Difficult embryo transfers or blood on catheter and assisted reproductive outcomes: a systematic review and meta-analysis

We performed a systematic review and meta-analysis to examine whether a difficult embryo transfer or the presence of blood on the transfer catheter affects assisted reproduction outcomes. We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). We aimed to determine the risk ratio (RR) associated with difficult embryo transfer or the presence of blood on the transfer catheter for the following outcomes: live birth, clinical pregnancy, and miscarriage. We identified 3066 papers, of which 194 were reviewed and nine were included. The outcome of live birth was not reported in any of the included studies and the effect on miscarriage was too imprecise for any conclusions. Pooled analysis of five studies demonstrated lower clinical pregnancy rates following a non-easy embryo transfer (RR = 0.75; 95% CI = 0.66–0.86). This included three studies showing subjectively difficult transfers reducing clinical pregnancies (RR = 0.67; 95% CI = 0.51–0.87) and two studies in which the need for additional manoeuvers reduced clinical pregnancies (RR = 0.78; 95% CI = 0.67–0.91). The presence of blood on the transfer catheter did not affect clinical pregnancy rates (RR = 0.96; 95% CI = 0.82–1.14) in five studies. We concluded that low quality evidence suggests that a difficult embryo transfer but not a bloody catheter reduces the chance of achieving a clinical pregnancy. More good quality studies are needed to evaluate the effect of difficult embryo transfer and the presence of blood on the catheter on the main outcomes of assisted reproduction.     

Effect of passive uterine straightening during embryo transfer: a systematic review and meta-analysis

BACKGROUND: Part of the success of ultrasound-guided embryo transfer has been associated with the beneficial effect of uterine straightening by passive bladder distention. Even so, this has not been properly analysed in the literature. METHODS: This is a systematic review and meta-analysis of prospective, randomised, controlled trials, comparing embryo transfer with a full versus empty bladder. Electronic (e.g. PubMed, EMBASE, Cochrane Library) and hand searches were performed to locate trials. Primary outcomes were live-birth, ongoing and clinical pregnancy rates. Secondary outcomes were rates of implantation, miscarriage, multiple and ectopic pregnancies, and retained embryos. Also, the ease of transfer, need for instrumental assistance, and presence of blood on the catheter tip were evaluated. Four studies were identified, of which 1 study was excluded. Meta-analysis was conducted with the Mantel-Haenszel method, utilising the fixed-effect model. RESULTS: For the primary outcome measures, no data was available for the LBR rate. There was a significantly higher chance of an ongoing pregnancy [OR=1.44 (95% CI=1.04-2.04)] and clinical pregnancy [OR=1.55 (95% CI=1.16-2.08)] with a full bladder. For the secondary outcomes, there was a significantly greater incidence of difficulty, or need for instrumental assistance, with an empty bladder. Other outcome measures were not significantly different. CONCLUSION: There is evidence in the literature advising to fill the bladder prior to embryo transfer.     

Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis

Purpose

The purpose of this study was to evaluate the best protocol to prepare endometrium for frozen embryo replacement (FER) cycles.

Methods

This study is a systematic review and meta-analysis. Following PubMed and OvidSP search, a total of 1166 studies published after 1990 were identified following removal of duplicates. Following exclusion of studies not matching our inclusion criteria, a total of 33 studies were analyzed. Primary outcome measure was live birth. The following protocols, including true natural cycle (tNC), modified natural cycle (mNC), artificial cycle (AC) with or without suppression, and mild ovarian stimulation (OS) with gonadotropin (Gn) or aromatase inhibitor (AI), were compared.

Results

No statistically significant difference for both clinical pregnancy and live birth was noted between tNC and mNC groups. When tNC and AC without suppression groups are compared, there was a statistically significant difference in clinical pregnancy rate in favor of tNC, whereas it failed to reach statistical significance for live birth. When tNC and AC with suppression groups are compared, there was a statistically significant difference in live birth rate favoring the latter. Similar pregnancy outcome was noted among mNC versus AC with or without suppression groups. Similarly, no difference in clinical pregnancy and live birth was noted when ACs with or without suppression groups are compared.

Conclusions

There is no consistent superiority of any endometrial preparation for FER. However, mNC has several advantages (being patient-friendly; yielding at least equivalent or better pregnancy rates when compared with tNC and AC with or without suppression; may not require LPS). Mild OS with Gn or AI may be promising.

     

Acupuncture performed around the time of embryo transfer: a systematic review and meta-analysis

This was a systematic review and meta-analysis to examine the efficacy, effectiveness and safety of acupuncture as an adjunct to embryo transfer compared with controls to improve reproductive outcomes. The primary outcome was clinical pregnancy. Twenty trials and 5130 women were included in the review. The meta-analysis found increased pregnancies (risk ratio [RR] 1.32, 95% confidence interval [CI] 1.07–1.62, 12 trials, 2230 women), live births (RR 1.30, 95% CI 1.00–1.68, 9 trials, 1980 women) and reduced miscarriage (RR 1.43, 95% CI 1.03–1.98, 10 trials, 2042 women) when acupuncture was compared with no adjunctive control. There was significant heterogeneity, but no significant differences between acupuncture and sham controls. Acupuncture may have a significant effect on clinical pregnancy rates, independent of comparator group, when used in women who have had multiple previous IVF cycles, or where there was a low baseline pregnancy rate. The findings suggest acupuncture may be effective when compared with no adjunctive treatment with increased clinical pregnancies, but is not an efficacious treatment when compared with sham controls, although non-specific effects may be active in both acupuncture and sham controls. Future research examining the effects of acupuncture for women with poorer IVF outcomes is warranted.     

Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis

Mechanical endometrial injury (biopsy/scratch or hysteroscopy) in the cycle preceding ovarian stimulation for IVF has been proposed to improve implantation in women with unexplained recurrent implantation failure (RIF). This is a systematic review and meta-analysis of studies comparing the efficacy of endometrial injury versus no intervention in women with RIF undergoing IVF. All controlled studies of endometrial biopsy/scratch or hysteroscopy performed in the cycle preceding ovarian stimulation were included and the primary outcome measure was clinical pregnancy rate. Pooling of seven controlled studies (four randomized and three non-randomized), with 2062 participants, showed that local endometrial injury induced in the cycle preceding ovarian stimulation is 70% more likely to result in a clinical pregnancy as opposed to no intervention. There was no statistically significant heterogeneity in the methods used, clinical pregnancy rates being twice as high with biopsy/scratch (RR 2.32, 95% CI 1.72–3.13) as opposed to hysteroscopy (RR 1.51, 95% CI 1.30–1.75). The evidence is strongly in favour of inducing local endometrial injury in the preceding cycle of ovarian stimulation to improve pregnancy outcomes in women with unexplained RIF. However, large randomized studies are required before iatrogenic induction of local endometrial injury can be warranted in routine clinical practice.Some women undergoing IVF treatment fail to conceive despite several attempts with good-quality embryos and no identifiable reason. We call this ‘recurrent implantation failure’ (RIF) where the embryo fails to embed or implant within the lining of the womb. Studies have shown that inducing injury to the lining of the womb in the cycle before starting ovarian stimulation for IVF can help improve the chances of achieving pregnancy. Injury can be induced by either scratching the lining of the womb using a biopsy tube or by telescopic investigation of the womb using a camera. We performed a collective review of the available good-quality studies that used the above two methods in the cycle prior to starting ovarian stimulation for IVF. We pooled results from seven studies, which included 2062 women with RIF and assessed the difference in clinical pregnancy rates for those undergoing injury to the womb lining compared with no injury prior to IVF. The results suggest that inducing injury is 70% more likely to result in a clinical pregnancy as opposed to no treatment. Furthermore, scratching of the lining was 2-times more likely to result in a clinical pregnancy compared with telescopic evaluation of the lining of the womb. This study suggests that in women with RIF, inducing local injury to the womb lining in the cycle prior to starting ovarian stimulation for IVF can improve pregnancy outcomes. However, large studies are required before this can be warranted in routine clinical practice.     

Association of embryo transfer type with infertility in endometriosis: a systematic review and meta-analysis

Journal of Assisted Reproduction and Genetics - The study aims to evaluate whether frozen embryo transfer can restore optimal receptivity leading to better assisted reproductive technology outcomes...     

Ectopic pregnancy rates in frozen versus fresh embryo transfer in in vitro fertilization: A systematic review and meta-analysis

ObjectiveTo evaluate whether the rate of ectopic pregnancy differs between fresh and frozen embryo transfers.DesignSystematic review and meta-analysis.SettingCenters for reproductive care.Materials and methodsAn electronic literature search in MEDLINE through PubMed was performed through December 2013. We included clinical trials comparing outcomes of in vitro fertilization (IVF) cycles between fresh and frozen embryo transfers.Main outcome measuresEctopic pregnancy rates from fresh versus frozen IVF cycles.ResultsA meta-analysis revealed no significant difference between ectopic pregnancy rates in fresh versus frozen embryo transfer. Similarly, there was no difference between ectopic pregnancy rates in natural-cycle frozen embryo transfer versus programmed cycles.ConclusionsDifferences in the hormonal milieu of the uterine environment between fresh and frozen embryo transfer stimulation do not appear to affect the ectopic pregnancy rate. More directed studies are needed before a definite recommendation can be made as to which is safer for prevention of ectopic pregnancy– fresh or frozen embryo transfer.     

GLP-1 receptor agonists versus metformin in PCOS: a systematic review and meta-analysis

This meta-analysis aimed to evaluate the efficacy and safety of glucagon-like peptide 1 (GLP-1) receptor agonists for women with polycystic ovary syndrome (PCOS) by comparing their effect with that of metformin. Electronic databases (PubMed, EMBASE, Cochrane Library, WanFang Database, CNKI) dating from their establishment to June 2018 were searched to find all randomized controlled trials (RCTs) reporting the efficacy of GLP-1 receptor agonists versus metformin for patients with PCOS. Therapeutic variables included menstrual cycle, sex hormone and clinical manifestations, glucose metabolism and other metabolic indexes. Eight RCTs among 462 related articles were included in the meta-analysis. Compared with metformin, GLP-1 receptor agonists were more effective in improving insulin sensitivity (standard mean difference [SMD] –0.40, 95% confidence interval [CI] –0.74 to –0.06, P = 0.02) and reducing body mass index (SMD –1.02, 95% CI –1.85 to –0.19, P = 0.02) and abdominal girth (SMD –0.45, 95% CI –0.89 to –0.00, P = 0.05). GLP-1 receptor agonists were associated with a higher incidence of nausea and headache than metformin, but there were no significant differences in other data. Therefore, compared with metformin, GLP-1 receptor agonists might be a good choice for obese patients with PCOS, especially those with insulin resistance. The available evidence is, however, inconclusive given its moderate to low quality. More high-quality research is needed to assess the efficacy of a GLP-1 receptor agonist on women with PCOS.     

Laparoendoscopic single-site surgery versus conventional laparoscopy for hysterectomy: a systematic review and meta-analysis

Purpose

To assess the safety and effectiveness of LESS compared to conventional hysterectomy.

Methods

The systematic review and meta-analysis was performed according to the MOOSE guideline, and quality of evidence was assessed using GRADE. Different databases were searched up to 4th of August 2016. Randomized controlled trials and cohort studies comparing LESS to the conventional laparoscopic hysterectomy were considered for inclusion.

Results

Of the 668 unique articles, 23 were found relevant. We investigated safety by analyzing the complication rate and found no significant differences between both groups [OR 0.94 (0.61, 1.44), I ² = 19%]. We assessed effectiveness by analyzing conversion risk, postoperative pain, and patient satisfaction. For conversion rates to laparotomy, no differences were identified [OR 1.60 (0.40, 6.38), I ² = 45%]. In 3.5% of the cases in the LESS group, an additional port was needed during LESS. For postoperative pain scores and patient satisfaction, some of the included studies reported favorable results for LESS, but the clinical relevance was non-significant. Concerning secondary outcomes, only a difference in operative time was found in favor of the conventional group [MD 11.3 min (5.45–17.17), I ² = 89%]. The quality of evidence for our primary outcomes was low or very low due to the study designs and lack of power for the specified outcomes. Therefore, caution is urged when interpreting the results.

Conclusion

The single-port technique for benign hysterectomy is feasible, safe, and equally effective compared to the conventional technique. No clinically relevant advantages were identified, and as no data on cost effectiveness are available, there are currently not enough valid arguments to broadly implement LESS for hysterectomy.

     

Endometrial preparation for frozen–thawed embryo transfer cycles: a systematic review and network meta-analysis

Purpose

To compare the effects of different endometrial preparation protocols for frozen–thawed embryo transfer (FET) cycles and present treatment hierarchy.

Methods

Systematic review with meta-analysis was performed by electronic searching of MEDLINE, the Cochrane Library, Embase, ClinicalTrials.gov and Google Scholar up to Dec 26, 2020. Randomised controlled trials (RCTs) or observational studies comparing 7 treatment options (natural cycle with or without human chorionic gonadotrophin trigger (mNC or tNC), artificial cycle with or without gonadotropin-releasing hormone agonist suppression (AC+GnRH or AC), aromatase inhibitor, clomiphene citrate, gonadotropin or follicle stimulating hormone) in FET cycles were included. Meta-analyses were performed within random effects models. Primary outcome was live birth presented as odds ratio (OR) with 95% confidence intervals (CIs).

Results

Twenty-six RCTs and 113 cohort studies were included in the meta-analyses. In a network meta-analysis, AC ranked last in effectiveness, with lower live birth rates when compared with other endometrial preparation protocols. In pairwise meta-analyses of observational studies, AC was associated with significant lower live birth rates compared with tNC (OR 0.81, 0.70 to 0.93) and mNC (OR 0.85, 0.77 to 0.93). Women who achieved pregnancy after AC were at an increased risk of pregnancy-induced hypertension (OR 1.82, 1.37 to 2.38), postpartum haemorrhage (OR 2.08, 1.61 to 2.78) and very preterm birth (OR 2.08, 1.45 to 2.94) compared with those after tNC.

Conclusion

Natural cycle treatment has a higher chance of live birth and lower risks of PIH, PPH and VPTB than AC for endometrial preparation in women receiving FET cycles.

     

Labor induction versus expectant management for postterm pregnancies: a systematic review with meta-analysis

OBJECTIVE: To compare routine labor induction with expectant management for patients who reach or exceed 41 weeks' gestation. DATA SOURCES: Computerized databases, references in published studies, and textbook chapters in all languages were used to identify randomized controlled trials (RCTs) evaluating induction and expectant management of labor for postterm pregnancies. METHODS OF STUDY SELECTION: We identified RCTs that compared induction and expectant management for uncomplicated, singleton, live pregnancies of at least 41 weeks' gestation and evaluated at least one of the following: perinatal mortality, mode of delivery, meconium-stained fluid, meconium aspiration syndrome, meconium below the cords, fetal heart rate (FHR) abnormalities during labor, cesarean deliveries for FHR abnormalities, abnormal Apgar scores, and neonatal intensive care unit (NICU) admissions. The primary outcomes assessed were cesarean delivery rate and perinatal mortality. TABULATION, INTEGRATION, AND RESULTS: Sixteen studies met inclusion criteria for this review. For each study with binary outcomes, an odds ratio (OR) with 95% confidence intervals (CIs) was calculated for selected outcomes. Estimates of ORs for dichotomous outcomes were calculated using fixed and random-effects models. Homogeneity was tested across the studies. Compared with women allocated to expectant management, those who underwent labor induction had lower cesarean delivery rates (20.1% versus 22.0%) (OR 0.88; 95% CI 0.78, 0.99). Although subjects whose labor was induced experienced a lower perinatal mortality rate (0.09% versus 0.33%) (OR 0.41; 95% CI 0.14, 1.18), this difference was not statistically significant. Similarly, no significant differences were noted for NICU admission rates, meconium aspiration, meconium below the cords, or abnormal Apgar scores. CONCLUSION: A policy of labor induction at 41 weeks' gestation for otherwise uncomplicated singleton pregnancies reduces cesarean delivery rates without compromising perinatal outcomes.     

Endometrial preparation for frozen–thawed embryo transfer cycles: a systematic review and network meta-analysis

PurposeTo compare the effects of different endometrial preparation protocols for frozen–thawed embryo transfer (FET) cycles and present treatment hierarchy.MethodsSystematic review with meta-analysis was performed by electronic searching of MEDLINE, the Cochrane Library, Embase, ClinicalTrials.gov and Google Scholar up to Dec 26, 2020. Randomised controlled trials (RCTs) or observational studies comparing 7 treatment options (natural cycle with or without human chorionic gonadotrophin trigger (mNC or tNC), artificial cycle with or without gonadotropin-releasing hormone agonist suppression (AC+GnRH or AC), aromatase inhibitor, clomiphene citrate, gonadotropin or follicle stimulating hormone) in FET cycles were included. Meta-analyses were performed within random effects models. Primary outcome was live birth presented as odds ratio (OR) with 95% confidence intervals (CIs).ResultsTwenty-six RCTs and 113 cohort studies were included in the meta-analyses. In a network meta-analysis, AC ranked last in effectiveness, with lower live birth rates when compared with other endometrial preparation protocols. In pairwise meta-analyses of observational studies, AC was associated with significant lower live birth rates compared with tNC (OR 0.81, 0.70 to 0.93) and mNC (OR 0.85, 0.77 to 0.93). Women who achieved pregnancy after AC were at an increased risk of pregnancy-induced hypertension (OR 1.82, 1.37 to 2.38), postpartum haemorrhage (OR 2.08, 1.61 to 2.78) and very preterm birth (OR 2.08, 1.45 to 2.94) compared with those after tNC.ConclusionNatural cycle treatment has a higher chance of live birth and lower risks of PIH, PPH and VPTB than AC for endometrial preparation in women receiving FET cycles.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-021-02125-0.     

Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis

Abstract

The objective of the present systematic review and meta-analysis was to examine the literature and to identify the results of randomized controlled trials (RCTs) comparing the use of letrozole to clomiphene citrate (CC) for ovulation induction in patients with polycystic ovary syndrome (PCOS). An exhaustive electronic literature search was performed using the MEDLINE and EMBASE databases until October 2014. Seven prospective RCTs comparing the use of letrozole to CC in PCOS patients met the inclusion criteria. Overall, the seven included studies accounted for 1833 patients (906 in the letrozole group and 927 in the CC group) and for 4999 ovulation induction cycles (2455 in the letrozole group and 2544 in the CC group). Five of the included studies reported data on live birth rates. There was a statistically significant increase in the live birth and pregnancy rates in the letrozole group when compared to the CC group, with a relative risk (RR)?=?1.55 (95% confidence interval (CI): 1.26–1.90; I^2?=?0%) and RR?=?1.38 (95% CI: 1.05–1.83; I^2?=?61%), respectively. There were no differences in the multiple pregnancy, miscarriage and ovulation rates between the two groups. Our study found that letrozole is superior to CC when considering the live birth and pregnancy rates in patients with PCOS.