Studies of the Fallopian tube environment and an assessment of its role in assisted reproduction

The role of the Fallopian tube in assisted reproduction remains unclear. The work described in this thesis was undertaken; (1) to study cyclical oestrogen and progesterone receptor changes in the endometrium and Fallopian tube, (2) to determine ultrastructural similarities and differences between endometrial and endosalpingeal epithelia at the different stages of the cycle, (3) to collect tubal fluid and attempt to isolate tubal specific proteins, and (4) to determine the clinical impact of tubal environment in assisted reproduction by conducting a randomised trial comparing tubal and uterine embryo replacements after in vitro fertilization of oocytes. Oestrogen (ER) and progesterone receptors were studied with specific monoclonal antibodies and employing an immunohistochemical technique. The results showed that, in the tube, both the isthmic and ampullary epithelial and stromal ER increased in the follicular phase to a peak at mid cycle, then declined in the late luteal phase whilst the fimbrial end depicted an opposite pattern of staining. Progesterone receptors persisted in all tubal wall layers and endometrial stroma throughout the cycle, but disappeared completely from endometrial gland epithelium in the late luteal phase. The ultrastructural study showed; (1) an increase in ciliated cells along the tube being highest at the fimbria, (2) late follicular phase increase in cytoplasmic fragments and cellular material within the isthmic lumen, but not in the outer tubal segments and (3) similar secretory pattern and surface epithelial changes in the endometrial gland, isthmic and ampullary tubal epithelia. Gel electrophoresis of tubal flushing demonstrated two non-serum bands appearing in the late follicular and luteal phases of the cycle. One hundred and two women were included in the randomised controlled study. Analysis of all treatment cycles (n=227) showed that; (1) the first attempt resulted in a pregnancy rate per embryo transfer (PR/ET) of 29% for tubal and 20% for uterine replacements, and an implantation rate (IR) of 15% and 12% respectively, and (2) women with unexplained infertility benefit most following tubal transfer (PR/ET; tubal 32%, uterine 15% - IR; 14% and 7% respectively). Factors associated with increased PR in the first attempt include previous pregnancies, absent female or male factors, unexplained infertility, and human chorionic gonadotrophin luteal support. Despite an apparently higher PR and IR following tubal transfer, no significant differences were observed in the multiple pregnancy and live birth rates, nor in the implantation rate in cycles resulting in pregnancy. These findings suggest that the embryos' quality is not enhanced following tubal transfer

Telomere instability in the male germline

Telomeres play a key role in upholding the integrity of the genome, and telomerase expression in spermatogonial stem cells is responsible for the maintenance of telomere length in the human male germline. We have previously described extensive allelic variation in somatic cell telomere length that is set in the zygote, the ultimate source of which may be the germline. This implies that despite telomerase activity, substantial telomere length variation can be generated and tolerated in the germline; in order to investigate this further, we have examined the nature of telomere length variation in the human male germline. Here, we describe an analysis of both genome-wide telomere length and single molecule analysis of specific chromosome ends in human sperm. We observed individual specific differences in genome-wide telomere length. This variation may result from genetic differences within the components that determine the telomere length setting of each individual. Superimposed on the genome wide telomere length setting was a stochastic component of variation that generates germ-cells containing severely truncated telomeres. If not re-lengthened during early embryogenesis, such telomeres may limit the replicative capacity of cells derived from the zygote and have the potential to create fusagenic chromosomes, unbalanced translocations and terminal micro-deletions. These data may have implications for the genetic determination of ageing, genetic disease and fertility

Feasibility and acceptability of text messaging to support antenatal healthcare in Iraqi pregnant women: a pilot study

Objective: To determine the feasibility and acceptability of mobile health technology and its potential to improve antenatal care (ANC) services in Iraq. Methods: This was a controlled experimental study conducted at primary health care centers. One hundred pregnant women who attended those centres for ANC were exposed to weekly text messages varying in content, depending on the week of gestation, while 150 women were recruited for the unexposed group. The number of ANC visits in the intervention and control groups, was the main outcome measure. The Mann-Whitney test and the Poisson regression model were the two main statistical tests used. Results: More than 85% of recipients were in agreement with the following statements: “the client recommends this program for other pregnant women”, “personal rating for the message as a whole” and “obtained benefit from the messages”. There was a statistically significant increase in the median number of antenatal clinic visits from two to four per pregnancy, in addition to being relatively of low cost, and could be provided for a larger population with not much difference in the efforts. Conclusions: Text messaging is feasible, low cost and reasonably acceptable to Iraqi pregnant women, and encourages their ANC visits

Medical terminations of pregnancy: A viable source of tissue for cell replacement therapy for neurodegenerative disorders

“Proof-of-principle” that cell replacement therapy works for neurodegeneration has been reported, but only using donor cells collected from fetal brain tissue obtained from surgical terminations of pregnancy. Surgical terminations of pregnancy represent an increasingly limited supply of donor cells due to the tendency towards performing medical termination in much of Europe. This imposes a severe constraint on further experimental and clinical cell transplantation research. Therefore, we explore here the feasibility of using medical termination tissue as a donor source. Products of conception were retrieved from surgical terminations over the last 7 years and from medical terminations over the last 2.5 years. The number of collections that yielded fetal tissue, viable brain tissue, and identifiable brain regions (ganglionic eminence, ventral mesencephalon, and neocortex) were recorded. We studied cell viability, cell physiological properties, and differentiation potential both in vitro and following transplantation into the central nervous system of rodent models of neurodegenerative disease. Within equivalent periods, we were able to collect substantially greater numbers of fetal remains from medical than from surgical terminations of pregnancy, and the medical terminations yielded a much higher proportion of identifiable and dissectible brain tissue. Furthermore, we demonstrate that harvested cells retain the capacity to differentiate into neurons with characteristics appropriate to the region from which they are dissected. We show that, contrary to widespread assumption, medical termination of pregnancy-derived fetal brain cells represent a feasible and more readily available source of human fetal tissue for experimental cell transplantation with the potential for use in future clinical trials in human neurodegenerative disease

Clinical and health service implications of second generation endometrial ablation devices

PURPOSE OF REVIEW: This review evaluates the current evidence on the efficacy, safety and cost-effectiveness of the ever-increasing number of second-generation endometrial ablation devices. RECENT FINDINGS: The literature covered by this review includes (1) evidence on long-term benefit, avoidance of hysterectomy and improvement in quality of life, (2) applicability of these techniques in the outpatient environment under local or no anaesthesia, (3) frequency and nature of early and delayed complications associated with these devices, (4) impact on clinical practice and the health service, and (5) implications for research. SUMMARY: Where appropriate, second-generation devices are rapidly becoming the first-line surgical choice for the management of heavy menstrual bleeding. This has both cost-savings and negative implications for the health service. There is also emerging evidence that improvement in quality of life is more relevant to women than amenorrhoea rates. What has come to light from this review is the lack of accurate data on adverse events rate, and the urgent need for a better appreciation of the frequency and nature of complications

The role and applications of ultrasound in ambulatory gynaecology

Ultrasound has changed gynaecological practice and continues to do so. One of the earliest applications of abdominal scanning in gynaecology was for monitoring follicular development during fertility treatment with clomiphene citrate or gonadotrophins in the 1960s and 1970s. Subsequently, it was natural that with the introduction of in vitro fertilization, abdominal and transvaginal ultrasound played a key role in the development of oocyte retrieval techniques. These were truly the first interventional ultrasound-guided ambulatory procedures in gynaecology. In this chapter, the reader will be introduced to the roles that the various ultrasound modalities play in our current daily practice, and how they have changed the management of numerous gynaecological conditions in both diagnostic and therapeutic contexts. We will also outline the recent developments and the ‘hot’ research topics in this field

Embryo freezing for preventing ovarian hyperstimulation syndrome: a Cochrane review

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition resulting from an excessive ovarian response to superovulation medication. The objective of this review was to evaluate the effectiveness of cryopreservation (embryo freezing) when compared with human i.v. albumin infusion and with fresh embryo transfer for the prevention of OHSS. METHODS: This was based on a Cochrane Review. Randomized controlled trials in which either human i.v. albumin or cryopreservation of all embryos was used as a therapeutic approach to OHSS were included. The participants were women down-regulated by GnRH agonist, undergoing superovulation in IVF/ICSI cycles. The interventions compared were cryopreservation versus i.v. human albumin administration and elective cryopreservation of all embryos versus fresh embryo transfer. The primary outcomes were: incidence of moderate and severe OHSS versus nil/mild OHSS, and clinical pregnancies/woman. Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines. RESULTS: Seventeen studies were identified, two of which met our inclusion criteria. One study was included where cryopreservation was compared with i.v. human albumin administration and another where elective cryopreservation of all embryos was compared with fresh embryo transfer. In both interventions no difference was found in all the outcomes examined between the two groups. CONCLUSIONS: This review has shown that there is insufficient evidence to support routine cryopreservation and insufficient evidence for the relative merits of i.v. albumin versus cryopreservation

Coasting (withholding gonadotrophins) for preventing ovarian hyperstimulation syndrome

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life threatening condition resulting from excessive ovarian stimulation. Its reported incidence varies from 1% to 10% of in vitro fertilization (IVF) cycles. The factors leading to this syndrome have not been completely explained. It seems likely that the release of vasoactive substances, secreted by the ovaries under human chorionic gonadotropin (hCG) stimulation plays a key role in triggering this syndrome. The hallmark of this condition, is a massive shift of fluid from the intra-vascular compartment to the third space resulting in profound intra-vascular depletion and hemoconcentration. OBJECTIVES: The objective of this review is to assess the effect of "coasting" (withholding gonadotrophins) as a preventative strategy in the management of OHSS following superovulation in assisted reproduction treatment on the incidence of all clinical grades of OHSS, in comparison with "early unilateral follicular aspiration (EUFA)" or other interventions. SEARCH STRATEGY: Publications in the literature that described randomised controlled trials (RCTs) in which "coasting" was used as a preventative strategy to OHSS were included. The Cochrane Menstrual Disorders and Subfertility Review Group specialised register of controlled trials was searched. In addition, MEDLINE (PUBMED) 1985 to 2002, EMBASE (1985 to 2001), CINHAL (1985 to 2001) and National Research Register were also searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which coasting was used as a preventative strategy to OHSS were included. DATA COLLECTION AND ANALYSIS: Two reviewers, Mr N.N. Amso (NNA) and Dr A. D'Angelo (ADA) scanned the titles and the abstracts of the reports identified by electronic searching in order to find relevant papers. One reviewer (ADA) obtained copies of the full text articles and made copies for the other reviewer (NNA) in which details of authors, institution, results and discussion were removed in order to assess their eligibility for inclusion. Then, both reviewers extracted data independently using forms designed according to Cochrane guidelines. Disagreements were resolved by discussion. Additional information on the trial methodology or data were requested by writing twice to the corresponding authors directly. The interventions compared were "coasting" versus "early unilateral follicular aspiration (EUFA)" or no "coasting" or other interventions. Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines. MAIN RESULTS: This review identified thirteen studies but only one trial met our inclusion criteria. There was no difference in the incidence of moderate and severe OHSS (n=30, OR 0.76, 95% CI 0.18, 3.24)and in the clinical pregnancy rate (n=30, OR 0.75, 95% CI 0.17, 3.33) between the groups. REVIEWER'S CONCLUSIONS: There is a lack of randomised controlled trials for where coasting is compared with no coasting or other interventions such as embryo freezing or intra-venous albumin infusion for prevention of OHSS. There is insufficient evidence to determine if coasting is an effective strategy for preventing OHSS