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.

The diagnosis of unexplained infertility can be made only after excluding common causes of infertility using standard fertility investigations,which include semen analysis, assessment of ovulation, and tubal patency test. These tests have been selected as they have definitive correlation with pregnancy. It is estimated that a standard fertility evaluation will fail to identify an abnormality in approximately 15% to 30% of infertile couples. The reported incidence of such unexplained infertility varies according to the age and selection criteria in the study population. We conducted a review of the literature via MEDLINE. Articles were limited to English-language, human studies published between 1950 and 2013. Since first coined more than 50 years ago, the term unexplained infertility has been a subject of debate. Although additional investigations are reported to explain or define other causes of infertility, these have high false-positive results and therefore cannot be recommended for routine clinical practice. Couples with unexplained infertility might be reassured that even after 12 months of unsuccessful attempts, 50% will conceive in the following 12 months and another 12% in the year after.

BACKGROUND Poor fertility outcomes in women with recurrent implantation failure (≥ RIF) present significant challenges in assisted reproduction, and various adjuncts, including heparin, are used for potential improvement in pregnancy rates. We performed this systematic review and meta-analysis to evaluate the effect of low-molecular-weight heparin (LMWH) on live birth rates (LBRs) and implantation rates (IRs) in women with RIF and undergoing IVF. METHODS Studies comparing LMWH versus control/placebo in women with RIF were searched for on MEDLINE, EMBASE, Cochrane Library, conference proceedings and databases for registered and ongoing trials (1980-2012). Statistical analysis was performed using Review Manager 5.1. The main outcome measure was LBR per woman. RESULTS Two randomized controlled trials (RCTs) and one quasi-randomized trial met the inclusion criteria. One study included women with at least one thrombophilia ( Qublan et al., 2008) and two studies included women with unexplained RIF ( Urman et al., 2009; Berker et al., 2011). Pooled risk ratios in women with ≥ 3 RIF (N = 245) showed a significant improvement in the LBR (risk ratio (RR) = 1.79, 95% confidence interval (CI) = 1.10-2.90, P = 0.02) and a reduction in the miscarriage rate (RR = 0.22, 95% CI = 0.06-0.78, P = 0.02) with LMWH compared with controls. The IR for ≥ 3 RIF (N = 674) showed a non-significant trend toward improvement (RR = 1.73, 95% CI 0.98-3.03, P = 0.06) with LMWH. However, the beneficial effect of LMWH was not significant when only studies with unexplained RIF were pooled. The summary analysis for the numbers needed to be treated with LMWH showed that approximately eight women would require treatment to achieve one extra live birth. CONCLUSIONS In women with ≥3 RIF, the use of adjunct LMWH significantly improves LBR by 79% compared with the control group; however, this is to be considered with caution, since the overall number of participants in the studies was small. Further evidence from adequately powered multi-centered RCTs is required prior to recommending LMWH for routine clinical use. This review highlights the need for future basic science and clinical research in this important field.

In women with threatened miscarriage, serum CA 125 has high predictive value in identifying pregnancies that are 'likely to continue', whereas the most commonly used biomarkers of serum hCG and progesterone are not useful in predicting outcome of a pregnancy with a viable fetus. Other markers such as inhibin A and a combination of markers need to be investigated to hopefully improve the prediction of outcome in women with threatened miscarriage.