Tocolysis with nifedipine versus atosiban and perinatal outcome: an individual participant data meta-analysis.

BACKGROUND: Worldwide, nifedipine and atosiban are the two most commonly used tocolytic agents for the treatment of threatened preterm birth. The aim of this study was to evaluate the effectiveness of nifedipine and atosiban in an individual participant data meta-analysis (IPDMA). METHODS: We investigated the occurrence of adverse neonatal outcomes in women with threatened preterm birth by performing an IPDMA, and sought to identify possible subgroups in which one treatment may be preferred. We searched PubMed, Embase, and Cochrane for trials comparing nifedipine and atosiban for treatment of threatened preterm birth between 240/7 and 340/7 weeks' gestational age. Primary outcome was a composite of perinatal mortality and neonatal morbidities including respiratory distress syndrome, intraventricular haemorrhage, periventricular leucomalacia, necrotising enterocolitis, and sepsis. Secondary outcomes included NICU admission, prolongation of pregnancy and GA at delivery. For studies that did not have the original databases available, metadata was used. This led to a two-stage meta-analysis that combined individual participant data with aggregate metadata. RESULTS: We detected four studies (N = 791 women), of which two provided individual participant data (N = 650 women). The composite neonatal outcome occurred in 58/364 (16%) after nifedipine versus 69/359 (19%) after atosiban (OR 0.76, 95%CI 0.47-1.23). Perinatal death occurred in 14/392 (3.6%) after nifedipine versus 7/380 (1.8%) after atosiban (OR 2.0, 95%CI 0.80-5.1). Nifedipine results in longer prolongation of pregnancy, with a 18 days to delivery compared with 10 days for atosiban (HR 0.83 (96% CI 0.69-0.99)). NICU admission occurred less often after nifedipine (46%) than after atosiban (59%), (OR 0.32, 95%CI 0.14-0.75). The sensitivity analysis revealed no difference in prolongation of pregnancy for 48 hours (OR 1.0, 95% CI 0.73-1.4) or 7 days (OR 1.3, 95% CI 0.85-5.8) between nifedipine and atosiban. There was a non-significant higher neonatal mortality in the nifedipine-exposed group (OR 1.4, 95% CI 0.60-3.4). CONCLUSIONS: In this IPDMA, we found no differences in composite outcome between nifedipine and atosiban in the treatment of threatened preterm birth. However, the non-significant higher mortality after administering nifedipine warrants further investigation of the use of nifedipine as a tocolytic drug. STUDY REGISTRATION: We conducted this study according to a prospectively prepared protocol, registered with PROSPERO (the International Prospective Register of Systematic Reviews) under CRD42016024244.

Admixed human embryos and stem cells: legislative, ethical and scientific advances.

This paper examines the regulatory framework currently governing the creation of animal-human hybrids and chimera embryos in stem cell research, and some of the ethical implications of such research. It discusses the findings of a recent government select committee that considered the topic. It considers the debate around the precise definition of a human embryo, and whether such hybrids therefore fall within the remit of the Human Fertilisation and Embryology Authority. It outlines the advantages of such hybrids, in lessening the need for human egg donors, as well as the moral objections to species boundary violation. It calls for an examination of the scientific benefits of such research to inform debate on the question, and argues for the need to take genuine account of the public's views on this matter.

Atosiban and nifedipine in acute tocolysis: a comparative study.

OBJECTIVE: The objective was to compare the effectiveness, efficacy, and safety of atosiban and nifedipine in preventing or delaying premature labor. DESIGN: An interventional, randomized, controlled trial of 63 women experiencing preterm labor varying from 24 to 35 completed weeks of gestation. The women were randomized to receive either atosiban intravenously (group I, n=31), or nifedipine orally (group II, n=32). RESULTS: There were no significant differences in effectiveness and efficacy of tocolysis between the two groups. Women with a history of preterm labor responded significantly better to atosiban than those with no such history. Those at 28 weeks or less responded significantly better to nifedipine, while those at more than 28 weeks' gestation showed an equal response in the two groups. Nifedipine achieved uterine quiescence in a significantly shorter time than atosiban. The maternal side effects were higher with nifedipine. Neonatal complications were comparable in both groups. CONCLUSIONS: Both drugs are equally effective and efficacious in acute tocolysis. Subgrouping of patients according to gestational age and history of preterm labor may be applied in selecting the line of treatment. The maternal side effects were higher with nifedipine.

Semen quality before and after gonadotoxic treatment.

BACKGROUND: The aim of this study was to analyse the semen quality of patients before and after gonadotoxic therapy. PATIENTS AND METHODS: We evaluated semen quality in 314 patients over a 26 year period. The diagnostic categories were leukaemia (n = 13); lymphoma (n = 128); testicular cancer (n = 102); benign conditions (n = 13); and other malignant neoplasms (n = 58). The degree of azoospermia or oligozoospermia for each disease category was recorded. We then analysed the recovery in semen quality over time for each disease category. RESULTS: The mean patient age was 27.9 years (range 13-65 years). A total of 1115 post-treatment semen samples were analysed from 314 patients. There was a significant reduction in the post-treatment sperm concentration, sperm motility and semen volume compared with pre-treatment levels (P < 0.05) in the entire cohort. However, the sperm movement and motility grade remained unaffected. Patients with testicular carcinoma had the lowest pre-treatment sperm concentrations but also the lowest incidence of azoospermia after cancer treatment. Patients with lymphoma and leukaemia had the highest incidence of post-treatment azoospermia and oligospermia. Patients having the largest reductions in their sperm concentration after treatment required the longest recovery period for spermatogenesis. The diagnostic category was the only significant predictor of post-treatment azoospermia. CONCLUSION: Gonadotoxic treatment results in a significant reduction in sperm quality. The type of cancer or disease, and the pre-treatment sperm concentrations were found to be the most significant factors governing post-treatment semen quality and recovery of spermatogenesis. All categories of patients displayed varying degrees of azoospermia and oligozoospermia, and recovery of gonadal function from these states was not significant. This highlights the importance of ensuring sperm banking before treatment, including for patients with benign conditions. Several factors and associations are discussed further in order to give an insight into the pre- and post-gonadotoxic treatment effects.

Semen quality and cryopreservation in adolescent cancer patients.

BACKGROUND: Adult cancer patients are routinely offered pre-treatment sperm cryopreservation. However, only recently has the welfare of adolescent cancer sufferers gained momentum, including their infertility, and unsurprisingly relatively little is known about their semen quality and feasibility of cryopreservation. METHODS AND RESULTS: A total of 238 adolescent cancer patients referred to our centre between 1991 and 2000, from post-pubertal age up to 19 years 11.9 months, were included. Their semen was processed after appropriate counselling. Semen cryopreservation was possible in 205 of the initial 238 patients referred (86.1%). The pathology of the cancer cases included Hodgkin's lymphoma, non-Hodgkin's lymphoma, osteosarcoma, Ewing's sarcoma, acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), testicular, leukaemia, and others. The mean sperm counts were broadly uniform across the disease and age groups, except for the AML group. There was no cancer group analysed in which sperm could not be stored. Semen volume was broadly uniform across the disease groups, except the ALL and Ewing's sarcoma groups, which showed relatively lower and higher mean semen volumes respectively. Older adolescent patients appeared to have a higher mean semen volume. CONCLUSIONS: Semen cryopreservation was possible in most adolescent cancer cases regardless of age or diagnosis. In all cases the quality of the semen was potentially useful for assisted conception procedures. An offer to freeze sperm in all patients aged >12 years should be made. Adequate support and counselling of both the boys and their parents is essential.

Semen production in adolescent cancer patients.

BACKGROUND: The influence of an accompanying person (parent, guardian or nurse) on the ability of an adolescent (post-pubescent, <20 years of age) to produce a semen sample for cryopreservation, is undetermined, as is the potential for use of urine samples to retrieve sperm in those adolescents that are unable to produce a semen sample. METHODS: The records from 1991-2000 inclusive were reviewed to derive those adolescent patients who were unable to produce semen for cryopreservation prior to undergoing treatment for a malignant condition. RESULTS: During the study period 238 adolescents attended our unit of whom 205 (86.1%) banked semen ('producers'). The remaining 33 adolescents (13.9%) were initially unable to produce a sample ('non-producers'), four of these provided a urine specimen for analysis (12.1%) and of these one had sufficient sperm for cryopreservation. Of the 'accompanied' patients 29.7% (19/64) were non-producers while in the 'unaccompanied' patients only 8.0% (14/174) were non-producers (chi(2) = 16.58, P < 0.001). The relative risk (RR) of not producing a semen sample for the accompanied group of patients was greater than that for the unaccompanied group (RR = 3.689, 95% confidence interval: 2.0-6.9). One patient returning alone successfully provided a semen sample for storage. CONCLUSION: Units should consider the effect of the presence of an accompanying person when an adolescent is unable to produce a semen sample and should consider requesting urine to retrieve sperm.