Neelam Potdar

Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study

Correction to Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study, dx.doi.org/10.1136/bmj.a2332 available on the LRA at http://hdl.handle.net/2381/16058

First-trimester increase in oxidative stress and risk of small-for-gestational-age fetus

Objective  Investigation of increased oxidative stress in early pregnancy and association with an increased risk of small‐for‐gestational‐age (SGA) fetus.

Oocyte vitrification in the 21st century and post-warming fertility outcomes: a systematic review and meta-analysis

Oocyte cryopreservation is a rapidly developing technology, which is increasingly being used for various medical, legal and social reasons. There are inconsistencies in information regarding survival rate and fertility outcomes. This systematic review and meta-analysis provides evidence-based information about oocyte survival and fertility outcomes post warming to help women to make informed choices. All randomized and non-randomized, controlled and prospective cohort studies using oocyte vitrification were included. The primary outcome measure was ongoing pregnancy rate/warmed oocyte. Sensitivity analysis for donor and non-donor oocyte studies was performed. Proportional meta-analysis of 17 studies, using a random-effects model, showed pooled ongoing pregnancy and clinical pregnancy rates per warmed oocyte of 7%. Oocyte survival, fertilization, cleavage, clinical pregnancy and ongoing pregnancy rates per warmed oocyte were higher in donor versus non-donor studies. Comparing vitrified with fresh oocytes, no statistically significant difference was observed in fertilization, cleavage and clinical pregnancy rates, but ongoing pregnancy rate was reduced in the vitrified group (odds ratio 0.74), with heterogeneity between studies. Considering the age of women and the reason for cryopreservation, reasonable information can be given to help women to make informed choices. Future studies with outcomes from oocytes cryopreserved for gonadotoxic treatment may provide more insight.

THE ENDOCRINOLOGICAL BASIS OF RECURRENT MISCARRIAGES

Purpose of review This review discusses the endocrinological aspects of recurrent miscarriage based on the literature from January 2004 to January 2005, elaborating on the advances in the field and their impact on diagnosis and management. Recent findings Endometrial luteal phase defect is associated with recurrent miscarriage. Fifty years have passed since the diagnostic criteria for dating the endometrial biopsy was established by Noyes et al. This has been the gold standard and last year its accuracy and clinical utility were critically analysed. A Cochrane review has shown a small but statistically significant difference in the live birth rate in the subgroup of women in which progestogen was used to prevent recurrent miscarriage. Endocannabinoids and fatty acid amide hydrolase have been found to have a potential role in signalling for implantation and maintenance of pregnancy. Summary Abnormal secretory endometrial changes may adversely affect the early pregnancy outcome. Other dating techniques using biochemical and molecular markers of endometrial function may prove useful in predicting outcome. Use of progestogens with or without estrogens for prevention of recurrent miscarriage needs to be investigated further in larger randomized controlled trials. The role of endocannabinoids and agents modulating their receptors are potentially very exciting areas to be explored further.

Interlaboratory comparison of methodologies for the measurement of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine

Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) is widely used as a marker of oxidative stress. Here we report the comparison of two, distinct chromatographic assays with an enzyme-linked immunosorbent assay (ELISA). The chromatographic assays displayed good agreement (r =:0.89, p < 0.0001), whereas there was markedly worse, albeit still significant, agreement with the ELISA (high-pressure liquid chromatography followed by gas chromatography (HPLC-GC/MS), r = 0.43; HPLC with electrochemical detection (HPLC-EC), r = 0.56; p < 0.0001). Mean values differed significantly between the chromatographic assays and the ELISA (HPLC-GC/MS 3.86, HPLC-EC 4.20, ELISA 18.70 ng mg−1 creatinine; p < 0.0001). While it is reassuring to note good agreement between chromatographic assays, this study reveals significant short-comings in the ELISA, which brings into question its continued use in its present form.

Definition and epidemiology of unexplained infertility.

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. Target Audience Obstetricians and gynecologists, family Physicians Learning Objectives After completing this CME activity, physicians should be better able to identify the epidemiology of unexplained infertility and standard investigations for infertile couples and to consider other possible causes of infertility before making a diagnosis of unexplained infertility.

Adjunct low-molecular-weight heparin to improve live birth rate after recurrent implantation failure: a systematic review and meta-analysis

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.

British Fertility Society Policy and Practice Committee: adjuvants in IVF: evidence for good clinical practice.

Abstract Optimisation of the environment favourable for satisfactory ovarian response to stimulation and successful embryo implantation remains at the core of assisted conception programmes. The evidence base for the routine use of different adjuvants, alone or in combination, for women undergoing their first in vitro fertilisation (IVF) treatment cycle and for those with poor prognosis is inadequate. The aim of this document is to update the last review of the available literature carried out by the British Fertility Society Policy and Practice Committee (BFS P&P) published in 2009 and to provide fertility professionals with evidence-based guidance and recommendations regarding the use of immunotherapy, vasodilators, uterine relaxants, aspirin, heparin, growth hormone, dehydroepiandrosterone, oestrogen and metformin as adjuvants in IVF. Unfortunately despite the lapse of 5 years since the last publication, there is still a lack of robust evidence for most of the adjuvants searched and large well-designed randomised controlled trials are still needed. One possible exception is metformin, which seems to have a positive effect in women with polycystic ovary syndrome undergoing IVF. Patients who are given other adjuvants on an empirical basis should always be informed of the lack of evidence and the potential side effects.

Donor oocyte conception and pregnancy complications: a systematic review and meta‐analysis

Observational studies showed that women with a donor oocyte (DO) pregnancy have an increased risk of pregnancy complications.

Three-arm age-matched retrospective cohort study of obstetric outcomes of donor oocyte pregnancies

To evaluate and compare obstetric complications between women who conceived after oocyte donation and age‐matched control women who conceived spontaneously or by autologous in vitro fertilization (IVF).