birth was 11 (95% CI 7-16). Hysteroscopy in asymptomatic woman prior to their first IVF cycle could improve treatment outcome when performed just before commencing the IVF cycle. Robust and high-quality randomized trials to confirm this finding are warranted. Currently, there is evidence that performing hysteroscopy (camera examination of the womb cavity) before starting IVF treatment could increase the chance of pregnancy in the subsequent IVF cycle in women who had one or more failed IVF cycles. However, recommendations regarding the efficacy of routine use of hysteroscopy prior to starting the first IVF treatment cycle are lacking. We reviewed systematically the trials related to the impact of hysteroscopy prior to starting the first IVF cycle on treatment outcomes of pregnancy rate and live birth rate in asymptomatic women. Literature searches were conducted in all major database and all randomized and non-randomized controlled trials were included in our study (up to March 2013). The main outcome measures were the clinical pregnancy rate and live birth rate. The secondary outcome measure was the procedure related complication rate. A total of 3179 women, of which 1277 had hysteroscopy and 1902 did not have a hysteroscopy prior to first IVF treatment, were included in six controlled studies. Hysteroscopy in asymptomatic woman prior to their first IVF cycle was found to be associated with improved chance of achieving a pregnancy and live birth when performed just before commencing the IVF cycle. The procedure was safe. Larger studies are still required to confirm our findings.

Robotic-assisted laparoscopic vs abdominal and laparoscopic myomectomy: systematic review and meta-analysis.

Herein is presented a systematic review and meta-analysis of evidence related to operative outcomes associated with robotic-assisted laparoscopic myomectomy (RLM) compared with abdominal myomectomy (AM) and laparoscopic myomectomy (LM). Outcome measures included estimated blood loss (EBL), blood transfusion, operating time, complications, length of hospital stay (LOHS), and costs. Meta-analysis 1 compared RLM vs AM, and meta-analysis 2 compared RLM vs LM. Studies scored moderately well on the Newcastle-Ottawa Quality Assessment Scale. No significant differences were found in age, body mass index, or number, diameter, and weight of myomas. In meta-analysis 1, EBL, blood transfusion, and LOHS were significantly lower; risk of complications was similar; and operating time and costs were significantly higher with RLM. In meta-analysis 2, no significant differences were noted in EBL, operating time, complications, and LOHS with RLM; however, blood transfusion risk and costs were higher. It was concluded that insofar as operative outcomes, RLM has significant short-term benefits compared with AM and no benefits compared with LM. Long-term benefits such as recurrence, fertility, and obstetric outcomes remain uncertain.

Meta-analysis of GnRH antagonist protocols: do they reduce the risk of OHSS in PCOS?

This systematic review and meta-analysis investigated whether gonadotrophin-releasing hormone (GnRH) antagonist protocols reduce the risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovary syndrome undergoing IVF compared with the long agonist protocol. Searches were conducted on MEDLINE, EMBASE, Cochrane Library, National Research Register and ISI Conference Proceedings. Primary outcome was OHSS incidence. Secondary outcomes were total duration and dose of gonadotrophin, number of oocytes retrieved and clinical pregnancy and miscarriage rates. A total of 966 women were included in nine randomized controlled trials. There was inconsistency in definition, classification of severity and reporting of the OHSS rate. There was no difference in the incidence of severe OHSS in the antagonist group compared with the long agonist group (relative risk 0.61; 95% CI 0.23 to 1.64). However, when all moderate and severe OHSS cases were pooled, the antagonist protocol was associated with significantly lower risk of OHSS (relative risk 0.60; 95% CI 0.48-0.76; P<0.0001). A possible reduction in the incidence of severe OHSS with the GnRH antagonist protocol should be viewed with caution since the data is inconclusive. Larger randomized trials with adequate sample size and standardized definition, classification and diagnosis of OHSS remain necessary.

Uterine cavity assessment prior to IVF.

Approximately 15% of couples are affected with subfertility, of which up to 20% remain unexplained. Uterine cavity abnormalities can be a contributing cause of subfertility and recurrent implantation failure. Uterine cavity assessment has been suggested as a routine investigation in the evaluation of subfertile women. Traditionally, hysterosalpingography has been the most commonly used technique in the evaluation of infertility. Transvaginal ultrasound scan allows visualization of the endometrial lining and cavity, and has been used as a screening test for the assessment of uterine cavity. Abnormal uterine findings on a baseline scan can be further evaluated with saline hysterosonography, which is highly sensitive and specific in identifying intrauterine abnormalities. Hysteroscopy is considered as the definitive diagnostic tool to evaluate any abnormality suspected on hysterosalpingography, transvaginal ultrasound scan or saline hysterosonography during routine investigation of infertile patients. Minimally invasive hysteroscopes have minimized the pain experienced by patients during the procedure and made it feasible to use hysteroscopy as a routine outpatient examination. Following recurrent IVF failure there is some evidence of benefit from hysteroscopy in increasing the chance of pregnancy in the subsequent IVF cycle, both in those with abnormal and normal hysteroscopic findings. Various possible mechanisms have been proposed for this beneficial effect, but more randomized controlled trials are needed before its routine use in the general subfertile population can be recommended.