Paternity pseudo-exclusion caused by tetragametic chimerism in a gestational surrogacy case

Chimerism is a condition when an organism is composed of two or more populations of genetically distinct cells. Chimerism often produces curious results of medical and genetic investigations and could be a major cause of false negative conclusions in parentage testing. Here we describe a paternity pseudo-exclusion due to tetragametic chimerism in a gestational surrogacy case originated in a fertility clinic. Initial analysis using a buccal swab from the child and a peripheral blood sample from the father showed paternity exclusion at 6 STR loci. To find out the reason for observed paternal discrepancy father's semen sample used for IVF and samples from other tissues were genotyped. Buccal swabs, semen, hair follicles, nail clippings and cerumen showed identical mixed autosomal STR profiles originated from two genetically different cell lines and for all the 24 informative loci contain paternal obligate alleles. Results of Y-STR profiling of all paternal sample types showed a DNA profile originated from a single man. The mixed profiles obtained for different tissue types suggest that two genetically different cell lines contributed to formation of both the endoderm and the ectoderm of the father. The mesoderm seems to be monoclonal having originated from a genetically homogenous cell line as evidenced by the STR profile of peripheral blood. Such allelic pattern for various tissues suggests that the clonal origin happened at the very early stage of embryonic development. Approaches to minimise the rate of false exclusions in DNA parentage tests due to chimerism are discussed.     

Gestational surrogacy: a feasible option for patients with Rokitansky syndrome

Rokitansky syndrome is a developmental defect characterized by agenesis of the uterus and vagina but normal gonads and secondary sexual characters. It is not commonly transmitted as a dominant genetic trait. Surrogacy, which is legally and ethically accepted in the UK and other countries, has made it possible for the patients with this syndrome to have their own genetic children. Six patients with Rokitansky syndrome underwent 11 ovarian stimulation cycles that resulted in 11 fresh and three frozen embryo transfer procedures into six prospective surrogate mothers. Both commissioning and surrogate couples were properly screened and counselled and their treatment was approved by the clinic internal review committee (ethics committee). The treatment cycles resulted in six clinical pregnancies (42.9% pregnancy rate per embryo transfer and 54.5% per oocyte retrieval) and three live births (21. 4% per embryo transfer, 27.3% per retrieval and 50% per patient). Gestational surrogacy is a viable treatment for patients with Rokitansky syndrome. Such patients should be well informed and supported to be able to have a family using their own genetic gametes.     

Experience with diagnosis and treatment of sterility due to abnormality of th inundibulum of the Fallopian tube

The diagnosis and treatment of sterility due to abnormalitiesof the infundibulum of the Fallopian tube are reviewed. Knowledgeon the physiology of the distal part of the tube explains themechanisms of sterility when a lesion occurs, although diagnosisis based mainly on hysterosalpingography and laparoscopy. Therequisite treatments are either per-coelioscopk or surgical,and techniques and results with these treatments are reviewed.Special attention is given to tubal stenosis as a consequenceof embryonic cysts of the tube.     

Inhibition of glycopeptidolipid synthesis resulting from treatment of Mycobacterium avium with 2-deoxy-D-glucose

Exponentially growing cultures of Mycobacterium avium complex serovar 4 were treated with 2-deoxy-D-glucose (2-DDG) and incubated with radiolabelled components which incorporate into the serovar-specific glycopeptidolipids (GPL) associated with the L1 layer. Following treatment with the drug, radiolabelled lipids were extracted from the mycobacteria and examined by thin-layer chromatography, high performance liquid chromatography and autoradiography to determine the percent distribution of radioactivity in the GPL and other related lipids. Treatment of serovar 4 with 2-DDG resulted in a dose-dependent inhibition of GPL biosynthesis, as judged by a reduction in the incorporation of radiolabelled phenylalanine, mannose and methionine into the GPL. In addition, a concomitant accumulation of at least two phenylalanine-containing lipopeptides was observed in cells treated with 2-DDG. Cultivation of serovar 4 in the presence of 2-deoxy-D-1,2-(3)H-glucose did not result in internal radiolabelling of the GPL, indicating that 2-DDG was not being incorporated into the GPL as an analogue of mannose, but rather was acting as a metabolic inhibitor of GPL biosynthesis.     

Increased hepatic iron deposition resulting from treatment of chronic hepatitis C with ribavirin

Increased levels of hepatic iron may impair the response of patients with chronic hepatitis C to treatment with interferon-alfa, but combination therapy with ribavirin has demonstrated efficacy in the treatment of hepatitis C. When used alone or with interferon-alfa, ribavirin may cause a dose-dependent reversible hemolytic anemia. We compared the extent and cellular localization of iron deposition in liver tissue from biopsy specimens obtained before and after 36 weeks of therapy with ribavirin or placebo for 59 patients with chronic hepatitis C. Paired slides were available for review from 26 ribavirin and 27 placebo recipients. Iron deposition was assessed using coded slides stained with Perls Prussian blue and was semi-quantitated in hepatocytes, Kupffer cells, and areas of fibrosis. The overall iron score fell by 0.96 in the placebo group and increased 1.69 in the ribavirin recipients. Iron was deposited mainly in hepatocytes; the hepatocyte iron score increased from 2.19 to 3.81 in the ribavirin group. The amount of iron staining in Kupffer cells declined in the placebo group and increased slightly in the ribavirin group. Iron changes in areas of fibrosis were minor and did not differ between groups. Increased total hepatic iron deposition occurred during a 9-month course of ribavirin. Ribavirin-associated hemolysis deposits iron preferentially in hepatocytes. This increased deposition of hepatic iron does not seem to affect the biochemical or histologic response to ribavirin therapy but may have implications for hepatocyte susceptibility to future injury.     

妊娠合并糖尿病的母婴监护体会

妊娠合并糖尿病(GDM)主要指在原有糖尿病基础上合并妊娠者，或妊娠前为隐性糖尿病，妊娠后发展为临床糖尿病患者。现将我院2003年1月至2004年12月对36例GDM患者进行母婴监护的体会介绍如下。     

Simplifying ovulation induction for surrogacy in women with Mayer- Rokitansky-Kuster-Hauser syndrome

A simple approach for ovulation induction in women with Mayer- Rokitansky-Kuster-Hauser Syndrome (MRKH-S) during in-vitro fertilization (IVF)/freezing/surrogacy cycles was evaluated. Weekly progesterone plasma concentrations were measured in order to accurately establish the luteal phase in MRKH-S women. When a rising titre was detected, a gonadotrophin-releasing hormone analogue (GnRHa) was administered as part of a long protocol. Two weeks later human menopausal gonadotrophin (HMG) therapy was started. Ten treatment cycles in four women with MRKH-S were carried out. In all cases, three or less progesterone estimations were needed. Three of the four women are now, through surrogacy, genetic mothers; one of them has two children. We concluded that weekly determination of progesterone plasma concentration is a convenient, efficient and inexpensive simple approach to identify the luteal phase, and therefore suitable to the start of a GnRHa/HMG protocol in MRKH-S women enrolled in an assisted reproduction technology programme.      

Healthy conversation skills as an intervention to support healthy gestational weight gain: Experience and perceptions from intervention deliverers and participants

Objective

In a pilot RCT we assessed training a dietitian in “Healthy Conversation Skills” (HCS) to support behavior change. This study describes the acceptability of the intervention from the participant and practitioner perspective.

腹腔镜对102例女性不孕症诊治的评价分析

目的探讨腹腔镜检查术对女性不孕症的诊治价值。方法回顾性分析腹腔镜检查的102例女性不孕症患者（术后随访2年）,对腹腔镜诊治的结果进行评价。结果镜下诊断盆腔各种病变101例（99.02%）,未发现异常1例（0.08%）。其中输卵管因素54例,子宫内膜异位症34例,卵巢异常8例,子宫异常5例,其他1例。术后随访2年,其妊娠率分别为：输卵管异常31.50%（17/54）,子宫内膜异位症38.24%（13/34）,卵巢异常12.5%（1/8）。结论输卵管因素和子宫内膜异位症是导致女性不孕的主要因素。腹腔镜对诊治输卵管性不孕和子宫内膜异位症,具有快速,准确,可靠,损伤小的特点。     

Endocrine-immune interaction: alteractions in immune function resulting from neonatal treatment with a GnRH antagonist and seasonality in male primates

PROBLEM: The effect of neonatal gonadotropin releasing hormone (GnRH) antagonist (Ant) treatment and seasonality on immune system development and function was investigated in male primates. METHOD OF STUDY: Neonatal male rhesus monkeys and marmosets were treated with Ant, and its effect on immune system morphology, circulating lymphocyte subsets, and cell- and humorally-mediated immune responses was assessed during development. In adult rhesus monkeys, we correlated seasonal changes in immune function with circannual fluctuations in immunoactive hormones. RESULTS: In neonatal marmosets, Ant reduced the number of B cells and T cells in the thymic medulla and T cells in the periarterial lymphatic sheaths (PALS) of the spleen. Ant also altered the development of, but did not permanently impair, the proliferative index (PI) of blood lymphocytes to mitogens. In vitro treatment of control lymphocytes with GnRH analogues altered their response to these proliferative agents. In neonatal rhesus monkeys, Ant treatment increased the frequency of clinical problems, lowered circulating levels of lymphocytes, total T cells, CD8+ T cells and B cells, and altered the PI of lymphocytes to mitogens. As adults, the cell- and humorally-mediated immune responses remained impaired. We also documented seasonal fluctuations in the prevalence of diseases, circulating immune cells and immune function in rhesus monkeys. The number of cases of campylobacteriosis and shigellosis was lowest in the winter and highest in the spring. Circulating numbers of white blood cells (WBC) and neutrophils and the PI of lymphocytes to mitogens were higher in the winter than in the summer. Natural killer cell activity also varied with season. Cortisol and leptin secretion exhibited circannual rhythms, rising in concert with decreasing photoperiod and increasing testicular activity in the fall. Conversely, prolactin levels declined with decreasing photoperiod and then rose in the spring. CONCLUSION: Neonatal exposure of male primates to Ant appears to alter early postnatal programming of immune function. In the rhesus monkey, immune function shows seasonal fluctuations that may be driven by circannual changes in the secretion of immunoactive hormones.