The effect of intrauterine HCG injection on IVF outcome: a systematic review and meta-analysis.

In this systematic review and meta-analysis, the effect of intrauterine HCG infusion before embryo transfer on IVF outcomes (live birth rate, clinical pregnancy rate and spontaneous aboretion rate) was investigated. Searches were conducted on MEDLINE, EMBASE and The Cochrane Library. Randomized studies in women undergoing IVF and intracytoplasmic sperm injection comparing intrauterine HCG administration at embryo transfer compared with no intrauterine HCG were eligible for inclusion. Eight randomized controlled trials were eligible for inclusion in the meta-analysis. A total of 3087 women undergoing IVF and intracytoplasmic sperm injection cycles were enrolled (intrauterine HCG group: n = 1614; control group: n = 1473). No significant difference was found in the live birth rate (RR 1.13; 95% CI 0.84 to 1.53) and spontaneous abortion rate (RR 1.00, 95% CI 0.74 to 1.34) between women who received intrauterine HCG and those who did not receive HCG. Although this review was extensive and included randomized controlled trials, no significant heterogeneity was found, and the overall included numbers are relatively small. In conclusion the current evidence does not support the use of intrauterine HCG administration before embryo transfer. Well-designed multicentre trials are needed to provide robust evidence.

Diagnostic accuracy of saline infusion sonography in the evaluation of uterine cavity abnormalities prior to assisted reproductive techniques: a systematic review and meta-analyses.

BACKGROUND: The diagnostic accuracy of a 2-D transvaginal scan, which is commonly employed to evaluate the regularity and shape of the uterine cavity in subfertile women, is relatively poor compared with other diagnostic modalities like saline infusion sonography (SIS) or hysteroscopy. SIS is a minimally invasive, cost-effective and acceptable diagnostic modality. Therefore the aim of this systematic review was to assess the diagnostic accuracy of SIS in the evaluation of the uterine cavity in subfertile women. METHODS: A systematic review was conducted of diagnostic studies that compared SIS with hysteroscopy. Twenty relevant studies (including 1645 procedures) were identified and a subsequent meta-analysis was performed. Electronic databases were searched for relevant studies and references of relevant studies were cross checked. Validity was assessed and data were extracted independently by two authors. Heterogeneity was examined, studies were plotted in an ROC area and data were pooled. The main outcome measure was the diagnostic accuracy of saline infusion sonography. The pooled sensitivity, specificity, likelihood ratios and the post-test probabilities of saline infusion sonography on the prediction of uterine cavity abnormalities were calculated. RESULTS: The pooled sensitivity of SIS in the detection of all intrauterine abnormalities was 0.88 (95% confidence interval (CI): 0.85-0.90). The pooled specificity was 0.94 (95% CI 0.93-0.96). The positive and negative likelihood ratios were 20.93 (95% CI: 9.06-48.34) and 0.15 (95% CI: 0.10-0.22), respectively. SIS had good accuracy in the detection of all intrauterine abnormalities (area under the summary receiver operating curve (sROC) = 0.97 ± 0.01). SIS also had a high pooled sensitivity and specificity in the detection of congenital uterine anomalies, 0.85 (95% CI: 0.79-0.90) and 1.00 (95% CI 0.99-1.00), respectively. However the limitations of the review include the heterogeneity amongst the included studies. CONCLUSIONS: SIS is a highly sensitive investigative modality and comparable to the gold standard tool, hysteroscopy in the detection of intrauterine abnormalities in subfertile women. SIS is a highly sensitive and specific test in the diagnosis of uterine polyps, submucous myomas, uterine anomalies and intrauterine adhesions and can be used as a screening tool for subfertile patients prior to IVF treatment.

The effect of sperm DNA fragmentation on live birth rate after IVF or ICSI: a systematic review and meta-analysis.

A systematic review and meta-analysis was conducted to evaluate the relationship between the extent of sperm DNA damage and live birth rate (LBR) per couple and the influence of the method of fertilization on treatment outcome. Searches were conducted on MEDLINE, EMBASE and Cochrane Library. Six studies were eligible for inclusion in the meta-analysis. Overall, LBR increased signficantly in couples with low sperm DNA fragmentation compared with those with high sperm DNA fragmentation (RR 1.17, 95% CI 1.07 to 1.28; P = 0.0005). After IVF and intracytoplasmic sperm injection (ICSI), men with low sperm DNA fragmentation had significantly higher LBR (RR 1.27, 95% CI 1.05 to 1.52; P = 0.01) and (RR 1.11, 95% CI 1.00 to 1.23, P = 0.04), respectively. A sensitivity analysis showed no statistically significant difference in LBR between low and high sperm DNA fragmentation when ICSI treatment was used (RR 1.08, 95% CI 0.39 to 2.96; P = 0.88). High sperm DNA fragmentation in couples undergoing assisted reproduction techniques is associated with lower LBR. Well-designed randomized studies are required to assess the role of ICSI over IVF in the treatment of men with high sperm DNA fragmentation.

Reproductive outcome following abdominal myomectomy for a very large fibroid uterus.

The aim of this study was to assess the long-term reproductive outcome following abdominal myomectomy in women with very large fibroid uteri. It is a retrospective study of 90 subfertile women with the main outcome measure of live-birth rate following spontaneous and assisted conception. Mean age of the study population was 37 ± 5 years and mean uterine size was 21 ± 6 weeks. During follow-up (mean 50 ± 10 months), 28 (31%) pregnancies occurred; 18 spontaneous and 10 following IVF. The live-birth rate was 20% and the miscarriage rate was 32%. Multivariate analysis demonstrated that the chance of live birth was significantly reduced with increasing female age at the time of surgery (OR = 0.67, 95% CI 0.51-0.86, p = 0.002). The perioperative blood transfusion rate was 30% and the incidence of major complications was 6%. Fertility after abdominal myomectomy for very large fibroid uteri is possible, and its major determinant is female age at the time of surgery.

Perioperative morbidity associated with abdominal myomectomy compared with total abdominal hysterectomy for uterine fibroids.

The aim of the study was to systematically review and summarise existing evidence related to the perioperative morbidity associated with abdominal myomectomy in comparison with abdominal hysterectomy for uterine fibroids. A review of MEDLINE and EMBASE was carried out. The primary outcome was the major morbidity rate and secondary outcomes were uterine size, estimated blood loss, blood transfusion, operating time and duration of hospital stay. The results identified six observational studies including 1520 participants. All studies scored moderately on the N-OQA scale and were limited to a uterine size of up to 18 weeks. There was no significant difference in the rate of major morbidity (RR 0.94; 95% CI = 0.31, 2.81; p = 0.91) between the two operations. It was concluded that based on variable quality data from retrospective cohort studies, abdominal myomectomy and hysterectomy appear to have similar major morbidity rates for the uterine size up to 16-18 weeks. Well-designed trials with a standardised morbidity outcome and including uterine size greater than 18 weeks are required.

Peri-operative morbidity associated with abdominal myomectomy for very large fibroid uteri.

OBJECTIVE: To evaluate the safety of abdominal myomectomy for very large fibroid uteri, and to assess the effect of relevant confounding variables on the occurrence of major peri-operative complications. STUDY DESIGN: A cohort study of 200 abdominal myomectomies for fibroid uteri of 16 gestational weeks or greater. Logistic regression analysis was used to examine the influence of important clinical variables on the risk of complications. A systematic literature search was conducted for evidence related to peri-operative morbidity associated with abdominal myomectomy for very large fibroid uteri. RESULTS: The mean (±standard deviation) uterine size was 21±5 weeks. The overall rate of major complications was 30%. Peri-operative bleeding necessitating blood transfusion occurred in 49 (24.5%) cases. During surgery, two patients had bowel injury, two had bladder injury, seven women returned to theatre and two (1%) had hysterectomy. Four patients were re-admitted within 14 days of surgery. Multivariable logistic regression analysis showed that the risk of major complications was significantly higher in cases with a uterine size of 20 gestational weeks or more [odds ratio (OR) 3.4, 95% confidence interval (CI) 1.1-10.2; p=0.03], where 10 or more fibroids were removed (OR 3.5, 95% CI 1.1-10.8; p=0.05) and where midline skin incision was required (OR 6.1, 95% CI 1.7-22.3; p=0.006). On comparison of primary vs repeat abdominal myomectomy, there was significantly higher blood loss (mean 1023±1112 ml vs 579±787 ml; p=0.02) and risk of major complications in the repeat myomectomy group (40% vs 5%; p<0.001). The systematic review identified only one study that reported a comparable risk of major complications related to abdominal myomectomy for very large fibroid uteri. CONCLUSION: The risk of organ injury, hysterectomy, re-operation or hospital re-admission after abdominal myomectomy for very large fibroid uteri is low, but the procedure is associated with a significant risk of bleeding necessitating blood transfusion. This risk is increased after repeat myomectomy, and in patients with a uterine size of 20 gestational weeks or larger, requiring removal of 10 or more fibroids, and requiring a midline skin incision.

Effect of heparin on the outcome of IVF treatment: a systematic review and meta-analysis.

The effect of heparin on IVF outcome has been widely debated in the literature. A systematic review and meta-analysis of the published literature was conducted to evaluate the effect of heparin treatment on IVF outcome. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science and identified 10 relevant studies (five observational and five randomized) comprising 1217 and 732 IVF cycles, respectively. The randomized studies included small numbers of women and exhibited high methodological heterogeneity. Meta-analysis of the randomized studies showed no difference in the clinical pregnancy rate (RR 1.23, 95% CI 0.97-1.57), live birth rate (RR 1.27, 95% CI 0.89-1.81) implantation rate (RR 1.39, 95% CI 0.96-2.01) and miscarriage rate (RR 0.77, 95% CI 0.24-2.42) in women receiving heparin compared with placebo during IVF treatment. However, meta-analysis of the observational studies showed a significant increase in the clinical pregnancy rate (RR 1.83, 95% CI 1.04-3.23, P=0.04) and live birth rate (RR 2.64, 95% CI 1.84-3.80, P<0.0001). The role of heparin as an adjuvant therapy during IVF treatment requires further evaluation in adequately powered high-quality randomized studies. The effect of heparin on IVF outcome is widely debated. Despite the results of published studies being conflicting, it has been suggested that the use of heparin results in increased pregnancy rates following IVF treatment. We conducted a systematic and comprehensive of the published literature to evaluate the effect of heparin treatment on IVF outcome. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science. We identified 10 studies from the literature and extracted the relevant data from the studies. Analyses of the data from randomized trials showed no improvement in the clinical pregnancy rate or the live birth rate in the group that received heparin. However, the studies included had small numbers of women and high methodological heterogeneity. The role of heparin in this context requires further evaluation in adequately powered randomized studies.

Outcomes of ovarian stimulation in a two-day oocyte collection week with PGD cycles compared to a five-day oocyte collection week with conventional IVF/ICSI cycles.

We assessed the outcomes of ovarian stimulation in a two-day egg collection (EC) week with preimplantation genetic diagnosis (PGD) cycles (N = 307) compared to a five-day EC week with conventional in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles (N = 2,417). The mean (SD) age of women undergoing PGD was 34 (3.97) and 35 (3.85) for IVF/ICSI (P < 0.001), the number of oocytes collected was 13 (7.37) and 11 (7.02), (P < 0.001), while the mean (SD) number of fertilized oocytes was 8 (5.09) and 6 (4.58), respectively (P < 0.001). The clinical pregnancy rate per embryo transfer (ET) was 37% with PGD and 38% with IVF/ICSI (P = 0.49), while the implantation rate was 0.35 and 0.30, respectively (P = 0.05). After adjusting for age and confounding variables including the number of oocytes collected and fertilized normally, the mode of treatment (PGD or IVF/ICSI) had no effect on clinical pregnancy (P = 0.48). In conclusion, scheduling of PGD cycles to a two-day EC week did not compromise the outcomes of ovarian stimulation when compared to a five-day EC week with conventional IVF/ICSI cycles. This can allow the provision of a more patient friendly service, increase the flexibility of satellite PGD services, and facilitate cycle programming with the genetics team providing PGD.

The impact of raised BMI on the outcome of assisted reproduction: current concepts.

Obesity contributes to worse outcomes following treatment using assisted reproductive technology (ART), including lower pregnancy and live birth rates and a higher miscarriage rate. This could be mediated through a detrimental effect on oocyte and embryo quality. Oocyte donation studies have suggested that endometrial changes also play a significant role. Endocrine changes associated with obesity, including hyperandrogenism and insulin resistance, as well as changes in local levels of IGFs, cytokines and leptin are thought to underlie the relationship between raised BMI and adverse ART outcomes. This review aims to highlight these underlying mechanisms.

Delayed blastocyst development does not influence the outcome of frozen-thawed transfer cycles.

OBJECTIVE: To compare the outcome of transfer of thawed blastocysts frozen on either day 5 or day 6 after in vitro fertilisation. DESIGN: Cohort observational study. SETTING: Tertiary assisted conception unit in London, UK. POPULATION: Six hundred and forty-two consecutive nondonor programmed thawed blastocyst transfer (TBT) cycles. METHODS: High-grade blastocysts were frozen on day 5 (n = 314) or day 6 (n = 328) after fertilisation using a slow-freezing protocol. Endometrial preparation was performed using estradiol valerate. Progesterone supplementation was commenced when the endometrial thickness had reached 7 mm or more. Frozen blastocysts were thawed on day 6 of progesterone supplementation and assessed immediately after thawing for survival, and after 3-4 hours for blastocoele re-expansion. Main outcome measures Thawed blastocyst survival and re-expansion rates, and pregnancy and live birth rates, per TBT. RESULTS: Thawed blastocyst survival and re-expansion rates were comparable between the day 5 and day 6 groups (87% versus 87%, P = 0.50 and 73% versus 71%, P = 0.35, respectively). The live birth rate was similar between the two groups (29% versus 28.5%, P = 0.93, respectively). After adjusting for confounding variables, the odds ratio (OR) of a live birth in cycles in which the thawed blastocysts were frozen on day 6 compared with day 5 was 1.23 [95% confidence interval (CI), 0.81-1.86, P = 0.34]. CONCLUSION: The pregnancy potential of high-grade blastocysts frozen on day 5 and day 6 after in vitro fertilisation and replaced in programmed TBT cycles is comparable.

A systematic review of the effect of oral antioxidants on male infertility.

The use of antioxidants in treatment of infertile men has been suggested, although the evidence base for this practice is unclear. A systematic review of randomized studies was conducted to evaluate the effects of oral antioxidants (vitamins C and E, zinc, selenium, folate, carnitine and carotenoids) on sperm quality and pregnancy rate in infertile men. MEDLINE, EMBASE, Cochrane Library and CINAHL were searched for relevant trials published from respective database inception dates to May 2009. Study selection, quality appraisal and data extraction were performed independently and in duplicate. Seventeen randomized trials, including a total of 1665 men, were identified, which differed in the populations studied and type, dosage and duration of antioxidants used. Only two-thirds of the studies (11/17) reported using allocation concealment and three studies (18%) used intention-to-treat analysis. Despite the methodological and clinical heterogeneity, 14 of the 17 (82%) trials showed an improvement in either sperm quality or pregnancy rate after antioxidant therapy. Ten trials examined pregnancy rate and six showed a significant improvement after antioxidant therapy. The use of oral antioxidants in infertile men could improve sperm quality and pregnancy rates. Adequately powered robust trials of individual and combinations of antioxidants are needed to guide clinical practice.

A systematic review and meta-analysis of acupuncture in in vitro fertilisation.

BACKGROUND: Numerous randomised studies have reported pregnancy outcome in women who received acupuncture during their in vitro fertilisation (IVF) treatment cycle. OBJECTIVE: The objective of this study was to conduct a systematic review with meta-analysis of the trials of acupuncture during IVF treatment on the outcomes of clinical pregnancy and live birth rates. SEARCH STRATEGY: Searches were conducted in MEDLINE, EMBASE, Cochrane Library, ISI Proceedings and SCISEARCH. SELECTION CRITERIA: All randomised controlled trials that evaluated the effects of acupuncture compared with no treatment or sham acupuncture in women undergoing IVF-intracytoplasmic sperm injection treatment were included. DATA COLLECTION AND ANALYSIS: Study selection, quality appraisal and data extraction were performed independently and in duplicate. A sensitivity analysis was conducted where the meta-analysis was restricted to trials in which sham acupuncture was used in the control group. Meta-regression analysis was used to explore the association between study characteristics and pregnancy rates. MAIN RESULTS: Thirteen relevant trials, including a total of 2500 women randomised to either acupuncture or control group, were identified. No evidence of publication bias was found (Begg's test, P = 0.50). Five trials (n = 877) evaluated IVF outcome when acupuncture was performed around the time of transvaginal oocyte retrieval, while eight trials (n = 1623) reported IVF outcome when acupuncture was performed around the time of embryo transfer (ET). Meta-analysis of the five studies of acupuncture around the time of egg collection did not show a significant difference in clinical pregnancy (relative risks [RR] = 1.06, 95% CI 0.82-1.37, P = 0.65). Meta-analysis of the eight studies of acupuncture around the time of ET showed no difference in the clinical pregnancy rate (RR = 1.23, 95% CI 0.96-1.58, P = 0.1). Live birth data were available from five of the eight studies of acupuncture around the time of ET. Meta-analysis of these studies did not show a significant increase in live birth rate with acupuncture (RR = 1.34, 95% CI 0.85-2.11). Using meta-regression, no significant association between any of the studied covariates and clinical pregnancy rate was found (P > 0.05 for all covariates). CONCLUSION: Currently available literature does not provide sufficient evidence that adjuvant acupuncture improves IVF clinical pregnancy rate.

Selective single blastocyst transfer reduces the multiple pregnancy rate and increases pregnancy rates: a pre- and postintervention study.

OBJECTIVE: To examine the clinical pregnancy rate (CPR) and multiple pregnancy rate (MPR) in a large in vitro fertilisation (IVF) programme before and after the introduction of single blastocyst transfer (SBT) strategy in a selected group of women. DESIGN: A 3-year pre- and postintervention study. SETTING: A tertiary reproductive medicine and assisted conception unit in a London teaching hospital. POPULATION: Two thousand four hundred and fifty-one fresh IVF cycles performed between July 2004 and June 2007 at the Assisted Conception Unit at Guy's and St Thomas' Hospital NHS Foundation Trust were included in the study. METHODS: In January 2006, we implemented a multidisciplinary intervention involving the introduction of a selective day 5 SBT service together with an educational programme on the risks of multiple pregnancy and potential advantages of blastocyst transfer aimed at couples at high risk of multiple pregnancy. MAIN OUTCOME MEASURES: The CPR per cycle started and MPR per clinical pregnancy achieved. RESULTS: A statistically significant increase in the CPR from 27% (324/1198) to 32% (395/1253) (risk difference [RD] 5%, risk ratio [RR] 1.17, 95% CI 1.03-1.32, P= 0.015) and reduction in the MPR per clinical pregnancy from 32% (103/272) to 17% (69/395) (RD 15%, RR 0.46, 95% CI 0.35-0.60, P < 0.001) were observed after introduction of the SBT service. CONCLUSION: Selective SBT in women with good prognosis can reduce the MPR after IVF while maintaining the overall success rate of the IVF programme.

Primary amenorrhea in non-identical twins: an improbable cause.

BACKGROUND: Primary amenorrhea is often the first presenting symptom in müllerian agenesis. A thorough history and physical examination focusing on pubertal development assist in diagnosis and management. Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is the second most common cause of primary amenorrhea with a reported incidence of 1:4000. CASE: Non-identical 18-year-old twins presented with primary amenorrhea. They both had well developed secondary sexual characteristics, with no menarche. One of the twins complained of lower abdominal pain. They were initially assessed within a primary care setting. They were referred to a secondary care center for further investigations to reach a definite diagnosis and management. Further management was planned within a multidisciplinary approach involving gynecologists, psychologists and surgeons with a special interest in vaginal reconstructive surgery. CONCLUSION: Primary amenorrhea affects approximately 5% of amenorrheic women. Diagnosis and management are reached by following a diagnostic algorithm. Reports of MRKH in siblings or non-identical twins are rare. We believe this to be the first case of MRKH syndrome to be reported in dichorionic twins.