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Background: Embryos created following in-vitro fertilisation (IVF) are usually replaced within the uterus within a few days (fresh embryo transfer). It has been suggested that elective freezing of all embryos followed by transfer at a later date (freeze-all) could make treatment safer and more effective. The aim of this trial was to compare the clinical and cost-effectiveness of a strategy of freeze-all versus fresh embryo transfer. Methods: A two arm, non-blinded, parallel group pragmatic randomised trial was conducted across 18 IVF clinics in the UK. Couples undergoing IVF, where the woman was

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 fetus in women seeking pregnancy. Objective: To determine the risks of congenital malformations and pregnancy loss with letrozole compared with clomiphene primarily, and against other fertility drugs and natural conception. Methods: A systematic review and meta-analysis. Findings: We included 45 studies (18 randomised trials; 20 comparative cohorts; 7 non-comparative cohorts). We did not observe a significant increase in congenital malformations with letrozole vs 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 -0.03, -0.004; I2 = 0%, 10 studies). The risks of pregnancy loss were not increased with letrozole vs 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 vs gonadotrophins, natural conception or natural cycle assisted reproductive technology, but the number of studies was small. Interpretation: There is no evidence that letrozole increases the risk of congenital fetal malformation or pregnancy loss than 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 fetus, clinicians should consider letrozole as first-line agent for ovulation induction. Funding Statement: None. Declaration of Interests: None.

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.

Objective To assess PGD outcome using FISH analysis in couples with a history of recurrent miscarriage associated with a parental carrier of reciprocal translocation. Study design Couples in whom one partner was a carrier of a reciprocal translocation and had a history of two or more miscarriages and a low risk of a live born offspring with an unbalanced chromosomal rearrangement, underwent PGD treatment between 2000 and 2012. Results 91 couples started 171 fresh and 11 frozen PGD cycles. Of the fresh cycles, 162 (95%) reached oocyte retrieval and 107 (63%) had embryo transfer. In 14 cycles (8%), surplus embryos were cryopreserved. Pregnancy was achieved in 52 fresh PGD cycles, leading to 20 miscarriages and 32 live births. Eleven frozen embryo transfer cycles resulted in two miscarriages and three live births. The overall live birth rate was 19% per fresh and frozen PGD cycle started (35/182) and miscarriage rate was 39% per pregnancy (22/57). The cumulative live birth rate was 32% per couple (29/91). Conclusion After PGD for recurrent miscarriage in low-risk reciprocal translocation carriers, the miscarriage risk remains high and chance of live birth is low. For those translocation carriers, natural conception may be a better option.

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.

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